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Supporting Information

A Visible-Light-Driven Flexible Synthesis of α-Alkylated Glycine


Derivatives Catalyzed by Reusable Covalent Organic
Frameworks

Yao Tian, ‡a Xiubin Bu, ‡a Luohe Wang, a Junnan E, a Liangliang Shi, *d, e
Hua Tian, *c Xiaobo Yang,*a,b Hua Fub and Zhen Zhaoa

aInstitute of Catalysis for Energy and Environment, College of Chemistry and Chemical Engineering, Shenyang

Normal University, Shenyang 110034, P. R. China. E-mail: bxy1223@gmail.com, yangxb@synu.edu.cn.


bKey Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department

of Chemistry, Tsinghua University, Beijing 100084, P. R. China.


cState Key Laboratory of Bioactive Substance and Function of Natural Medicines, and Beijing Key Laboratory of
Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of

Medical Sciences and Peking Union Medical College, Beijing 100050, P. R. China. E-mail: tianh@imm.ac.cn
dTianjin Lisheng Pharmaceutical Co., Ltd., Tianjin 300385, P. R. China. E-mail: taxxunmei@126.com.
eThe Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University,

Tianjin, 300385, P. R. China.


‡These two authors contributed equally to this work.

Total number of pages: 80 (S1-S80)


Total number of figures: 97 (Figure S1-Figure S97)
Total number of schemes and tables: 4

S1
Table of Contents

I. General information S3
II. Preparation of 2D-COFs and structural characterizations of 2D-COF-4 S4
III. Preparation of the substrates S8
IV. Optimization of the reaction conditions S11
V. General procedures for the synthesis of alkylated glycine derivatives S12
VI. Scale-up experiment S13
VII. Sustainability assessment for catalyst S14
VIII. Environmental benefits S18
IX. Strategies for the visible-light-driven alkylation of glycine derivatives S21
X. Mechanistic studies S23
XI. Calculation of Apparent Quantum Efficiency (A.Q.E.) S27
XII. Hot filtration test S28
XIII. Characterization data of compounds S29
XIV. References S42
XV. Copies of NMR spectra S44

S2
I. General information
All reagents and solvents were purchased from commercial sources and used as
received without further purification unless otherwise indicated. 1H NMR spectra were
recorded on a Bruker 400 or 500 MHz spectrometer with CDCl3 or DMSO-d6 as the
solvent; 13C NMR spectra were recorded on a Bruker 101 or 126 MHz spectrometer
with CDCl3 or DMSO-d6 as the solvent; 19F NMR spectra were recorded on a Bruker
376 MHz spectrometer with CDCl3 as the solvent. Chemical shifts were reported in
parts per million (δ) with TMS (0 ppm) as the internal standard. The peak patterns are
indicated as follows: s (singlet), d (doublet), dd (doublet of doublets), t (triplet), q
(quartet), and m (multiplet). The coupling constants (J) are reported in Hertz (Hz). The
unknown products were additionally characterized by high-resolution mass
spectrometry (HR-MS). HR-MS was performed in Thermo LCQ Deca XP Max mass
spectrometer.
Powder X-ray diffraction (PXRD) patterns of the as-prepared samples were obtained
on a powder X-ray diffractometer (Cu Kα radiation source, Ultima IV, Rigaku). The
solid 13C NMR spectra were obtained on a Bruker Avance Neo 400 MHz WB solid-
state NMR spectrometer. FT-IR spectra were collected in the 400-4000 cm-1 range on a
Bruker IFS 66 v/s Fourier transform infrared spectrometer. The nitrogen adsorption and
desorption isotherms were collected at 77 K using the micromeritics ASAP 2020 HD88
or Micromeritics ASAP 2460. The thermogravimetric analysis (TGA) was performed
on a Rigaku TG/DTA8122 thermogravimeter by measuring the weight loss while
heating at 10 °C min−1 from room temperature to 800 °C under nitrogen. Scanning
electron microscopy (SEM) images were captured on a Hitachi Regulus 8100,
microscope operated at an accelerating voltage of 0.02-30 kV. Transmission electron
microscopy (TEM) images were captured on a JEOL JEM-F200 microscope at an
accelerating voltage of 200 kV. UV/Vis diffuse reflectance spectra were performed
using a Hitachi UH4150 spectrophotometer in the wavelength range of 200‐800 nm, v
= 200 nm/min, and BaSO4 was used as a reference.
All visible-light-driven reactions were carried out in a 10 mL borosilicate glass tube.
Two Blue LEDs (40 W, the wavelength of peak intensity is at 456 nm, Kessil PR160)
were used as the light source. The distance from the Blue LED to the irradiation vessel
is approximately 5 cm. No filter was used.

S3
II. Preparation of 2D-COFs and structural characterizations of 2D-COF-4
(a) Preparation of 2D‐COFs
The following 2D‐COFs were synthesized according to the literature 1-6 and our
reported methods.7-10

Figure S1. The prepared 2D-COFs.

(b) Structural characterizations of 2D-COF-4

Figure S2. The FT-IR spectrum of 2D‐COF‐4.

S4
Figure S3. The UV/Vis diffuse reflectance spectrum of 2D-COF-4.

Figure S4. The direct Kubelka‐Munk plot for 2D‐COF‐4.

Figure S5. The powder X‐ray diffraction pattern of 2D‐COF-4.

S5
Figure S6. The 13C NMR spectrum of 2D‐COF‐4.

Figure S7. The SEM image of 2D‐COF‐4.

Figure S8. The TEM image of 2D‐COF‐4.

S6
Figure S9. (a) N2 adsorption and desorption isotherms of 2D-COF-4 measured at 77 K. (b) Pore size
distributions of 2D-COF-4 derived from N2 sorption isotherm measured at 77 K.

Figure S10. The TGA curve of the 2D-COF-4 under a N2 atmosphere.

S7
III. Preparation of the substrates
(a) Preparation of glycine esters

According to literature reports,11 aniline (10 mmol, 1.0 equiv.), ethyl bromide acetate
(1.0 equiv.), and anhydrous NaOAc (2.0 equiv.) in 10 mL of ethanol was refluxed in a
S8
25 mL sealed Schlenk tube and stirred overnight. The mixture was then cooled to room
temperature. Subsequently, the mixture was filtered and concentrated under reduced
pressure. The residue was purified by flash column chromatography (PE/EtOAc = 15:1
to 10:1) to give the compound 1a-1r.

According to literature reports,12 benzyl bromide (3.30 mmol, 1.1 equiv.) was added to
N-phenylglycine (3.0 mmol, 1.0 equiv.) and K2CO3 (6.0 mmol, 2.0 equiv.) in anhydrous
DMF, and the mixture was stirred at 60 °C overnight. The resulting mixture was
extracted with ethyl acetate, and the combined organic phase was washed with 0.2 M
NaOH, water, and brine in sequence. After being dried over MgSO4, the solvent was
removed under reduced pressure. The residue was purified by flash column
chromatography (PE/EtOAc = 10:1) to give the compound 1s.

(b) Preparation of glycine dipeptides

According to literature reports,11,13 N-phenyl glycine (5.0 mmol, 1.0 equiv.), 1-ethyl-3-
(3′-dimethylaminopropyl)carbodiimide hydrochloride (EDCI) (8.0 mmol, 1.6 equiv.),
1-hydroxybenzotriazole (HOBt) (7.0 mmol, 1.4 equiv.), and the corresponding amine
(5.0 mmol, 1.0 equiv.) were dissolved in 30 mL of DCM with a 100 mL round-bottomed
flask, then Et3N (10 mmol, 2.0 equiv.) was added. The reaction mixture was stirred
overnight. The resulting mixture was extracted with DCM, and the combined organic
layers were dried over MgSO4 and filtered. The filtrate was concentrated under reduced
S9
pressure. The residue was purified by flash column chromatography (PE/EtOAc = 2:1
to 1:1) to give the compound 1t-1w.

(c) Preparation of alkyl N-hydroxyphthalimide (NHPI) esters14

N‐hydroxyphthalimide (10 mmol, 1.0 equiv.), the corresponding alkyl carboxylic acids
(6 mmol, 1.2 equiv.), 4‐dimethylaminopyridine (DMAP, 10 mol%), and 20 mL of DCM
were mixed in a 100 mL round‐bottomed flask. A solution of N,N’‐
dicyclohexylcarbodiimide (DCC, 6 mmol, 1.2 equiv.) in 10 mL DCM was added slowly.
The reaction mixture was allowed to stir at room temperature for 1 hour. The white
precipitate was removed by filtration, and the filtrate was concentrated under reduced
pressure. The residue was purified by flash column chromatography (PE/EA = 10:1) to
give the compound 2a-2n.

S10
IV. Optimization of the reaction conditions

Table S1. Catalyst evaluation and optimization of reaction conditions.a,b

Entry Photocatalyst Solvent Light wavelength Yield (%)b


1 Eosin Y DMSO 456 nm 30
2 Ru(bpy)3Cl2 DMSO 456 nm 31
3 g-C3N4 DMSO 456 nm 58
4c 2D-COF-4 DMSO 456 nm 38
d
5 2D-COF-4 DMSO 456 nm 65
6e 2D-COF-4 DMSO 456 nm 79
f
7 2D-COF-4 DMSO 456 nm 82
8g 2D-COF-4 DMSO 456 nm 76
a
Reaction conditions: 1d (0.1 mmol, 1 equiv.), 2a (0.12 mmol, 1.2 equiv.), Photocatalyst (for
homogeneous photocatalyst, 5 mol%; for heterogeneous ones, 4 mg), solvent (2 mL), 2*40
W blue LED, Ar, r.t., 24 h. b Isolated yield. c DMSO (1.0 mL). d DMSO (3.0 mL). e 2a (0.1
mmol, 1.0 equiv.). f 2a (0.15 mmol, 1.5 equiv.). g 2a (0.2 mmol, 2.0 equiv.).

S11
V. General procedures for the synthesis of alkylated glycine derivatives

(GP1): The general procedure for the synthesis of alkylated glycine derivatives in
EtOH
A 10 mL glass tube was charged with the glycine derivative 1 (0.1 mmol, 1.0 equiv.),
alkyl NHPI ester 2 (1.2 mmol, 1.2 equiv.), and 2D‐COF‐4 (4 mg). The tube was
evacuated and filled with argon for three cycles. Then, 2 mL of EtOH was added via a
gastight syringe under an argon atmosphere. The reaction mixture was stirred (1000
rpm) with the irradiation of two 40 W blue LEDs (456 nm, the power density of the
incident light near the reactor is 0.003 W/cm2, and the distance between the reactor and
lamp is approximately 5 cm.) at room temperature for 24 h. Upon completion, the
solvent was removed under reduced pressure, and then 1 mL of toluene was added to
the residue. The mixture was filtered, and the filtrate was concentrated under a vacuum
to afford the compound 3.

