Ja7b09306 Si 001

Supporting Information
Direct γ-C(sp3)-H Alkylation of Carbonyls through Visible Light

Photoredox Catalysis
Dian-Feng Chen,† John C. K. Chu‡ and Tomislav Rovis*,†

†
Department of Chemistry, Columbia University, New York, New York 10027
‡
Department of Chemistry, Colorado State University, Ft Collins, Colorado 80523
Table of Contents
General Considerations ............................................................................................................................2
Amide Synthesis and Characterization ....................................................................................................3
Examination of Protecting Groups .........................................................................................................20
Examination of Bases .............................................................................................................................21
Examination of Photocatalysts ...............................................................................................................22
Examination of Solvents ........................................................................................................................23
Photoredox-Catalyzed γ-C(sp3)-H Alkylation (Alkene and Amide Scope) ...........................................24
Mechanistic Investigations .....................................................................................................................44
References ..............................................................................................................................................52
NMR Spectra ..........................................................................................................................................53
S1
General Considerations
Commercial reagents and anhydrous solvents were purchased from Sigma-Aldrich,
Alfa and TCI, and were used as received unless otherwise indicated. All catalytic
reactions were carried out under N2 with oven-dried vials. Thin layer chromatography
was performed on SiliCycle® 250 um, 60A plates. Column chromatography was
performed on SiliCycle®SilicaFlash® P60, 40-63 um, 60A. Visualization was
accomplished with I2-silica first, then with phosphomolybdate stain.
1
H, 13C, 31P, and 19F NMR spectra were recorded on a Bruker 500 Hz (126 Hz, 202
13 31 19
Hz and 471 Hz for C, P and F, respectively) spectrometer at ambient temperature.
All NMR spectra are referenced to the residual solvent (CHCl3) signal. Data for 1H, 19F
and 31P NMR are reported as follows: chemical shift (δ ppm), multiplicity (s = singlet, d
= doublet, t = triplet, q = quartet, m = multiplet, br = broad), coupling constant (Hz),
13
integration. Data for C NMR are reported as follows: chemical shift (δ ppm). Several
spectra are from mixtures of rotamers and deconvolution is not possible.
High resolution mass spectra (HRMS) were obtained from Columbia University
Mass Spectrometry Facility on a JOEL JMSHX110HF mass spectrometer using
ESI+/ESI-/ASAP- ionization model. Infrared spectra were recorded on a Perkin Elmer
Paragon 1000 FI-IR spectrometer.
All acrylates (except methyl 2-phenylacrylate1 and 2-benzylacrylate2), methyl vinyl
ketone, N,N-dimethylacrylamide, phenyl vinyl sulfone, diethyl vinylphosphate and
dimethyl maleate were purchased from Aldrich and used as received. All amide
substrates were synthesized according to the general methods as shown below.
S2
Amide Synthesis and Characterization
Procedure A: To a solution of carboxylic acid (1.0 equiv.) and 3 drops of anhydrous
DMF in anhydrous CH2Cl2 (0.2 M) at 0 ˚C, oxalyl chloride (1.2 equiv.) was added
dropwise over 5 mins. The reaction was vigorously stirred at room temperature for 3 h.
After removal of the solvent, the resulting acyl chloride was redissolved in anhydrous
toluene (1.0 M), followed by addition of ethyl carbamate (2.0 equiv.) The slurry was
vigorously stirred at 80 ˚C overnight. After cooling down to room temperature, the
solvent was removed and the residue was purified by flash column chromatography using
hexane/EtOAc as the eluent.
Procedure B: To a solution of carboxylic acid (1.0 equiv.) and Et3N (1.2 equiv.) in
anhydrous THF (0.1 M) at 0 ˚C, ethyl chloroformate (1.1 equiv.) was added dropwise
over 5 mins. The slurry was stirred for 1 h at 0 ˚C. Then 28-35% aq. NH3 (2 mL per
mmol of mixed anhydride) was added dropwise. The mixture was then warmed up to
room temperature and vigorously stirred overnight. The mixture was diluted with EtOAc,
then the organic and aqueous layer were separated. The aqueous layer was extracted with
EtOAc three times (5 mL per mmol of amide). The combined organic layer was washed
with brine, dried over anhydrous Na2SO4, concentrated in vacuo. The crude amide was
pure enough for direct use in further steps.
To a solution of crude amide (1.0 equiv.) and ethyl chloroformate (1.1 equiv.) or
benzoyl chloride (1.1 equiv.) or (-)-menthyl chloroformate (1.1 equiv) in anhydrous THF
(0.2 M) at -78˚C, LiOtBu (1.2 equiv., 1.0M in THF,) was added dropwise over 10 mins.
The reaction was gradually allowed to warm to room temperature over 3 h, and then was
stirred for another hour before being carefully quenched by slow addition of sat. aq.
NH4Cl (5 mL per mmol of amide). The mixture was diluted with EtOAc (5 mL per mmol
of amide), separated, and the aqueous layer was extracted with EtOAc three times (5 mL
per mmol of amide). The combined organic layers were washed with brine, dried over
anhydrous Na2SO4, concentrated in vacuo. The residue was purified by flash column
chromatography using mixed hexane/EtOAc as the eluent.
S3
O
Me
NHCO2Et
Me
Prepared according to Procedure A from commercially available 4-methyl pentanoic acid

(1.16g, 10.0 mmol). Colorless oil (1.39g, 74% yield for 2 steps). Rf = 0.40 (4:1
hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 7.71 (s, 1H), 4.22 (q, J = 7.2 Hz, 2H), 2.79 – 2.74 (m, 2H),
1.68 – 1.52 (m, 3H), 1.31 (t, J = 7.2 Hz, 3H), 0.93 (d, J = 6.5 Hz, 6H).
13
C NMR (126 MHz, CDCl3) δ 175.1, 151.8, 62.2, 34.1, 33.1, 27.7, 22.3, 14.2.
HRMS m/z calcd. for C9H18NO3 [M+H]+ 188.1287, found 188.1287.
IR (cm-1) 3279 (br), 2957, 2871, 1760, 1706, 1514, 1203, 1055.
O
Me
NHBz
Me
Prepared according to Procedure B from commercially available 4-methyl pentanoic acid

(348, 3.0 mmol). White solid (378 mg, 57% yield for 2 steps). Rf = 0.37 (4:1 hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 8.97 (brs, 1H), 8.01 – 7.79 (m, 2H), 7.66 – 7.60 (m, 1H),
7.55 – 7.49 (m, 2H), 3.11 – 2.99 (m, 2H), 1.73 – 1.59 (m, 3H), 0.97 (d, J = 6.4 Hz, 6H).
13
C NMR (126 MHz, CDCl3) δ 176.8, 165.6, 133.2, 132.9, 128.9, 127.7, 35.7, 32.9, 27.7,
22.4.
HRMS m/z calcd. for C13H16NO2 [M-H]- 218.1181, found 218.1178.
IR (cm-1) 3063 (br), 1780, 1723, 1690, 1451, 1210, 1037, 778, 701, 686.
O
Bu
NHCO2Et
Et
Prepared according to Procedure A from commercially available 4-ethyloctanoic acid

(516 mg, 3.0 mmol). Colorless oil (568 mg, 78% yield for 2 steps). Rf = 0.41 (4:1
hex:EtOAc).
S4
1
H NMR (500 MHz, CDCl3) δ 7.39 (s, 1H), 4.21 (q, J = 7.1 Hz, 2H), 2.82 – 2.59 (m,
2H), 1.64 – 1.57 (m, 2H), 1.36 – 1.20 (m, 12H), 0.91 – 0.82 (m, 6H).
13
C NMR (126 MHz, CDCl3) δ 175.0, 151.7, 62.2, 38.5, 33.6, 32.6, 28.8, 27.6, 25.6, 23.0,
14.2, 14.1, 10.7.
IR (cm-1) 3279 (br), 2958, 2927, 1760, 1696, 1499, 1200, 1073.
NHCO2Et
Prepared according to Procedure A from commercially available 3-cyclohexanepropionic

acid (1.56g, 10.0 mmol). Colorless oil (1.87g, 82% yield for 2 steps). Rf = 0.35 (4:1
hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 7.73 (s, 1H), 4.22 (q, J = 7.2 Hz, 2H), 2.77 (t, J = 7.9 Hz,
2H), 1.77 – 1.68 (m, 4H), 1.67 – 1.62 (m, 1H), 1.59 – 1.52 (m, 2H), 1.31 (t, J = 7.1 Hz,
3H), 1.28 – 1.12 (m, 4H), 0.98 – 0.87 (m, 2H).
13
C NMR (125 MHz, CDCl3) δ 175.3, 151.8, 62.2, 37.2, 33.7, 33.0, 31.6, 26.5, 26.2,
14.2.
IR (cm-1) 3279 (br), 2927, 2851, 1759, 1695, 1497, 1198, 1050.
Fe(acac)3 (30 mol%)

methyl acrylate (3.0 equiv)
PhSiH3 (2.0 equiv) NaOH
Cl EtOH, 60 ˚C, 1h Cl Me CO2Me MeOH, 70 ˚C Cl Me CO2H

1h
O O
Procedure B
N OEt
H
Cl Me
Methyl 8-chloro-4-methyloctanoate was synthesized according to Baran’s

procedure.3 To a solution of 6-chlorohex-1-ene (0.59g, 5.0 mmol, 1.0 equiv), methyl
acrylate (1.36 mL, 15.0 mmol, 3.0 equiv) and Fe(acac)3 (0.53g, 1.5 mmol, 0.30 equiv) in
S5
25 mL of anhydrous EtOH at 60 ˚C, PhSiH3 (1.23 mL, 10.0 mmol, 2.0 equiv) was added
dropwise. The mixture was then vigorously stirred at the same temperature for 1h. After
cooling down to room temperature, the solvent was removed in vacuo and the residue
was directly subjected to flash chromatography using 5% EtOAc in hexane as the eluent
to give the crude methyl 8-chloro-4-methyloctanoate with a large amount of
PhSi(OEt)H2.
The crude methyl 8-chloro-4-methyloctanoate was then dissolved in 10.0 mL of
MeOH before 3.0 mL of 2.0 M aq. NaOH was added dropwise. The mixture was
vigorously stirred at 70 ˚C for 1h. After cooling down to room temperature, the mixture
was carefully acidified by slow addition of 10% HCl until pH = 2. The mixture was
extracted with CH2Cl2 (20 mL×3). The organic layer was combined, washed with brine,
dried over anhydrous Na2SO4, and concentrated in vacuo to give the crude
8-chloro-4-methyloctanoic acid as a light yellow oil, which was pure enough for further
steps.
Ethyl (8-chloro-4-methyloctanoyl)carbamate was then synthesized according to
Procedure B. Colorless oil (411mg, 49% yield for 5 steps). Rf = 0.21 (9:1 hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 7.62 (brs, 1H), 4.23 (q, J = 7.1 Hz, 2H), 3.54 (t, J = 6.7
Hz, 2H), 2.95 – 2.65 (m, 2H), 1.82 – 1.66 (m, 3H), 1.57 – 1.27 (m, 8H), 1.24 – 1.14 (m,
1H), 0.92 (d, J = 6.2 Hz, 3H).
13
C NMR (126 MHz, CDCl3) δ 175.0, 151.8, 62.2, 45.1, 35.9, 33.8, 32.8, 32.3, 31.1, 24.3,
19.3, 14.2.
HRMS m/z calcd. for C12H23NO3Cl [M+H]+ 264.1367, found 264.1367.
IR (cm-1) 3280 (br), 2956, 2857, 1760, 1695, 1493, 1120, 1074, 835, 773.
O
TBSO
NHCO2Et
Me
Prepared according to Procedure B from 4-([tert-butyldimethylsilyl]oxy)pentanoic acid

(740 mg, 3.2 mmol).4 Colorless oil (209 mg, 22% for 2 steps). Rf = 0.35 (4:1
hex:EtOAc).
S6
1
2.86 – 2.79 (m, 2H), 1.85 – 1.80 (m, 1H), 1.78 – 1.71 (m, 1H), 1.32 (t, J = 7.1 Hz, 3H),
1.17 (d, J = 6.0 Hz, 3H), 0.90 (s, 9H), 0.07 (s, 6H).
13
C NMR (126 MHz, CDCl3) δ 174.5, 151.6, 67.6, 62.1, 33.6, 32.4, 25.9, 23.7, 18.1, 14.2,
-4.5, -4.8.
HRMS m/z calcd. for C14H30NO4Si [M+H]+ 304.1944, found 304.1940.
IR (cm-1) 3280 (br), 2956, 2857, 1760, 1695, 1493, 1120, 1074, 835, 773.
O
Boc
N
NHCO2Et
Prepared according to Procedure B from

4-(1-[tert-butoxycarbonyl]pyrrolidin-2-yl)butanoic acid (1.22g, 5.0 mmol).5 Colorless oil
(about 60:40 mixture of rotamers, 0.97g, 62% yield for 2 steps). Rf = 0.25 (2:1
hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 8.57 (s, 0.44H), 7.54 (s, 0.42H), 4.35 – 4.03 (m, 2H), 4.00
– 3.78 (m, 1H), 3.51 – 3.23 (m, 2H), 2.88 – 2.52 (m, 2H), 2.03 – 1.80 (m, 4H), 1.78 –
1.62 (m, 2H), 1.47 (s, 9H), 1.31 (t, J = 7.1 Hz, 3H).
13
C NMR (126 MHz, CDCl3) δ 174.3, 173.8, 155.5, 154.7, 151.8, 151.6, 79.3, 62.1, 61.8,
56.5, 56.2, 46.5, 46.0, 33.7, 33.1, 30.7, 30.5, 30.0, 29.1, 28.4, 23.6, 23.0, 14.2.
HRMS m/z calcd. for C15H25N2O5 [M-H]- 313.1764, found 313.1763.
IR (cm-1) 3274 (br), 2974, 1755, 1688, 1512, 1480, 1392, 1201, 1168, 1100, 1073, 773.
O
Me
NHBz
Prepared according to Procedure B from commercially available valeric acid (501mg,

5.0 mmol). Colorless oil (653 mg, 64% yield for 2 steps). Rf = 0.29 (4:1 hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 9.15 (s, 1H), 7.97 – 7.85 (m, 2H), 7.65 – 7.55 (m, 1H),
7.52 – 7.44 (m, 2H), 3.00 (t, J = 7.5 Hz, 2H), 1.74 – 1.63 (m, 2H), 1.48 – 1.36 (m, 2H),
0.95 (t, J = 7.4 Hz, 3H).
S7
13
C NMR (126 MHz, CDCl3) δ 176.8, 165.7, 133.1, 132.9, 128.9, 127.80, 37.4, 26.2,
22.3, 13.9.
IR (cm-1) 3289 (br), 2954, 2870, 1678, 1468, 1241, 706.
O LiOH (5.0 equiv) Procedure B O

MeO MeO
OMe NHCO2Et
0.2 M in THF/H2O (1:1)
rt, overnight
To a solution of methyl 4-methoxybutyrate (1.32g, 10 mmol) in 50 mL of mixed

THF/H2O (1:1) at room temperature, LiOH (1.20 g, 50 mmol) was added in portions. The
mixture was vigorously stirred overnight before being carefully quenched and acidified
until pH = 2. The mixture was extracted with CH2Cl2 (30 mL×3), and the organic layer
was combined, washed with brine, dried over anhydrous Na2SO4, and concentrated in
vacuo to give crude 4-methoxybutanoic acid, which was directly used for next step
without further purification. Ethyl (4-methoxybutanoyl)carbamate was then synthesized
according to Procedure B. Colorless oil (392 mg, 21%yield for 3 steps). Rf = 0.25 (2:1
hex:EtOAc).
1
2H), 3.32 (s, 3H), 2.80 (t, J = 7.3 Hz, 2H), 1.96 – 1.86 (m, 2H), 1.29 (t, J = 7.1 H, 3Hz).
13
C NMR (126 MHz, CDCl3) δ 174.3, 151.8, 71.6, 62.1, 58.5, 33.0, 24.1, 14.2.
IR (cm-1) 3255 (br), 2932, 2857, 1758, 1690, 1495, 1210, 1055.
O
TBSO
NHCO2Et
Prepared according to Procedure B from 4-((tert-butyldimethylsilyl)oxy)butanoic acid

(1.09g, 5.0 mmol).10 Colorless oil (377 mg, 26% yield). Rf = 0.35 (4:1 hex:EtOAc).
1
2H), 2.81 (t, J = 7.2 Hz, 2H), 1.93 – 1.84 (m, 2H), 1.31 (t, J = 7.1 Hz, 3H), 0.90 (s, 9H),
0.06 (s, 6H).
S8
13
C NMR (125 MHz, CDCl3) δ 174.3, 151.8, 62.2, 62.1, 32.8, 27.2, 25.9, 18.3, 14.2,
-5.4.
HRMS m/z calcd. for C13H26NO4Si [M-H]- 288.1631, found 288.1628.
IR (cm-1) 3246 (br), 2930, 2858, 1758, 1691, 1502, 1204, 1075, 845, 772.
Bn O
N
Boc NHBz

4-(benzyl(tert-butoxycarbonyl)amino)butanoic acid (587 mg, 2.0 mmol).11 Colorless oil
(~ 4:5 mixture of rotamers, 344 mg, 43% yield). Rf = 0.25 (3:1 hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 9.42 (brs, 0.47H), 8.85 (brs, 0.38H), 7.99 – 7.82 (m, 2H),
7.65 – 7.56 (m, 1H), 7.55 – 7.45 (m, 2H), 7.37 – 7.30 (m, 2H), 7.30 – 7.20 (m, 3H), 4.55
– 4.40 (m, 2H), 3.40 – 3.20 (m, 2H), 3.04 – 2.82 (m, 2H), 2.01 – 1.88 (m, 2H), 1.52 (s,
4H), 1.46 (s, 5H).
13
C NMR (126 MHz, CDCl3) δ 175.6, 174.9, 165.5, 156.1, 138.3, 133.2, 133.0, 129.0,
128.8, 128.5, 127.8, 127.7, 127.2, 80.1, 79.8, 50.5, 49.8, 45.6, 45.4, 34.8, 28.4, 22.9, 22.5.
IR (cm-1) 3275 (br), 2974, 2929, 1686, 1468, 1415, 1240, 1157, 700.
1. M in O 1. Pd/C, H2, O
O PPh3 MeOH
CH2Cl2 Me Me
Me + OEt OH
H Me CO2Et rt, 24h
Me Me 2. NaOH, MeOH Me Me
Me 70 ˚C, 1h
O
Procedure A
Me
NHCO2Et
Me Me
A solution of isobutyraldehyde (0.72g, 10.0 mmol) and ethyl

2-(triphenylphosphoranylidene)propionate (4.35g, 12.0 mmol) in 10 mL of anhydrous
CH2Cl2 was vigorously stirred at room temperature for 24h. After removal of CH2Cl2,
100 mL of pentane was added and the mixture was sonicated until light yellow precipitate
formed. The slurry was filtered and the filtrate was concentrated in vacuo. Repeated the
S9
Sonication (with Pentane)-Filter Procedure three more time to give crude ethyl
(E)-2,4-dimethylpent-2-enoate as a light yellow oil, which was pure enough for direct use
in the next step.
To a solution of the above ethyl (E)-2,4-dimethylpent-2-enoate in 100 mL of
anhydrous MeOH, 10% Pd/C (500 mg) was added in one portion. The black slurry was
stirred under a H2 atmosphere (balloon) overnight before being filtered through celite.
The filtrate was concentrated to about 20 mL, then 6.0 mL of 2.0 M aq. NaOH was added
dropwise. The mixture was vigorously stirred at 70 ˚C for 1h. After cooling down to
room temperature, the mixture was carefully acidified by slow addition of 10% HCl until
pH = 2. The mixture was extracted with CH2Cl2 (20 mL×3). The organic layer was
combined, washed with brine, dried over anhydrous Na2SO4, and concentrated in vacuo
to give crude 2,4-dimethylpentanoic acid as a light yellow oil.
Ethyl (2,4-dimethylpentanoyl)carbamate was then synthesized according Procedure
A. Colorless oil (407 mg, 20% yield for 5 steps). Rf = 0.40 (4:1 hex:EtOAc).
1
1.73 – 1.59 (m, 2H), 1.33 (t, J = 7.1 Hz, 3H), 1.30 – 1.22 (m, 1H), 1.17 (d, J = 6.9 Hz,
3H), 0.91 (dd, J = 6.5, 5.1 Hz, 6H).
13
C NMR (126 MHz, CDCl3) δ 177.9, 151.4, 62.2, 42.5, 37.5, 25.7, 22.8, 22.3, 17.4,
14.2.
IR (cm-1) 3273 (br), 2957, 2873, 1760, 1705, 1516, 1184, 1039.
Me O Me O Me O
NaOH, MeOH Procedure A
Me Me Me
OMe OH NHCO2Et
70 ˚C, 1h
Me Me Me
To a solution of methyl 3,4-dimethylpentanoate6 (0.72g, 5.0 mmol) in 10 mL of

MeOH, 3.0 mL of 2.0 M aq. NaOH was added dropwise. The mixture was vigorously
stirred at 70 ˚C for 1h. After cooling down to room temperature, the mixture was
carefully acidified by slow addition of 10% HCl until pH = 2. The mixture was extracted
with CH2Cl2 (10 mL×3). The organic layer was combined, washed with brine, dried over
S10
anhydrous Na2SO4, and concentrated in vacuum to give crude 2,4-dimethylpentanoic acid
as a light yellow oil, which was directly used for next step without further purification.
Ethyl (3,4-dimethylpentanoyl)carbamate was then synthesized according to
Procedure A. Colorless oil (285 mg, 28% yield for 3 steps). Rf = 0.41 (4:1 hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 7.80 (s, 1H), 4.22 (q, J = 7.2 Hz, 2H), 2.77 (dd, J = 15.7,
4.8 Hz, 1H), 2.54 (dd, J = 15.7, 9.2 Hz, 1H), 1.98 (ddt, J = 9.5, 7.1, 4.7 Hz, 1H), 1.69 –
1.58 (m, 1H), 1.31 (t, J = 7.1 Hz, 3H), 0.90 (dd, J = 7.0, 2.3 Hz, 6H), 0.87 (d, J = 6.9 Hz,
3H).
13
C NMR (126 MHz, CDCl3) δ 174.6, 151.8, 62.1, 40.6, 35.0, 32.1, 19.9, 18.2, 15.6,
14.2.
IR (cm-1) 3278 (br), 2960, 2875, 1760, 1704, 1506, 1198, 1053.
EDC·HCl (1.3 equiv)