(GP2): The general procedure for the synthesis of alkylated glycine derivatives in
DMSO
A 10 mL glass tube was charged with the glycine derivative 1 (0.1 mmol, 1.0 equiv.),
alkyl NHPI ester 2 (1.2 mmol, 1.2 equiv.), and 2D‐COF‐4 (4 mg). The tube was
evacuated and filled with argon for three cycles. Then, 2 mL DMSO was added via a
gastight syringe under an argon atmosphere. The reaction mixture was stirred (1000
rpm) with the irradiation of two 40 W blue LEDs (456 nm, the power density of the
incident light near the reactor is 0.003 W/cm2, and the distance between the reactor and
lamp is approximately 5 cm.) at room temperature for 24 h. Upon completion, the
photocatalyst 2D‐COF‐4 was removed by centrifugation and filtration, 10 mL of
deionized water was added to the filtrate, and the resulting mixture was extracted with
ethyl acetate (5 mL × 3). The organic layers were washed with saturated brine, dried
over MgSO4, and filtered. The solvent was removed under reduced pressure. The
residue was purified by flash column chromatography on silica gel (petroleum ether
and ethyl acetate) to afford the compound 3.

S12
VI. Scale-up experiment

A 100 mL round-bottomed flask equipped with a magnetic stir bar was charged with
ethyl (4–methoxyphenyl)glycinate 1d (2.4 mmol, 0.5 g), 1,3-dioxoisoindolin-2-yl
cyclohexanecarboxylate 2a (2.88 mmol, 0.79 g), and 2D-COF-4 (100 mg). Then, the
flask was evacuated and filled with argon for three cycles. Then, DMSO or EtOH (50
mL) was added via a gastight syringe under an argon atmosphere. The reaction mixture
was stirred with the irradiation of two 40 W blue LEDs (456 nm, the power density of
the incident light near the reactor is 0.003 W/cm2, and the distance between the reactor
and lamp is approximately 5 cm.) at room temperature for 120 h. Upon completion, the
photocatalyst 2D‐COF‐4 was removed by centrifugation and filtration. For DMSO, 50
mL of deionized water was added to the filtrate, and the resulting mixture was extracted
with ethyl acetate (50 mL × 3). The organic layers were washed with saturated brine,
dried over MgSO4, and filtered. The solvent was removed under reduced pressure. The
residue was purified by flash column chromatography on silica gel (petroleum ether
and ethyl acetate) to afford the compound 3da (0.432 g, 86%). For EtOH, the solvent
was removed under reduced pressure, and then 4 mL of toluene was added to the residue.
The mixture was filtered, and the filtrate was concentrated under a vacuum to afford
the compound 3da (0.432 g, 86%).

S13
VII. Sustainability assessment for catalyst
(a) A long-time light irradiation experiment

A 10 mL glass tube was charged with glycine derivatives 1d (0.1 mmol, 1.0 equiv.),
alkyl NHPI ester 2a (1.2 mmol, 1.2 equiv.), and 2D‐COF‐4 (4 mg). The tube was
evacuated and filled with argon for three cycles. Then, EtOH (2 mL) was added via a
gastight syringe under an argon atmosphere. The reaction mixture was stirred (1000
rpm) with the irradiation of two 40 W blue LEDs (456 nm, the power density of the
incident light near the reactor is 0.003 W/cm2, and the distance between the reactor and
lamp is approximately 5 cm.) at room temperature for 7 days. Upon completion, the
photocatalyst 2D‐COF‐4 was collected by centrifugation and filtration. The solvent was
removed under reduced pressure, and then 1 mL of toluene was added to the residue.
The mixture was filtered, and the filtrate was concentrated under a vacuum to afford
the compound 3da (82% yield). The recovery rate of 2D-COF-4 is 93%.

(b) Recycling experiments

A 10 mL glass tube was charged with ethyl (4-methoxyphenyl)glycinate 1d (0.1 mmol,


1.0 equiv.), 1,3-dioxoisoindolin-2-yl pivalate 2f (1.5 mmol, 1.5 equiv.), and 2D‐COF‐4
(4 mg). The tube was evacuated and filled with argon for three cycles. Then, EtOH (2
mL) was added via a gastight syringe under an argon atmosphere. The reaction mixture
was stirred (1000 rpm) with the irradiation of two 40 W blue LEDs (456 nm, the power
density of the incident light near the reactor is 0.003 W/cm2, and the distance between
the reactor and lamp is approximately 5 cm.) at room temperature for 24 h. Upon
completion, the photocatalyst 2D‐COF‐4 was removed by centrifugation and washed
with plenty of ethyl acetate and ethanol. Then, the powder was dried at 120 °C under
vacuum for 6 h to yield the recovered 2D‐COF‐4. The solvent was removed under
reduced pressure, and then 1 mL of toluene was added to the residue. The mixture was
filtered, and the filtrate was concentrated under a vacuum to afford the compound 3df.

S14
Figure S11. Catalyst recycling experiment.

(c) Structural characterizations of recycled 2D-COF-4

Figure S12. The FT-IR spectrum of recycled 2D‐COF‐4.

Figure S13. The powder X‐ray diffraction pattern of recycled 2D‐COF-4.

S15
Figure S14. The 13C NMR spectrum of recycled 2D‐COF‐4.

Figure S15. The SEM image of recycled 2D‐COF‐4.

Figure S16. The TEM image of recycled 2D‐COF‐4.

S16
Figure S17. (a) N2 adsorption and desorption isotherms of recycled 2D-COF-4 measured at 77 K. (b)
Pore size distributions of recycled 2D-COF-4 derived from N2 sorption isotherm measured at 77 K.

Figure S18. The TGA curve of the recycled 2D-COF-4 under a N2 atmosphere.

S17
VIII. Environmental benefits
(a) Typical work-up process for the reaction of 1d with 2a

A 10 mL round-bottomed flask equipped with a magnetic stir bar was charged with
ethyl (4-methoxyphenyl)glycinate 1d (1.0 mmol), 1,3-dioxoisoindolin-2-yl
cyclohexanecarboxylate 2a (1.2 equiv.), and 2D-COF-4 (40 mg). Then, the flask was
evacuated and filled with argon for three cycles. EtOH (5 mL) was added via a gastight
syringe under an argon atmosphere. The reaction mixture was stirred with blue LED
irradiation (2*40 W blue LEDs, 456 nm, the power density is 0.003 W/cm2, and the
distance between the reactor and lamp is approximately 5 cm.) for 48 h at room
temperature.

Part A: Upon completion, the solvent was removed under reduced pressure, and then
2 mL of toluene was added to the residue. The mixture was filtered, and the filtrate was
concentrated under a vacuum to obtain the 3da directly. 3da, brown oil, 250 mg, 86%.
1
H NMR (500 MHz, CDCl3) δ 6.75 (d, J = 8.9 Hz, 2H), 6.60 (d, J = 8.9 Hz, 2H), 4.14
(q, J = 7.2 Hz, 2H), 3.76 (d, J = 6.2 Hz, 1H), 3.73 (s, 3H), 1.88 – 1.65 (m, 6H), 1.28 –
1.13 (m, 8H); 13C{1H} NMR (126 MHz, CDCl3) δ 173.9, 152.4, 141.5, 115.0, 114.7,
63.2, 60.5, 55.6, 41.1, 29.5, 29.1, 26.1, 26.0, 25.9, 14.2.

S18
Part B: Then, 5 mL of EtOH was added to the above filtration residue. The mixture
was filtered, and the filtrate was concentrated under a vacuum to recover the
phthalimide directly. Phthalimide, light yellow solid, 161 mg, 91%. 1H NMR (500 MHz,
DMSO) δ 11.33 (s, 1H), 7.82 (s, 4H); 13C{1H} NMR (126 MHz, DMSO) δ 169.2, 134.3,
132.6, 122.9.

Part C: The above filtration residue was dried at 120 °C under vacuum for 6 h to afford
the recovered 2D‐COF‐4 in 95% yield.

(b) Calculation of the E-factor for the above protocol


Our protocol features a low Environmental factor. The calculation of the E-factor for
our process is described as follows.

𝑀𝑎𝑠𝑠 𝑜𝑓 𝑡𝑜𝑡𝑎𝑙 𝑤𝑎𝑠𝑡𝑒 100.24


E-factor = = = 0.40
𝑀𝑎𝑠𝑠 𝑜𝑓 𝑑𝑒𝑠𝑖𝑟𝑒𝑑 𝑝𝑟𝑜𝑑𝑢𝑐𝑡𝑠 250.41

Table S2. The calculation of the E-factor for the above protocol.

Mw Mass Product Waste


Reaction component mmol Comment
(g/mol) (mg) (mg) (mg)
1d 209.11 1.00 209.11 29.28 0.14 mmol of unproductive 1d
2a 273.10 1.20 327.72
2D-COF-4 40.00 2.00
CO2 43.99 1.20 52.79 52.79
Compound 3da 291.18 0.86 250.41 250.41
phthalimide 147.03 1.09 160.26 16.17 0.11 mmol of phthalimide
Total 250.41 100.24
E-factor = 0.40

S19
(c) The calculation of the Ecoscale value for the above protocol

15,16
The calculation of the Ecoscale value for the above protocol is depicted in Table
S3.

Table S3. The calculation of the Ecoscale value for the above procedure.

Entry Parameters of substrates and the desired product Penalty points


1 Yield (86%) 7
2 Price 0
3 Safety 0
Common Set-up
4 1
(Inert) gas atmosphere
5 Room temperature, 24 h 1
6 Workup and purification 0
Ecoscale value 91

Ecoscale value = 100 - the sum of total penalty points

http://ecoscale.cheminfo.org/calculator

S20
IX. Strategies for the visible-light-driven α-C(sp3)-H bond alkylation of glycine
derivatives

The reaction conditions and work-up procedures for visible-light-driven α-C(sp3)-H


bond alkylation of glycine derivatives are listed in Table S4.

Table S4. Previously reported protocols for visible-light-driven α-C(sp3)-H bond alkylation of glycine
derivatives.

Entry Reaction Conditions Light source Yield (%) Work-up Procedures

Ru(bpy)3Cl2, Cu(OTf)2, 450 nm blue varied from 52- Solvent removal;


Ref. 17
anhydrous toluene, air, RT, 24 h LED 93% Column chromatography

Ru(bpy)3Cl2·6H2O, Co(dmgH)2pyCl, 450 nm blue varied from 45- Solvent removal;


Ref. 18
anhydrous CH3CN, Ar, RT, 48 h LED 91% Column chromatography

Extraction;
[Ir(dtbbpy)(ppy)2]PF6 DMA (2 mL), 10 W blue varied from 56-
Ref. 19 Solvent removal;
H2O (180 μL), Ar, RT, 6 h LED 66%
Column chromatography
[Cu-(Xantphos)(dmp)]BF4, DABCO , 24 W blue varied from 40- Solvent removal;
Ref. 20
DMA, N2, RT, 65 h LED 87% Column chromatography
Filtration;
[Ir(dF(CF3)ppy)2(dtbbpy)(PF6), 450 nm blue
Ref. 22 73% or 75% Solvent removal;
Na2CO3, acetone, N2, 24°C, 24 h LED
Column chromatography

18 W blue varied from 41- Solvent removal;


Ref. 21 Ir(ppy)3, toluene, DCP, air, RT, 12 h
LED 73% Column chromatography

Ru(bpy)3(PF6)2, CuCl, DCM, O2, RT, 6 W blue varied from 23- Solvent removal;
Ref. 23
6-14 h LED 91% Column chromatography

3 W blue varied from 42- Solvent removal;


Ref. 24 Eosin Y, TBHP, THF, N2, RT, 12 h
LED 95% Column chromatography

Extraction;
Rhodamine B, CF3CO2Na, DMF, N2, 10 W blue varied from 27-
Ref. 25 Solvent removal;
RT, 12 h LED 92%
Column chromatography

5 W blue Solvent removal;


Ref. 27 3CzClIPN, MeCN, Ar, RT, 12 h Up to 93%
LED Column chromatography

Cu(MeCN)4BF4, LP1 (xantphos),


LN1 (dmp), aryl sulfonium salt, varied from 42- Solvent removal;
Ref. 28 Blue LED
DABCO, DCM, Ar, RT, 70% Column chromatography
4-8 h

S21
Extraction;
Cu(OTf)2, (S)-Xyl-BINAP, DABCO, 440 nm blue varied from 35-
Ref. 29 Solvent removal;
DMF, Ar, -10°C, 15 h LED 73%
Column chromatography

Extraction;
455 nm blue
Ref. 30 Ir(ppy)3, DMSO, N2, RT, 24 h Up to 88% Solvent removal;
LED
Column chromatography
Biacetyl, varied from 5- Solvent removal;
Ref. 34 Visible light
di-tert-butyl peroxide, 48 h 50% Column chromatography
Extraction;
395-400 nm varied from 61-
Ref. 37 DBU, MeCN, Ar, RT, 12 h Solvent removal;
blue LED 88%
Column chromatography
Extraction;
427 nm varied from 42-
Ref. 38 THAI, DMA, Ar, RT, 24 h Solvent removal;
purple light 88%
Column chromatography
[Ir(dF(CF3)ppy)2(dtbbpy)]PF6, Filtration;
7 W blue varied from 57-
Ref. 41 ligand, NaHCO3, 3 Å MS MeCN/1,4- Solvent removal;
LED 89%
dioxanen (1:1), N2, 15°C, 24 h Column chromatography
[Cu-(Xantphos)(dmp)]BF4
neocuproine, 4,5- Extraction;
18 W blue varied from 53-
Ref. 40 bis(diphenylphosphino)-9,9- Solvent removal;
LED 90%
dimethylxanthene, DABCO, DMF, Column chromatography
Ar, RT, 18 h
Extraction;
Cu(OTf)2, (S)-Xyl-BINAP, DABCO, varied from 72-
Ref. 42 Blue LED Solvent removal;
DMF, Ar, −10 °C, 60 h 91%
Column chromatography
Cu(OTf)2, Extraction;
7 W/20 W varied from 60-
Ref. 43 (S)-PHANEPHOS, DABCO, DMAc, Ar, Solvent removal;
blue LED 88%
RT/-10°C, 12-18 h Column chromatography

Extraction;
427 nm varied from 66-
Ref. 39 Li2S, DMA, r.t., 24 h Solvent removal;
purple LEDs 81%
Column chromatography

Extraction;
450 nm blue varied from 48-
Ref. 31 CdSe QDs, DMF, NiCl2, Ar, r.t., 12 h Solvent removal;
LED 84%
Column chromatography
CdSe QDs, PhCOOH, THF, Ar,16 h, 450 nm blue varied from 40- Solvent removal;
Ref. 32
r.t. LED 77% Column chromatography

Extraction;
15 W blue
Ref. 33 4CzIPN, DMSO, Ar, 60°C Up to 92% Solvent removal;
LED
Column chromatography

2D-COF-4,
456 nm Blue Solvent removal;
This work EtOH or DMSO, Ar, Up to 88%
LED Filtration
24 h

S22
X. Mechanistic studies
(a) Radical capture experiment

1,3-dioxoisoindolin-2-yl cyclohexanecarboxylate 2a (0.12 mmol, 33 mg), 2D‐COF‐4


(4 mg), and 2,2,6,6‐tetramethyl‐1‐piperidinyloxyl (TEMPO, 0.3 mmol, 47 mg) were
placed in a glass tube equipped with a stirring bar. The tube was evacuated and filled
with argon for three cycles. DMSO (2 mL) was added via a gastight syringe under an
argon atmosphere. The reaction mixture was stirred (1000 rpm) with the irradiation of
two 40 W blue LEDs (456 nm, the power density of the incident light near the reactor
is 0.003 W/cm2, and the distance between the reactor and lamp is approximately 5 cm.)
at room temperature for 24 h. HRMS detected the TEMPO-cyclohexyl adduct in the
resulting mixture. The HRMS spectrum of the TEMPO-cyclohexyl adduct is as follows.
(HR-MS (ESI) [M+H]+ m/z calcd for C15H30ON 240.2321, found 240.2321.)

Figure S19. The HRMS spectrum of the TEMPO-cyclohexyl adduct.

S23
Ethyl (4-methoxyphenyl)glycinate 1d (0.1 mmol, 21 mg), 1,3-dioxoisoindolin-2-yl
cyclohexanecarboxylate 2a (0.12 mmol, 33 mg), 2D‐COF‐4 (4 mg), and 2,2,6,6‐
tetramethyl‐1‐piperidinyloxyl (TEMPO, 0.3 mmol, 47 mg) were placed in a glass tube
equipped with a stirring bar. The tube was evacuated and filled with argon for three
cycles. DMSO (2 mL) was added via a gastight syringe under an argon atmosphere.
The reaction mixture was stirred (1000 rpm) with the irradiation of two 40 W blue LEDs
(456 nm, the power density of the incident light near the reactor is 0.003 W/cm2, and
the distance between the reactor and lamp is approximately 5 cm.) at room temperature
for 24 h. HRMS detected the TEMPO-cyclohexyl adduct and the TEMPO-Glycine
adduct in the resulting mixture. The HRMS spectra of them are as follows. (HR-MS
(ESI) [M+H]+ m/z calcd for C15H30ON 240.2321, found 240.2321; HR-MS (ESI)
[M+H]+ m/z calcd for C20H33O4N2 365.2435, found 365.2435.)

Figure S20. The HRMS spectrum of the TEMPO-cyclohexyl adduct.

S24
Figure S21. The HRMS spectrum of the TEMPO-Glycine adduct.

(b) Radical clock experiment

A 10 mL glass tube was charged with glycine derivatives 1d (0.1 mmol, 1.0 equiv.),
1,3-dioxoisoindolin-2-yl hept-6-enoate 2k (1.2 mmol, 2 equiv.), and 2D‐COF‐4 (4 mg).
The tube was evacuated and filled with argon for three cycles. Then, DMSO (2 mL)
was added via a gastight syringe under an argon atmosphere. The reaction mixture was
stirred (1000 rpm) with the irradiation of two 40 W blue LEDs (456 nm, the power
density of the incident light near the reactor is 0.003 W/cm2, and the distance between
the reactor and lamp is approximately 5 cm.) at room temperature for 24 h. Upon
completion, the photocatalyst 2D‐COF‐4 was removed by centrifugation and filtration,
10 mL deionized water was added into the filtrate, and the resulting mixture was
extracted with ethyl acetate (5 mL × 3). The organic layers were washed with saturated
brine, dried over MgSO4, and filtered. The filtrate was concentrated under reduced
pressure. The residue was purified by flash column chromatography on silica gel
(petroleum ether and ethyl acetate) to afford the compound 3dk.

S25
(c) The UV/Vis spectroscopic measurements of reaction mixtures in DMSO or
EtOH

A 10 mL glass tube was charged with glycine derivatives 1d (0.1 mmol, 0.05 mol/L,
1.0 equiv.), 1,3-dioxoisoindolin-2-yl cyclohexanecarboxylate 2a (1.2 mmol, 0.06 mol/L,
2 equiv.), and 2D-COFs (4 mg). The tube was evacuated and filled with argon for three
cycles. Then, EtOH (2 mL) or DMSO (2 mL) was added via a gastight syringe under
an argon atmosphere. After 8 hours of blue light irradiation, the reaction mixture was
diluted with the same concentration (5 x 10-3 mol/L) using EtOH or DMSO as a solvent
for the UV/Vis absorption spectroscopy (1 cm path quartz cuvettes, Hitachi UH5300
spectrophotometer). The UV/Vis absorption spectra are as follows.

Figure S22. The UV/Vis absorption spectra of reaction suspensions (EtOH).

Figure S23. The UV/Vis absorption spectra of reaction suspensions (DMSO).


S26
XI. Calculation of Apparent Quantum Efficiency (A.Q.E.)
In principle, it takes one photon to generate one radical to form one target product. The
energy of one photon (Ephoton) with a wavelength of λinc (nm) is calculated using eq.1.
hc 6.6310-34 Js3108 ms-1
Ephoton = = = 4.3610-19 J (eq.1)
λinc 45610-9 m
Where h (Js) is Planck’s constant, c (ms-1) is the speed of light and inc (m) is the
wavelength of the incident light, 456 nm. The total energy of the incident
monochromatic light (Etotal) is calculated using eq.2.
Etotal = PSt (eq.2)
Where P (Wcm-2) is the power density of the incident light (P = 0.003 W/cm2)8, S (cm2)
is the irradiation area, and t (s) is the photoreaction time. The total number of incident
photons can be obtained through eq.3.
Etotal
Number of incident photons = (eq.3)
Ephoton
The apparent quantum efficiency (A.Q.E.) is defined as eq.4.
Number of product
A.Q.E.(%) = 100% (eq.4)
Number of incident photons

A.Q.E% of the reaction of 1d with 2a.

Etotal = PSt = 0.003 W/cm2  2 cm-2  24  3600s = 518.4 J


Etotal 518.4
Number of incident photons = = = 1.19  1021 = 1.97 mmol
Ephoton 4.3610-19
Number of product 0.086 mmol
A.Q.E.(%) = 100% = 100% = 4.4%
Number of incident photons 1.97 mmol

S27
XII. Hot filtration test
A hot filtration test was performed to ensure the photo activity originates from the
undamaged 2D-COF-4. A 10 mL glass tube was charged with glycine derivatives 1d
(0.1 mmol, 1.0 equiv.), alkyl NHPI ester 2a (0.12 mmol, 1.2 equiv.), and 2D‐COF‐4 (4
mg). The tube was evacuated and filled with argon for three cycles. Then, DMSO (2
mL) was added via a gastight syringe under an argon atmosphere. The reaction mixture
was stirred (1000 rpm) with the irradiation of two 40 W blue LEDs (456 nm, the power
density of the incident light near the reactor is 0.003 W/cm2, and the distance between
the reactor and lamp is approximately 5 cm.) at room temperature for 8 h (labeled as
A). After the isolation, the typical reaction yield was calculated to be 34%.