(Boc)2O (1.5 equiv) Boc DMAP (2.5 equiv) Boc
NH2 O NH O NH O
NaHCO3 (5.0 equiv) Benzamide (1.0 eq)
Me Me Me
OH OH NHBz
H2O/acetone (1:1) CH2Cl2 (1M), rt, 24h
Me rt, 12h Me Me
To a solution of DL-β-Leucine (1.31g, 10.0 mmol) in 50 mL of 1:1 mixed

H2O/acetone at room temperature, NaHCO3 (4.2g, 50.0 mmol) and (Boc)2O (3.27g, 15.0
mmol) were added sequentially. The mixture was then vigorously stirred overnight. After
being carefully acidified by aq. HCl (0.5 M) until pH = 2. The mixture was extracted by
CH2Cl2 (30 mL × 3). The combined organic layer was washed by brine (50 mL), dried
over anhydrous Na2SO4 and concentrated in vacuo to give a light yellow solid as the
crude Boc-protected DL-β-Leucine, which was pure enough for the next step.
A mixture of EDC·HCl (500 mg, 2.6 mmol) and DMAP (611 mg, 5.0 mmol) in 2
mL of anhydrous CH2Cl2 was stirred at room temperature for 30 min. Then crude
Boc-protected DL-β-Leucine (462 mg, 2.0 mmol) and benzamide (243 mg, 2.0 mmol)
were then added and the resulting solution was vigorously stirred for 24h. After being
quenched and acidified by aq. HCl (0.5 M) until pH = 2, the reaction was diluted with 50
mL of CH2Cl2 and washed with H2O (30 mL) and brine (30 mL). The organic layer was
then dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was directly
S11
subjected to flash silica gel chromatography to give pure tert-butyl
(1-benzamido-4-methyl-1-oxopentan-3-yl)carbamate as a white solid (128mg, 19%
yield).
1
7.52 – 7.46 (m, 2H), 4.91 (d, J = 9.5 Hz, 1H), 3.98 – 3.82 (m, 1H), 3.20 – 3.01 (m, 2H),
1.96 – 1.84 (m, 1H), 1.39 (s, 10H), 0.97 (d, J = 1.2 Hz, 3H), 0.95 (d, J = 1.2 Hz, 3H).
13
C NMR (126 MHz, CDCl3) δ 174.2, 165.8, 155.8, 133.2, 132.8, 128.9, 127.9, 79.3,
53.1, 40.5, 32.2, 28.4, 19.2, 18.3.
IR (cm-1) 3294 (br), 2966, 1687, 1506, 1485, 1244, 1169, 710.
Me O Me O Me O
10% Pd/C, H2 Procedure A
Me OH Me OH Me NHCO2Et
MeOH, rt, 12h
Me Me
To a solution of 5-methyl-4-methylenehexanoic acid7 (0.71g, 5.0 mmol) in 50 mL of

The filtrate was concentrated to give 4,5-dimethylhexanoic acid as a light yellow oil.
Ethyl (4,5-dimethylhexanoyl)carbamate was then synthesized according to
1
1.80 – 1.55 (m, 2H), 1.51 – 1.42 (m, 1H), 1.41 – 1.35 (m, 1H), 1.32 (t, J = 7.2 Hz, 3H),
0.90 (d, J = 6.8 Hz, 3H), 0.85 (dd, J = 5.9, 5.8 Hz, 6H).
13
C NMR (126 MHz, CDCl3) δ 175.0, 151.7, 62.2, 38.2, 34.3, 31.9, 28.5, 20.1, 17.9, 15.1,
14.2.
IR (cm-1) 3279 (br), 2959, 2873, 1759, 1702, 1499, 1201, 1058.
O O O
10% Pd/C, H2 Procedure A
Me Me Me
OH OH NHCO2Et
MeOH, rt, 12h Me Me
Me Me Me
S12
To a solution of 6-methyl-4-methyleneheptanoic acid7 (0.78g, 5.0 mmol) in 50 mL
of anhydrous MeOH, 10% Pd/C (250 mg) was added in one portion. The black slurry was
The filtrate was concentrated to give 4,6-dimethylheptanoic acid as a light yellow oil.
Ethyl (4,6-dimethylheptanoyl)carbamate was then synthesized according to
1
1.71 – 1.60 (m, 2H), 1.58 – 1.49 (m, 1H), 1.47 – 1.38 (m, 1H), 1.30 (t, J = 7.1 Hz, 3H),
1.16 – 1.08 (m, 1H), 1.06 – 0.97 (m, 1H), 0.86 (d, J = 6.6 Hz, 6H), 0.83 (d, J = 6.5 Hz,
3H).
13
C NMR (126 MHz, CDCl3) δ 175.5, 151.9, 62.1, 46.4, 33.8, 31.5, 30.0, 25.2, 23.3, 22.2,
19.4, 14.2.
IR (cm-1) 3279 (br), 2955, 2870, 1760, 1697, 1467, 1200, 1053.
1. 10% Pd/C, H2
Me O Me O
CO2Et 1.0 M in CH2Cl2 MeOH, rt, 12h
Me H + Me OEt
PPh3 rt, 24h 2. NaOH, MeOH
Me Me 70 ˚C, 1h
Me O Me O
Procedure A
Me NHCO2Et Me OH
Me Me
The mixture of 2,5-dimethylhexanal8 (0.64g, 5.0 mmol) and ethyl

(triphenylphosphoranylidene)acetate (2.09g, 6.0 mmol) in 5.0 mL of anhydrous CH2Cl2
was vigorously stirred at room temperature for 24h. After removal of CH2Cl2, 50 mL of
pentane was added and the mixture was sonicated until light yellow precipitate formed.
The slurry was filtered and the filtrate was concentrated in vacuum. Repeated the
Sonication (with Pentane)-Filter Procedure three more time to give crude ethyl
(E)-4,7-dimethyloct-2-enoate as a light yellow oil, which was pure enough for direct use
in the next step.
S13
To a solution of the above ethyl (E)-4,7-dimethyloct-2-enoate in 50 mL of
to give crude 4,7-dimethyloctanoic acid as a light yellow oil.
Ethyl (4,7-dimethyloctanoyl)carbamate was then synthesized according to
1
1.76 – 1.64 (m, 1H), 1.52 – 1.39 (m, 3H), 1.35 – 1.27 (m, 1H), 1.30 (t, J = 7.1 Hz, 3H),
1.22 – 1.09 (m, 3H), 0.89 (d, J = 6.4 Hz, 3H), 0.86 (dd, J = 6.6, 2.3 Hz, 6H).
13
C NMR (126 MHz, CDCl3) δ 175.3, 151.8, 62.1, 36.2, 34.4, 33.9, 32.7, 31.2, 28.2, 22.7,
22.5, 19.4, 14.2.
IR (cm-1) 3279 (br), 2954, 2870, 1760, 1697, 1498, 1200, 1053.
1. 10% Pd/C, H2
O O
CO2Et MeOH, rt, 12h
1.0 M in CH2Cl2
Ph H + Ph OEt
PPh3 rt, 24h 2. NaOH, MeOH
Me Me 70 ˚C, 1h
O O
Procedure A
Ph NHCO2Et Ph OH
Me Me
The mixture of 2-methyl-3-phenylpropanal9 (0.72g, 5.0 mmol) and Ethyl

(triphenylphosphoranylidene)acetate (2.09g, 6.0 mmol) in 20.0 mL of anhydrous CH2Cl2
was vigorously stirred at room temperature for 24h. After removal of CH2Cl2, 50 mL of
pentane was added and the mixture was sonicated until light yellow precipitate formed.
S14
The slurry was filtered and the filtrate was concentrated in vacuo. Repeated the
Sonication with Pentane-Filter Procedure three more time to give crude ethyl
(E)-4-methyl-5-phenylpent-2-enoate as a light yellow oil, which was pure enough for
direct use in the next step.
To a solution of the above ethyl (E)-4-methyl-5-phenylpent-2-enoate in 50 mL of
to give crude 4-methyl-5-phenylpentanoic acid as a light yellow oil.
Ethyl (4-methyl-5-phenylpentanoyl)carbamate was then synthesized according to
1
4.23 (q, J = 7.1 Hz, 2H), 2.87 (ddd, J = 16.3, 9.8, 5.7 Hz, 1H), 2.79 (ddd, J = 16.2, 9.8,
5.7 Hz, 1H), 2.70 (dd, J = 13.4, 6.0 Hz, 1H), 2.44 (dd, J = 13.4, 8.1 Hz, 1H), 1.89 – 1.73
(m, 2H), 1.60 – 1.51 (m, 1H), 1.33 (t, J = 7.1 Hz, 3H), 0.91 (d, J = 6.6 Hz, 3H).
13
C NMR (126 MHz, CDCl3) δ 174.9, 151.8, 140.9, 129.2, 128.2, 125.8, 62.2, 43.4, 34.6,
33.9, 30.9, 19.1, 14.2.
IR (cm-1) 3278 (br), 2958, 2925, 1759, 1703, 1494, 1199, 1049, 739, 700.
O O
Me Me
N O
H
Me Me
Prepared according to Procedure B from commercially available 4-methyl pentanoic acid

(580 mg, 5.0 mmol). Colorless oil (537 mg, 50% yield). Rf = 0.35 (4:1 hex:EtOAc).
S15
1
H NMR (500 MHz, CDCl3) δ 7.92 (s, 1H), 3.94 (d, J = 6.7 Hz, 2H), 2.76 (t, J = 7.8 Hz,
2H), 2.03 – 1.91 (m, 1H), 1.67 – 1.49 (m, 3H), 0.95 (d, J = 6.8 Hz, 6H), 0.92 (d, J = 6.5
Hz, 6H).
13
C NMR (126 MHz, CDCl3) δ 175.3, 152.0, 72.1, 34.1, 33.0, 27.7, 27.6, 22.3, 18.9.
IR (cm-1) 3268 (br), 2957, 2873, 1757, 1687, 1501, 1215, 1050.
Me
O O
Me
N O
H
Me
Me Me
Prepared according to Procedure B from commercially available 4-methyl

pentanoic acid (348 mg, 3.0 mmol). Colorless oil (407 mg, 46% yield). Rf = 0.42 (4:1
hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 7.42 (brs, 1H), 4.64 (td, J = 10.9, 4.4 Hz, 1H), 2.89 – 2.65
(m, 2H), 2.08 (dtd, J = 11.9, 4.0, 1.7 Hz, 1H), 1.95 – 1.85 (m, 1H), 1.75 – 1.46 (m, 6H),
1.39 (ddt, J = 12.5, 10.7, 3.1 Hz, 1H), 1.15 – 0.99 (m, 2H), 0.93 (dd, J = 8.9, 6.7 Hz,
13H), 0.81 (d, J = 7.0 Hz, 3H).
13
C NMR (126 MHz, CDCl3) δ 175.1, 151.5, 47.0, 40.9, 34.2, 34.1, 33.0, 31.4, 27.7, 26.3,
23.4, 22.3, 22.0, 20.7, 16.4.
IR(cm-1) 3270(br), 2953, 2927, 1754, 1694, 1467, 1207, 1178.
CONHCO2Et

(1S,2S,5R)-2-isopropyl-5-methylcyclohexane-1-carboxylic acid (295 mg, 1.6 mmol).12
White solid (257 mg, 59% yield). Rf = 0.40 (4:1 hex:EtOAc).
S16
1
H NMR (500 MHz, CDCl3) δ 7.59 (s, 1H), 4.23 (q, J = 7.1 Hz, 2H), 3.54 (brs, 1H), 1.96
– 1.84 (m, 2H), 1.82 – 1.75 (m, 1H), 1.75 – 1.63 (m, 2H), 1.62 – 1.52 (m, 1H), 1.32 (t, J
= 7.1 Hz, 3H), 1.26 (ddd, J = 13.9, 12.5, 5.8 Hz, 1H), 1.03 (ddt, J = 12.3, 9.6, 4.3 Hz, 1H),
0.92 (d, J = 6.6 Hz, 3H), 0.86 (dd, J = 10.3, 6.6 Hz, 6H).
13
C NMR (126 MHz, CDCl3) δ 175.4, 151.5, 62.0, 46.5, 41.5, 37.8, 35.2, 30.0, 27.1, 26.0,
22.3, 21.5, 21.4, 14.2.
IR (cm-1) 3271 (br), 2953, 2924, 2871, 1759, 1696, 1517, 1222, 1050, 929.
Me Me Me Me
O Ir(dF-CF3ppy)2(dtbbpy)PF6 (2 mol%)
O O K2HPO4 (1.2 equiv) O O
+
Me NHBz
MeO2C CO2H DMF (0.4M), blue LED MeO2C
NHCOPh
Me
O
Methyl
(4R,5S)-5-(4-benzamido-4-oxobutan-2-yl)-2,2-dimethyl-1,3-dioxolane-4-carboxylate was
synthesized according to MacMillan’s procedure.13 A solution of
14
(4R,5R)-5-(methoxycarbonyl)-2,2-dimethyl-1,3-dioxolane-4-carboxylic acid (613 mg,
3.0 mmol), (E)-N-(but-2-enoyl)benzamide (568 mg, 3.0 mmol),
Ir(dF-CF3ppy)(dtbbpy)PF6 (34 mg, 0.03 mmol) and K2HPO4 (627 mg, 3.6 mmol) in 7.5
mL of anhydrous DMF. The mixture was then degassed with nitrogen gas for 15 mins
before being tightly capped. The reaction was illuminated with a blue LED (Kessil, 34W)
for 12h (the distance between the vial and the LED was about 10 cm and the temperature
was about 45 ˚C). The mixture was diluted with ether (50 mL) and filtered through celite
before being concentrated in vacuo. The residue was directly subjected to flash silica gel
chromatography for purification (EtOAc/hexane = 5:1) to give methyl
(4R,5S)-5-(4-benzamido-4-oxobutan-2-yl)-2,2-dimethyl-1,3-dioxolane-4-carboxylate as a
colorless oil (392 mg, 38% yield).
1
7.65 – 7.59 (m, 1H), 7.55 – 7.48 (m, 2H), 4.39 (d, J = 7.2 Hz, 0.5H), 4.35 (d, J = 6.6 Hz,
0.5H), 4.26 – 4.21 (m, 1H), 3.80 (s, 1.5H), 3.79 (s, 1.5H), 3.28 – 3.20 (m, 1H), 3.02 –
S17
2.92 (m, 1H), 2.61 – 2.47 (m, 1H), 1.49 (s, 1.5H), 1.48 (s, 1.5H), 1.44 (s, 1.5H), 1.43 (s,
1.5H), 1.14 – 1.08 (m, 3H).
13
C NMR (126 MHz, CDCl3) δ 174.9, 174.8, 172.0, 171.8, 165.5, 165.5, 133.3, 133.2,
132.8, 132.7, 129.0, 129.0, 127.7, 111.2, 111.0, 82.4, 81.9, 77.2, 76.6, 52.4, 52.4, 41.4,
40.5, 32.8, 31.4, 27.0, 26.80, 25.6, 25.6, 16.1, 14.5.
IR (cm-1) 3290 (br), 2988, 1681, 1469, 1239, 1207, 1095, 708.
Fe(dibm)3 (30 mol%)

methyl acrylate (6.0 equiv)
O O NaOH O
BnO PhSiH3 (6.0 equiv) BnO BnO
CO2Me MeOH, 70 ˚C CO2H
BnO EtOH, 60 ˚C, 2h BnO BnO
1h
OBn OBn OBn
O
O Procedure B
BnO NHBz
BnO
OBn
Methyl
3-((2R,4R,5S,6R)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)pr
opanoate was synthesized according to Baran’s procedure.3 To a solution of Methyl
opanoate (1.09g, 2.0 mmol) in 10 mL of MeOH, 2.0 mL of 2.0 M aq. NaOH was added
combined, washed with brine, dried over anhydrous Na2SO4, and concentrated in vacuum
to give the crude
opanoic acid as a light yellow oil, which was pure enough for further steps.
N-(3-((2R,4R,5S,6R)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyra
n-2-yl)propanoyl)benzamide was then synthesized according to Procedure B. Colorless
oil (617mg, 53% yield). Rf = 0.37 (2:1 hex:EtOAc).
S18
1
7.65 – 7.59 (m, 1H), 7.55 – 7.48 (m, 2H), 4.39 (d, J = 7.2 Hz, 0.5H), 4.35 (d, J = 6.6 Hz,
0.5H), 4.26 – 4.21 (m, 1H), 3.80 (s, 1.5H), 3.79 (s, 1.5H), 3.28 – 3.20 (m, 1H), 3.02 –
2.92 (m, 1H), 2.61 – 2.47 (m, 1H), 1.49 (s, 1.5H), 1.48 (s, 1.5H), 1.44 (s, 1.5H), 1.43 (s,
1.5H), 1.14 – 1.08 (m, 3H).
13
C NMR (126 MHz, CDCl3) δ 13C NMR (126 MHz, Chloroform-d) δ 175.9, 165.7,
138.5, 138.4, 138.2, 133.1, 132.9, 128.9, 128.5, 128.4, 128.4, 128.0, 127.9, 127.9, 127.7,
127.7, 127.6, 77.0, 76.7, 74.1, 73.4, 72.6, 71.5, 70.2, 69.2, 34.2, 33.5, 26.6.
IR (cm-1) 3280 (br), 2924, 2865, 1681, 1453, 1241, 1092, 1071, 746, 696.
O
H
H NHBz
H H
TBSO
H
Prepared according to Procedure B from TBS-protected lithocholic acid (491 mg,

1.0 mmol).15 White solid (366 mg, 62% yield). Rf = 0.38 (4:1 hex:EtOAc).
1
7.55 – 7.49 (m, 2H), 3.60 (tt, J = 10.9, 4.6 Hz, 1H), 3.07 (ddd, J = 16.5, 10.5, 4.9 Hz, 1H),
2.94 (ddd, J = 16.3, 10.1, 5.7 Hz, 1H), 2.01 – 1.73 (m, 6H), 1.62 – 1.03 (m, 20H), 1.00 (d,
J = 6.5 Hz, 3H), 0.92 (s, 3H), 0.91 (s, 9H), 0.67 (s, 3H), 0.08 (s, 6H).
13
C NMR (126 MHz, CDCl3) δ 177.1, 165.5, 133.1, 132.9, 129.0, 127.7, 72.8, 56.4, 56.1,
42.8, 42.3, 40.2, 40.1, 36.9, 35.9, 35.6, 35.6, 34.8, 34.6, 31.0, 30.2, 28.3, 27.3, 26.4, 26.0,
24.3, 23.4, 20.8, 18.5, 18.3, 12.1, -4.6.
IR (cm-1) 2925, 2860, 1698, 1658, 1275, 1250, 1097, 870, 773, 706, 697.
S19
Examination of Protecting Groups
O
[IrIII{(dF-CF3)ppy}2(dtbpy)] (2 mol%) Me
O Me PG
Me Me Saturated aq. K3PO4 (2.0 eq) N
Me PG + H
N Me
H CO2Me
H 0.2 M in DMF, ~ 40 ˚C
34 W Blue LED, 12h CO2Me 3aa
1a 2a (1.5 equiv)
F CF3
Me Me
Me
CF3
CF3 CF3
F CF3
No product No product 5% 18% 10%
F
Me
F F O O
O O
S OEt OtBu
F R
O
F
R = Me, 32%
No product No product R = Ph, 37% 41% (76%)c 23%
Note:
a0.10 mmol scale reaction.
bNMR yields were presented using trimethoxylbenzene as the internal standard.
c5.0 equiv of methyl methacrylate was used.
S20
Examination of Bases
O
O Me
Me Me Saturated aq. Base (2.0 eq) NHCO2Et
Me
NHCO2Et + Me
CO2Me 0.2 M in DMF, ~ 40 ˚C
H
1a 34 W Blue LED, 12h CO2Me 3aa
2a (5.0 equiv)
Entry Base Conv. % NMR Yield %b

1 K2CO3 90 48
2 Na2CO3 65 38
3 Cs2CO3 95 66
4 Na3PO4 77 53
5 K2HPO4 80 11
6 KH2PO4 <10 trace
7 KHCO3 35 26
8 NaHCO3 <10 trace
9 KOH 80 trace
10 NaOH 50 trace
11 Quinuclidine <10 trace
12 1.1 equiv of K3PO4 95 83
Note:
a
0.10 mmol scale reactions.
b
Trimethoxybenzene as the internal standard.
c
Isolated yield.
S21
Examination of Photocatalysts
O
Photocatalyst (2 mol%) Me
O Me
Me Me Saturated aq. K3PO4 (1.1 eq) NHCO2Et
Me
NHCO2Et + Me
CO2Me 0.2 M in DMF, ~ 40 ˚C
H 34 W Blue LED, 12h
1a 2a (5.0 equiv) CO2Me 3aa
Mes
Ru(ppy)(PF6)2, ~ 25% conv., trace roduct
Ru(bpz)(PF6)2, ~ 20% conv., no product ~ 20% conv., no product
Ir(ppy)2(dtbpy)PF6, ~ 20% conv, trace product N
Me ClO4
CF3 CF3 CF3

F F F
R PF6 PF6
PF6
N N N
N N N
F Ir F Ir F Ir
F3C F3C F3C
N N N N N N
R
F F F F F F
R = 5-CF3
40% conv. ~ 20 % conv. ~ 20 % conv.
22% yield trace product trace product
R CN
NC CN R R
~ 60% conv. ~ 60% conv.
29% yield R=
33% yield R R N
R R
R CN
Note:
a
b
NMR yields were presented using trimethoxybenzene as the internal standard.
S22
Examination of Solvents
O
O Me
Me Me Saturated aq. K3PO4 (1.1 eq) NHCO2Et
Me
NHCO2Et + Me
CO2Me 0.2 M in Solvent, ~ 40 ˚C
H
1a 2a (5.0 equiv) 34 W Blue LED, 12h CO2Me 3aa
Entry Solvent Conv. % NMR Yield %b

1 DMA 88 76
2 DMSO 90 63
3 MeCN 87 33
4 PhCF3 80 trace
5 Toluene 40 trace
6 CHCl3 75 44
7 DCE 75 45
8 Acetone 60 35
9 THF 50 trace
DMF/t-AmylOH
10c 95 84(74)d
(1:1)
Note:
a
b
Trimethoxybenzene as the internal standard.
c
3.0 equiv of methyl methacrylate was used.
d
Isolated yield.
S23
Photoredox-Catalyzed γ-C(sp3)-H Alkylation (Alkene and Amide Scope)
Procedure C: A magnet stir bar, the amide (0.1 mmol, 1.0 equiv.), alkene (1.2 – 3.0
equiv.), sat. aq. K3PO4 (1.1 equiv.) and [Ir{dF-(CF3)ppy}2(dtbbpy)]PF6 (2 mol %) were
charged into an oven-dried vial (4 mL), followed by 1.0 mL of 1:1 mixed
DMF:t-AmylOH. The vial was then bubbled with nitrogen gas for 15 mins before being
tightly capped. The reaction was illuminated with a blue LED (Kessil, 34W) for 12h (the
distance between the vial and the LED was about 15 cm and the temperature was ~40 ˚C).
The mixture was diluted with ether (5.0 mL) and filtered through celite before being
concentrated in vacuo. The residue was directly subjected to flash silica gel
chromatography for purification, using hexane and EtOAc (or acetone) as the eluent.
O
Me
Me
NHCO2Et
Me
CO2Me
Prepared according to Procedure C (with 3.0 equiv. of methyl methacrylate). Colorless

oil (21.3 mg, 74% yield). Rf = 0.20 (4:1 hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 7.59 (s, 1H), 4.23 (q, J = 7.2 Hz, 2H), 3.68 (s, 3H), 2.73 –
2.65 (m, 2H), 2.59 – 2.50 (m, 1H), 1.91 (dd, J = 14.2, 9.5 Hz, 1H), 1.60 – 1.50 (m, 2H),
1.32 (t, J = 7.2 Hz, 3H), 1.23 – 1.14 (m, 4H), 0.89 (s, 6H).
13
C NMR (126 MHz, CDCl3) δ 178.3, 174.8, 151.6, 62.1, 51.7, 45.3, 36.0, 35.6, 32.9,
31.5, 26.8, 26.7, 20.4, 14.2.
IR (cm-1) 3286 (br), 2956, 2874, 1759, 1736, 1710, 1494, 1198, 1049.
O
Me
Me
NHCO2Et
Me
CO2Bn
S24
Prepared according to Procedure C (with 1.5 equiv. of benzyl methacrylate). Colorless
1
H NMR (500 MHz, CDCl3) δ 7.54 (brs, 1H), 7.41 – 7.31 (m, 5H), 5.14 (d, J = 12.3 Hz,
1H), 5.10 (d, J = 12.3 Hz, 1H), 4.23 (q, J = 7.1 Hz, 2H), 2.77 – 2.66 (m, 2H), 2.60 (dqd, J
= 9.9, 7.0, 2.9 Hz, 1H), 1.95 (dd, J = 14.3, 9.3 Hz, 1H), 1.61 – 1.52 (m, 2H), 1.32 (t, J =
7.1 Hz, 3H), 1.26 – 1.13 (m, 4H), 0.88 (s, 6H).
13
C NMR (126 MHz, CDCl3) δ 177.7, 174.8, 151.6, 136.0, 128.5, 128.2, 128.2, 66.3,
62.2, 45.2, 36.0, 35.7, 33.0, 31.5, 26.8, 26.7, 20.4, 14.3.
IR (cm-1) 3285 (br), 2959, 1758, 1707, 1495, 1199, 1074, 750, 698.
O
Me
Me
NHCO2Et
Bn
CO2Me
Prepared according to Procedure C (with 1.5 equiv. of methyl 2-benzylacrylate).