Then, a parallel reaction was conducted. A 10 mL glass tube was charged with glycine
derivatives 1d (0.1 mmol, 1.0 equiv.), alkyl NHPI ester 2a (0.12 mmol, 1.2 equiv.), and
2D‐COF‐4 (4 mg). The tube was evacuated and filled with argon for three cycles. Then,
DMSO (2 mL) was added via a gastight syringe under an argon atmosphere. The
reaction mixture was stirred (1000 rpm) with the irradiation of two 40 W blue LEDs
(456 nm, the power density of the incident light near the reactor is 0.003 W/cm2, and
the distance between the reactor and lamp is approximately 5 cm.) at room temperature
(labeled as B). The reaction was interrupted after 8 hours. And the catalyst 2D-COF-4
was then removed immediately by hot filtration. The filtrate was then irradiated for
another 8 hours. Upon isolation, no increase in product yield was observed after another
8 hours. The outcome for B was still 34%.

40
A, 34 B, 34
35
30
25
Yield of 3da (%)

20
15
10
5
0
A B

Figure S24. The results of the hot filtration test.

S28
XIII. Characterization data of compounds 3aa-3dn
ethyl 2-cyclohexyl-2-(phenylamino)acetate (3aa).17

3aa (20 mg, 77%, EtOH, GP1; 21 mg, 80%, DMSO, GP2; PE:EA = 15:1). Brown solid,
mp 52-53 °C. 1H NMR (500 MHz, CDCl3) δ 7.16 (dd, J = 7.2, 8.6 Hz, 2H), 6.72 (t, J =
7.3 Hz, 1H), 6.63 (d, J = 7.6 Hz, 2H), 4.19 – 4.14 (m, 3H), 3.87 (d, J = 6.1 Hz, 1H),
1.88 – 1.67 (m, 6H), 1.32 – 1.12 (m, 8H); 13C{1H} NMR (126 MHz, CDCl3) δ 173.6,
147.3, 129.1, 117.9, 113.4, 61.9, 60.7, 41.2, 29.5, 29.1, 26.1, 26.0, 25.9, 14.2. HR-MS
(ESI) [M+H]+ m/z calcd for C16H24NO2 262.1807, found 262.1803.

ethyl 2-cyclohexyl-2-(p-tolylamino)acetate (3ba).18

3ba (19 mg, 69%, EtOH, GP1; 20 mg, 73%, DMSO, GP2; PE:EA = 15:1). Yellow oil.
1
H NMR (500 MHz, CDCl3) δ 6.97 (d, J = 8.0 Hz, 2H), 6.55 (d, J = 8.4 Hz, 2H), 4.16
(q, J = 7.1 Hz, 2H), 3.82 (d, J = 6.2 Hz, 1H), 2.23 (s, 3H), 1.87 – 1.65 (m, 6H), 1.28 –
1.12 (m, 8H); 13C{1H} NMR (126 MHz, CDCl3) δ 173.7, 145.0, 129.6, 127.2, 113.6,
62.3, 60.6, 41.2, 29.5, 29.1, 26.1, 26.0, 25.9, 20.3, 14.2. HR-MS (ESI) [M+H]+ m/z
calcd for C17H26NO2 276.1964, found 276.1958.

ethyl 2-cyclohexyl-2-((4-isopropylphenyl)amino)acetate (3ca).18

3ca (20 mg, 66%, EtOH, GP1; 21 mg, 69%, DMSO, GP2; PE:EA = 15:1). Yellow oil.
1
H NMR (500 MHz, CDCl3) δ 7.03 (d, J = 8.4 Hz, 2H), 6.57 (d, J = 8.5 Hz, 2H), 4.16
(q, J = 7.1 Hz, 2H), 3.82 (d, J = 6.1 Hz, 1H), 2.82 – 2.76 (m, 1H), 1.86 – 1.65 (m, 7H),
1.26 – 1.23 (m, 5H), 1.19 (d, J = 6.9 Hz, 6H), 1.17-1.13 (m, 2H); 13C{1H} NMR (126
MHz, CDCl3) δ 173.8, 145.3, 138.4, 127.0, 113.4, 77.2, 76.9, 76.7, 62.2, 60.6, 41.3,
33.0, 29.5, 29.0, 26.1, 26.0, 26.0, 24.1, 14.2. HR-MS (ESI) [M+H]+ m/z calcd for
C19H30NO2 304.2277, found 304.2270.

S29
ethyl 2-cyclohexyl-2-((4-methoxyphenyl)amino)acetate (3da).18

3da (25 mg, 86%, EtOH, GP1; 25 mg, 86%, DMSO, GP2; the amount of 1d = 0.5 g,
86%; PE:EA = 15:1). Brown oil. 1H NMR (500 MHz, CDCl3) δ 6.75 (d, J = 8.9 Hz,
2H), 6.60 (d, J = 8.9 Hz, 2H), 4.15 (q, J = 7.2 Hz, 2H), 3.76 (d, J = 6.2 Hz, 1H), 3.73
(s, 3H), 1.88 – 1.66 (m, 6H), 1.29 – 1.13 (m, 8H); 13C{1H} NMR (126 MHz, CDCl3) δ
173.9, 152.5, 141.5, 115.1, 114.7, 63.3, 60.6, 55.6, 41.2, 29.5, 29.1, 26.1, 26.0, 26.0,
14.2. HR-MS (ESI) [M+H]+ m/z calcd for C17H26NO3 292.1913, found 292.1909.

ethyl 2-cyclohexyl-2-((4-phenoxyphenyl)amino)acetate (3ea).17

3ea (22 mg, 62%, EtOH, GP1; 27 mg, 76%, DMSO, GP2; PE:EA = 15:1). Yellow solid,
mp 136-137 °C. 1H NMR (500 MHz, CDCl3) δ 7.24 (dd, J = 1.7, 6.9 Hz, 2H), 6.98 (t,
J = 7.4 Hz, 1H), 6.90 – 6.85 (m, 4H), 6.60 (d, J = 8.8 Hz, 2H), 4.16 (q, J = 7.2 Hz, 2H),
3.79 (d, J = 6.1 Hz, 1H), 1.86 – 1.65 (m, 6H), 1.25 – 1.13 (m, 8H); 13C{1H} NMR (126
MHz, CDCl3) δ 173.6, 158.8, 148.1, 143.9, 129.4, 121.9, 121.0, 117.1, 114.6, 77.2, 76.9,
76.7, 62.7, 60.7, 41.2, 29.5, 29.1, 26.1, 26.0, 25.9, 14.2. HR-MS (ESI) [M+H]+ m/z
calcd for C22H28NO3 354.2069, found 354.2064.

ethyl 2-cyclohexyl-2-((4-fluorophenyl)amino)acetate (3fa).17

3fa (18 mg, 64%, EtOH, GP1; 19 mg, 68%, DMSO, GP2; PE:EA = 15:1). Yellow solid,
mp 51-52 °C. 1H NMR (500 MHz, CDCl3) δ 6.86 (t, J = 8.7 Hz, 2H), 6.56 (dd, J = 4.4,
9.0 Hz, 2H), 4.16 (q, J = 7.1 Hz, 2H), 3.77 (d, J = 6.2 Hz, 1H), 1.87 – 1.66 (m, 6H),
1.28 – 1.13 (m, 8H); 13C{1H} NMR (126 MHz, CDCl3) δ 173.6, 156.1 (d, J = 236.9
Hz), 143.7 (d, J = 2.5 Hz), 115.5 (d, J = 22.7 Hz), 114.5 (d, J = 7.6 Hz), 62.8, 60.7,
41.1, 29.5, 29.1, 26.0, 25.9, 25.9, 14.2. 19F NMR (376 MHz, CDCl3) δ -127.05. HR-
MS (ESI) [M+H]+ m/z calcd for C16H23FNO2 280.1713, found 280.1708.

S30
ethyl 2-((4-chlorophenyl)amino)-2-cyclohexylacetate (3ga).17

3ga (16 mg, 54%, EtOH, GP1; 17 mg, 58%, DMSO, GP2; PE:EA = 15:1). Brown solid,
mp 52-53 °C. 1H NMR (500 MHz, CDCl3) δ 7.10 (d, J = 8.8 Hz, 2H), 6.54 (d, J = 8.8
Hz, 2H), 4.17 (q, J = 7.1 Hz, 2H), 3.80 (d, J = 6.1 Hz, 1H), 1.84 – 1.65 (m, 6H), 1.28 –
1.12 (m, 8H); 13C{1H} NMR (126 MHz, CDCl3) δ 173.3, 145.9, 129.0, 122.6, 114.5,
62.1, 60.8, 41.1, 29.5, 29.0, 26.0, 25.9, 25.9, 14.2. HR-MS (ESI) [M+H]+ m/z calcd for
C16H23ClNO2 296.1417, found 296.1414.

ethyl 2-((4-bromophenyl)amino)-2-cyclohexylacetate (3ha).17

3ha (24 mg, 71%, EtOH, GP1; 30 mg, 88%, DMSO, GP2; PE:EA = 15:1). Brown solid,
mp 46-47 °C. 1H NMR (500 MHz, CDCl3) δ 7.23 (d, J = 8.7 Hz, 2H), 6.50 (d, J = 8.8
Hz, 2H), 4.17 (q, J = 7.1 Hz, 2H), 3.80 (d, J = 6.1 Hz, 1H), 1.84 – 1.65 (m, 6H), 1.28 –
1.12 (m, 8H); 13C{1H} NMR (126 MHz, CDCl3) δ 173.2, 146.3, 131.9, 115.0, 109.6,
61.9, 60.8, 41.1, 29.5, 29.0, 26.0, 25.9, 25.9, 14.2. HR-MS (ESI) [M+H]+ m/z calcd for
C16H23BrNO2 340.0912, found 340.0908.

ethyl 2-cyclohexyl-2-((4-iodophenyl)amino)acetate (3ia).17

3ia (24 mg, 62%, EtOH, GP1; 28 mg, 72%, DMSO, GP2; PE:EA = 15:1). Yellow solid,
mp 59-60 °C. 1H NMR (500 MHz, CDCl3) δ 7.40 (d, J = 8.7 Hz, 2H), 6.40 (d, J = 8.7
Hz, 2H), 4.17 (q, J = 7.2 Hz, 2H), 3.80 (d, J = 6.1 Hz, 1H), 1.83 – 1.65 (m, 6H), 1.28 –
1.12 (m, 8H); 13C{1H} NMR (126 MHz, CDCl3) δ 173.1, 147.0, 137.7, 115.6, 77.2,
76.9, 76.7, 61.7, 60.9, 41.1, 29.4, 29.0, 26.0, 25.9, 25.9, 14.2. HR-MS (ESI) [M+H]+
m/z calcd for C16H23INO2 388.0774, found 388.0769.

S31
ethyl2-cyclohexyl-2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2
yl)phenyl)amino) acetate (3ja).17

3ja (5 mg, 13%, EtOH, GP1; 16 mg, 41%, DMSO, GP2; PE:EA = 10:1). Yellow solid,
mp 92-93 °C. 1H NMR (500 MHz, CDCl3) δ 7.61 (d, J = 8.3 Hz, 2H), 6.59 (d, J = 8.3
Hz, 2H), 4.16 (q, J = 6.3 Hz, 2H), 3.92 (d, J = 6.1 Hz, 1H), 1.84 – 1.65 (m, 6H), 1.31
(s, 12H), 1.27 – 1.13 (m, 8H); 13C{1H} NMR (126 MHz, CDCl3) δ 173.2, 149.8, 136.2,
112.3, 83.1, 61.1, 60.8, 41.2, 29.4, 29.0, 26.0, 26.0, 25.9, 24.7, 24.7, 14.2. HR-MS (ESI)
[M+H]+ m/z calcd for C22H35BNO4 388.2659, found 388.2659.

ethyl 2-cyclohexyl-2-((3,4-dimethylphenyl)amino)acetate (3ka).18

3ka (23 mg, 80%, EtOH, GP1; 24 mg, 83%, DMSO, GP2; PE:EA = 15:1). Brown oil.
1
H NMR (500 MHz, CDCl3) δ 6.92 (d, J = 8.0 Hz, 1H), 6.48 (d, J = 2.5 Hz, 1H), 6.40
(dd, J = 2.6, 8.1 Hz, 1H), 4.19 – 4.14 (m, 2H), 3.97 (s, 1H), 3.83 (d, J = 6.1 Hz, 1H),
2.19 (s, 3H), 2.14 (s, 3H), 1.87 – 1.67 (m, 6H), 1.29 – 1.14 (m, 8H); 13C{1H} NMR
(126 MHz, CDCl3) δ 173.8, 145.5, 137.2, 130.1, 126.0, 115.4, 110.7, 62.2, 60.6, 41.2,
29.5, 29.0, 26.1, 26.0, 25.9, 19.9, 18.6, 14.2. HR-MS (ESI) [M+H]+ m/z calcd for
C18H28NO2 290.2120, found 290.2115.

ethyl 2-((3-chloro-4-methylphenyl)amino)-2-cyclohexylacetate (3la).18

3la (19 mg, 61%, EtOH, GP1; 20 mg, 65%, DMSO, GP2; PE:EA = 15:1). Yellow oil.
1
H NMR (500 MHz, CDCl3) δ 6.98 (d, J = 8.2 Hz, 1H), 6.63 (d, J = 2.5 Hz, 1H), 6.44
(dd, J = 2.5, 8.2 Hz, 1H), 4.20 – 4.15 (m, 2H), 3.79 (d, J = 6.1 Hz, 1H), 2.23 (s, 3H),
1.84 – 1.65 (m, 7H), 1.25 (t, J = 7.1 Hz, 3H), 1.22 – 1.11 (m, 4H); 13C{1H} NMR (126

S32
MHz, CDCl3) δ 173.4, 146.5, 134.7, 131.2, 124.9, 113.8, 112.2, 77.2, 76.9, 76.7, 62.0,
60.8, 41.1, 29.5, 29.0, 26.0, 25.9, 25.9, 18.8, 14.2. HR-MS (ESI) [M+H]+ m/z calcd for
C17H25ClNO2 310.1574, found 310.1568.

ethyl 2-cyclohexyl-2-(m-tolylamino)acetate (3ma).18

3ma (18 mg, 65%, EtOH, GP1; 17 mg, 62%, DMSO, GP2; PE:EA = 10:1). Yellow oil.
1
H NMR (500 MHz, CDCl3) δ 7.06 (t, J = 7.7 Hz, 1H), 6.55 (d, J = 7.4 Hz, 1H), 6.45
(t, J = 7.5 Hz , 2H), 4.20 – 4.15 (m, 2H), 4.09 (s, 1H), 3.86 (d, J = 6.1 Hz, 1H), 2.27 (s,
3H), 1.88 – 1.67 (m, 6H), 1.29 – 1.15 (m, 8H). 13C{1H} NMR (126 MHz, CDCl3) δ
173.6, 147.4, 138.9, 129.0, 118.9, 114.3, 110.4, 61.9, 60.6, 41.2, 29.5, 29.1, 26.1, 26.0,
25.9, 21.4, 14.2. HR-MS (ESI) [M+H]+ m/z calcd for C17H26NO2 276.1964, found
276.1958.

ethyl 2-cyclohexyl-2-(o-tolylamino)acetate (3na).18

3na (9 mg, 33%, EtOH, GP1; 9 mg, 33%, DMSO, GP2; PE:EA = 10:1). Yellow oil. 1H
NMR (400 MHz, CDCl3) δ 7.14 – 7.09 (m, 2H), 6.71 (t, J = 7.4 Hz, 1H), 6.61 (d, J =
8.1 Hz, 1H), 4.24 – 4.18 (m, 2H), 4.10 (s, 1H), 3.96 (dd, J = 3.0, 6.2 Hz, 1H), 2.26 (s,
3H), 1.97 – 1.71 (m, 6H), 1.34 – 1.22 (m, 8H). 13C{1H} NMR (101 MHz, CDCl3) δ
173.6, 145.2, 130.1, 126.8, 122.4, 117.3, 110.2, 61.6, 60.5, 41.1, 29.4, 29.1, 26.0, 25.9,
25.8, 17.3, 14.0. HR-MS (ESI) [M+H]+ m/z calcd for C17H26NO2 276.1964, found
276.1959.

ethyl 2-((2-bromophenyl)amino)-2-cyclohexylacetate (3oa).

3oa (3 mg, 9%, EtOH, GP1; 3 mg, 9%, DMSO, GP2; PE:EA = 10:1). Yellow oil. 1H
NMR (500 MHz, CDCl3) δ 7.42 (dd, J = 1.5, 8.2 Hz, 1H), 7.15 – 7.11 (m, 1H), 6.59 –

S33
6.56 (m, 2H), 4.81 (d, J = 8.9 Hz, 1H), 4.18 (q, J = 7.1 Hz, 2H), 3.88 (dd, J = 6.0, 8.9
Hz, 1H), 1.90 – 1.67 (m, 6H), 1.28 – 1.17 (m, 8H). 13C{1H} NMR (126 MHz, CDCl3)
δ 172.8, 144.2, 132.5, 128.3, 118.3, 111.7, 110.3, 61.9, 60.9, 41.0, 29.5, 29.1, 26.0, 26.0,
25.9, 14.2. HR-MS (ESI) [M+H]+ m/z calcd for C16H23BrNO2 340.0912, found
340.0908.

ethyl 2-(benzo[d][1,3]dioxol-5-ylamino)-2-cyclohexylacetate (3pa).17

3pa (18 mg, 59%, EtOH, GP1; 21 mg, 69%, DMSO, GP2; PE:EA = 10:1). Brown solid,
mp 75-77 °C. 1H NMR (500 MHz, CDCl3) δ 6.62 (d, J = 8.3 Hz, 1H), 6.26 (d, J = 2.3
Hz, 1H), 6.06 (dd, J = 2.4, 8.3 Hz, 1H), 5.84 (s, 2H), 4.16 (q, J = 7.1 Hz, 2H), 3.72 (d,
J = 6.1 Hz, 1H), 1.86 – 1.65 (m, 6H), 1.27 – 1.11 (m, 8H); 13C{1H} NMR (126 MHz,
CDCl3) δ 173.7, 148.2, 143.0, 140.0, 108.4, 105.5, 100.5, 96.8, 63.2, 60.7, 41.1, 29.5,
29.1, 26.1, 26.0, 25.9, 14.2. HR-MS (ESI) [M+H]+ m/z calcd for C17H24NO4 306.1705,
found 306.1702.

ethyl 2-cyclohexyl-2-(naphthalen-2-ylamino)acetate (3qa).17

3qa (21 mg, 67%, EtOH, GP1; 24 mg, 77%, DMSO, GP2; PE:EA = 10:1). Brown solid,
mp 94-96 °C. 1H NMR (500 MHz, CDCl3) δ 7.67 – 7.59 (m, 3H), 7.36 (t, J = 7.6 Hz,
1H), 7.20 (t, J = 7.5 Hz, 1H), 6.93 (dd, J = 2.4, 8.8 Hz, 1H), 6.82 (d, J = 2.4 Hz, 1H),
4.22 – 4.15 (m, 2H), 4.01 (d, J = 6.2 Hz, 1H), 1.93 – 1.68 (m, 6H), 1.31 – 1.17 (m, 8H);
13
C{1H} NMR (126 MHz, CDCl3) δ 173.5, 145.0, 134.9, 128.9, 127.7, 127.5, 126.2,
125.9, 122.1, 118.1, 105.3, 61.9, 60.8, 41.1, 29.5, 29.2, 26.1, 26.0, 26.0, 14.2. HR-MS
(ESI) [M+H]+ m/z calcd for C20H26NO2 312.1964, found 312.1959.

tert-butyl 2-cyclohexyl-2-(p-tolylamino)acetate (3ra).17

S34
3ra (22 mg, 73%, EtOH, GP1; 22 mg, 73%, DMSO, GP2; PE:EA = 10:1). Yellow oil.
1
H NMR (500 MHz, CDCl3) δ 6.97 (d, J = 8.3 Hz, 2H), 6.55 (d, J = 8.4 Hz, 2H), 3.72
(d, J = 5.7 Hz, 1H), 2.23 (s, 3H), 1.82 – 1.71 (m, 6H), 1.42 (s, 9H), 1.27 – 1.15 (m, 5H);
13
C{1H} NMR (126 MHz, CDCl3) δ 172.9, 145.2, 129.5, 126.9, 113.6, 81.2, 62.7, 41.2,
29.4, 29.0, 28.0, 26.2, 26.1, 26.0, 20.3. HR-MS (ESI) [M+H]+ m/z calcd for C19H30NO2
304.2277, found 304.2272.

benzyl 2-cyclohexyl-2-(phenylamino)acetate (3sa).

3sa (14 mg, 43%, EtOH, GP1; 18 mg, 56%, DMSO, GP2; PE:EA = 10:1). Yellow solid,
mp 31-32 °C. 1H NMR (500 MHz, CDCl3) δ 7.35 – 7.32 (m, 3H), 7.29 – 7.27 (m, 2H),
7.16 (dd, J = 7.3, 8.6 Hz, 2H), 6.73 (t, J = 7.3 Hz, 1H), 6.63 (d, J = 7.4 Hz, 2H), 5.14
(s, 2H), 3.93 (d, J = 6.1 Hz, 1H), 1.85 – 1.73 (m, 5H), 1.68 – 1.65 (m, 2H), 1.24 – 1.15
(m, 4H); 13C{1H} NMR (126 MHz, CDCl3) δ 173.5, 147.3, 135.5, 129.2, 128.4, 128.2,
118.1, 113.5, 66.5, 62.0, 41.2, 29.5, 29.0, 26.0, 25.9, 25.9. HR-MS (ESI) [M+H]+ m/z
calcd for C21H26NO2 324.1964, found 324.1958.

2-cyclohexyl-2-(phenylamino)-1-(pyrrolidin-1-yl)ethan-1-one (3ta).