Colorless oil (24.7 mg, 68% yield). Rf = 0.25 (3:1 hex:EtOAc).
1
4.23 (q, J = 7.1 Hz, 2H), 3.56 (s, 3H), 2.91 (dd, J = 12.8, 7.6 Hz, 1H), 2.80 – 2.57 (m,
3H), 2.50 (ddd, J = 16.2, 11.3, 5.5 Hz, 1H), 1.89 (dd, J = 14.3, 10.0 Hz, 1H), 1.59 – 1.43
(m, 2H), 1.37 – 1.30 (m, 4H), 0.85 (s, 3H), 0.84 (s, 3H).
13
C NMR (126 MHz, CDCl3) δ 177.1, 174.7, 151.6, 138.9, 129.0, 128.4, 126.4, 62.1,
51.5, 43.7, 42.7, 40.9, 35.7, 32.8, 31.4, 26.9, 26.8, 14.3.
IR (cm-1) 3288(br), 2955, 1733, 1704, 1494, 1198, 1074, 735, 700.
O
Me
Me
NHCO2Et
Ph
CO2Me
S25
Prepared according to Procedure C (with 1.5 equiv. of methyl 2-phenylacrylate).
1
4.23 (q, J = 7.1 Hz, 2H), 3.70 (dd, J = 9.2, 3.8 Hz, 1H), 3.66 (s, 3H), 2.82 – 2.53 (m, 2H),
2.36 (dd, J = 14.2, 9.2 Hz, 1H), 1.63 – 1.57 (m, 3H), 1.32 (t, J = 7.1 Hz, 3H), 0.93 (s, 3H),
0.92 (s, 3H).
13
C NMR (126 MHz, CDCl3) δ 175.2, 174.7, 151.6, 140.6, 128.7, 127.8, 127.1, 62.2,
52.2, 47.5, 44.9, 35.9, 33.2, 31.5, 26.9, 14.3.
IR (cm-1) 3286 (br), 2955, 1758, 1734, 1494, 1202, 1074, 775, 732, 700.
O
Me
Me
NHCO2Et
CO2Bn
Prepared according to Procedure C (with 1.2 equiv. of benzyl acrylate). Colorless oil
(21.4 mg, 61% yield). Rf = 0.25 (3:1 hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 7.50 – 7.32 (m, 6H), 5.13 (s, 2H), 4.23 (q, J = 7.2 Hz, 2H),
2.75 (t, J = 8.3 Hz, 2H), 2.37 (t, J = 8.3 Hz, 2H), 1.67 – 1.56 (m, 4H), 1.32 (t, J = 7.1 Hz,
3H), 0.92 (s, 6H).
13
C NMR (126 MHz, CDCl3) δ 174.9, 174.0, 151.6, 136.0, 128.5, 128.2, 128.2, 66.2,
62.2, 36.2, 35.5, 32.2, 31.3, 29.7, 26.4, 14.2.
IR (cm-1) 3278 (br), 2923, 2854, 1733, 1705, 1496, 1198, 1074, 738, 698.
O
Me
Me
NHCO2Et
CO2tBu
S26
Prepared according to Procedure C (3.0 equiv. of tert-butyl acrylate). Colorless oil (20.9
mg, 66% yield). Rf = 0.38 (4:1 hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 7.53 (brs, 1H), 4.23 (q, J = 7.1 Hz, 2H), 2.89 – 2.58 (m,
2H), 2.37 – 1.98 (m, 2H), 1.61 – 1.53 (m, 4H), 1.45 (s, 9H), 1.32 (t, J = 7.1 Hz, 3H), 0.91
(s, 6H).
13
C NMR (126 MHz, CDCl3) δ 175.1, 173.6, 151.7, 80.1, 62.2, 36.3, 35.6, 32.2, 31.4,
30.7, 28.1, 26.5, 14.2.
HRMS m/z calcd. for C16H29NO5Na [M+Na]+ 338.1943, found 338.1946
IR (cm-1) 3277 (br), 2971, 2933, 1762, 1727, 1519, 1152, 1042.
O
Me
Me
NHCO2Et
O O
Prepared according to Procedure C (with 2.0 equiv. of allyl acrylate). Colorless oil (18.6
1
H NMR (500 MHz, CDCl3) δ 7.46 (brs, 1H), 5.94 (ddt, J = 17.3, 10.4, 5.7 Hz, 1H), 5.34
(dd, J = 17.2, 1.6 Hz, 1H), 5.25 (dd, J = 10.4, 1.4 Hz, 1H), 4.59 (d, J = 5.7, 2H), 4.23 (q,
J = 7.1 Hz, 2H), 2.79 – 2.70 (m, 2H), 2.40 – 2.26 (m, 2H), 1.65 – 1.53 (m, 4H), 1.32 (t, J
= 7.1 Hz, 3H), 0.92 (s, 6H).
13
C NMR (126 MHz, CDCl3) δ 175.0, 173.8, 151.7, 132.2, 118.2, 65.1, 62.2, 36.2, 35.5,
32.2, 31.3, 29.5, 26.4, 14.2.
IR (cm-1) 3281 (br), 2958, 1757, 1735, 1706, 1492, 1199, 1074, 775.
O
Me
Me
NHCO2Et
Me
CN
S27
Prepared according to Procedure C (with 3.0 equiv. of methacrylonitrile). Colorless oil
1
2H), 2.65 (dtt, J = 10.2, 7.1, 3.6 Hz, 1H), 1.79 (dd, J = 14.3, 10.3 Hz, 1H), 1.67 (qdd, J =
13.9, 10.0, 6.2 Hz, 2H), 1.40 – 1.30 (m, 7H), 1.04 (s, 3H), 1.02 (s, 3H).
13
C NMR (126 MHz, CDCl3) δ 174.6, 151.7, 124.2, 62.3, 45.9, 35.9, 33.0, 31.3, 26.9,
26.6, 20.7, 20.5, 14.2.
IR (cm-1) 3290 (br), 2952, 2115, 1730, 1599, 1456, 1424, 1219, 1191, 630.
O
Me
Me
NHBz
COMe
Prepared according to Procedure C (with 1.5 euqiv. of methyl vinyl ketone). Colorless
1
7.56 – 7.50 (m, 2H), 3.04 – 2.88 (m, 2H), 2.54 – 2.39 (m, 2H), 2.19 (s, 3H), 1.70 – 1.63
(m, 2H), 1.62 – 1.55 (m, 2H), 0.95 (s, 6H).
13
C NMR (126 MHz, CDCl3) δ 209.4, 176.5, 165.4, 133.3, 132.8, 129.0, 127.6, 38.8,
35.4, 35.0, 32.9, 32.1, 30.0, 26.7.
IR (cm-1) 3284 (br), 2955, 2868, 1710, 1682, 1504, 1471, 1241, 710.
O
Me
Me
NHBz
CONMe2
Prepared according to Procedure C (with 2.0 equiv. of N,N´-dimethylacrylamide).

S28
1
7.56 – 7.48 (m, 2H), 3.05 (s, 3H), 2.99 – 2.89 (m, 5H), 2.40 – 2.28 (m, 2H), 1.73 – 1.59
(m, 4H), 0.98 (s, 6H).
13
C NMR (126 MHz, CDCl3) δ 176.3, 173.5, 165.4, 133.2, 132.9, 129.0, 127.6, 37.4,
36.3, 35.5, 33.0, 32.4, 28.3, 26.8.
IR (cm-1) 3262 (br), 2924, 2858, 1685, 1626, 1504, 1481, 1245, 1142, 712.
O
Me
Me
NHBz
SO2Ph
Prepared according to Procedure C (with 1.5 equiv. of vinyl phenyl sulfone) White solid
1
7.69 – 7.62 (m, 2H), 7.61 – 7.57 (m, 2H), 7.56 – 7.50 (m, 2H), 3.21 – 3.11 (m, 2H), 2.98
– 2.85 (m, 2H), 1.75 – 1.68 (m, 2H), 1.65 – 1.55 (m, 2H), 0.94 (s, 6H).
13
C NMR (126 MHz, CDCl3) δ 176.0, 165.3, 139.2, 133.6, 133.3, 132.7, 129.3, 129.1,
128.1, 127.6, 52.3, 35.2, 33.4, 32.6, 32.4, 26.6.
HRMS m/z calcd. for C21H24NO4S [M-H]- 386.1426, found 386.1425.
IR (cm-1) 3290 (br), 2957, 1684, 1473, 1301, 1242, 1148, 1075, 711, 689.
O
Me
Me
NHBz
PO(OEt)2
Prepared according to Procedure C (with 1.5 equiv. of vinyl phosphonate). Colorless oil
(29.8 mg, 78% yield). Rf = 0.35 (5:1 hex:acetone).
S29
1
7.56 – 7.45 (m, 2H), 4.28 – 4.00 (m, 4H), 3.05 – 2.83 (m, 2H), 1.79 – 1.68 (m, 2H), 1.68
– 1.62 (m, 2H), 1.60 – 1.53 (m, 2H), 1.33 (t, J = 7.1 Hz, 6H), 0.95 (s, 6H).
13
C NMR (126 MHz, CDCl3) δ 176.4, 165.5, 133.2, 132.9, 128.9, 127.7, 61.5 (d, J = 6.5
Hz), 35.1, 33.6 (d, J = 5.0 Hz), 32.9, 32.6 (d, J = 16.4 Hz), 26.3, 20.6 (d, J = 141.2 Hz),
16.5 (d, J = 6.0 Hz).
31
P NMR (202 Hz, CDCl3) δ 33.6.
HRMS m/z calcd. for C19H29NO5P [M-H]- 382.1783, found 382.1779.
IR (cm-1) 3239 (br), 2956, 2869, 1684, 1508, 1477, 1242, 1025, 961, 711.
O
Me
Me
NHBz
MeO2C
CO2Me
Prepared according to the Procedure C (with 1.5 equiv. of dimethyl maleate). Colorless
oil (17.2 mg, 47% yield; 8.9 mg starting material was recovered). Rf = 0.20 (3:1
hex:EtOAc).
1
7.53 (dd, J = 8.4, 7.2 Hz, 2H), 3.72 (s, 3H), 3.68 (s, 3H), 3.13 – 2.95 (m, 2H), 2.91 – 2.80
(m, 2H), 2.55 (dd, J = 14.7, 0.9 Hz, 1H), 1.81 – 1.68 (m, 2H), 1.03 (s, 3H), 1.02 (s, 3H).
13
C NMR (126 MHz, CDCl3) δ 175.9, 174.4, 173.0, 165.4, 133.3, 132.7, 129.0, 127.6,
51.8, 51.6, 49.4, 34.9, 34.6, 32.7, 32.2, 25.0, 24.6.
IR (cm-1) 3273 (br), 2967, 1727, 1682, 1469, 1435, 1239, 1159, 1075, 707, 694.
O
Et
Bu
NHCO2Et
CO2tBu
S30
Prepared according to Procedure C (with 3.0 equiv. of tert-butyl acrylate). Colorless oil
1
2H), 2.24 – 2.06 (m, 2H), 1.59 – 1.49 (m, 4H), 1.46 (s, 9H), 1.37 – 1.13 (m, 11H), 0.91 (t,
J = 7.3 Hz, 3H), 0.80 (t, J = 7.5 Hz, 3H).
13
C NMR (126 MHz, CDCl3) δ 175.0, 173.7, 151.6, 80.1, 62.1, 36.7, 35.4, 30.6, 30.4,
29.9, 29.8, 28.2, 28.1, 25.1, 23.5, 14.2, 14.1, 7.5.
HRMS m/z calcd. for C20H37NO5Na [M+Na]+ 394.2570, found 394.2564.
IR (cm-1) 3283 (br), 2960, 2871, 1759, 1709, 1495, 1201, 1152, 1074.
NHCO2Et
Me
CO2Me

1
H NMR (500 MHz, CDCl3) δ 7.70 (brs, 1H), 4.23 (q, J = 7.1 Hz, 2H), 3.67 (s, 3H), 2.85
– 2.44 (m, 2H), 1.94 (dd, J = 14.7, 9.5 Hz, 1H), 1.67 (ddd, J = 14.3, 12.0, 5.4 Hz, 1H),
1.52 (ddd, J = 14.3, 11.9, 4.6 Hz, 1H), 1.48 – 1.35 (m, 6H), 1.34 – 1.28 (m, 2H), 1.31 (t, J
= 7.1 Hz, 3H), 1.28 – 1.21 (m, 3H), 1.18 (d, J = 7.1 Hz, 3H).
13
C NMR (126 MHz, CDCl3) δ 178.6, 174.7, 151.6, 62.1, 51.8, 35.7, 35.5, 35.1, 34.6,
30.7, 26.2, 21.5, 21.4, 20.5, 14.2.
IR (cm-1) 3285 (br), 2924, 2852, 1757, 1706, 1495, 1195, 1073.
O O
Me
N OEt
H
Cl
CO2Bn
S31
1
3.55 (t, J = 6.7 Hz, 2H), 2.77 – 2.67 (m, 2H), 2.38 – 2.30 (m, 2H), 1.79 – 1.72 (m, 2H),
1.67 – 1.57 (m, 3H), 1.44 – 1.36 (m, 2H), 1.32 (t, J = 7.1 Hz, 3H), 1.29 – 1.21 (m, 3H),
0.89 (s, 3H).
13
C NMR (126 MHz, CDCl3) δ 174.8, 173.9, 151.6, 136.0, 128.6, 128.2, 66.3, 62.3, 44.9,
38.1, 34.5, 33.6, 33.2, 33.0, 30.8, 29.0, 24.2, 20.8, 14.2.
HRMS m/z calcd. for C22H33NO5Cl [M+H]+ 426.2047, found 426.2042.
IR (cm-1) 3283 (br), 2936, 1705, 1496, 1201, 1074, 740, 699.
O
OTBS
Me
NHCO2Et
CO2tBu
1
H NMR (500 MHz, CDCl3) δ 7.51 (brs, 1H), 4.23 (q, J = 7.1 Hz, 2H), 2.82 (dd, J = 9.0,
7.2 Hz, 2H), 2.41 – 2.24 (m, 2H), 1.89 – 1.73 (m, 4H), 1.46 (s, 12H), 1.32 (t, J = 7.1 Hz,
3H), 0.88 (s, 9H), 0.12 (s, 6H).
13
C NMR (126 MHz, CDCl3) δ 174.6, 173.3, 151.6, 80.1, 74.4, 62.2, 37.1, 36.0, 31.3,
30.6, 28.1, 27.1, 25.9, 18.2, 14.2, -2.0, -2.1.
HRMS m/z calcd. for C21H41NO6Si [M+Na]+ 454.2601, found 454.2603.
IR (cm-1) 3283 (br), 2930, 2857, 1760, 1710, 1495, 1202, 1153, 1053, 835, 773.
O
NBoc
NHCO2Et
CO2Bn
S32
1
H NMR (500 MHz, CDCl3) δ 7.85 (brs, 0.37H), 7.43 – 7.32 (m, 6H), 5.14 (s, 1.2H),
5.13 (s, 0.8H), 4.22 (q, J = 7.1 Hz, 2H), 3.57 – 3.34 (m, 2H), 2.87 (ddd, J = 16.6, 11.9,
5.0 Hz, 0.5H), 2.72 – 2.58 (m, 1H), 2.56 – 2.47 (m, 0.55H), 2.44 – 2.19 (m, 4H), 2.10 –
2.00 (m, 1H), 1.98 – 1.84 (m, 2H), 1.82 – 1.69 (m, 3H), 1.46 (s, 9H), 1.35 – 1.28 (m, 3H).
13
C NMR (126 MHz, CDCl3) δ 174.1, 173.6, 173.3, 173.2, 154.0, 153.9, 151.6, 151.5,
1136.0, 135.9, 128.6, 128.3, 128.3, 128.2, 128.2, 80.1, 79.3, 66.4, 66.3, 64.7, 63.9, 62.3,
62.0, 49.0, 48.8, 35.8, 34.6, 33.8, 33.0, 32.6, 31.5, 29.8, 29.7, 28.5, 28.4, 21.8, 21.7, 14.2.
IR (cm-1) 3276 (br), 2972, 1731, 1685, 1497, 1390, 1201, 1163, 1075, 699.
O
Me
NHBz
O Me
Prepared according to Procedure C (with 1.5 equiv. of methyl vinyl ketone). Colorless
1
7.53 – 7.47 (m, 2H), 3.08 – 2.92 (m, 2H), 2.55 – 2.38 (m, 2H), 2.15 (s, 3H), 1.81 – 1.64
(m, 2H), 1.60 – 1.42 (m, 3H), 0.94 (d, J = 6.1 Hz, 3H).
13
C NMR (126 MHz, CDCl3) δ 209.2, 176.1, 165.4, 133.2, 132.8, 129.0, 127.6, 41.3,
35.2, 32.1, 30.7, 30.4, 29.9, 19.3.
IR (cm-1) 3286 (br), 2925, 1708, 1681, 1471, 1241, 709.
O
MeO
NHCO2Et
CO2Bn
Prepared according to Procedure C (0.10 mmol of benzyl acrylate and 1.2 equiv. of the
S33
amide). Colorless oil (27.1 mg, 77% yield). Rf = 0.20 (2:1 hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 7.52 (brs, 1H), 7.42 – 7.32 (m, 5H), 5.14 (s, 2H), 4.23 (q,
J = 7.1 Hz, 2H), 3.32 (s, 3H), 3.32 – 3.25 (m, 1H), 2.92 – 2.75 (m, 2H), 2.47 (t, J = 7.6
Hz, 2H), 1.92 – 1.77 (m, 4H), 1.32 (t, J = 7.1 Hz, 3H).
13
C NMR (126 MHz, CDCl3) δ 174.1, 173.4, 151.6, 136.0, 128.5, 128.2, 128.2, 78.9,
66.2, 62.2, 56.7, 31.9, 30.0, 28.4, 27.6, 14.2.
IR (cm-1) 3285 (br), 2931, 1702, 1691, 1497, 1200, 1074, 750, 698.
O
TBSO
NHCO2Et
CO2Bn
Prepared according to Procedure C (0.10 mmol of benzyl acrylate and 1.2 equiv. of the
amide). Colorless oil (22.2mg, 49% yield). Rf = 0.29 (4:1 hex:EtOAc).
1
3.87 – 3.77 (m, 1H), 2.90 – 2.76 (m, 2H), 2.45 (ddd, J = 8.3, 7.2, 1.3 Hz, 2H), 1.92 – 1.72
(m, 4H), 1.32 (t, J = 7.1 Hz, 3H), 0.90 (s, 9H), 0.07 (s, 3H), 0.06 (s, 3H).
13
C NMR (126 MHz, CDCl3) δ 174.3, 173.5, 151.6, 136.0, 128.5, 128.2, 128.2, 70.0,
66.2, 62.2, 31.9, 31.6, 30.8, 29.8, 25.9, 18.0, 14.2, -4.6, -4.6.
IR (cm-1) 3288 (br), 2928, 2855, 1734, 1705, 1702, 1495, 1200, 1073, 836, 750, 697.
O
OTBS
BnO2C
NHCO2Et
CO2Bn
S34
1
H NMR (500 MHz, CDCl3) δ 7.44 – 7.31 (m, 11H), 5.13 (s, 4H), 4.22 (q, J = 7.1 Hz,
2H), 2.88 – 2.76 (m, 2H), 2.49 – 2.39 (m, 4H), 1.92 – 1.78 (m, 6H), 1.31 (t, J = 7.1 Hz,
3H), 0.89 (s, 9H), 0.13 (s, 6H).
13
C NMR (126 MHz, CDCl3) δ 174.0, 173.3, 151.5, 135.9, 128.5, 128.2, 128.2, 76.1,
66.4, 62.3, 34.0, 33.1, 31.0, 29.0, 26.0, 18.5, 14.2, -1.9.
IR (cm-1) 3288 (br), 2928, 2854, 1735, 1496, 1200, 1163, 1098, 835, 774, 697.
Boc O
N
Bn NHBz
PO(OEt)2
Prepared according to Procedure C (with 2.0 equiv. of vinyl phosphate). Colorless oil
(21.2 mg, 38% yield; 20.0 mg starting material was recovered). Rf = 0.20 (5:1
hex:acetone).
1
7.68 – 7.58 (m, 1H), 7.57 – 7.47 (m, 2H), 7.40 – 7.15 (m, 5H), 4.50 (brd, J = 15.4 Hz,
0.5H), 4.40 – 4.30 (m, 1.5H), 4.09 – 3.84 (m, 4H), 2.95 – 2.70 (m, 2H), 2.05 – 1.39 (m,
15H), 1.30 (t, J = 7.1 Hz, 6H).
13
C NMR (126 MHz, CDCl3) δ 175.0, 174.7, 165.2, 165.1, 156.5, 156.4, 139.3, 139.3,
133.2, 133.1, 132.8, 129.0, 128.9, 128.5, 127.6, 127.5, 127.4, 127.1, 80.4, 80.4, 61.5, 61.5,
56.4, 56.0, 47.2, 34.3, 28.5, 28.4, 27.4, 27.3, 26.5, 26.1, 23.5, 22.4, 16.5, 16.4.
31
P NMR (202 MHz, CDCl3) δ 31.9, 31.7.
HRMS m/z calcd. for C29H40N2O7P [M-H]- 559.2573, found 559.2570.
IR (cm-1) 3270 (br), 2976, 2930, 1683, 1453, 1365, 1242, 1161, 1026, 961, 705.
O
Me
Me
NHCO2Et
Me
CO2tBu
S35
1
H NMR (500 MHz, CDCl3) δ 7.44 (brs, 1H), 4.24 (q, J = 7.1 Hz, 2H), 3.36 (brs, 1H),
2.22 – 2.16 (m, 2H), 2.08 (dd, J = 14.3, 8.9 Hz, 1H), 1.54 – 1.49 (m, 2H), 1.45 (s, 9H),
1.33 (t, J = 7.1 Hz, 3H), 1.20 (d, J = 7.0 Hz, 3H), 1.16 (dd, J = 14.3, 2.9 Hz, 1H), 0.87 (s,
3H), 0.84 (s, 3H).
13
C NMR (126 MHz, CDCl3) δ 178.2, 173.6, 151.4, 80.0, 62.2, 44.6, 37.0, 32.9, 30.8,
28.1, 26.8, 26.7, 20.7, 14.2.
IR (cm-1) 3278 (br), 2970, 1756, 1719, 1501, 1201, 1155, 1045.
Me O
Me
Me
NHCO2Et
CO2tBu
Prepared according to Precedure C (with 3.0 equiv. of tert-butyl acrylate). Colorless oil
1
H NMR (500 MHz, CDCl3) δ 7.56 (brs, 1H), 4.22 (q, J = 7.1 Hz, 2H), 2.84 (dd, J = 16.1,
2.8 Hz, 1H), 2.52 (dd, J = 16.0, 10.8 Hz, 1H), 2.21 (dd, J = 8.9, 7.7 Hz, 2H), 1.98 (dqd, J
= 13.5, 6.8, 2.8 Hz, 1H), 1.65 – 1.51 (m, 2H), 1.46 (s, 9H), 1.32 (t, J = 7.1 Hz, 3H), 0.91
(d, J = 6.8 Hz, 3H), 0.87 (s, 3H), 0.86 (s, 3H).
13
C NMR (126 MHz, CDCl3) δ 174.5, 173.8, 151.6, 80.1, 62.2, 38.5, 36.6, 34.8, 34.7,
30.4, 28.1, 28.1, 24.2, 24.0, 14.5, 14.2.
IR (cm-1) 3283 (br), 2970, 1760, 1725, 1499, 1202, 1153, 1047.
Boc
NH O
Me
NHBz
Me
CO2Bn
S36
Prepared according to the Procedure C (with 1.2 equiv. of Benzyl acrylate). Colorless oil
(21.1 mg, 43% yield; 14.2 mg starting material was recovered). Rf = 0.22 (4:1
hex:EtOAc).
1
7.56 – 7.46 (m, 2H), 7.44 – 7.31 (m, 5H), 5.13 (s, 2H), 4.78 (d, J = 10.2 Hz, 1H), 4.12 (td,
J = 10.5, 3.7 Hz, 1H), 3.26 (dd, J = 13.8, 3.6 Hz, 1H), 2.92 (dd, J = 13.8, 10.5 Hz, 1H),
2.51 – 2.39 (m, 2H), 1.80 – 1.61 (m, 2H), 1.38 (s, 9H), 0.97 (d, J = 10.5 Hz, 6H).
13
C NMR (126 MHz, CDCl3) δ 173.9, 173.7, 165.7, 155.8, 136.0, 133.2, 132.9, 128.9,
128.5, 128.2, 128.1, 127.8, 79.4, 66.3, 54.4, 39.0, 37.2, 33.8, 29.2, 28.3, 23.4, 23.1.
IR (cm-1) 3298 (br), 2967, 1712, 1681, 1502, 1474, 1242, 1161, 709, 697.
Me O
Me
Me NHCO2Et
CO2tBu
(14.5 mg, 42% yield; 7.9 mg starting material was recovered). Rf = 0.41 (4:1 hex:EtOAc).
1
2H), 2.24 – 2.21 (m, 2H), 1.69 – 1.51 (m, 5H), 1.46 (s, 9H), 1.32 (t, J = 7.2 Hz, 3H), 0.87
(s, 3H), 0.86 (s, 3H), 0.81 (s, 3H).
13
C NMR (126 MHz, CDCl3) δ 175.1, 173.7, 151.6, 80.1, 62.2, 36.6, 33.6, 31.1, 30.8,
30.6, 30.1, 28.1, 20.6, 17.0, 17.0, 14.2.
IR (cm-1) 3283 (br), 2967, 2875, 1758, 1709, 1495, 1200, 1152, 1073.
O
Me
Me
NHCO2Et
Me
CO2tBu
S37
1
2H), 2.31 – 2.04 (m, 2H), 1.75 – 1.65 (m, 1H), 1.64 – 1.51 (m, 4H), 1.45 (s, 9H), 1.31 (t,
J = 7.1 Hz, 3H), 1.16 (d, J = 5.3 Hz, 2H), 0.94 (s, 3H), 0.92 (s, 3H), 0.89 (s, 3H).
13
C NMR (126 MHz, CDCl3) δ 175.1, 173.6, 151.7, 80.1, 62.2, 47.9, 35.2, 34.3, 33.6,
31.0, 30.4, 28.1, 25.51, 24.7, 23.7, 14.2.
IR (cm-1) 3282 (br), 2956, 2870, 1759, 1709, 1493, 1367, 1200, 1151, 1074.
Me O
Me
Me NHCO2Et
CO2tBu
1
2H), 2.24 – 2.10 (m, 2H), 1.60 – 1.52 (m, 4H), 1.50 – 1.40 (m, 1H), 1.46 (s, 9H), 1.32 (t,
J = 7.1 Hz, 3H), 1.24 – 1.17 (m, 2H), 1.15 – 1.08 (m, 2H), 0.90 (s, 3H), 0.89 (s, 3H), 0.86
(s, 3H).
13
C NMR (126 MHz, CDCl3) δ 175.0, 173.7, 151.6, 80.1, 62.2, 36.5, 34.3, 33.8, 33.1,
32.3, 30.9, 30.3, 28.7, 28.1, 24.3, 22.7, 14.2.
IR (cm-1) 3282 (br), 2955, 2929, 2869, 1759, 1709, 1468, 1366, 1200, 1151, 1074.
O
Me
Ph NHCO2Et
CO2tBu
Prepared according to the Procedure C (with 3.0 equiv. of tert-butyl acrylate). Colorless
S38
oil (16.9 mg, 43% yield; 12.1 mg starting material was recovered). Rf = 0.22 (4:1
hex:EtOAc).
1
7.17 – 7.13 (m, 2H), 4.24 (q, J = 7.1 Hz, 2H), 2.88 – 2.72 (m, 2H), 2.57 (s, 2H), 2.40 –
2.19 (m, 2H), 1.68 – 1.54 (m, 4H), 1.47 (s, 9H), 1.33 (t, J = 7.1 Hz, 3H), 0.87 (s, 3H).
13
C NMR (126 MHz, CDCl3) δ 174.7, 173.4, 151.6, 138.1, 130.6, 127.9, 126.1, 80.2,
62.2, 45.6, 36.0, 33.3, 32.8, 31.0, 30.4, 28.1, 24.0, 14.2.
IR (cm-1) 3280 (br), 2975, 2928, 1758, 1709, 1494, 1367, 1200, 1150, 1074, 737, 703.
O O
Me Me
Me Me
N O
H
Me H
CO2Me

1
H NMR (500 MHz, CDCl3) δ 7.57 (brs, 1H), 3.95 (d, J = 6.6 Hz, 2H), 3.68 (s, 3H), 2.71
(ddd, J = 10.0, 5.5, 2.3 Hz, 2H), 2.60 – 2.50 (m, 1H), 2.07 – 1.84 (m, 2H), 1.62 – 1.50 (m,
2H), 1.23 – 1.15 (m, 4H), 0.97 (d, J = 6.8 Hz, 6H), 0.89 (s, 6H).
13
C NMR (126 MHz, CDCl3) δ 178.3, 174.8, 151.8, 72.1, 51.7, 45.3, 36.0, 35.6, 32.9,
31.5, 27.7, 26.8, 26.7, 20.4, 18.9.
IR (cm-1) 3280 (br), 2957, 2875, 1736, 1497, 1199, 1075.
Me
O O
Me
Me
N O
H
Me
Me Me
CO2Me
S39
oil (~1:1 mixed diastereomers, 24.7 mg, 62% yield). Rf = 0.23 (4:1 hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 7.56 (brd, 1H), 4.63 (td, J = 10.9, 4.4 Hz, 1H), 3.67 (s,
3H), 2.77 – 2.64 (m, 2H), 2.55 (tt, J = 9.9, 6.9 Hz, 1H), 2.11 – 2.03 (m, 1H), 1.97 – 1.84
(m, 2H), 1.74 – 1.65 (m, 2H), 1.60 – 1.45 (m, 3H), 1.43 – 1.33 (m, 1H), 1.24 – 1.14 (m,
4H), 1.12 – 0.97 (m, 2H), 0.95 – 0.86 (m, 13H), 0.80 (d, J = 6.9 Hz, 3H).
13
C NMR (126 MHz, CDCl3) δ 178.3, 178.3, 175.0, 151.4, 151.4, 51.7, 51.7, 47.0, 45.4,
40.9, 40.9, 36.0, 36.0, 35.6, 34.1, 32.9, 31.5, 31.5, 31.4, 26.8, 26.7, 26.3, 26.3, 23.4, 23.4,
22.0, 20.7, 20.4, 16.4, 16.4.
IR (cm-1) 3276 (br), 2953, 1737, 1457, 1370, 1201, 1178.
NHCO2Et
O
Me Me
CO2Bn
Prepared according to Procedure C (1.2 equiv. of benzyl accrylate). Colorless oil (22.6
1
H NMR (500 MHz, CDCl3) δ 7.42 – 7.31 (m, 6H), 5.12 (d, J = 1.6 Hz, 2H), 4.24 (q, J =
7.1 Hz, 2H), 3.32 (brs, 1H), 2.40 (ddd, J = 16.5, 11.6, 5.2 Hz, 1H), 2.32 (ddd, J = 16.1,
11.6, 5.3 Hz, 1H), 1.93 – 1.86 (m, 1H), 1.86 – 1.79 (m, 2H), 1.76 – 1.63 (m, 2H), 1.52
(ddd, J = 14.0, 11.5, 5.2 Hz, 1H), 1.42 – 1.28 (m, 1H), 1.33 (t, J = 7.1 Hz, 3H), 1.23 -
1.13 (m, 1H), 1.13 – 1.04 (m, 1H), 1.00 – 0.93 (m, 1H), 0.89 (d, J = 6.5 Hz, 3H), 0.87 (s,
6H).
13
C NMR (126 MHz, CDCl3) δ 178.2, 174.2, 151.4, 136.1, 128.5, 128.2, 128.1, 66.1,
62.2, 43.3, 40.8, 35.9, 35.9, 34.5, 31.8, 29.2, 26.7, 26.1, 25.2, 22.1, 14.2.
HRMS m/z calcd. for C24H34NO5 [M-H]- 416.2437, found 416, 2439.
IR (cm-1) 3271 (br), 2949, 1759, 1735, 1704, 1498, 1159, 1182, 1045, 749, 697.
S40
Me Me
O O CO2Bn
MeO2C
NHCOPh
Me
O
Prepared according to Procedure C (1.2 equiv. of benzyl accrylate). Colorless oil (18.8
mg, 37% yield; 20.0 mg starting material was recovered). Rf = 0.24 (3:1 hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 8.81 – 8.66 (m, 1H), 7.92 – 7.84 (m, 2H), 7.66 – 7.58 (m,
1H), 7.56 – 7.47 (m, 2H), 7.41 – 7.32 (m, 5H), 5.22 – 4.98 (m, 2H), 4.75 – 4.42 (m, 1H),
3.86 – 3.69 (m, 3H), 3.57 – 3.21 (m, 1H), 3.06 – 2.44 (m, 4H), 2.34 – 1.91 (m, 2H), 1.64
– 1.53 (m, 3H), 1.49 – 1.36 (m, 3H), 1.18 – 0.89 (m, 3H).
13
C NMR (126 MHz, CDCl3) δ 175.0, 174.9, 174.6, 173.8, 173.5, 173.3, 173.0, 169.8,
169.4, 168.9, 165.4, 165.4, 165.3, 165.3, 135.9, 133.3, 133.2, 133.1, 133.1, 133.0, 132.7,
129.0, 129.0, 129.0, 129.0, 128.6, 128.6, 128.5, 128.5, 128.4, 128.3, 128.3, 128.2, 127.6,
127.6, 127.6, 127.6, 110.4, 110.1, 109.6, 109.5, 87.0, 86.3, 86.3, 80.7, 79.8, 66.5, 66.5,
66.3, 52.4, 52.4, 40.5, 40.5, 40.3, 39.7, 37.2, 35.1, 32.7, 32.6, 29.7, 29.4, 28.9, 28.9, 28.7,
28.5, 28.1, 27.8, 27.7, 27.6, 27.2, 27.0, 27.0, 26.6, 26.5, 26.5, 16.0, 15.2, 15.2, 15.1.
HRMS m/z calcd. for C28H34NO8 [M+H]+ 512.2285, found 512, 2295.
IR (cm-1) 3292 (br), 2935, 1731, 1680, 1467, 1382, 1240, 1207, 1173, 1102, 699.
OBn
H
BnO O
BnO PO(OEt)2
H H
H
H
NOE CONHBz
Prepared according to Procedure C (with 2.0 equiv of ethyl phosphate). Light yellow oil
(~4.4:1 mixture of diastereomers, 30.8 mg, 41% yield; 30.1 mg starting material was
recovered). Rf = 0.41 (1:4 hex:EtOAc).
1
H NMR (500 MHz, CDCl3) δ 8.73 (s, 0.77H), 8.71 (s, 0.17H), 7.88 – 7.80 (m, 2H), 7.65
– 7.58 (m, 1H), 7.54 – 7.47 (m, 3H), 7.40 – 7.20 (m, 15H), 4.90 (d, J = 10.9 Hz, 0.79H),
4.74 – 4.43 (m, 5.2H), 4.25 – 4.20 (m, 0.17H), 4.15 – 4.02 (m, 4H), 3.93 – 3.85 (m,
S41
0.79H), 3.77 – 3.40 (m, 4H), 3.11 – 2.88 (m, 2H), 2.75 – 2.65 (m, 0.18H), 2.23 – 2.12 (m,
0.82H), 2.09 – 1.98 (m, 1.80H), 1.93 – 1.62 (m, 5H), 1.35 – 1.29 (m, 6H).
13
C NMR (126 MHz, CDCl3) δ 175.3, 165.4, 138.5, 138.4, 138.4, 133.1, 132.9, 129.0,
128.9, 128.4, 128.4, 128.4, 128.3, 128.3, 127.9, 127.8, 127.7, 127.7, 127.6, 127.6, 127.5,
127.5, 127.4, 127.4, 78.9, 78.3, 75.2, 75.1, 75.0, 73.8, 73.4, 73.3, 72.8, 72.5, 72.4, 72.2,
71.8, 71.2, 70.1, 69.9, 67.5, 61.7, 61.7, 61.6, 61.5, 37.7, 33.0, 32.2, 32.1, 31.1, 29.7, 28.0,
25.6, 25.6, 19.6, 18.4, 16.5, 16.5.
31
P NMR (202 MHz, CDCl3) δ 33.5, 32.9.
HRMS m/z calcd. for C43H53NO9P [M+H]+ 758.3458, found 758, 3454.
IR (cm-1) 3249 (br), 2927, 1686, 1453, 1246, 1097, 1058, 1027, 964, 738, 699.
CO2Bn
O
H
H NHBz
H H
TBSO
H
Prepared according to Procedure C (with 1.5 equiv of benzyl acrylate). White solid (~3:4
mixture of diastereomers, 42.1 mg, 56% yield; 19.9 mg starting material was recovered).
Rf = 0.28 (4:1 hex:EtOAc).
1
7.65 – 7.60 (m, 1H), 7.56 – 7.49 (m, 2H), 7.44 – 7.30 (m, 5H), 5.16 – 5.11 (m, 2H), 3.64
– 3.53 (m, 1H), 3.02 – 2.87 (m, 2H), 2.49 – 2.29 (m, 2H), 2.06 – 1.99 (m, 1H), 1.93 –
1.03 (m, 26H), 1.02 – 0.98 (m, 3H), 0.94 – 0.89 (m, 12H), 0.79 (s, 3H), 0.10 – 0.06 (m,
6H).
13
C NMR (126 MHz, CDCl3) δ 176.5, 174.2, 165.3, 136.1, 136.1, 133.2, 133.2, 132.9,
132.9, 129.0, 129.0, 128.6, 128.5, 128.1, 128.1, 128.1, 127.6, 127.6, 127.6, 72.7, 72.7,
66.2, 66.1, 56.7, 56.6, 43.9, 43.9, 42.2, 40.9, 40.8, 40.2, 40.2, 38.4, 36.9, 35.6, 35.4, 34.6,
33.5, 33.2, 32.8, 32.6, 32.3, 32.2, 31.0, 29.3, 29.0, 27.3, 26.3, 26.0, 26.0, 23.7, 23.4, 22.9,
22.7, 22.6, 20.7, 18.3, 15.0, -4.6, -4.6.
S42
IR (cm-1) 3278 (br), 2927, 2856, 1735, 1712, 1680, 1469, 1249, 1160, 1094, 1078, 835,
774, 707.
S43
Mechanistic Investigations
1. Cyclic Voltammetry (CV) Study: a glassy electrode, a Pt mesh counter electrode and
an Ag/AgCl reference electrode were used and measurement was taken in a 5 mM
solution of a specific compound in DMF containing 0.1 M NBu4PF6.
(a) CV study of amide 1a: no oxidation was observed even at voltage >2V vs Ag/AgCl,
suggesting that neutral 1a cannot be oxidized by the excited IrIII complex (1.21V vs
SCE in MeCN).
(b) CV study of 1a potassium salt: 1a potassium salt was prepared by treatment of 1a
with 1.0 equiv of KOtBu in DMF (0.1 M). As shown below, Ep and E1/2 of 1a
potassium salt were determined to be 1.18 V and 1.09 V vs Ag/AgCl (i.e. 1.13 V and
1.04 V vs SCE in DMF), which suggest that single electron oxidation of 1a potassium
salt by the excited IrIII complex is feasible (1.21 V vs SCE in MeCN).
O O
Me
N OEt
Me
K
S44
2. Stern-Volmer experiments were operated with different solutions containing 0.01 mM
Ir[(dF-CF3)ppy]2(dtbbpy)PF6 and x mM (x = 0. 0.2, 0.4, 0.6, 0.8) 1a or potassium salt
of 1a, under irradiation at 380 nm. The luminescence was measured at 470 nm. Data from
three different runs were collected.
(a) Stern-Volmer experiments of 1a:
c (M) 0 0.0002 0.0004 0.0006 0.0008
Run 1 1 0.98628 0.97410 0.98015 0.99338
Run 2 1 0.97995 0.99311 1.00396 1.00565

I0/I
Run 3 1 0.99323 0.97491 0.97853 0.98555
Average 1 0.98641 0.98075 0.98757 0.99488
(b) Stern-Volmer experiments of potassium salt of 1a:

c (mM) 0 0.0002 0.0004 0.0006 0.0008
Run 1 1 1.10945 1.22282 1.38817 1.59465
Run 2 1 1.10729 1.23392 1.38874 1.58631

I0/I
Run 3 1 1.09738 1.21584 1.37353 1.56921
Average 1 1.10469 1.22443 1.38376 1.58334
Stern-Volmer Experiments
1.7
1.6 y = 673.03x + 1
1.5 R² = 0.975
1.4
I0/I
1.3
1.2
1.1
1 y = -18.31x + 1
R² = -0.4625
0.9
0 0.0001 0.0002 0.0003 0.0004 0.0005 0.0006 0.0007 0.0008 0.0009
Concetration (M)
•1a and Ir[(dF-CF3)ppy]2(dtbbpy)PF6;
• Potassium salt of 1a and Ir[(dF-CF3)ppy]2(dtbbpy)PF6
S45
3. Determination of quantum yield (Φ).
2 mol% of [Ir(dF-CF3ppy)dtbpy]PF6
O O 1.1 aq. K3PO4 O O
Me Me
Me Me
N OEt + 0.5 mL DMF, blue LED, N2
N OEt
H CO2Me H
Me Me
0.1 mmol 5.0 equiv
CO2Me
A magnetic stir bar, the amide substrate (0.1 mmol, 1.0 equiv.), methyl methacrylate
(5.0 equiv), sat. aq. K3PO4 (1.1 equiv) and [Ir{dF-(CF3)ppy}2(dtbbpy)]PF6 (2 mol %)
were charged into an oven-dried NMR tube, followed by 0.5 mL of anhydrous DMF. The
mixture was then bubbled with nitrogen gas for 15 mins before being tightly capped. The
mixture was stirred and irradiated (𝜆 = 419 nm) for 4h (14400 s). The yield was
determined to be 4.7% by 1H NMR, using the trimethoxylbenzene as the internal
standard. The quantum yield can be calculated by using the equation as shown below:
mol product
Φ=
photon flux・f・t
UV-Vis spectrum of [Ir(dF-CF3ppy)dtbpy]PF6 in DMF

c = 4.0 mM
4.5
4
3.5
3
Absorbance (AU)
2.5
2
1.5
1
0.5
0
0 100 200 300 400 500 600 700 800 900 1000
-0.5
-1
Wavelength (nm)
S46
The absorbance of Ir(dF-CF3ppy)dtbpy]PF6 at 419 nm was determined to be
2.431427 according to its UV-Vis spectrum at the reaction concentration (4 mM). The
fraction of light absorbed at 419 nm was calculated using the equation as shown below:
f = 1 - 10-A = 1 – 10-2.431427 = 0.996297
The photon flux of the spectrophotometer (Newport TLS300XU) at 300 W and 419
nm was determined to be 5.2 x 10-9 einstein s-1 following the ferrioxalate actinometry
procedure16 in a NMR tube.
Thus, the quantum yield was:
4.7% x 0.1/1000
Φ= = 6.3%
5.2 x 10!! x 0.996297 x 14400
S47
4. On/off study.
2 mol% of [Ir(dF-CF3ppy)dtbpy]PF6
O O 1.1 aq. K3PO4 O O
Me Me
Me Me
N OEt + N OEt
H CO2Me 2.0 mL DMF/t-Amyl H
Me Me
0.2 mmol 3.0 equiv Blue LED, N2
CO2Me
The reaction was set up on a 0.20 mmol scale according to the General Procedure
C. The reaction mixture was irradiated for an hour. An aliquot (300 µL) was taken from
the reaction mixture, filtered through a 1 cm-silica plug and washed with Et2O (3.0 mL x
3). The filtrate was concentrated in vacuo and was redissolved in 0.50 mL of CDCl3
containing trimethoxylbenzene (4.2 mg) as the internal standard. The yield of product
was determined by 1H NMR. The reaction mixture was then degassed (by bubbling N2
for 10 mins), tightly capped, wrapped by aluminum foil and re-subject to the Blue LED.
The yields later on were determined in the same way after a 1 h light on or off.
Light on Light off On/Off Study
45
40
35
30
NMR Yield%
25
20
15
10
5
0
0 1 2 3 4 5 6
Time (h)
S48
5. By-product analysis by UPLC.
5.1 Reaction of 1a (0.10 mmol) and benzyl acrylate (2.0 equiv) under optimal conditions.
c b+c
e+f
d
a
b d
e f
(1) a is assigned to starting material [1a+Na]+ (210.2), tR = 1.04 min.