3ta (21 mg, 73%, EtOH, GP1; 20 mg, 70%, DMSO, GP2m PE:EA = 3:1). White solid,
mp 149-151 °C. 1H NMR (500 MHz, CDCl3) δ 7.15 – 7.12 (m, 2H), 6.67 (t, J = 7.3 Hz,
1H), 6.62 (d, J = 7.9 Hz, 2H), 4.46 (d, J = 9.3 Hz, 1H), 3.97 – 3.94 (m, 1H), 3.54 (t, J
= 6.8 Hz, 2H), 3.50 – 3.42 (m, 2H), 1.97 – 1.93 (m, 3H), 1.86 – 1.82 (m, 2H), 1.78 –
1.65 (m, 6H), 1.21 – 1.09 (m, 4H); 13C{1H} NMR (126 MHz, CDCl3) δ 171.5, 148.2,
129.1, 117.4, 113.5, 60.5, 46.5, 45.6, 41.9, 30.0, 28.8, 26.1, 26.0, 26.0, 24.0. HR-MS
(ESI) [M+H]+ m/z calcd for C18H27N2O 287.2123, found 287.2119.

2-cyclohexyl-1-morpholino-2-(phenylamino)ethan-1-one (3ua).19

S35
3ua (24 mg, 79%, EtOH, GP1; 16 mg, 53%, DMSO, GP2; PE:EA = 3:1). Yellow solid,
mp 140-142 °C. 1H NMR (500 MHz, CDCl3) δ 7.15 (t, J = 7.7 Hz, 2H), 6.71 (t, J = 7.3
Hz, 1H), 6.62 (d, J = 7.9 Hz, 2H), 4.48 (d, J = 9.0 Hz, 1H), 4.11 – 4.08 (m, 1H), 3.66 –
3.57 (m, 8H), 1.90 – 1.65 (m, 6H), 1.26 – 1.10 (m, 5H); 13C{1H} NMR (126 MHz,
CDCl3) δ 171.7, 148.0, 129.1, 117.9, 113.8, 77.2, 76.9, 76.7, 66.8, 66.5, 58.2, 46.1, 42.3,
41.8, 30.2, 28.6, 26.1, 26.0, 26.0. HR-MS (ESI) [M+H]+ m/z calcd for C18H27N2O2
303.2073, found 303.2067.

N-benzyl-2-cyclohexyl-2-(phenylamino)acetamide (3va).20

3va (19 mg, 59%, EtOH, GP1; 21 mg, 65%, DMSO, GP2; PE:EA = 3:1). White solid,
mp 132-134 °C. 1H NMR (500 MHz, CDCl3) δ 7.25 – 7.14 (m, 6H), 7.06 (t, J = 7.5 Hz,
1H), 6.78 (t, J = 7.3 Hz, 1H), 6.60 (d, J = 7.9 Hz, 2H), 4.49 (dd, J = 6.2, 14.9 Hz, 1H),
4.37 (dd, J = 5.7, 14.9 Hz, 1H), 3.93 (s, 1H), 3.62 (t, J = 4.1 Hz, 1H), 2.07 – 2.02 (m,
1H), 1.80 – 1.68 (m, 5H), 1.32 – 1.13 (m, 5H); 13C{1H} NMR (126 MHz, CDCl3) δ
172.5, 147.2, 138.0, 129.2, 128.4, 127.5, 127.2, 118.9, 113.6, 64.8, 43.1, 41.0, 30.2,
28.1, 26.1, 26.1, 26.0. HR-MS (ESI) [M+H]+ m/z calcd for C21H27N2O 323.2123, found
323.2119.

2-cyclohexyl-N-(furan-2-ylmethyl)-2-(phenylamino)acetamide (3wa).

3wa (19 mg, 61%, EtOH, GP1; 18 mg, 58%, DMSO, GP2; PE:EA = 3:1). Yellow solid,
mp 128-129 °C. 1H NMR (500 MHz, CDCl3) δ 7.19 – 7.12 (t, J = 7.5 Hz, 2H), 7.07 (t,
J = 6.0 Hz, 1H), 6.77 (t, J = 7.4 Hz, 1H), 6.58 (d, J = 7.9 Hz, 2H), 6.24 (dd, J = 1.9, 3.2
Hz, 1H), 6.09 (d, J = 3.2 Hz, 1H), 4.50 (dd, J = 6.3, 15.6 Hz, 1H), 4.33 (dd, J = 5.4,
15.6 Hz, 1H), 3.92 (d, J = 3.9 Hz, 1H), 3.58 (t, J = 4.1 Hz, 1H), 2.03 – 1.98 (m, 1H),
1.76 (d, J = 10 Hz, 2H), 1.67 (d, J = 11.2 Hz, 3H), 1.30 – 1.11 (m, 6H); 13C{1H} NMR
(126 MHz, CDCl3) δ 172.5, 151.2, 147.2, 141.9, 129.2, 118.8, 113.5, 110.1, 107.0, 64.7,
41.0, 36.0, 30.1, 28.0, 26.1, 26.1, 26.0. HR-MS (ESI) [M+H]+ m/z calcd for C19H25N2O2
313.1916, found 313.1910.
S36
ethyl 2-cyclopentyl-2-((4-methoxyphenyl)amino)acetate (3db).17

3db (21 mg, 76%, EtOH, GP1; 21 mg, 76%, DMSO, GP2; PE:EA = 10:1). Brown oil.
1
H NMR (500 MHz, CDCl3) δ 6.75 (d, J = 8.9 Hz, 2H), 6.61 (d, J = 8.9 Hz, 2H), 4.14
(q, J = 7.1 Hz, 2H), 3.77 (d, J = 8.0 Hz, 1H), 3.73 (s, 3H), 2.25 – 2.17 (m, 1H), 1.85 –
1.82 (m, 1H), 1.72 – 1.43 (m, 7H), 1.22 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (126 MHz,
CDCl3) δ 174.3, 152.5, 141.3, 115.0, 114.7, 77.2, 76.9, 76.7, 62.0, 60.6, 55.6, 43.1, 29.3,
28.9, 25.2, 25.0, 14.2. HR-MS (ESI) [M+H]+ m/z calcd for C16H24NO3 278.1756, found
278.1751.

ethyl 2-cyclobutyl-2-((4-methoxyphenyl)amino)acetate (3dc).21

3dc (19 mg, 72%, EtOH, GP1; 17 mg, 65%, DMSO, GP2; PE:EA = 10:1). Brown oil.
1
H NMR (500 MHz, CDCl3) δ 6.76 (d, J = 8.9 Hz, 2H), 6.60 (d, J = 8.9 Hz, 2H), 4.18
– 4.11 (m, 2H), 3.88 (d, J = 8.2 Hz, 1H), 3.73 (s, 3H), 2.67 – 2.62 (m, 1H), 2.09 – 1.83
(m, 6H), 1.22 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ 173.6, 152.6,
141.3, 115.0, 114.7, 62.2, 60.6, 55.6, 38.2, 25.4, 24.6, 18.0, 14.2. HR-MS (ESI) [M+H]+
m/z calcd for C15H22NO3 264.1600, found 264.1594.

ethyl 3-ethyl-2-((4-methoxyphenyl)amino)pentanoate (3dd).

3dd (19 mg, 68%, EtOH, GP1; 19 mg, 68%, DMSO, GP2; PE:EA = 10:1). Brown oil.
1
H NMR (500 MHz, CDCl3) δ 6.76 (d, J = 8.9 Hz, 2H), 6.61 (d, J = 8.9 Hz, 2H), 4.20
– 4.10 (m, 2H), 3.97 (d, J = 5.5 Hz, 1H), 3.73 (s, 3H), 1.70 – 1.64 (m, 1H), 1.55 – 1.34
(m, 4H), 1.23 (t, J = 7.1 Hz, 3H), 0.96 – 0.93 (m, 6H); 13C{1H} NMR (126 MHz, CDCl3)
δ 174.3, 152.5, 141.5, 115.1, 114.7, 77.2, 77.1, 76.9, 76.7, 60.6, 59.8, 55.6, 44.3, 22.4,

S37
21.9, 14.1, 11.4, 11.3. HR-MS (ESI) [M+H]+ m/z calcd for C16H26NO3 280.1913, found
280.1907.

ethyl 3-ethyl-2-((4-methoxyphenyl)amino)heptanoate (3de).

3de (21 mg, 68%, EtOH, GP1; 21 mg, 68%, DMSO, GP 2; PE:EA = 10:1; 1:1 d.r.).
Yellow oil. 1H NMR (500 MHz, CDCl3) δ 6.76 (d, J = 8.9 Hz, 2H), 6.60 (d, J = 8.9 Hz,
2H), 4.18 – 4.12 (m, 2H), 3.99 – 3.96 (m, 1H), 3.73 (s, 3H), 1.75 – 1.71 (m, 1H), 1.43
– 1.29 (m, 8H), 1.23 (t, J = 7.1 Hz, 3H), 0.97 – 0.93 (m, 3H), 0.92 – 0.89 (m, 3H);
13
C{1H} NMR (126 MHz, CDCl3) δ 174.2, 152.5, 141.6, 141.5, 115.1, 115.1, 114.7,
60.6, 60.1, 60.0, 55.6, 42.7, 29.4, 29.2, 29.2, 29.0, 23.0, 22.8, 22.8, 22.4, 14.2, 13.9,
13.9, 11.5, 11.3. HR-MS (ESI) [M+H]+ m/z calcd for C18H30NO3 308.2226, found
308.2221.

ethyl 2-((4-methoxyphenyl)amino)-3,3-dimethylbutanoate (3df).

3df (23 mg, 87%, EtOH, GP1; 20 mg, 75%, DMSO, GP2; PE:EA = 10:1). Brown oil.
1
H NMR (500 MHz, CDCl3) δ 6.76 (d, J = 8.9 Hz, 2H), 6.64 (d, J = 8.9 Hz, 2H), 4.15
– 4.10 (m, 2H), 3.73 (s, 3H), 3.66 (s, 1H), 1.22 (t, J = 7.1 Hz, 3H), 1.06 (s, 9H); 13C{1H}
NMR (126 MHz, CDCl3) δ 173.5, 152.7, 141.6, 115.5, 114.7, 67.0, 60.4, 55.6, 34.2,
26.7, 14.2. HR-MS (ESI) [M+H]+ m/z calcd for C15H24NO3 266.1756, found 266.1752.

ethyl 2-(adamantan-2-yl)-2-((4-methoxyphenyl)amino)acetate (3dg).17

3dg (26 mg, 76%, EtOH, GP1; 30 mg, 87%, DMSO, GP2; PE:EA = 10:1). Yellow oil.
1
H NMR (500 MHz, CDCl3) δ 6.75 (d, J = 8.9 Hz, 2H), 6.63 (d, J = 8.9 Hz, 2H), 4.13

S38
(q, J = 7.1 Hz, 2H), 3.73 (s, 3H), 3.54 (s, 1H), 2.02 (s, 3H), 1.83 – 1.56 (m, 12H), 1.23
(t, J = 7.1 Hz, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ 173.0, 152.5, 141.8, 115.4,
114.7, 67.9, 60.3, 55.6, 38.9, 36.8, 36.0, 28.3, 14.2. HR-MS (ESI) [M+H]+ m/z calcd
for C21H30NO3 344.2226, found 344.2220.

ethyl 2-((4-methoxyphenyl)amino)butanoate (3dh).21

3dh (16 mg, 67%, EtOH, GP1; 19 mg, 80%, DMSO, GP2; PE:EA = 10:1). Brown oil.
1
H NMR (500 MHz, CDCl3) δ 6.76 (d, J = 8.9 Hz, 2H), 6.60 (d, J = 8.8 Hz, 2H), 4.17
(q, J = 6.4 Hz, 2H), 3.92 (t, J = 6.3 Hz, 1H), 3.73 (s, 3H), 1.89 – 1.76 (m, 2H), 1.23 (d,
J = 7.2 Hz, 3H), 1.00 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ 174.2,
152.5, 140.9, 115.0, 114.7, 60.8, 58.9, 55.6, 26.1, 14.1, 9.9. HR-MS (ESI) [M+H]+ m/z
calcd for C13H20NO3 238.1443, found 238.1439.

ethyl 2-((4-methoxyphenyl)amino)nonanoate (3di).