(2) b is assigned to product 3ae (tR = 1.22 min) and Michael product (tR = 1.39 min)
([M+H]+, 350.2); c is assigned to product 3ae (tR = 1.22 min) and Michael product (tR =
1.39 min) ([M+Na]+, 372.2).

(3) d is assigned to two products ([M+Na]+, 534.2) as shown below:
O O
Me Me
Me Me
NHCO2Et NCO2Et
BnO2C
CO2Bn CO2Bn CO2Bn
(4) e is assigned to two products ([M+Na]+, 696.4) as shown below:

O O
Me Me
Me Me
NHCO2Et NCO2Et
BnO2C CO2Bn BnO2C
CO2Bn
CO2Bn CO2Bn
S49
(5) f is assigned to two products ([M+Na]+, 858.5) as shown below:
O O
Me Me
Me Me
NHCO2Et NCO2Et
BnO2C CO2Bn BnO2C CO2Bn
CO2Bn
BnO2C CO2Bn CO2Bn
5.2 Reaction of 1a (0.10 mmol) and tert-butyl acrylate (3.0 equiv) under optimal
conditions.
b b
a
cc d
a
d
(1) a is assigned to starting material [1a+Na]+ (210.2), tR = 1.04 min.
(2) b is assigned to product 3af ([M+Na]+, 338.1, tR = 1.25 min) and trace Michael
product.
S50
(3) c is assigned to two products ([M+Na]+, 466.3, tR = 1.39 min, 1.52 min) as shown
below:
O O
Me Me
Me Me
NHCO2Et NCO2Et
tBuO2C
CO2tBu CO2tBu CO2tBu
(4) d is assigned to two products ([M+Na]+, 466.3, tR = 1.39 min, 1.52 min) as shown
below:
O O
Me Me
Me Me
NHCO2Et NCO2Et
tBuO C tBuO C
2 CO2tBu 2
CO2tBu
tBu CO2 tBu

CO2
S51
Reference
1. Kawashima, S.; Aikawa K. and Mikami, K. Eur. J. Org. Chem. 2016, 3166.
2. Ullaha, H.; Ferreira, A. V.; Bendassolli, J. A.; Rodrigues, Jr. M. T.; Formiga, A. L. B.
and Coelho, F. Synthesis 2015, 47, 113.
3. Lo, J. C.; Gui, J.; Yabe, Y.; Pan, C.-M.; Baran, P. S. Nature 2014, 516, 343-348.
4. Linderman, R. J. Tetrahedron Lett. 1992, 33, 6767.
5. Yoshimi, Y.; Masuda, M.; Mizunashi, T.; Nishikawa, K.; Maeda, K.; Koshida, N.;
Itou, T.; Morita, T. and Hatanaka, M. Org. Lett. 2009, 11, 4652.
6. Behforouz, M.; Curran, T. T. and Bolan, J. L. Tetrahedron Lett. 1986, 27, 3107-3110.
7. Barberis, M. and Pérez-Prieto, J. Tetrahedron Lett. 2003, 44, 6683.
8. Negishi, E. and Idacavage, M. J. Organic Reactions (Hoboken, NJ, United States),
1985, 33.
9. Tuokko, S. and Pihko, P. M. Org. Process Res. Dev., 2014, 18, 1740.
10. Bajpai, R.; Yang, F. and Curran, D. P. Tetrahedron Lett. 2007, 48, 7965.
11. Pellacini, F.; Ungheri, D.; Schioppacassi, G.; Kraus, J.; Camplo, M.; Mourier, N. and
Chermann, J. Preparation of pyrimidinone-1,3-oxathiolane nucleosides as antiviral
agents. US 6214833 B1, April 10, 2001.
12. Johnson, W. E. Process for preparing alicyclic carboxylic acid compounds. US
20100168470, July 1, 2010.
13. Chu, L.; Ohta, C.; Zuo, Z.; MacMillan, D. W. C. J. Am. Chem. Soc. 2014, 136, 10886.
14. Trost, B. M.; Miege, F. J. Am. Chem. Soc. 2014, 136, 3016.
15. Chu, X.; Battle, C. H.; Zhang, N.; Aryal, G. H.; Mottamal, M. and Jayawickramarajah,
J. Bioconugate Chem. 2015, 26, 1606.
16. Cismesia, M. A.; Yoon, T. P. Chem. Sci. 2015, 6, 5426.
S52
NMR Spectra
7.71
4.24
4.23
4.22
4.20
2.78
2.76
2.76
2.75
1.65
1.64
1.63
1.63
1.62
1.61
1.60
1.58
1.58
1.57
1.57
1.56
1.56
1.56
1.56
1.55
1.55
1.54
1.54
1.53
1.33
1.31
1.30
0.93
0.92
100000
90000
80000
70000
O
60000
Me
NHCO2Et
50000
Me
40000
30000
20000
10000
0
0.91
2.00
2.01
3.03
3.01
6.09
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
175.1
151.8
62.2
34.1
33.1
27.7
22.3
14.2
2000
1900
1800
1700
1600
1500
1400
1300
1200
O 1100
Me 1000
NHCO2Et 900
Me 800
700
600
500
400
300
200
100
-100
-200
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S53
8.97
7.92
7.92
7.92
7.91
7.90
7.90
7.64
7.64
7.64
7.63
7.62
7.62
7.61
7.61
7.61
7.54
7.53
7.52
7.52
7.52
7.52
7.51
7.50
3.05
3.04
3.04
3.03
3.03
3.02
1.71
1.70
1.69
1.69
1.68
1.67
1.66
1.64
1.64
1.64
1.63
1.63
1.63
1.61
1.61
0.98
0.97
55000
50000
45000
O 40000
Me
NHBz 35000
Me
30000
25000
20000
15000
10000
5000
0
0.92
2.03
1.01
2.04
2.00
3.15
6.02
-5000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
176.8
165.6
133.2
132.9
128.9
127.7
2800
35.7
32.9
27.7
22.4
2600
2400
2200
2000
1800
O
1600
Me
NHBz 1400
Me 1200
1000
800
600
400
200
-200
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S54
7.39
4.23
4.21
4.20
4.19
2.75
2.73
2.73
2.72
2.71
1.61
1.60
1.60
1.59
1.31
1.30
1.28
1.27
1.26
1.25
0.90
0.88
0.87
0.87
0.85
0.84
34000
32000
30000
28000
26000
O 24000
22000
Bu
NHCO2Et 20000
Et 18000
16000
14000
12000
10000
8000
6000
4000
2000
12.60
-2000
0.93
2.00
2.06
2.75
6.22
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
175.0
151.7
62.2
38.5
33.6
32.6
28.8
27.6
25.6
23.0
14.2
14.1
10.7
40000
35000
O
30000
Bu
NHCO2Et
Et 25000
20000
15000
10000
5000
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S55
7.73
4.25
4.23
4.22
4.20
2.79
2.77
2.76
1.75
1.75
1.75
1.74
1.73
1.72
1.70
1.69
1.69
1.66
1.66
1.64
1.63
1.58
1.57
1.55
1.54
1.33
1.31
1.30
1.29
1.28
1.27
1.27
1.26
1.25
1.24
1.24
1.22
1.22
1.21
1.20
1.19
1.19
1.17
1.16
1.16
1.14
0.96
0.96
0.94
0.93
0.91
0.89
18000
17000
16000
15000
14000
O
13000
NHCO2Et 12000
11000
10000
9000
8000
7000
6000
5000
4000
3000
2000
1000
-1000
2.00
2.00
4.34
1.10
2.16
3.46
3.95
2.16
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
50000
175.3
151.8
62.2
37.2
33.7
33.0
31.6
26.5
26.2
14.2
45000
40000
35000
30000
O
25000
NHCO2Et
20000
15000
10000
5000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S56
10.0
220
7.62
4.25
9.5
210
4.23
4.22
4.20
9.0
200
Cl
Cl
3.56
3.54
190
8.5
3.53
2.80
180
2.79
8.0
175.0 2.78
0.96 2.78
170
7.5
2.77
Me
Me
2.77
160
7.0
2.76
151.8 2.75
150
1.78
6.5
1.78
O
140
1.77
6.0
1.77
H
N
H
N
1.77
130
O
O
1.76
5.5
1.76
120
1.75
5.0
1.75
OEt
OEt
1.74
1.73
4.5
1.72
110 100
f1 (ppm)
f1 (ppm)
2.00 1.72
4.0
1.51
90
S57
1.50
2.07 1.50
3.5
80
1.49
1.49
3.0
70
1.48
2.05 1.47
62.2 1.47
60
2.5
1.46
1.45
50
2.0
1.44
45.1 1.44
35.9 3.46
40
1.43
1.5
33.8 8.62
1.06 1.42
32.8 1.38
30
2.89
1.0
32.3 1.37
31.1 1.36
20
24.3 1.36
0.5
19.3 1.35
10
14.2 1.35
0.0
1.33
0
1.32
1.30
-0.5
0.93
-10
0.91
-1.0
0
0
500
-500
1500
1000
1000
7000
2500
2000
2000
3500
4500
5000
5000
3000
3000
6000
8000
9000
4000
4000
65000
7.53
4.25
4.25
4.24
4.24
4.23
4.22
4.21
3.92
3.91
3.91
3.91
3.90
3.90
3.89
2.84
2.84
2.84
2.83
2.82
2.82
2.82
2.82
2.81
2.80
1.83
1.83
1.82
1.82
1.82
1.81
1.81
1.76
1.76
1.74
1.74
1.73
1.73
1.33
1.32
1.32
1.30
1.19
1.18
1.18
1.17
0.91
0.91
0.90
0.90
0.08
0.08
0.07
0.07
60000
55000
50000
O 45000
TBSO 40000
NHCO2Et
Me 35000
30000
25000
20000
15000
10000
5000
0
0.92
2.00
1.02
2.00
1.03
1.02
3.08
3.12
9.37
6.18
-5000
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
174.5
151.6
22000
67.6
62.1
33.6
32.4
25.9
23.7
18.1
14.2
-4.5
-4.8
21000
20000
19000
18000
17000
16000
15000
14000
13000
O 12000
TBSO 11000
NHCO2Et 10000
Me 9000
8000
7000
6000
5000
4000
3000
2000
1000
0
-1000
-2000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S58
7.96
4.20
4.20
4.20
4.19
4.19
4.17
4.16
3.91
3.90
3.90
3.30
3.29
3.29
3.28
3.27
3.27
2.74
2.73
2.71
2.64
2.63
2.61
2.61
2.60
2.59
1.96
1.94
1.93
1.92
1.90
1.89
1.88
1.88
1.85
1.84
1.82
1.81
1.80
1.80
1.79
1.78
1.72
1.69
1.63
1.61
1.60
1.43
1.41
1.28
1.27
1.26
1.23
1.23
32000
30000
28000
26000
24000
22000
O
Boc 20000
N
NHCO2Et 18000
16000
14000
12000
10000
8000
6000
4000
2000
0
0.44
0.42
2.00
0.96
2.00
1.98
4.09
2.02
9.08
3.28
-2000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
174.4
173.8
155.3
154.7
151.8
151.6
90000
79.3
62.1
61.8
56.5
56.2
46.5
46.0
33.7
33.1
30.7
30.5
29.9
29.1
28.4
23.6
23.0
14.2
85000
80000
75000
70000
O 65000
Boc
N 60000
NHCO2Et
55000
50000
45000
40000
35000
30000
25000
20000
15000
10000
5000
-5000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S59
7.55
4.26
4.25
4.23
4.22
3.28
3.27
3.26
3.24
1.69
1.68
1.67
1.66
1.66
1.65
1.65
1.65
1.64
1.64
1.64
1.62
1.61
1.61
1.34
1.33
1.31
1.28
1.26
1.25
1.25
1.20
1.18
1.17
0.93
0.92
0.92
0.91
0.91
0.90
34000
32000
30000
28000
26000
24000
O
22000
Me
NHCO2Et 20000
18000
Me Me
16000
14000
12000
10000
8000
6000
4000
2000
-2000
0.93
2.00
0.93
2.13
3.04
1.12
3.07
6.44
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)
177.9
151.4
62.2
42.5
37.5
25.7
22.8
22.3
17.4
14.2
32000
30000
28000
26000
24000
22000
O
20000
Me
NHCO2Et 18000
Me Me 16000
14000
12000
10000
8000
6000
4000
2000
-2000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S60
7.80
4.24
4.22
4.21
4.20
2.79
2.78
2.76
2.75
2.56
2.54
2.53
2.51
1.99
1.99
1.98
1.98
1.97
1.97
1.97
1.96
1.66
1.65
1.64
1.63
1.63
1.62
1.62
1.32
1.31
1.29
1.29
0.91
0.90
0.89
0.89
0.87
0.86
0.86
32000
30000
28000
26000
24000
22000
20000
Me O
18000
Me
NHCO2Et 16000
Me 14000
12000
10000
8000
6000
4000
2000
0
0.94
2.00
1.00
0.99
1.04
1.03
3.07
6.07
3.22
-2000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)
174.6
151.8
62.1
40.6
35.0
32.1
19.9
18.2
15.6
14.2
50000
45000
40000
35000
30000
Me O
Me 25000
NHCO2Et
Me 20000
15000
10000
5000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S61
7.50
4.25
4.25
4.24
4.24
4.23
4.22
4.21
4.21
2.81
2.80
2.79
2.78
2.76
2.75
2.74
2.73
1.74
1.73
1.62
1.62
1.61
1.61
1.60
1.60
1.59
1.48
1.47
1.46
1.45
1.39
1.39
1.38
1.38
1.37
1.36
1.35
1.35
1.34
1.34
1.32
1.32
1.31
1.31
1.27
0.92
0.90
0.90
0.89
0.89
0.86
0.86
0.85
0.84
24000
23000
22000
21000
20000
19000
18000
17000
Me O 16000
15000
14000
Me NHCO2Et
13000
Me 12000
11000
10000
9000
8000
7000
6000
5000
4000
3000
2000
1000
0
-1000
0.93
2.00
0.95
1.04
0.93
1.33
1.03
1.21
3.33
2.98
5.50
-2000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)
175.04
151.73
62.18
38.19
34.31
31.87
28.54
20.13
17.90
15.10
14.22
30000
28000
26000
24000
22000
Me O 20000
18000
Me NHCO2Et
16000
Me
14000
12000
10000
8000
6000
4000
2000
-2000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S62
4.23
4.22
4.20
4.19
2.78
2.76
2.75
2.74
2.74
2.73
2.72
1.69
1.68
1.68
1.67
1.66
1.64
1.63
1.62
1.56
1.55
1.53
1.52
1.46
1.45
1.44
1.43
1.43
1.42
1.42
1.41
1.31
1.30
1.28
1.25
1.16
1.14
1.13
1.12
1.12
1.10
1.05
1.04
1.02
1.01
1.00
0.88
0.87
0.87
0.86
0.85
0.84
0.82
1.11
14000
13000
12000
11000
10000
9000
O
8000
Me
NHCO2Et 7000
Me Me 6000
5000
4000
3000
2000
1000
0
0.95
2.00
2.00
2.08
1.05
1.07
3.12
1.06
1.07
3.22
6.11
-1000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
175.5
151.9
62.1
46.4
33.8
31.5
30.0
25.2
23.3
22.2
19.4
14.2
18000
17000
16000
15000
14000
13000
12000
O 11000
Me 10000
NHCO2Et 9000
Me Me 8000
7000
6000
5000
4000
3000
2000
1000
-1000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S63
10.0
220
7.85
4.24
9.5
210
4.22
4.21
9.0
4.19
200
2.78
Me
Me
2.77
190
8.5
2.76
2.75
Me
Me
180
8.0
2.74
175.3 0.92
2.72
1.69
170
7.5
1.50
1.49
160
Me
Me
7.0
1.48
151.8 1.48
150
1.47
6.5
1.46
140
1.46
O
O
6.0
1.45
1.45
130
1.44
5.5
1.44
120
1.43
5.0
1.43
1.42
NHCO2Et
NHCO2Et
1.33
4.5
1.32
110 100
f1 (ppm)
f1 (ppm)
2.05
1.31
4.0
1.30
90
S64
1.30
1.29
3.5
80
1.28
1.20
3.0
70
1.19
2.00 1.19
62.1 1.18
2.5
60
1.18
1.17
50
2.0
1.16
36.2 1.04
1.16
34.4 3.01
40
1.15
1.5
33.9 4.19
1.14
32.7 3.10
1.14
30
1.0
31.2 2.95
1.13
28.2 5.93
1.13
20
22.7 1.12
0.5
22.5 0.90
10
19.4 0.89
0.0
14.2 0.88
0
0.87
0.87
-0.5
0.86
-10
0.85
-1.0
0
0
100
700
200
500
300
600
800
900
400
-100
1100
1200
1000
1000
7000
2000
5000
3000
6000
8000
9000
4000
10000
10.0
220
7.60
Ph
7.31
9.5
210
7.31
7.30
9.0
7.29
200
7.29
Me
7.29
Ph
190
8.5
7.28
7.28
180
8.0
7.28
174.9 7.27
O
0.88
Me
7.22
170
7.5
2.22 7.21
3.07 7.20
160
7.0
7.19
151.8 7.18
150
O
7.18
6.5
7.17
140.9
NHCO2Et
140
7.17
6.0
7.16
129.2 7.16
130
128.2 7.16
5.5
125.8 4.25
120
NHCO2Et
4.24
5.0
4.23
4.21
2.87
4.5
2.87
110 100
f1 (ppm)
f1 (ppm)
2.00
2.86
4.0
2.85
90
S65
2.82
2.81
3.5
80
2.80
2.79
3.0
0.99
70
2.72
0.98 2.71
62.2 1.00 2.69
2.5
60
1.02 2.68
2.46
50
2.0
2.44
43.4 2.03 2.43
1.01
40
2.41
1.5
34.6 3.07 1.83

33.9
1.82
30
30.9
1.0
3.04 1.81
1.80
20
19.1 1.78
0.5
14.2 1.56
10
1.54
0.0
1.34
0
1.33
1.31
-0.5
0.92
-10
0.91
-1.0
0
0
2000
5000
6000
8000
4000
-2000
12000
15000
16000
18000
10000
14000
10000
22000
24000
25000
26000
28000
20000
20000
35000
30000
30000
40000
60000
7.92
3.94
3.93
2.78
2.77
2.76
2.76
2.75
1.98
1.97
1.95
1.62
1.61
1.57
1.56
1.56
1.55
1.54
1.54
1.53
0.96
0.94
0.92
0.91
55000
50000
45000
40000
35000
O O
Me Me 30000
N O
H
Me Me 25000
20000
15000
10000
5000
0
0.93
2.00
2.00
1.00
1.01
2.01
5.94
6.16
-5000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)
175.3
152.0
72.1
34.1
33.0
27.7
27.6
22.3
18.9
7500
7000
6500
6000
5500
5000
4500
O O
4000
Me Me
N O 3500
H
Me Me 3000
2500
2000
1500
1000
500
-500
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S66
9.15
7.92
7.91
7.91
7.91
7.90
7.89
7.89
7.60
7.60
7.60
7.59
7.59
7.58
7.58
7.57
7.57
7.50
7.50
7.50
7.49
7.48
7.48
7.47
7.47
7.46
7.26
3.02
3.00
2.99
1.70
1.69
1.68
1.67
1.44
1.43
1.43
1.43
1.42
1.41
1.41
1.40
1.37
0.96
0.95
0.93
50000
45000
40000
35000
30000
O
Me 25000
NHBz
20000
15000
10000
5000
0
1.00
2.03
1.00
2.05
2.08
2.10
2.31
3.27
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)
4200
176.8
165.7
133.1
132.9
128.9
127.8
37.4
26.2
22.3
13.9
4000
3800
3600
3400
O 3200
3000
Me
NHBz 2800
2600
2400
2200
2000
1800
1600
1400
1200
1000
800
600
400
200
-200
-400
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S67
34000
8.09
4.22
4.20
4.19
4.18
3.44
3.43
3.41
3.32
2.81
2.80
2.78
1.93
1.93
1.91
1.91
1.90
1.90
1.30
1.29
1.27
32000
30000
28000
26000
24000
22000
O 20000
MeO 18000
NHCO2Et
16000
14000
12000
10000
8000
6000
4000
2000
0
0.92
2.00
2.01
3.01
1.96
2.00
3.03
-2000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)
174.3
151.8
71.6
62.1
58.5
33.0
24.1
14.2
700
650
600
550
500
450
O
400
MeO
NHCO2Et 350
300
250
200
150
100
50
-50
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S68
7.82
4.24
4.23
4.21
4.20
3.70
3.69
3.68
2.82
2.81
2.79
1.90
1.89
1.88
1.88
1.88
1.87
1.87
1.32
1.31
1.29
0.91
0.90
0.89
0.07
0.06
0.06
85000
80000
75000
70000
65000
60000
55000
50000
O
45000
TBSO
NHCO2Et 40000
35000
30000
25000
20000
15000
10000
5000
0
0.91
2.00
2.01
1.99
2.01
3.02
9.07
6.03
-5000
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
174.3
151.6
62.1
62.1
32.8
27.2
25.9
18.3
14.2
-5.4
7000
6500
6000
5500
5000
4500
4000
O
3500
TBSO
NHCO2Et 3000
2500
2000
1500
1000
500
-500
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S69
220
210
200
11.0 10.5 10.0
Boc
190
9.5
0.47 9.42
180
Bn
175.6
174.9
9.0
0.38 8.85
170
Boc
165.5 7.95
8.5
7.93
160
N
156.1 7.89
Bn
7.87
8.0
1.96
138.3
150
7.62
O
0.99
133.2 7.61
2.02
7.5
133.0 7.59
5.30
140
129.0 7.52
7.0
128.8 7.50
130
NHBz
128.5 7.49
O
127.8
6.5
7.35
127.7
120
7.33
127.2 7.32
6.0
7.29
7.28
NHBz
5.5
7.26
110 100
f1 (ppm)
7.25
7.23
f1 (ppm)
90
4.50
2.00
5.0 4.5
80.1 4.45
S70
80
79.8 3.37
4.0
3.36
70
3.35
3.34
3.5
2.02 3.28
60
3.26
3.0
50.5 1.98
49.8 3.25
50
45.6 3.01
2.5
45.4 2.99
40
2.98
34.8
2.0
2.04 2.89
28.4 2.88
30
22.9 9.20 2.86
1.5
22.5 1.97
20
1.96
1.0
1.95
10
1.94
0.5
1.94
0
1.92
1.55
0.0
1.52
-10
1.46
-0.5
0
1000
7000
2000
5000
3000
6000
8000
9000
4000
-1000
11000
10000
0
1000
7000
2000
5000
3000
6000
8000
9000
4000
-1000
11000
12000
13000
10000
14000
220
7.42
4.66
Me
9.5
210
4.64
4.63
9.0
4.62
Me
200
2.80
Me
2.80
8.5
190
2.79
2.79
Me
180
O
8.0
2.79
175.1 2.78
H
N
2.77
170
7.5
0.90 2.77
O
O
2.09
160
7.0
O 2.07
H
N
151.5 2.07
150
1.90
Me
6.5
O
1.90
140
1.73
O
6.0
Me
1.72
1.72
Me
130
Me
1.70
5.5
1.70
120
1.69
Me
5.0
1.67
Me
1.65
1.00
1.64
4.5
1.62
110 100
f1 (ppm)
f1 (ppm)
1.59
4.0
1.58
90
S71
1.57
1.57
3.5
80
1.56
1.56
3.0
70
1.55
2.00 1.54
1.39
60
2.5
47.0 1.39
40.9 1.09
1.02
50
34.1
2.0
1.04 1.07
34.1 1.07
33.0 6.52
40
1.05
1.5
31.4 1.06
2.24 1.04
27.7 1.02
30
13.36
1.0
26.3 1.02
23.4 3.06
0.94
20
22.3 0.93
0.5
22.0 0.93
10
20.7 0.91
16.4
0.0
0.91
0
0.90
0.88
-0.5
0.81
-10
0.80
0
0
500
1500
1000
2500
2000
5000
15000
10000
25000
20000
35000
45000
50000
30000
40000
9.14
7.92
7.91
7.91
7.90
7.90
7.90
7.63
7.62
7.62
7.61
7.60
7.60
7.60
7.54
7.53
7.53
7.52
7.52
7.50
7.50
7.28
4.95
4.93
3.96
3.95
3.94
3.93
3.14
3.13
3.12
1.96
1.94
1.93
1.92
1.42
1.41
0.99
0.98
0.97
0.97
3.11
28000
26000
24000
22000
Boc
NH O
20000
Me
NHBz 18000
Me 16000
14000
12000
10000
8000
6000
4000
2000
10.39
-2000
1.00
2.09
1.03
2.10
1.03
1.05
2.12
1.04
7.18
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
f1 (ppm)
174.2
165.8
155.8
133.2
132.8
128.9
127.9
79.3
53.1
40.5
32.2
28.4
19.2
18.3
8000
7500
7000
6500
Boc
NH O 6000
Me 5500
NHBz
5000
Me
4500
4000
3500
3000
2500
2000
1500
1000
500
-500
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S72
10.0
220
7.59
4.25
9.5
210
4.23
4.22
9.0
4.20
200
3.54
1.91
190
8.5
1.91
1.90
180
8.0
1.90
175.4
1.89
0.93 1.88
170
7.5
1.88
1.87
160
7.0
1.87
151.5 1.86
150
1.79
6.5
1.77
140
1.73
6.0
1.73
CONHCO2Et
1.73
130
CONHCO2Et
1.71
5.5
1.70
120
1.69
5.0
1.67
1.67
1.66
4.5
1.65
110 100
f1 (ppm)
f1 (ppm)
2.00
1.64
4.0
1.33
90
S73
1.32
0.94 1.30
3.5
80
1.29
1.28
3.0
70
1.26
1.26
62.0 1.25
2.5
60
1.25
46.5 2.01 1.24
50
1.02
2.0
41.5 1.23
37.8 2.07 1.05
1.01
40
35.2 1.03
1.5
30.0 2.99 1.02

27.1 1.10 0.92
30
1.0
26.0 1.03 0.92

22.3 3.13 0.91
20
21.5 6.86 0.89
0.5
21.4 0.89
10
14.2 0.89
0.0
0.88
0
0.88
0.87
-0.5
0.86
-10
0.84
-1.0
0
0
100
700
200
500
300
600
800
900
400
-100
1100
1000
1000
7000
2000
5000
3000
6000
8000
9000
4000
-1000
11000
12000
15000
13000
16000
10000
14000
8.94
8.92
7.90
7.90
7.89
7.88
7.64
7.64
7.62
7.62
7.62
7.61
7.61
7.61
7.54
7.53
7.53
7.52
7.52
7.50
7.50
4.40
4.38
4.36
4.34
4.25
4.25
4.24
4.24
4.23
4.23
4.22
3.79
3.79
3.31
3.30
3.28
3.27
3.26
3.25
3.23
3.22
3.01
2.99
2.98
2.97
2.96
2.96
2.95
2.93
1.49
1.48
1.44
1.43
1
H NMR (500 MHz, Chloroform-d) δ 4.39 (d, J = 7.2 Hz, 1H), 4.35 (d, J = 6.6 Hz, 1H). 18000
17000
16000
15000
14000
Me Me 13000
12000
O O 11000
10000
MeO2C 9000
NHCOPh
Me 8000
O
7000
6000
5000
4000
3000
2000
1000
-1000
0.46
0.46
2.00
1.00
2.03
0.51
0.45
0.97
0.98
0.99
0.98
1.36
1.47
1.51
1.40
2.99
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)
174.9
174.8
172.0
171.8
165.5
165.5
133.2
133.2
132.8
132.7
129.0
129.0
127.7
111.2
111.0
82.4
81.9
77.2
76.6
52.4
52.4
41.4
40.5
32.8
31.4
27.0
26.8
25.6
25.6
16.1
14.5
13000
12000
77.2
76.6
Me Me 11000
5000
O O 10000
9000
0 MeO2C
NHCOPh 8000
Me
77.4 77.2 77.0 76.8 76.6 76.4
f1 (ppm) O 7000
6000
5000
4000
3000
2000
1000
-1000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S74
10.0
220
7.87
7.87
9.5
210
7.86
7.85
7.85
9.0
200
0.95
7.85
7.61
190
8.5
7.59
7.59
180
7.52
8.0
175.9 2.13
7.51
1.07
7.50
170
7.5
165.7 2.24
7.49
138.5 15.52
7.35
160
138.4
7.0
7.34
138.2 7.34
150
133.1 7.33
6.5
132.9 7.33
128.9
140
7.32
128.5
6.0
7.31
128.4 7.31
130
BnO
128.4 7.29
5.5
127.9 7.29
120
BnO
127.9 7.28
127.9
5.0
7.28
127.7 1.00 7.27
127.7 5.30 7.26
O
4.5
127.6 7.26
110 100
f1 (ppm)
f1 (ppm)
77.5 1.21 7.25
OBn
4.0
BnO
77.2 3.04 7.24
90
S75
77.0 1.05 7.23
BnO
76.9 1.01 4.83
3.5
80
76.7 4.81
74.1 2.01 4.66
3.0
O
70
73.4 4.64
O
72.6 4.62
71.5 4.61
60
2.5
OBn
70.2 4.59
1.03
69.2 4.59
NHBz
1.03
50
2.0
4.57
2.12
4.55
40
4.51
1.5
O
34.2 4.49
33.5 3.81
30
1.0
26.6 3.81
3.79
20
3.73
0.5
NHBz
3.56
10
3.05
0.0
3.03
0
3.02
2.03
-0.5
1.88
-10
1.88
-1.0
0
0
100
700
200
500
300
600
800
900
400
-100
1100
1200
1000
1000
7000
2000
5000
3000
6000
8000
9000
4000
-1000
11000
12000
15000
13000
16000
10000
14000
10.0
220
8.87
7.91
9.5
210
7.91
7.90
9.0
7.89
200
0.91
TBSO
TBSO
7.89
7.63
190
8.5
7.61
7.54
180
8.0
177.1 1.91 7.54
7.53
H
H
1.00
7.53
170
1.94
7.5
165.5
H
H
7.52
7.51
160
H
7.0
H
7.51
1.83
150
H
H
1.81
6.5
1.43
140
133.1 1.43
6.0
132.9 1.43
H
H
1.42
130
129.0
1.42
5.5
127.7
1.41
120
1.41
5.0
1.41
1.40
O
O
1.40
4.5
1.39
110 100
f1 (ppm)
f1 (ppm)
72.8 1.39
NHBz
NHBz
4.0
56.4 1.38
90
S76
56.1 1.03 1.38
42.8 1.37
3.5
80
42.3 1.35
40.2 3.0 0.93 1.28
0.94
70
40.1 1.28
36.9 1.24
35.9 1.19
2.5
60
35.6 1.17
35.6 1.15
2.0
50
34.8 6.48 1.08
34.6 1.07
40
1.5
31.0 1.01
30.2 21.71 1.00
28.3 2.99 0.95
30
1.0
27.3 14.24 0.95

26.4 2.82 0.94
20
0.5
26.0 0.93
24.3 0.92
10
23.4 6.40 0.92
0.0
20.8 0.91
0
18.5 0.91
18.3 0.67
-0.5
12.1 0.65
-10
-4.6 0.08
-1.0
0
0
1000
7000
2000
5000
5000
3000
6000
8000
9000
4000
-1000
11000
17000
-2000
12000
21000
15000
15000
13000
16000
18000
19000
10000
14000
10000
22000
24000
25000
23000
20000
20000
32000
7.60
4.25
4.24
4.22
4.21
3.68
2.71
2.71
2.69
2.68
2.68
2.67
2.56
2.55
2.55
2.55
2.54
2.54
1.93
1.93
1.92
1.91
1.91
1.91
1.90
1.89
1.88
1.56
1.55
1.54
1.33
1.33
1.33
1.32
1.32
1.32
1.31
1.31
1.30
1.30
1.30
1.19
1.19
1.18
1.18
1.18
1.17
1.17
1.17
1.16
0.89
0.89
0.89
0.88
30000
28000
26000
24000
O 22000
Me
Me 20000
NHCO2Et
18000
Me
16000
CO2Me 14000
12000
10000
8000
6000
4000
2000
0
0.94
2.00
3.05
2.06
1.01
2.09
4.31
6.46
1.11
3.11
-2000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
30000
178.3
174.8
151.6
62.1
51.7
45.3
36.0
35.6
32.9
31.5
26.8
26.7
20.4
14.2
28000
26000
24000
22000
20000
18000
O 16000
Me
Me
NHCO2Et 14000
Me 12000
10000
CO2Me
8000
6000
4000
2000
-2000
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S77
10.0
220
7.54
7.54
9.5
210
7.39
7.38
9.0
7.38
200
7.38
Me
7.37
190
8.5
7.37
7.36
Me
180
177.7
8.0
7.36
174.8 7.35
170
0.95 7.35
7.5
Me
5.02 7.35
CO2Bn
O
7.34
Me
160
7.0
5.15
151.6 5.13
150
5.11
Me
6.5
5.09
140
136.0 4.25
6.0
128.5 4.23
Me
NHCO2Et
128.2 4.22
130
CO2Bn
O
128.2 4.21
5.5
2.71
120
2.02 2.70
5.0
2.69
2.69
2.69
4.5
2.68
f1 (ppm)
110 100
f1 (ppm)
2.00
2.61
NHCO2Et
4.0
2.60
90
S78
2.60
2.59
3.5
80
2.59
3.0 1.97
1.96
70
66.3 2.00 1.95
62.2 1.04 1.93
2.5
60
1.58
1.57
50
2.0
1.57
45.2 1.00
1.57
36.0 2.03
40
1.56
1.5
35.7 3.12
1.55
33.0 4.12
1.33
30
6.18
1.0
31.5 1.32
26.8 1.30
20
26.7 1.23
0.5
20.4 1.23
10
14.3 1.21
0.0
1.21
1.20
0
1.19
-0.5
0.88
-10
0.88
0
0
100
700
200
500
300
600
800
900
400
-100
1100
2000
6000
8000
4000
1200
1500
1300
1000
1400
-2000
12000
16000
18000
10000
14000
22000
24000
26000
20000
10.0
220
7.60
7.30
9.5
210
7.30
7.30
Me
9.0
7.28
200
7.27
7.27
190
8.5
Me
7.27
7.22
180
177.1
8.0
7.22
174.7 Me 7.22
Bn
0.92
7.21
170
7.5
O
2.20
CO2Me
7.19
Me
1.00
7.18
160
2.01
7.0
7.17
151.6 7.17
150
Bn
7.16
6.5
O
CO2Me
7.16
140
138.9 7.16
NHCO2Et
6.0
4.25
129.0 4.24
130
128.4 4.22
5.5
126.4 4.21
120
3.56
5.0
NHCO2Et
2.93
2.91
2.90
4.5
2.89
110 100
f1 (ppm)
f1 (ppm)
2.00 2.75
4.0
2.73
90
S79
2.70
3.01 2.68
3.5
80
2.67
2.66
0.99
3.0
70
2.62
1.03 1.91
62.1 2.01 1.89
60
2.5
51.5 0.98 1.88

43.7 1.86
50
2.0
42.7 1.54
40.9 1.00 1.53
2.06
40
35.7 1.52
1.5
32.8 4.04 1.51

31.4 1.50
30
1.0
26.8 6.10 1.49

26.8 1.36
20
1.35
0.5
14.3 1.34
10
1.33
0.0
1.32
0
1.31
1.27
-0.5
0.85
-10
0.84
0
0
1000
7000
2000
5000
5000
3000
6000
8000
9000
4000
-1000
11000
17000
12000
15000
15000
13000
16000
18000
10000
14000
10000
25000
20000
35000
45000
50000
30000
40000
10.0
220
7.49
7.36
9.5
210
7.35
7.35
Me
9.0
7.35
200
7.34
7.34
190
8.5
Me
Me
7.34
7.33
180
8.0
175.2 7.33
174.7 Me 7.33
Ph
0.92 7.32
170
7.5
CO2Me
4.06 7.32
1.02 7.32
Ph
160
7.0
7.31
O
CO2Me
151.6 7.31
150
7.30
6.5
7.28
140.6
140
7.27
NHCO2Et
6.0
7.27
128.7
7.26
130
127.8
7.26
NHCO2Et
5.5
127.1
7.25
120
4.25
5.0
4.24
4.22
4.21
4.5
3.71
110 100
f1 (ppm)
f1 (ppm)
2.00
3.71
4.0
3.70
90
S80
1.03 3.69
3.01 3.66
3.5
80
2.72
2.71
3.0
70
2.69
2.01 2.67
62.2 2.66
60
2.5
1.02 2.38
52.2 2.37
50
2.0
47.5 2.36
44.9 2.34
3.02
40
1.63
1.5
35.9
33.2 3.10 1.62
1.61
30
31.5
1.0
26.9 6.11 1.60

1.60
20
1.59
0.5
14.2 1.59
10
1.58
0.0
1.34
0
1.32
1.31
-0.5
0.93
-10
0.92
0
0
100
700
200
500
300
600
800
900
400
-100
1100
1000
2000
6000
8000
4000
-2000
12000
16000
18000
10000
14000
22000
24000
26000
28000
20000
30000
7.39
7.38
7.36
7.36
7.28
5.13
4.25
4.24
4.22
4.21
2.76
2.75
2.73
2.38
2.37
2.37
2.36
2.36
2.35
1.65
1.64
1.63
1.63
1.62
1.62
1.61
1.59
1.58
1.34
1.32
1.31
1.28
0.92
28000
26000
24000
22000
O 20000
Me
Me
NHCO2Et 18000
16000
14000
CO2Bn
12000
10000
8000
6000
4000
2000
0
6.09
2.07
2.00
1.95
2.12
4.71
3.69
6.97
-2000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)
174.9
174.0
151.6
136.0
128.5
128.2
128.2
66.2
62.2
36.2
35.5
32.2
31.3
29.7
29.5
26.4
14.2
110000
100000
90000
80000
O
Me 70000
Me
NHCO2Et
60000
50000
CO2Bn
40000
30000
20000
10000
-10000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S81
40000
7.54
7.53
7.28
4.25
4.23
4.22
4.21
2.75
2.75
2.74
2.74
2.73
2.73
2.72
2.22
2.21
2.21
2.21
2.20
2.20
2.19
1.59
1.59
1.58
1.58
1.58
1.57
1.57
1.56
1.56
1.55
1.55
1.54
1.53
1.48
1.47
1.47
1.45
1.44
1.33
1.33
1.32
1.31
0.93
0.91
0.89
38000
36000
34000
32000
30000
28000
26000
O 24000
Me
Me 22000
NHCO2Et 20000
18000
16000
CO2tBu 14000
12000
10000
8000
6000
4000
2000
-2000
0.92
2.00
1.99
2.04
4.17
9.56
3.20
6.25
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
175.1
173.6
151.7
80.1
62.2
36.3
35.6
32.2
31.4
30.7
28.1
26.5
14.2
19000
18000
17000
16000
15000
14000
13000
12000
O
Me 11000
Me
NHCO2Et 10000
9000
8000
CO2tBu 7000
6000
5000
4000
3000
2000
1000
-1000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S82
10.0
220
7.29
5.95
9.5
210
5.93
5.91
9.0
5.36
200
5.35
5.32
190
8.5
5.32
5.27
180
8.0
5.26
175.0
173.8
Me 5.25
Me
5.24
170
O
7.5
0.90
4.60
Me
O
4.60
160
Me
7.0
4.59
O
151.7 4.59
150
4.59
O
6.5
O
4.58
140
4.25
O
6.0
0.98 4.24
132.2
4.22
130
4.21
5.5
1.01 2.77
120
118.2 1.00 2.75
5.0
NHCO2Et
2.75
2.74
NHCO2Et
2.03 2.74
4.5
2.73
110 100
f1 (ppm)
f1 (ppm)
2.00 2.36
4.0
2.35
90
S83
2.34
2.34
3.5
80
2.33
2.33
3.0
70
2.32
65.1 1.98 1.65
62.2 1.64
60
2.5
2.05 1.63
1.62
50
2.0
1.62
36.2 1.61
4.74
40
1.61
1.5
35.5
32.2 3.16 1.60
1.60
30
31.3
1.0
29.5 6.16 1.59