3di (16 mg, 52%, EtOH, GP1; 20 mg, 65%, DMSO, GP2; PE:EA = 10:1). Brown oil.
1
H NMR (500 MHz, CDCl3) δ 6.76 (d, J = 8.9 Hz, 2H), 6.60 (d, J = 8.9 Hz, 2H), 4.16
(q, J = 7.1 Hz, 2H), 3.95 (t, J = 6.5 Hz, 1H), 3.73 (s, 3H), 1.83 – 1.68 (m, 2H), 1.45 –
1.38 (m, 2H), 1.31 – 1.26 (m, 8H), 1.23 (t, J = 7.1 Hz, 3H), 0.88 (t, J = 6.8 Hz, 3H);
13
C{1H} NMR (126 MHz, CDCl3) δ 174.5, 152.5, 141.0, 115.0, 114.7, 60.7, 57.8, 55.6,
33.1, 31.6, 29.2, 29.0, 25.5, 22.5, 14.1, 14.0. HR-MS (ESI) [M+H]+ m/z calcd for
C18H30NO3 308.2226, found 308.2224.

ethyl 2-((4-methoxyphenyl)amino)nonadecanoate (3dj).17

3dj (17 mg, 38%, EtOH, GP1; 27 mg, 60%, DMSO, GP2; PE:EA = 10:1). Brown solid,
mp 59-60 °C. 1H NMR (500 MHz, CDCl3) δ 6.76 (d, J = 8.8 Hz, 2H), 6.60 (d, J = 8.9
Hz, 2H), 4.16 (q, J = 7.1 Hz, 2H), 3.95 (t, J = 6.5 Hz, 1H), 3.73 (s, 3H), 1.83 – 1.68 (m,

S39
2H), 1.44 – 1.22 (m, 33H), 0.88 (t, J = 6.8 Hz, 3H); 13C{1H} NMR (126 MHz, CDCl3)
δ 174.5, 152.5, 141.0, 115.0, 114.7, 60.7, 57.8, 55.6, 33.1, 31.8, 29.6, 29.5, 29.5, 29.4,
29.3, 29.2, 25.5, 22.6, 14.1, 14.0. HR-MS (ESI) [M+H]+ m/z calcd for C28H50NO3
448.3791, found 448.3785.

ethyl 3-cyclopentyl-2-((4-methoxyphenyl)amino)propanoate (3dk).

3dk (23 mg, 79%, EtOH, GP1; 25 mg, 86%, DMSO, GP2; PE:EA = 15:1). Brown oil.
1
H NMR (400 MHz, CDCl3) δ 6.76 (d, J = 8.9 Hz, 2H), 6.60 (d, J = 8.9 Hz, 2H), 4.14
(q, J = 7.1 Hz, 2H), 3.96 (t, J = 8.0 Hz, 1H), 3.73 (s, 3H), 1.99 – 1.73 (m, 5H), 1.65 –
1.52 (m, 4H), 1.22 (t, J = 7.1 Hz, 3H), 1.17 – 1.10 (m, 2H); 13C{1H} NMR (101 MHz,
CDCl3) δ 174.7, 152.5, 140.9, 114.9, 114.6, 114.4, 60.6, 57.4, 55.5, 39.5, 36.6, 32.6,
32.4, 25.0, 24.9, 24.8, 14.0. HR-MS (ESI) [M+H]+ m/z calcd for C17H26NO3 292.1913,
found 292.1908.

ethyl 2-((4-methoxyphenyl)amino)-5-phenylpentanoate (3dl).

3dl (20 mg, 61%, EtOH, GP1; 20 mg, 61%, DMSO, GP2; PE:EA = 10:1). Brown oil.
1
H NMR (500 MHz, CDCl3) δ 7.27 – 7.23 (m, 2H), 7.18 – 7.14 (m, 3H), 6.74 (d, J =
8.9 Hz, 2H), 6.57 (d, J = 8.8 Hz, 2H), 4.13 (q, J = 7.1 Hz, 2H), 3.96 (t, J = 5.9 Hz, 1H),
3.72 (s, 3H), 2.65 – 2.62 (m, 2H), 1.85 – 1.73 (m, 4H), 1.20 (t, J = 7.1 Hz, 3H); 13C{1H}
NMR (126 MHz, CDCl3) δ 174.3, 152.6, 141.6, 140.9, 128.3, 128.2, 125.8, 115.0, 114.7,
60.8, 57.7, 55.6, 35.4, 32.6, 27.2, 14.1. HR-MS (ESI) [M+H]+ m/z calcd for C20H26NO3
328.1913, found 328.1907.

ethyl N-(4-methoxyphenyl)-O-phenylserinate (3dm).

S40
3dm (21 mg, 67%, EtOH, GP1; 21 mg, 67%, DMSO, GP2; PE:EA = 10:1). Brown oil.
1
H NMR (500 MHz, CDCl3) δ 7.29 – 7.25 (m, 2H), 6.97 (t, J = 7.4 Hz, 1H), 6.90 (d, J
= 7.7 Hz, 2H), 6.78 (d, J = 8.9 Hz, 2H), 6.66 (d, J = 8.9 Hz, 2H), 4.37 – 4.34 (m, 2H),
4.30 (t, J = 7.5 Hz, 1H), 4.21 (q, J = 7.1 Hz, 2H), 3.74 (s, 3H), 1.23 (t, J = 7.2 Hz, 3H);
13
C{1H} NMR (126 MHz, CDCl3) δ 171.5, 158.2, 152.9, 140.3, 129.4, 121.3, 115.4,
114.8, 114.6, 68.3, 61.4, 57.6, 55.6, 14.1. HR-MS (ESI) [M+H]+ m/z calcd for
C18H22NO4 316.1549, found 316.1543.

ethyl (5R)-5-((3R,5R,8S,9S,10R,13R,14S,17R)-3-hydroxy-5,10,13-
trimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)-2-((4-
methoxyphenyl) amino)hexanoate (3dn).

3dn (38 mg, 70%, EtOH, GP1; 37 mg, 69%, DMSO, GP2; PE:EA = 5:1; 1:1 d.r.).
Yellow solid, mp 137-138 °C. 1H NMR (500 MHz, CDCl3) δ 6.75 (d, J = 8.7 Hz, 2H),
6.59 (d, J = 7.1 Hz, 2H), 4.15 (q, J = 7.0 Hz, 2H), 3.90 (t, J = 7.5 Hz, 1H), 3.73 (s, 3H),
3.65 – 3.58 (m, 1H), 1.96 – 1.93 (m, 1H), 1.84 – 1.74 (m, 6H), 1.71 – 1.64 (m, 3H),
1.57 – 1.49 (m, 4H), 1.41 – 1.31 (m, 8H), 1.24 – 1.22 (m, 5H), 1.15 – 1.03 (m, 5H),
0.99 – 0.96 (m, 1H), 0.92 – 0.90 (m, 6H), 0.63 (d, J = 5.9 Hz, 3H); 13C{1H} NMR (126
MHz, CDCl3) δ 174.5, 174.4, 152.5, 141.1, 141.0, 115.0, 115.0, 114.7, 71.7, 60.7, 58.2,
58.1, 56.4, 55.8, 55.6, 42.6, 42.0, 40.3, 40.0, 36.3, 35.7, 35.4, 35.3, 35.2, 34.5, 31.5,
30.4, 29.7, 29.6, 28.1, 28.0, 27.1, 26.3, 24.1, 23.3, 20.7, 18.5, 14.2, 11.9. HR-MS (ESI)
[M+H]+ m/z calcd for C34H54NO4 540.4053, found 540.4047.

S41
XIV. References
(1) Chen, X.; Huang, N.; Gao, J.; Xu, H.; Xu, F.; Jiang, D. Towards covalent organic
frameworks with predesignable and aligned open docking sites. Chem. Commun., 2014,
50, 6161-6163.
(2) Jiménez-Almarza, A.; López-Magano, A.; Marzo, L.; Cabrera, S.; Mas-Ballesté, R.;
Alemán, J. Imine-Based Covalent Organic Frameworks as Photocatalysts for Metal
Free Oxidation Processes under Visible Light Conditions. ChemCatChem, 2019, 11,
4916-4922.
(3) Liu, W.; Su, Q.; Ju, P.; Guo, B.; Zhou, H.; Li, G.; Wu, Q. A Hydrazone-Based
Covalent Organic Framework as an Efficient and Reusable Photocatalyst for the Cross-
Dehydrogenative Coupling Reaction of N-Aryltetrahydroisoquinolines. ChemSusChem,
2017, 10, 664-669.
(4) Lyu, H.; Diercks, C. S.; Zhu, C.; Yaghi, O. M. Porous Crystalline Olefin-Linked
Covalent Organic Frameworks. J. Am. Chem. Soc., 2019, 141, 6848-6852.
(5) Yu, J.; Lan, J.; Wang, S.; Zhang, P.; Liu, K.; Yuan, L.; Chai, Z.; Shi, W. Robust
covalent organic frameworks with tailor-made chelating sites for synergistic capture of
U(vi) ions from highly acidic radioactive waste. Dalton Trans., 2021, 50, 3792-3796.
(6) Zhang, Y.; Shen, X.; Feng, X.; Xia, H.; Mu, Y.; Liu, X. Covalent organic frameworks
as pH responsive signaling scaffolds. Chem. Commun., 2016, 52, 11088-11091.
(7) Jia, J.; Bu, X.; Yang, X. A cobalt covalent organic framework: a dual-functional
atomic-level catalyst for visible-light-driven C–H annulation of amides with alkynes. J.
Mater. Chem. A, 2022, 10, 11514-11523.
(8) Liu, S.; Pan, W.; Wu, S.; Bu, X.; Xin, S.; Yu, J.; Xu, H.; Yang, X. Visible-light-
induced tandem radical addition–cyclization of 2-aryl phenyl isocyanides catalysed by
recyclable covalent organic frameworks. Green Chem., 2019, 21, 2905-2910.
(9) Tian, M.; Wang, Y.; Bu, X.; Wang, Y.; Yang, X. An ultrastable olefin-linked covalent
organic framework for photocatalytic decarboxylative alkylations under highly acidic
conditions. Catal. Sci. Technol. 2021, 11, 4272-4279.
(10) Wang, H.; Li, S.; Cui, Y.; Liu, M.; Bu, X.; Tian, H.; Yang, X. A covalent organic
framework-catalyzed visible-light-induced three-component cascade synthesis of
trifluoroalkyl and trifluoroalkenyl quinoxalin-2(1H)-one derivatives. New J. Chem.,
2022, 46, 20412-20418.
(11) Tian, H.; Xu, W.; Liu, Y.; Wang, Q. Unnatural α-Amino Acid Synthesized through
α-Alkylation of Glycine Derivatives by Diacyl Peroxides. Org. Lett., 2020, 22, 5005-
5008.
(12) Jakob, A. K. M. H.; Sundermann, T. R.; Klein, C. D. Backbone modifications in
peptidic inhibitors of flaviviral proteases. Bioorg. Med. Chem. Lett., 2019, 29, 1913-
1917.
(13) Xin, H.; Yuan, Z.-H.; Yang, M.; Wang, M.-H.; Duan, X.-H.; Guo, L.-N. Metal-free,
visible-light driven C–H ketoalkylation of glycine derivatives and peptides. Green