26.4 1.59
20
1.59
0.5
14.2 1.58
10
1.58
0.0
1.34
0
1.32
1.31
-0.5
0.93
-10
0.92
0
0
500
-500
1500
1000
2500
5500
2000
2000
3500
4500
5000
3000
6000
6000
8000
4000
4000
-2000
12000
16000
18000
10000
14000
22000
24000
26000
28000
20000
7.56
7.29
4.25
4.24
4.22
4.21
2.78
2.77
2.76
2.76
2.75
2.73
2.67
2.66
2.66
2.65
2.64
2.64
2.63
1.81
1.79
1.79
1.76
1.70
1.70
1.69
1.68
1.68
1.67
1.66
1.66
1.65
1.64
1.64
1.38
1.37
1.36
1.35
1.34
1.34
1.32
1.32
1.31
1.27
1.04
1.02
25000
20000
O
Me
Me 15000
NHCO2Et
Me
CN 10000
5000
0
0.92
2.00
1.97
1.01
1.01
2.28
7.17
5.97
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)
174.6
151.7
124.2
62.3 34000
45.9
35.9
33.0
31.3
26.9
26.6
20.7
20.5
14.2
32000
30000
28000
26000
24000
22000
20000
O
Me 18000
Me
NHCO2Et 16000
Me 14000
12000
CN 10000
8000
6000
4000
2000
-2000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S84
42000
8.61
7.88
7.88
7.88
7.87
7.87
7.86
7.86
7.65
7.64
7.63
7.63
7.62
7.62
7.62
7.55
7.54
7.53
7.52
7.29
2.99
2.98
2.96
2.48
2.47
2.46
2.45
2.19
1.67
1.66
1.65
1.65
1.64
1.64
1.59
1.58
1.57
1.57
1.56
0.97
0.95
40000
38000
36000
34000
32000
30000
28000
26000
O
Me 24000
Me 22000
NHBz
20000
18000
16000
COMe
14000
12000
10000
8000
6000
4000
2000
-2000
0.96
1.97
1.02
2.19
2.00
2.05
3.06
3.00
2.08
6.29
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)
209.4
176.4
165.4
133.2
132.8
129.0
127.6
38.8
35.4
35.0
32.9
32.1
30.0
26.7
17000
16000
15000
14000
13000
12000
O 11000
Me
Me 10000
NHBz
9000
8000
COMe 7000
6000
5000
4000
3000
2000
1000
-1000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S85
65000
8.73
7.88
7.88
7.88
7.88
7.87
7.87
7.87
7.86
7.64
7.63
7.62
7.62
7.61
7.61
7.61
7.54
7.54
7.53
7.52
7.52
7.52
7.52
7.51
7.51
7.51
7.29
3.05
2.97
2.95
2.95
2.95
2.93
2.36
2.34
2.33
1.69
1.68
1.68
1.67
1.67
1.67
1.66
1.66
1.65
1.64
1.64
1.63
0.98
60000
55000
50000
45000
40000
O
Me
Me 35000
NHBz
30000
25000
CONMe2
20000
15000
10000
5000
0
0.96
2.07
1.03
2.08
3.00
5.12
2.08
5.05
6.23
-5000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
176.3
173.5
165.4
133.2
132.9
129.0
127.6
21000
37.4
36.3
35.5
33.0
32.4
28.3
26.8
20000
19000
18000
17000
16000
15000
14000
13000
O
Me 12000
Me 11000
NHBz
10000
9000
8000
CONMe2 7000
6000
5000
4000
3000
2000
1000
-1000
-2000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S86
8.54
7.97
7.97
7.97
7.96
7.96
7.96
7.87
7.86
7.86
7.85
7.85
7.85
7.67
7.66
7.66
7.66
7.65
7.65
7.65
7.63
7.63
7.63
7.61
7.60
7.59
7.59
7.59
7.58
7.57
7.55
7.55
7.54
7.52
3.18
3.15
2.91
2.89
2.88
1.72
1.69
1.63
1.62
1.61
1.61
1.60
0.94
17000
16000
15000
14000
13000
12000
O 11000
Me
Me 10000
NHBz
9000
8000
SO2Ph 7000
6000
5000
4000
3000
2000
1000
0
0.97
2.06
2.07
2.14
2.21
2.12
2.00
2.03
2.09
3.21
6.21
-1000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
176.0
165.3
139.2
133.6
133.3
132.7
129.3
129.1
128.1
127.6
52.3
35.2
33.4
32.6
32.4
26.6
12000
11000
10000
9000
O 8000
Me
Me 7000
NHBz
6000
5000
SO2Ph
4000
3000
2000
1000
-1000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S87
10.0
220
9.5
210
Me
9.0
200
0.94 8.90
7.89
7.89
8.5
190
Me
7.89
7.88
180
8.0
176.4 1.99 7.88
0.98 7.87
Me
170
2.01 7.63
7.5
O
165.5 7.62
PO(OEt)2
7.62
160
Me
7.0
7.61
7.60
150
NHBz
7.60
6.5
7.60
140
O
133.2 7.53
6.0
132.9 7.52
PO(OEt)2
130
128.9 7.51
7.51
5.5
127.7
7.51
120
NHBz
7.50
5.0
7.50
4.13
4.5
4.13
110 100
f1 (ppm)
f1 (ppm)
4.11
4.00 4.11
4.0
90
S88
4.10
4.08
3.5
80
2.96
2.95
3.0
1.96
70
2.95
61.6 2.95
60
2.5
61.5 2.94
2.93
50
1.73
2.0
35.1
2.02 1.69
33.6
1.66
40
33.6 1.99
1.5
1.99 1.65
32.9
6.01 1.65
32.6
30
1.65
1.0
32.5 5.97
1.64
26.3
20
1.63
21.1
0.5
1.59
20.0
1.57
10
16.5
1.56
0.0
16.5
1.55
0
1.35
-0.5
1.33
-10
1.32
0.95
-1.0
0
0
500
-500
1500
1000
2500
5500
2000
3500
4500
5000
3000
4000
5000
-5000
15000
10000
25000
55000
20000
35000
45000
50000
30000
40000
33.6
P NMR (202 MHz, Chloroform-d) δ 33.60.
31 22000
21000
20000
19000
18000
17000
16000
15000
14000
O
Me 13000
Me 12000
NHBz
11000
10000
9000
PO(OEt)2 8000
7000
6000
5000
4000
3000
2000
1000
0
-1000
-2000
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90
f1 (ppm)
S89
10.0
220
8.71
7.89
9.5
210
7.89
7.88
9.0
7.88
200
0.94 7.87
7.87
190
8.5
7.65
7.64
180
8.0
175.9 7.63
Me
Me
MeO2C
2.02
MeO2C
174.4 1.03 7.63
170
173.0 2.08 7.62
7.5
7.62
Me
Me
165.4
7.62
160
7.0
7.55
7.54
150
7.53
6.5
O
O
CO2Me
CO2Me
7.53
140
133.3 7.53
6.0
7.52
132.7
7.52
130
129.0
7.29
5.5
NHBz
NHBz
127.6
3.72
120
3.71
5.0
3.71
3.68
3.07
4.5
3.06
f1 (ppm)
110 100
f1 (ppm)
3.05
4.0
3.04
90
S90
3.07 3.03
3.00 3.01
3.5
80
3.00
2.99
2.07
3.0
2.89
70
2.07 2.87
1.03 2.84
2.5
60
2.83
51.8
2.83
51.6
50
2.0
2.81
49.4 2.03 2.56
34.9
40
2.56
1.5
34.6 2.53
32.7 2.53
30
6.10
1.0
32.2 1.77
25.0 1.76
20
24.6 1.75
0.5
1.75
10
1.74
0.0
1.73
1.72
0
1.67
-0.5
1.03
-10
1.02
0
0
5000
1000
7000
2000
5000
3000
6000
8000
9000
4000
-5000
15000
10000
-1000
11000
25000
55000
20000
35000
45000
50000
30000
60000
40000
12000
15000
13000
16000
10000
14000
10.0
220
7.49
7.28
9.5
210
4.25
4.23
9.0
4.22
200
4.20
2.68
190
8.5
2.66
2.64
180
8.0
Bu
175.0 2.15
173.7 2.14
2.13
170
Et
0.84
7.5
Bu
2.12
2.12
160
7.0
Et
2.11
CO2
151.6 1.56
150
1.55
6.5
tBu
1.55
140
1.54
6.0
1.54
O
CO2tBu
1.53
130
1.52
5.5
1.52
120
1.52
NHCO2Et
5.0
1.51
1.47
1.46
4.5
NHCO2Et
1.46
110 100
f1 (ppm)
f1 (ppm)
2.00
1.45
4.0
1.33
90
S91
1.33
1.32
3.5
80.1
80
1.31
1.30
3.0
70
1.30
62.1 1.81 1.29
36.7 1.29
2.5
60
35.4 1.29
30.6 1.84 1.28
50
2.0
30.4 1.27
29.9 3.83 1.26
40
1.24
1.5
29.8 10.17
28.2 8.13 1.23
28.1 1.18
30
3.81
1.0
25.1 3.29 1.18

23.5 2.80 1.17
20
1.17
0.5
14.2
1.17
14.1
10
0.93
7.4
0.0
0.91
0
0.90
0.81
-0.5
0.80
-10
0.78
-1.0
0
0
5000
5000
-5000
15000
15000
10000
10000
70000
25000
25000
55000
20000
20000
35000
35000
65000
45000
50000
45000
50000
30000
30000
60000
40000
40000
7.70
4.25
4.23
4.22
4.21
3.68
3.67
2.63
2.56
2.56
2.55
2.54
2.54
2.53
2.52
1.96
1.94
1.93
1.91
1.73
1.68
1.67
1.52
1.45
1.45
1.45
1.44
1.44
1.43
1.43
1.42
1.41
1.41
1.40
1.33
1.33
1.32
1.32
1.32
1.31
1.31
1.30
1.29
1.29
1.27
1.26
1.26
1.25
1.24
1.23
1.23
1.22
1.19
1.17
80000
75000
70000
65000
60000
55000
O
50000
NHCO2Et 45000
Me 40000
35000
CO2Me
30000
25000
20000
15000
10000
5000
0
0.89
2.00
3.01
3.01
1.01
1.04
1.14
6.10
4.62
3.07
3.04
-5000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)
178.6
174.7
151.6
24000
62.1
51.8
35.7
35.5
35.1
34.6
30.7
26.2
21.5
21.4
20.5
14.2
23000
22000
21000
20000
19000
18000
17000
16000
15000
14000
O 13000
12000
NHCO2Et 11000
10000
Me
9000
8000
CO2Me 7000
6000
5000
4000
3000
2000
1000
0
-1000
-2000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S92
10.0
220
7.41
7.40
9.5
210
7.40
7.39
9.0
7.39
200
7.39
Cl
7.38
190
8.5
7.37
7.37
180
8.0
174.8 7.36
173.9 7.36
7.29
170
Cl
7.5
6.22 5.13
4.25
160
7.0
Me
4.23
151.6 4.22
150
4.20
6.5
3.56
140
3.55
CO2Bn
136.0
O
6.0
3.54
Me
128.6
2.74
130
H
N
128.2
2.72
5.5
2.70
120
2.04 2.35
CO2Bn
5.0
O
2.33
2.32
OEt
H
N
1.77
4.5
1.75
110 100
f1 (ppm)
f1 (ppm)
2.00
O
1.74
4.0
1.65
90
S93
1.64
1.99
OEt
1.64
3.5
80
1.64
1.63
3.0
70
1.62
66.3 1.97 1.61
62.3 1.60
2.5
60
2.00 1.60
44.9 1.59
50
2.0
38.1 2.06 1.59

34.5 5.98 1.58
40
1.34
1.5
33.6 2.08
33.2 3.33 1.32
1.31
30
33.0 3.30
1.0
30.8 3.01 1.28

29.0 1.28
20
1.27
0.5
24.2
20.8 1.26
10
14.2 1.25
0.0
1.24
0
1.23
1.23
-0.5
1.22
-10
0.89
-1.0
0
0
500
-500
1500
1000
1000
7500
7000
7000
2500
5500
2000
2000
3500
6500
4500
5000
5000
3000
3000
6000
6000
8000
9000
4000
4000
-1000
11000
12000
10000
4.25
4.23
4.22
4.21
2.84
2.83
2.82
2.82
2.81
2.32
2.32
2.30
2.30
2.30
2.30
2.29
2.28
1.82
1.82
1.81
1.80
1.80
1.79
1.79
1.78
1.78
1.78
1.77
1.77
1.76
1.48
1.47
1.47
1.47
1.46
1.46
1.45
1.44
1.33
1.32
1.31
1.30
1.27
1.27
1.23
0.90
0.90
0.90
0.89
0.88
0.88
0.12
0.12
0.11
80000
75000
70000
65000
60000
55000
O 50000
OTBS
Me 45000
NHCO2Et
40000
35000
CO2 tBu 30000
25000
20000
15000
10000
5000
12.84
-5000
0.85
2.00
1.85
1.91
4.26
3.46
9.98
6.28
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)
174.6
173.3
151.6
80.1
74.4
62.2
37.1
36.0
31.3
30.6
28.1
27.1
25.9
18.2
14.2
-2.0
-2.1
65000
60000
55000
50000
O
OTBS 45000
Me
NHCO2Et 40000
35000
CO2tBu 30000
25000
20000
15000
10000
5000
-5000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S94
10.0
220
7.40
7.39
7.9
9.5
210
7.41 7.38
0.37 7.40 7.38
7.8
9.0
7.39 7.37
200
7.38 7.37
7.38 7.37
190
8.5
7.7
7.37 7.36
174.1 7.37 7.36
180
8.0
7.37 7.35
7.6
173.6 0.37
f1 (ppm)
173.3 7.36 7.35
7.35
170
7.36
7.5
173.2 5.98
7.5
7.35 7.34
NBoc
154.0 7.35 7.34
160
7.0
153.9 7.35 7.28
7.4
5.98 7.34 5.14

151.6
150
151.5 7.34 5.13
6.5
CO2Bn
NBoc
O
4.24
0
136.0
140
135.9 4.23
2000
6000
8000
4000
6.0
128.6 4.22
4.22
130
128.5
CO2Bn
O
128.5 4.21
5.5
128.3 4.20
120
128.3 2.31 2.36 3.41
0.50
NHCO2Et
5.0
128.2 2.35 3.37
2.8
128.2 2.35 2.36

128.2 0.99 2.34 2.35
4.5
2.35
2.6
2.33
110 100
f1 (ppm)
f1 (ppm)
2.00
NHCO2Et
0.55 2.31 2.34
4.0
2.30 2.33
90
S95
2.4
80.1 4.15 2.30 2.32

f1 (ppm)
79.3 1.94 2.31
3.5
2.08
80
2.2
66.4 1.93 2.30

66.3 1.93 2.30
3.0
70
64.7 0.50 1.07 1.79 1.95
2.0
63.9 0.99 2.21 1.77 1.94

62.3 0.55 1.76 1.93
60
2.5
2.81
1.8
62.0 4.15 1.76 1.93

49.0 1.07 1.79
0
50
2.0
48.8 2.21 1.77

1000
2000
3000
2.81 1.76
40
9.23 1.76
1.5
35.8
4.01 1.75
34.6
1.67
30
33.8
1.0
1.47
33.0
1.47
20
32.6
1.46
0.5
31.5
1.45
29.8
10
1.44
29.7
0.0
1.33
28.5
0
1.32
28.4
1.31
-0.5
21.8
1.29
21.7
-10
1.28
14.2
0
0
1000
7000
2000
5000
5000
3000
6000
8000
9000
4000
-1000
11000
17000
12000
-5000
15000
15000
13000
16000
18000
10000
10000
14000
25000
55000
20000
35000
45000
50000
30000
40000
8.60
7.85
7.85
7.85
7.84
7.84
7.83
7.62
7.61
7.60
7.59
7.59
7.59
7.52
7.52
7.51
7.50
7.49
7.49
3.03
3.02
3.02
3.01
3.00
3.00
2.99
2.98
2.49
2.48
2.48
2.47
2.46
2.46
2.45
2.15
2.13
1.77
1.76
1.63
1.56
1.55
1.55
1.54
1.53
1.53
1.52
1.52
1.52
1.50
1.48
1.47
1.46
0.95
0.94
22000
21000
20000
19000
18000
17000
O 16000
15000
Me 14000
NHBz
13000
12000
11000
10000
O Me 9000
8000
7000
6000
5000
4000
3000
2000
1000
0
-1000
0.97
2.03
1.00
2.06
2.07
2.05
2.92
2.09
3.12
2.89
-2000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)
209.2
176.1
165.4
133.2
132.8
129.0
127.6
41.3
35.2
32.1
30.7
30.4
29.9
19.3
1100
1000
900
O 800
Me
NHBz 700
600
500
O Me
400
300
200
100
-100
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S96
10.0
220
7.52
7.39
9.5
210
7.39
7.38
7.38
9.0
200
7.37
7.37
190
8.5
7.37
MeO
7.36
180
MeO
7.35
8.0
174.1
7.35
173.4
7.34
170
0.93
7.5
5.10 7.34
7.28
160
7.0
5.14
CO2Bn
151.6 4.25
O
150
4.24
CO2Bn
6.5
O
4.22
140
136.0 4.21
6.0
128.5 3.33
128.2 3.32
130
128.2 3.28
5.5
2.85
NHCO2Et
120
2.10 2.84
NHCO2Et
5.0
2.84
2.83
2.83
4.5
2.82
110 100
f1 (ppm)
f1 (ppm)
2.00 2.82
4.0
2.81
90
S97
2.48
2.47
3.5
80
78.9 2.92 2.45
1.03 1.90
70
3.0
1.89
3.40
66.2 2.03
3.33 1.88
62.2 3.33 1.88
60
2.5
56.7 2.01
3.32 1.88
3.35
3.32 1.87
50
2.92
2.0
4.09 3.31 1.87

3.30 1.87
3.30
40
3.30 1.86
1.5
31.9 1.03
3.14 3.28 1.86
30.0
f1 (ppm)
1.86
30
3.28
28.4
1.0
3.25
3.27 1.85
27.6
3.27 1.85
20
3.26 1.85
0.5
14.2 1.84
3.20
10
1.84
0.0
1.83
0
1.65
0
1.34
-0.5
5000
1.32
-10
1.31
0
0
2000
6000
8000
4000
5000
-2000
12000
16000
18000
10000
14000
22000
24000
20000
-5000
15000
10000
25000
55000
20000
35000
45000
50000
30000
40000
10.0
220
7.41
7.40
9.5
210
7.40
7.39
3.90
7.39
9.0
200
3.84 7.39
3.84 7.38
190
8.5
3.85
3.83 7.38
1.00 7.37
3.82
180
7.37
8.0
174.3 3.82
3.80
TBSO
173.5 3.81 7.36
7.36
170
7.5
f1 (ppm)
6.39 7.34
3.75 7.28
160
7.0
5.14
151.6 4.25
150
3.70
4.24
6.5
TBSO 4.22
CO2Bn
O
140
136.0 4.21
3.65
6.0
128.5 3.83
0
128.2 2.83
130
1000
2000
5000
3000
4000
128.2 2.82
5.5
2.82
120
2.21 2.82
CO2Bn
5.0
2.81
O
NHCO2Et
2.47
1.99 2.82
2.47
2.8
4.5
2.82
2.46
110 100
f1 (ppm)
f1 (ppm)
2.00 2.47
2.45
2.47
2.6
4.0
2.45
90
S98
1.00 2.46
2.44
2.05 2.45
2.44
2.4
NHCO2Et
3.5
2.45
80
1.85
2.44
1.84
f1 (ppm)
70.0 2.44
3.0
2.2
70
1.83
66.2 1.99 1.84
1.83
62.2 1.83
1.83
60
2.5
2.05 1.82
2.0
1.82
1.81
1.81
1.81
50
4.08
2.0
1.81
1.8
4.08 1.80
1.81
0
40
1.80
1.5
31.9 3.22 1.78

1000
2000
5000
3000
6000
4000
31.6 1.33
30
1.0
30.8 9.41 1.32

29.8 1.31
20
25.9 0.91
0.5
18.0 0.90
14.2
10
6.06 0.90
0.0
0.07
0
0.07
-4.6 0.06
-0.5
-4.6 0.06
-10
0.05
0
0
1000
7000
2000
5000
5000
3000
6000
8000
9000
4000
-1000
11000
12000
-5000
15000
13000
10000
14000
10000
25000
55000
20000
35000
45000
50000
30000
60000
40000
10.0
220
7.40
7.40
9.5
210
7.39
7.38
7.38
9.0
200
7.38
7.37
190
8.5
7.37
BnO2C
7.37
180
7.36
8.0
174.0
173.3 7.36
7.35
170
7.5
BnO2C
11.47 7.35
7.35
160
7.0
7.34
151.5 7.34
150
7.28
OTBS
6.5
5.13
140
135.9 4.24
CO2Bn
6.0
128.5 4.23
O
128.2 4.21
OTBS
130
128.2 4.20
5.5
2.81
120
CO2Bn
3.97 2.79
O
5.0
2.46
2.45
2.44
NHCO2Et
4.5
2.44
110 100
f1 (ppm)
f1 (ppm)
2.00 2.43
4.0
2.43
90
S99
2.42
NHCO2Et
1.88
3.5
80
1.87
76.1
1.87
3.0
70
1.86
66.4 1.83 1.86
62.3 1.85
60
2.5
3.90
1.85
1.83
50
2.0
5.99 1.81
1.60
40
1.33
1.5
34.0
3.25 1.31
33.1
1.30
30
31.0
1.0
9.73 1.28
29.0
1.28
20
26.0
0.89
0.5
18.5
0.89
14.2
10
5.73 0.88
0.0
0.87
0
0.87
-1.9
0.14
-0.5
0.13
-10
0.12
0
0
5000
15000
10000
10000
70000
25000
20000
20000
35000
50000
45000
30000
30000
60000
80000
90000
40000
40000
7.44
7.28
4.26
4.25
4.24
4.24
4.23
4.22
2.20
2.19
2.19
2.19
2.19
2.18
2.18
2.17
2.10
2.08
2.07
2.05
1.70
1.53
1.53
1.52
1.52
1.52
1.51
1.51
1.50
1.50
1.48
1.47
1.47
1.46
1.46
1.46
1.45
1.34
1.34
1.33
1.32
1.31
1.27
1.21
1.20
1.18
1.18
1.15
1.15
0.90
0.88
0.87
0.84
0.83
45000
40000
35000
O
Me
Me 30000
NHCO2Et
Me
25000
CO2 tBu
20000
15000
10000
5000
10.25
0.86
2.00
0.93
1.96
1.02
2.00
3.16
2.93
1.18
5.95
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)
178.2
173.6
151.3
90000
80.0
62.2
44.6
37.0
32.9
30.8
28.1
26.8
26.7
20.7
14.2
85000
80000
75000
70000
65000
60000
O
Me 55000
Me
NHCO2Et 50000
Me 45000
40000
CO2tBu 35000
30000
25000
20000
15000
10000
5000
-5000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S10
0
40000
7.56
4.24
4.23
4.22
4.20
2.86
2.85
2.83
2.82
2.55
2.53
2.52
2.50
2.23
2.21
2.21
2.20
2.00
1.99
1.99
1.98
1.98
1.97
1.97
1.96
1.62
1.60
1.60
1.59
1.58
1.57
1.56
1.55
1.55
1.48
1.47
1.46
1.45
1.45
1.44
1.33
1.33
1.32
1.30
1.27
0.91
0.90
0.90
0.89
0.88
0.87
0.86
0.84
0.84
38000
36000
34000
32000
30000
28000
Me O 26000
Me 24000
Me
NHCO2Et 22000
20000
18000
CO2tBu 16000
14000
12000
10000
8000
6000
4000
2000
-2000
10.74
0.91
2.00
0.94
0.94
2.08
1.05
2.19
3.23
3.30
6.21
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
174.5
173.8
151.6
80.1
62.2
38.5
36.6
34.8
34.7
30.4
28.1
28.1
24.2
24.0
14.5
14.2
35000
30000
25000
Me O
Me 20000
Me
NHCO2Et
15000
CO2tBu
10000
5000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S10
1
7.49
7.49
7.28
4.25
4.23
4.22
4.21
2.72
2.71
2.70
2.70
2.69
2.68
2.68
2.19
2.19
2.18
2.17
2.17
2.16
2.15
1.65
1.63
1.63
1.62
1.61
1.61
1.61
1.60
1.59
1.59
1.58
1.57
1.57
1.56
1.56
1.55
1.54
1.47
1.46
1.46
1.45
1.44
1.33
1.33
1.32
1.30
1.28
1.27
0.87
0.86
0.86
0.84
0.81
36000
34000
32000
30000
28000
26000
Me O 24000
Me
22000
Me NHCO2Et 20000
18000
16000
CO2tBu 14000
12000
10000
8000
6000
4000
2000
-2000
0.89
2.00
1.80
1.94
5.21
9.85
3.32
5.96
2.67
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
175.1
173.7
151.6
200000
80.1
62.2
36.6
33.6
31.1
30.8
30.6
30.1
28.1
20.6
17.0
17.0
14.2
190000
180000
170000
160000
150000
140000
130000
Me O 120000
Me
110000
Me NHCO2Et 100000
90000
80000
CO2tBu 70000
60000
50000
40000
30000
20000
10000
-10000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S10
2
7.64
7.63
7.62
4.24
4.23
4.21
4.20
2.72
2.71
2.70
2.70
2.69
2.19
2.18
2.18
2.17
2.17
2.16
1.71
1.70
1.69
1.69
1.68
1.68
1.61
1.60
1.60
1.59
1.58
1.58
1.57
1.57
1.56
1.56
1.55
1.55
1.47
1.46
1.45
1.33
1.31
1.30
1.27
1.26
1.17
1.16
0.94
0.92
0.89
0.87
65000
60000
55000
50000
45000
40000
O
Me
Me 35000
NHCO2Et
30000
Me
25000
CO2tBu
20000
15000
10000
5000
0
0.91
2.00
1.96
2.03
1.12
4.07
9.75
3.19
1.98
5.89
3.17
-5000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
175.1
173.6
151.7
28000
80.1
62.2
47.9
35.2
34.3
33.6
31.0
30.4
28.1
25.5
24.7
23.7
14.2
26000
24000
22000
O
Me 20000
Me
NHCO2Et 18000
Me 16000
14000
CO2tBu
12000
10000
8000
6000
4000
2000
-2000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S10
3
7.49
4.25
4.24
4.22
4.21
2.72
2.71
2.70
2.70
2.69
2.19
2.18
2.17
2.17
2.16
2.16
2.15
1.59
1.57
1.57
1.57
1.56
1.56
1.55
1.55
1.54
1.54
1.54
1.54
1.53
1.47
1.46
1.45
1.34
1.32
1.31
1.22
1.21
1.20
1.20
1.19
1.18
1.13
1.13
1.12
1.10
1.10
1.10
0.90
0.89
0.88
0.86
1.11
1.11
24000
23000
22000
21000
20000
19000
18000
17000
O 16000
Me 15000
Me
NHCO2Et 14000
13000
Me 12000
11000
CO2tBu 10000
9000
8000
7000
6000
5000
4000
3000
2000
1000
0
-1000
10.01
0.93
2.00
2.00
2.08
4.15
3.28
2.20
2.10
6.18
3.11
-2000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
175.0
173.7
151.6
80.1
62.2
36.5
34.3
33.8
33.1
32.3
30.9
30.3
28.7
28.1
24.3
22.7
14.2
9000
8000
7000
O 6000
Me
Me
NHCO2Et 5000
Me
4000
CO2tBu
3000
2000
1000
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S10
4
10.0
220
7.43
7.30
9.5
210
7.30
7.28
7.28
9.0
200
7.27
7.27
Ph
190
8.5
7.24
7.23
180
Ph
7.22
8.0
174.7
173.4 7.16
Me
0.80
170
7.16
7.5
2.75 7.15
1.03 7.15
160
Me
7.0
2.09 7.14
151.6 7.14
150
CO2tBu 4.26
O
6.5
4.25
140
138.1 4.23
CO2tBu
O
6.0
130.6 4.22
127.9 2.81
130
126.1 2.79
5.5
2.57
120
2.29
NHCO2Et
5.0
2.28
2.27
NHCO2Et
2.26
4.5
2.25
f1 (ppm)
110 100
f1 (ppm)
2.00
5
1.64
4.0
1.63
90
S10
1.63
1.62
3.5
80.2
80
1.61
3.0 1.61
1.60
70
1.81 1.59
62.2 1.91 1.59
2.5
60
2.18 1.58
1.58
45.6
50
2.0
1.56
36.0 1.49
33.3 4.29
40
1.48
1.5
32.8 9.54
3.41 1.47
31.0 1.47
30
30.4
1.0
3.01 1.45
28.1 1.45
20
24.0 1.43
0.5
14.2 1.34
10
1.34
0.0
1.33
1.32
0
1.32
-0.5
1.28
-10
0.87
0
0
5000
-5000
15000
10000
25000
55000
20000
35000
65000
45000
50000
30000
60000
40000
10000
70000
20000
50000
30000
60000
80000
90000
40000
-10000
110000
120000
100000
10.0
220
9.5
210
9.0
200
Me
7.57
Me
8.5
190
3.96
3.95
Me 3.69
180
178.3
8.0
Me
174.8 3.68
0.94 2.72
170
7.5
2.72
Me 2.71
CO2Me
O
Me
160
2.71
7.0
CO2Me
O
2.70
H
N
151.8
2.69
150
H
N
6.5
2.69
O
2.57
140
O
O
2.57
6.0
2.56
130
2.55
5.5
2.55
H
2.54
120
Me
2.53
H
5.0
Me
2.01
Me
1.99
Me
4.5
1.98
110 100
f1 (ppm)
f1 (ppm)
1.97
6
1.95
4.0
2.00
90
S10
1.94
3.11 1.92
3.5
1.91
80
1.89
72.1 1.58
3.0
70
1.58
2.03
1.57
1.06
60
2.5
1.56
1.55
51.7
50
1.55
2.0
45.3 2.12 1.54