S42
Chem., 2021, 23, 9549-9553.
(14) Wang, G.-Z.; Shang, R.; Cheng, W.-M.; Fu, Y. Decarboxylative 1,4-Addition of α-
Oxocarboxylic Acids with Michael Acceptors Enabled by Photoredox Catalysis. Org.
Lett., 2015, 17, 4830-4833.
(15) Prat, D.; Wells, A.; Hayler, J.; Sneddon, H.; McElroy, C. R.; Abou-Shehada, S.;
Dunn, P. J. CHEM21 selection guide of classical- and less classical-solvents. Green
Chem., 2016, 18, 288-296.
(16) Van Aken, K.; Strekowski, L.; Patiny, L. EcoScale, a semi-quantitative tool to
select an organic preparation based on economical and ecological parameters. Beilstein
J. Org. Chem., 2006, 2, 3.
(17) Wang, G.-Z.; Fu, M.-C.; Zhao, B.; Shang, R. Photocatalytic decarboxylative
alkylations of C(sp3)-H and C(sp2)-H bonds enabled by ammonium iodide in amide
solvent. Sci. China Chem., 2021, 64, 439-444.
(18) Wang, J.; Su, Y.; Quan, Z.; Li, J.; Yang, J.; Yuan, Y.; Huo, C. Visible-light promoted
α-alkylation of glycine derivatives with alkyl boronic acids. Chem. Commun., 2021, 57,
1959-1962.
(19) Cardinale, L.; Schmotz, M.-O. W. S.; Konev, M. O.; Jacobi von Wangelin, A.
Photoredox-Catalyzed Synthesis of α-Amino Acid Amides by Imine Carbamoylation.
Org. Lett., 2022, 24, 506-510.
(20) Shimizu, H.; Kobayashi, S. Convenient synthesis of α-amino amides using low-
valent tantalum prepared from TaCl5 and Zn. Tetrahedron Lett., 2005, 46, 7593-7595.
(21) Yang, L.; Qiu, Z.; Wu, J.; Zhao, J.; Shen, T.; Huang, X.; Liu, Z.-Q. Molecular
Oxygen-Mediated Radical Alkylation of C(sp3)–H Bonds with Boronic Acids. Org.
Lett., 2021, 23, 3207-3210.

S43
XV. Copies of NMR spectra

Figure S25. 1H NMR Spectrum of compound 3aa (500 MHz, CDCl3)

Figure S26. 13C{1H} NMR Spectrum of compound 3aa (126 MHz, CDCl3)

S44
Figure S27. 1H NMR Spectrum of compound 3ba (500 MHz, CDCl3)

Figure S28. 13C{1H} NMR Spectrum of compound 3ba (126 MHz, CDCl3)

S45
Figure S29. 1H NMR Spectrum of compound 3ca (500 MHz, CDCl3)

Figure S30. 13C{1H} NMR Spectrum of compound 3ca (126 MHz, CDCl3)

S46
Figure S31. 1H NMR Spectrum of compound 3da (500 MHz, CDCl3)

Figure S32. 13C{1H} NMR Spectrum of compound 3da (126 MHz, CDCl3)

S47
Figure S33. 1H NMR Spectrum of compound 3ea (500 MHz, CDCl3)

Figure S34. 13C{1H} NMR Spectrum of compound 3ea (126 MHz, CDCl3)

S48
Figure S35. 1H NMR Spectrum of compound 3fa (500 MHz, CDCl3)

Figure S36. 13C{1H} NMR Spectrum of compound 3fa (126 MHz, CDCl3)

S49
Figure S37. 19F NMR Spectrum of compound 3fa (376 MHz, CDCl3)

Figure S38. 1H NMR Spectrum of compound 3ga (500 MHz, CDCl3)

S50
Figure S39. 13C{1H} NMR Spectrum of compound 3ga (126 MHz, CDCl3)

Figure S40. 1H NMR Spectrum of compound 3ha (500 MHz, CDCl3)

S51
Figure S41. 13C{1H} NMR Spectrum of compound 3ha (126 MHz, CDCl3)

Figure S42. 1H NMR Spectrum of compound 3ia (500 MHz, CDCl3)

S52
Figure S43. 13C{1H} NMR Spectrum of compound 3ia (126 MHz, CDCl3)

Figure S44. 1H NMR Spectrum of compound 3ja (500 MHz, CDCl3)

S53
Figure S45. 13C{1H} NMR Spectrum of compound 3ja (126 MHz, CDCl3)

Figure S46. 1H NMR Spectrum of compound 3ka (500 MHz, CDCl3)

S54
Figure S47. 13C{1H} NMR Spectrum of compound 3ka (126 MHz, CDCl3)

Figure S48. 1H NMR Spectrum of compound 3la (500 MHz, CDCl3)

S55
Figure S49. 13C{1H} NMR Spectrum of compound 3la (126 MHz, CDCl3)

Figure S50. 1H NMR Spectrum of compound 3ma (500 MHz, CDCl3)

S56
Figure S51. 13C{1H} NMR Spectrum of compound 3ma (126 MHz, CDCl3)

Figure S52. 1H NMR Spectrum of compound 3na (400 MHz, CDCl3)

S57
Figure S53. 13C{1H} NMR Spectrum of compound 3na (101 MHz, CDCl3)

Figure S54. 1H NMR Spectrum of compound 3oa (500 MHz, CDCl3)

S58
Figure S55. 13C{1H} NMR Spectrum of compound 3oa (126 MHz, CDCl3)

Figure S56. 1H NMR Spectrum of compound 3pa (500 MHz, CDCl3)

S59
Figure S57. 13C{1H} NMR Spectrum of compound 3pa (126 MHz, CDCl3)

Figure S58. 1H NMR Spectrum of compound 3qa (500 MHz, CDCl3)

S60
Figure S59. 13C{1H} NMR Spectrum of compound 3qa (126 MHz, CDCl3)

Figure S60. 1H NMR Spectrum of compound 3ra (500 MHz, CDCl3)

S61
Figure S61. 13C{1H} NMR Spectrum of compound 3ra (126 MHz, CDCl3)

Figure S62. 1H NMR Spectrum of compound 3sa (500 MHz, CDCl3)

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Figure S63. 13C{1H} NMR Spectrum of compound 3sa (126 MHz, CDCl3)

Figure S64. 1H NMR Spectrum of compound 3ta (500 MHz, CDCl3)

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Figure S65. 13C{1H} NMR Spectrum of compound 3ta (126 MHz, CDCl3)

Figure S66. 1H NMR Spectrum of compound 3ua (500 MHz, CDCl3)

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Figure S67. 13C{1H} NMR Spectrum of compound 3ua (126 MHz, CDCl3)

Figure S68. 1H NMR Spectrum of compound 3va (500 MHz, CDCl3)

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Figure S69. 13C{1H} NMR Spectrum of compound 3va (126 MHz, CDCl3)

Figure S70. 1H NMR Spectrum of compound 3wa (500 MHz, CDCl3)

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Figure S71. 13C{1H} NMR Spectrum of compound 3wa (126 MHz, CDCl3)

Figure S72. 1H NMR Spectrum of compound 3db (500 MHz, CDCl3)

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Figure S73. 13C{1H} NMR Spectrum of compound 3db (126 MHz, CDCl3)

Figure S74. 1H NMR Spectrum of compound 3dc (500 MHz, CDCl3)

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Figure S75. 13C{1H} NMR Spectrum of compound 3dc (126 MHz, CDCl3)

Figure S76. 1H NMR Spectrum of compound 3dd (500 MHz, CDCl3)

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Figure S77. 13C{1H} NMR Spectrum of compound 3dd (126 MHz, CDCl3)

Figure S78. 1H NMR Spectrum of compound 3de (500 MHz, CDCl3)

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Figure S79. 13C{1H} NMR Spectrum of compound 3de (126 MHz, CDCl3)

Figure S80. 1H NMR Spectrum of compound 3df (500 MHz, CDCl3)

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Figure S81. 13C{1H} NMR Spectrum of compound 3df (126 MHz, CDCl3)

Figure S82. 1H NMR Spectrum of compound 3dg (500 MHz, CDCl3)

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Figure S83. 13C{1H} NMR Spectrum of compound 3dg (126 MHz, CDCl3)

Figure S84. 1H NMR Spectrum of compound 3dh (500 MHz, CDCl3)

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Figure S85. 13C{1H} NMR Spectrum of compound 3dh (126 MHz, CDCl3)

Figure S86. 1H NMR Spectrum of compound 3di (500 MHz, CDCl3)

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Figure S87. 13C{1H} NMR Spectrum of compound 3di (126 MHz, CDCl3)

Figure S88. 1H NMR Spectrum of compound 3dj (500 MHz, CDCl3)

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Figure S89. 13C{1H} NMR Spectrum of compound 3dj (126 MHz, CDCl3)

Figure S90. 1H NMR Spectrum of compound 3dk (400 MHz, CDCl3)

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Figure S91. 13C{1H} NMR Spectrum of compound 3dk (101 MHz, CDCl3)

Figure S92. 1H NMR Spectrum of compound 3dl (500 MHz, CDCl3)

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Figure S93. 13C{1H} NMR Spectrum of compound 3dl (126 MHz, CDCl3)

Figure S94. 1H NMR Spectrum of compound 3dm (500 MHz, CDCl3)

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Figure S95. 13C{1H} NMR Spectrum of compound 3dm (126 MHz, CDCl3)

Figure S96. 1H NMR Spectrum of compound 3dn (500 MHz, CDCl3)

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Figure S97. 13C{1H} NMR Spectrum of compound 3dn (126 MHz, CDCl3)

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