35.9 2.12 1.27
40
1.5
35.6 4.44 1.22

32.9 6.15 1.22
30
31.5 6.13 1.19
1.0
27.7 1.19
26.8
20
1.19
0.5
26.7 1.17
20.4 0.97
10
18.9 0.96
0.0
0.89
0
-0.5
-10
0
0
5000
5000
15000
10000
25000
20000
15000
10000
25000
20000
10.0
220
8.77
8.39
9.5
210
7.86
7.84
7.63
9.0
200
0.50 7.52
7.36
Bn
190
8.5
0.51 7.31
7.29
180
7.20
8.0
175.0 2.00
Boc
174.7 1.05 4.48
4.38
170
2.12
7.5
165.2 5.99 4.35
1.27 4.14
160
7.0
156.4 4.07
4.07
150
O
139.3 4.06
6.5
133.1 4.06
PO(OEt)2
128.9
140
4.05
Bn
128.4
6.0
4.04
127.6 4.04
130
NHBz
N
127.5 4.04
5.5
127.4
Boc
4.03
120
127.1 4.03
5.0
4.02
4.01
0.52 4.01
4.5
1.58 4.00
110 100
f1 (ppm)
f1 (ppm)
7
O
0.70 3.99
4.0
4.28 3.98
90
S10
PO(OEt)2
3.37
2.88
3.5
80.4
80
2.79
NHBz
3.0 1.94
70
2.13 1.88
61.5 1.78
1.67
60
2.5
61.5
56.4 1.66
1.57
50
34.3
2.0
1.54
29.7 18.58 1.52
28.5
40
1.43
1.5
28.4 6.68 1.36

27.4 1.35
30
1.0
27.3 1.34
26.5 1.34
20
26.1 1.33
0.5
23.5 1.32
22.4
10
1.31
0.0
16.5 1.30
16.4
0
1.30
1.29
-0.5
1.28
-10
1.28
-1.0
0
0
500
500
-500
1500
1500
1000
1000
7500
7000
2500
2500
5500
2000
2000
3500
3500
6500
4500
5000
4500
3000
3000
6000
8000
4000
4000
31.9
31.7
1600
1500
31.9
31.7
1400
1000
1300
Boc O
1200
500 N
Bn NHBz 1100
0 1000
900
32.2 32.0 31.8 31.6
f1 (ppm)
31.4 31.2 PO(OEt)2
800
700
600
500
400
300
200
100
-100
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90
f1 (ppm)
S10
8
25000
7.55
4.64
4.63
3.67
3.67
2.72
2.71
2.71
2.70
2.69
2.55
2.09
2.06
1.93
1.91
1.90
1.89
1.88
1.72
1.71
1.71
1.69
1.69
1.68
1.57
1.56
1.55
1.55
1.55
1.54
1.53
1.53
1.39
1.38
1.22
1.21
1.19
1.18
1.18
1.16
1.09
1.07
1.06
1.04
1.03
1.01
1.00
0.94
0.92
0.92
0.90
0.88
0.81
0.79
24000
23000
22000
21000
20000
19000
18000
Me
17000
16000
O O 15000
Me 14000
Me
N O 13000
H 12000
Me 11000
Me Me 10000
CO2Me 9000
8000
7000
6000
5000
4000
3000
2000
1000
0
-1000
13.00
0.90
1.00
1.95
1.00
1.04
2.03
1.06
4.12
2.32
3.04
3.11
2.11
3.11
-2000
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)
4000
178.3
178.3
175.0
151.4
151.4
51.7
51.6
47.0
45.4
40.9
40.8
36.0
36.0
35.6
34.1
32.9
31.5
31.5
31.4
26.8
26.7
26.3
26.2
23.4
23.4
21.9
20.7
20.4
16.4
16.4
3800
3600
3400
3200
3000
2800
2600
Me
2400
2200
O O
Me 2000
Me
N O 1800
H 1600
Me
Me Me 1400
CO2Me 1200
1000
800
600
400
200
-200
-400
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)
S10
9
10.0
220
8.85
7.89
9.5
210
7.88
7.88
9.0
7.87
200
0.97 7.87
7.87
190
8.5
7.62
7.62
180
8.0
2.02 7.61
173.9 1.00 7.61
173.7 7.53
170
2.07
7.5
165.7 5.05 7.53
7.52
160
7.0
155.8 7.50
Me
Me
7.50
150
136.0 7.38
Boc
6.5
133.2 7.38
Me
Me
140
132.9 7.38
6.0
7.37
Boc
128.9
NH
128.5 7.36
130
128.2 7.36
5.5
CO2Bn
128.1 7.35
O
NH
120
127.8 2.17 7.34
5.0
7.34
CO2Bn
O
1.02 7.33
5.14
4.5
NHBz
5.13
110 100
f1 (ppm)
f1 (ppm)
0
1.06 4.79
4.0
4.77
90
S11
NHBz
4.14
4.12
3.5
80
79.4 4.12
0.83
3.25
3.0
70
0.84 3.24
66.3 2.94
2.92
2.5
60
2.05
2.48
54.4
2.47
50
2.0
2.47
39.0 2.38 2.46
40
37.1 2.45
1.5
33.8 9.02 2.44

29.2 1.70
30
1.0
28.3 6.18 1.69

23.4 1.68
20
23.1 1.68
0.5
1.67
10
1.66
0.0
1.66
0
1.64
1.38
-0.5
0.98
-10
0.96
-1.0
0
0
5000
5000
15000
15000
10000
10000
25000
25000
20000
20000
35000
30000
10.0
220
7.39
7.39
9.5
210
7.38
7.38
9.0
7.37
200
7.37
7.36
190
8.5
7.35
7.35
180
8.0
7.35
Me
174.2 7.34
7.34
170
7.5
6.15 7.28
5.13
160
7.0
Me
5.12
O
151.4 4.26
150
4.24
6.5
CO2Bn
4.23
140
136.1 4.21
Me
6.0
128.5 2.40
128.2 2.39
130
128.1 2.38
5.5
2.37
NHCO2Et
120
2.10 2.34
Me
5.0
2.33
O
2.32
1.89
CO2Bn
4.5
1.88
110 100
f1 (ppm)
f1 (ppm)
2.00
1
1.84
4.0
1.83
90
S11
1.83
1.81
3.5
NHCO2Et
80
0.82 1.80
3.0 1.74
70
1.73
66.1 1.72
62.2 1.71
60
2.5
2.11 1.70
43.3 3.07 1.70
50
2.0
40.8 2.65 1.69

35.9 1.06 1.67
40
35.9 1.66
1.5
4.35
34.5 2.21 1.34
31.8 1.33
30
1.12
1.0
29.2 3.11 1.31

26.7 5.86 1.28
20
26.1 1.10
0.5
25.2 1.07
10
22.1 0.97
0.0
14.2 0.97
0
0.96
0.90
-0.5
0.89
-10
0.87
0
0
1000
7000
2000
5000
5000
3000
6000
8000
9000
4000
-1000
11000
12000
15000
13000
10000
14000
10000
25000
20000
30000
10.0
220
175.0 7.89
173.0 7.89
9.5
210
168.9 7.89
165.3 7.88
9.0
133.3 7.88
MeO2C
200
O
Me
133.2 0.99 7.88
133.1 7.88
190
8.5
129.0 5.19 7.87
Me
129.0 5.16 7.87
O
Me
180
5.16
8.0
129.0 2.02 7.87
128.9 1.00 5.14 7.86
2.16 5.13
128.6 7.54
170
2.11
O
7.5
128.6 5.26 f1 (ppm) 5.12 7.53
128.5 5.09 7.52
160
5.06
7.0
128.5 7.52
128.4 5.04 7.52
150
128.3 7.40
CO2Bn
6.5
128.3 7.39
140
128.2 7.39
5.25 5.20 5.15 5.10 5.05 5.00 4.95
6.0
127.7 7.38
0
NHCOPh
127.6 7.37
130
1000
2000
3000
4000
127.6 7.37
5.5
MeO2C
O
Me
127.6 7.36
120
109.6 2.16 7.36
5.0
109.5 7.35
87.0 7.34
Me
O
86.3 1.03 7.29

Me
4.5
86.3 5.16
110 100
f1 (ppm)
f1 (ppm)
2
79.8 5.16
O
4.0
66.5 5.14
90
S11
66.5 3.00 4.72
66.3 4.55
3.5
80
52.4 0.87 4.50
52.4 1.65 3.82
CO2Bn
3.0
70
40.5 1.62 3.80
40.5 4.49 3.78
1.58
35.2 1.65
2.5
60
3.27 1.56
NHCOPh
32.7 1.53 1.62

32.7 2.28 1.58
1.47
50
2.0
29.4 3.24 1.56

1.43
28.9 1.39 1.53
40
28.9 3.27 1.47
f1 (ppm)
1.5
1.39
28.6 3.24 1.28 1.43
27.8 3.54 1.39
30
1.15
1.0
27.6 1.07 1.39

27.2 3.54 1.28
1.05
20
27.0 1.17
0.5
0.94
26.9 1.15
1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9
0.93
10
26.6 1.15
0
0.0
26.5 1.13
0
1000
2000
16.0 1.07
5000
3000
6000
4000
15.2 1.05
-0.5
15.2 0.94
-10
15.1 0.93
-1.0
0
0
500
-500
1500
1000
1000
7000
7000
2500
5500
2000
2000
3500
6500
5000
4500
5000
3000
3000
6000
8000
9000
6000
4000
4000
-1000
11000
17000
-2000
12000
21000
15000
13000
16000
18000
19000
10000
14000
22000
24000
23000
20000
220
175.3 7.85
10.0
BnO
165.4 7.85
210
138.5 7.83
9.5
BnO
138.5 0.77 7.83
8.75
138.4 8.73 7.52
200
9.0
133.1 7.51
f1 (ppm)
0.77 0.17 8.71
132.9 7.49
8.70
190
129.0 0.17 7.37
8.5
128.9 7.36
OBn
180
128.4 7.36
8.65
0
8.0
128.4 2.00 7.36
500
1000
128.3 7.35
170
1.02
O
128.3 2.00 7.35
7.5
2.17 7.37
7.8
128.3 16.04 7.36 7.35
160
127.9 7.36 7.34
7.0
127.8 1.02 7.34
7.6
7.34
150
127.7 2.17 7.32 7.33
NHBz
f1 (ppm)
127.7 7.32
6.5
7.31
7.4
140
127.6 7.30 7.31
127.6 16.04 7.31
PO(OEt)2
7.30
BnO
6.0
7.2
127.5 7.30
130
7.28
127.5 7.30
BnO
0
5.5
127.4 7.30
120
4000
127.4 7.29
78.9 4.91 7.28
5.0
78.3 0.79 7.27
O
0.79 4.89
75.3 5.29 4.69 7.26
4.5
OBn
75.1 7.24
110 100
f1 (ppm)
f1 (ppm)
0.17 4.66
3
75.0 4.17 4.64 7.24
73.4 4.61 7.22
4.0
90
S11
0.91
f1 (ppm)
73.3 4.23 4.59 4.89

O
72.8 5.29 4.58 4.69
80
3.5
72.5 4.56 4.66
72.4 4.54 4.59
70
72.2 2.11 4.58
3.0
5.0 4.9 4.8 4.7 4.6 4.5 4.4
4.52
71.8 4.54
NHBz
0.18
0
71.2 4.10
60
2.5
1000
2000
3000
70.1 4.10
PO(OEt)2
69.9 0.82 4.09
50
1.84
2.0
67.5 4.09
61.7 4.99 1.34 4.09
40
61.7 1.33 4.08
1.5
61.6 6.06 1.32 4.08

6.06
61.6 4.07
30
1.32
1.0
37.7 1.31 4.07

f1 (ppm)
33.0 1.30 3.71
20
32.2 1.30 3.70
0.5
32.0 1.28 3.70

1.40 1.35 1.30 1.25 1.20
10
25.6 1.28 3.70
0.0
25.6 1.68
0
0
19.6 1.34
2000
6000
4000
18.5 1.32
-0.5
16.5 1.32
-10
16.5 1.31
-1.0
0
0
500
500
-500
1500
1500
1000
1000
7500
7000
2500
2500
5500
2000
2000
3500
3500
6500
4500
5000
3000
3000
6000
4000
4000
33.47
32.85
55000
50000
45000
O PO(OEt)2
BnO
40000
BnO NHBz 35000
OBn
O 30000
25000
20000
15000
10000
5000
-5000
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90
f1 (ppm)
S11
4
10.0
220
176.5 7.89
174.2 7.88
9.5
210
165.3 7.88
136.1 7.87
9.0
133.2 7.87
200
TBSO
133.1 7.87
132.9 0.93 7.62
8.5
190
129.0 7.54
129.0 7.52
180
8.0
128.5 1.96 7.51
128.1 7.38
H
0.98
128.1 7.37
170
2.02
TBSO
7.5
H
128.1 5.26 7.37
127.6 7.28
160
H
7.0
127.6 5.14
72.7 5.13
150
72.7 1.84
6.5
H
66.2 1.81
1.80
140
66.2
H
6.0
56.6 1.78
H
56.6 1.69
130
H
43.9 1.63
5.5
CO2Bn
43.9 1.63
H
120
42.2 1.90 1.62
5.0
40.9 1.62
40.8 1.61
O
40.2 1.42
4.5
H
40.2 1.41
110 100
f1 (ppm)
f1 (ppm)
5
38.4 1.40
NHBz
CO2Bn
4.0
36.9 1.39
90
S11
35.6 1.39
35.4 1.00 1.37
3.5
80
34.6
O
1.37
33.5 1.36
3.0
1.84
70
32.6 1.35
NHBz
32.3 1.34
32.2 1.28
60
2.5
31.0 2.09 1.23

29.3 1.01
0.93
50
2.0
29.0 0.99
27.3 0.94
40
26.3 0.94
1.5
28.91
26.0 0.93
26.0 2.81 0.93
30
1.0
23.7 13.84 0.92

23.4 3.05 0.92
20
22.9 0.91
0.5
22.7 0.90
10
22.6 6.25 0.79
0.0
20.7 0.09
0
18.3 0.08
14.9 0.08
-0.5
-4.5 0.08
-10
-4.6 0.07
0
0
1000
7000
2000
5000
3000
6000
8000
9000
4000
1000
7000
2000
5000
3000
6000
8000
9000
4000
-1000
10000
11000
12000
13000
10000
14000

Ja7b09306 Si 001

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Supporting Information

Direct γ-C(sp3)-H Alkylation of Carbonyls through Visible Light

Dian-Feng Chen,† John C. K. Chu‡ and Tomislav Rovis*,†

General Considerations ............................................................................................................................2

Amide Synthesis and Characterization ....................................................................................................3

Examination of Protecting Groups .........................................................................................................20

Examination of Bases .............................................................................................................................21

Examination of Photocatalysts ...............................................................................................................22

Examination of Solvents ........................................................................................................................23

Photoredox-Catalyzed γ-C(sp3)-H Alkylation (Alkene and Amide Scope) ...........................................24

Mechanistic Investigations .....................................................................................................................44

NMR Spectra ..........................................................................................................................................53

Prepared according to Procedure A from commercially available 4-methyl pentanoic acid

Prepared according to Procedure B from commercially available 4-methyl pentanoic acid

Prepared according to Procedure A from commercially available 4-ethyloctanoic acid

Prepared according to Procedure A from commercially available 3-cyclohexanepropionic

Fe(acac)3 (30 mol%)

Cl EtOH, 60 ˚C, 1h Cl Me CO2Me MeOH, 70 ˚C Cl Me CO2H

Methyl 8-chloro-4-methyloctanoate was synthesized according to Baran’s

Prepared according to Procedure B from 4-([tert-butyldimethylsilyl]oxy)pentanoic acid

Prepared according to Procedure B from

Prepared according to Procedure B from commercially available valeric acid (501mg,

O LiOH (5.0 equiv) Procedure B O

To a solution of methyl 4-methoxybutyrate (1.32g, 10 mmol) in 50 mL of mixed

Prepared according to Procedure B from 4-((tert-butyldimethylsilyl)oxy)butanoic acid

Prepared according to Procedure B from

A solution of isobutyraldehyde (0.72g, 10.0 mmol) and ethyl

To a solution of methyl 3,4-dimethylpentanoate6 (0.72g, 5.0 mmol) in 10 mL of

EDC·HCl (1.3 equiv)

To a solution of DL-β-Leucine (1.31g, 10.0 mmol) in 50 mL of 1:1 mixed

To a solution of 5-methyl-4-methylenehexanoic acid7 (0.71g, 5.0 mmol) in 50 mL of

The mixture of 2,5-dimethylhexanal8 (0.64g, 5.0 mmol) and ethyl

The mixture of 2-methyl-3-phenylpropanal9 (0.72g, 5.0 mmol) and Ethyl

Prepared according to Procedure B from commercially available 4-methyl pentanoic acid

Prepared according to Procedure B from commercially available 4-methyl

Prepared according to Procedure B from

Fe(dibm)3 (30 mol%)

Prepared according to Procedure B from TBS-protected lithocholic acid (491 mg,

Entry Base Conv. % NMR Yield %b

CF3 CF3 CF3

Entry Solvent Conv. % NMR Yield %b

Prepared according to Procedure C (with 3.0 equiv. of methyl methacrylate). Colorless

Prepared according to Procedure C (with 1.5 equiv. of methyl 2-benzylacrylate).

Prepared according to Procedure C (with 2.0 equiv. of N,N´-dimethylacrylamide).

Prepared according to Procedure C (with 3.0 equiv. of methyl methacrylate). Colorless

Prepared according to Procedure C (with 3.0 equiv. of methyl methacrylate). Colorless

Prepared according to Procedure C (with 3.0 equiv. of methyl methacrylate). Colorless

Run 1 1 0.98628 0.97410 0.98015 0.99338

Run 2 1 0.97995 0.99311 1.00396 1.00565

Average 1 0.98641 0.98075 0.98757 0.99488

(b) Stern-Volmer experiments of potassium salt of 1a:

Run 1 1 1.10945 1.22282 1.38817 1.59465

Run 2 1 1.10729 1.23392 1.38874 1.58631

Average 1 1.10469 1.22443 1.38376 1.58334

•1a and Ir[(dF-CF3)ppy]2(dtbbpy)PF6;

• Potassium salt of 1a and Ir[(dF-CF3)ppy]2(dtbbpy)PF6

UV-Vis spectrum of [Ir(dF-CF3ppy)dtbpy]PF6 in DMF

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