Professional Documents
Culture Documents
Stefani
Stefani
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
A Journal of
www.chemcatchem.org
ChemCatChem 10.1002/cctc.201901403
COMMUNICATION
Accepted Manuscript
with thiols and selenols in the presence of molybdenum hexacarbonyl
as a solid source of carbon monoxide is described. This methodology
permitted the synthesis of 29 C2-glycosides bearing thioester and
selenoester functionalities in moderate to excellent yields and high
functional group tolerance. Moreover, this communication describes
the first catalytic carbonylative coupling reaction of selenols with a
carbon electrophile.
COMMUNICATION
Table 1. Optimization of the reaction conditions.
Effect of catalyst
Accepted Manuscript
2 Pd(dba)2/XantPhos NaOAc anisole 5 90 95
Effect of ligand
Effect of temperature
Effect of base
Effect of solvent
We started the screening of the reaction conditions by testing in 72% yield, while at 75 °C it was isolated in only 50% after 18 h
different sources of palladium in combination with the bidentate (Entries 8–9). A survey of inorganic and organic bases showed
phosphine ligand XantPhos in anisole. [23] Excellent yields of 3a that NaOAc was the best option for the thiocarbonylation reaction
were obtained in all cases, with Pd(PhCN) 2Cl2 giving the (Entry 1), however, bases such as Et3N and K2CO3 were still
carbonylated product in 98% (Entry 3). Different ligands were then active and could deliver 3a in good yields (Entries 11–12). Finally,
investigated and, while bidentate electron-rich phosphine dppf the reaction solvent was investigated. Toluene and THF gave 3a
delivered 3a in 75%, monodentate SPhos, RuPhos and DpePhos in good yields (Entries 13-14), whilst MeCN had a negative effect
completely shut down the reaction (Entries 4–7). The reason for in the reaction progress and no carbonylated product was
this trend is still not clear, however, we speculate that the observed (Entry 15).
bidentate nature of XanPhos and dppf might facilitate reductive
With the best conditions established, we then examined the
elimination by increasing the energy of the intermediate, as
scope for the thiocarbonylation reaction for both the thiol and the
observed by Hartwig and co-workers.[24] Next, the effect of the
2-iodoglycal partners (Table 2).
reaction temperature was examined: at 110 °C 3a was obtained
COMMUNICATION
Table 2. Scope of the thiocarbonylation reaction.
Accepted Manuscript
Reaction conditions: 0.25 mmol (1a-g). aReaction time: 5 h. bReacton time: 15 h.
COMMUNICATION
Thiols bearing strongly electron-donating groups were well
tolerated for both 2-iodoglycals 1a and 1b. Moderately donating Table 3. Scope of the selenocarbonylation reaction.
groups featuring tert-butyl and methyl groups also furnished
thioesters 3d and 3e in 81% and 95% yield, respectively.
Interestingly, o-aminothiol 2f gave product 3f in only 32% yield.
This diminished performance is likely the consequence of the
chelation of the metal center with 2f.[25] Thiophenol, on the other
hand, efficiently participated in this reaction with both 1a and 1b
and products 3g and 3h were isolated in 72% and 93% yield,
respectively. We were also pleased to find that electron-
withdrawing groups were well tolerated and 2i-k gave the
carbonylated products 3i-k in excellent yields. In the case of
Accepted Manuscript
thiophenols 2l-m we observed a slightly reduced isolated yield of
3l-m, possible due to competitive oxidative addition of the metal
catalyst. p-Nitrothiophenol gave 3m in low yield and acetamide-
containing thiophenol 2o failed to deliver thioester 3o, possible
due to Pd competitive coordination with this substrate. [26] Moving
from aromatic thiols, the benzylic substrate 2p was amenable to
this methodology and 3p was obtained in 53% yield. Aliphatic thiol
2q also allowed access to thioester 3q bearing an alcohol
functionality in 42%. A boc-protected cysteine derivative proved
to be a competent coupling partner in this transformation, yielding
products 3r-t in good to excellent yields for three different 2-
iodoglycals (1), demonstrating that different protecting groups do
not significantly impact the reaction outcome. Finally, a range of
different sugar derivatives (glucose, xylose, arabinose and Reaction conditions: 0.2 mmol (1a,b-d). Reaction time: 15 h.
COMMUNICATION
(2R,3S,4S)-S-(4-methoxyphenyl) 3,4-bis(benzyloxy)-2-
((benzyloxy)methyl)-3,4-dihydro-2H-pyran-5-carbothioate (3b):
Product 3b was obtained as a yellow oil (111 mg, 0.190 mmol, 76%).
1H NMR (300 MHz, CDCl ): δ = 7.78 (s, 1H), 7.40 – 7.11 (m, 17H), 6.86 (d,
3
J = 8.4 Hz, 2H), 4.56 (m, 2H), 4.53 – 4.29 (m, 6H), 3.79 – 3.50 (m, 5H),
3.55 (dd, J = 10.6, 5.0 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ = 188.9,
160.6, 155.2, 138.0, 137.7, 137.3, 136.9, 128.5, 128.4, 128.3, 128.0, 128.0,
127.8, 127.8, 127.7, 127.7, 117.9, 114.8, 114.4, 77.7, 73.3, 72.6, 71.6,
71.4, 68.2, 67.9, 55.3. IR (, cm−1) = 2959, 2928, 2766, 1601, 1566, 1540,
1445, 1248, 1136, 1052, 994. HRMS (ESI-TOF) calc. [C35H34O6SNa+]
605.1968, found 605.1997. [α]20D = +36.2 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-(((4-
(dimethylamino)phenyl)thio)carbonyl)-3,4-dihydro-2H-pyran-3,4-diyl
Accepted Manuscript
diacetate (3c):Product 3c was obtained as a yellow oil (86 mg, 0.190
mmol, 76%). 1H NMR (300 MHz, CDCl3): δ = 7.82 (s, 1H), 7.19 (d, J = 2.1
Hz, 2H), 6.64 (d, J = 7.7 Hz, 2H), 5.71 – 5.63 (m, 1H), 5.17 – 5.02 (m, 1H),
4.58 – 4.51 (m, 1H), 4.40 (dd, J = 12.0, 7.9 Hz, 1H), 4.12 (dd, J = 11.9, 4.6
Hz, 1H), 2.91 (s, 6H), 2.09 – 1.88 (m, 9H). 13C NMR (75 MHz, CDCl3): δ =
188.2, 170.2, 169.3, 169.2, 155.2, 151.2, 136.3, 112.7, 112.2, 110.6, 74.9,
65.9, 62.1, 60.8, 40.1, 20.7, 20.7, 20.6. IR (, cm−1) = 2861, 2829, 2762,
1685, 1609, 1574, 1460, 1322, 1173, 1149, 992. HRMS (ESI-TOF) calc.
[C21H25NO8SNa+], 474.1193 found 474.1156. [α]20D = +37.2 (0.05, CHCl3).
COMMUNICATION
(2R,3S,4S)-2-(acetoxymethyl)-5-((phenylthio)carbonyl)-3,4-dihydro- 125.5, 124.3, 112.1, 75.2, 65.8, 61.9, 60.7, 20.7, 20.6, 20.6. IR (, cm−1) =
2H-pyran-3,4-diyl diacetate (3h): Product 3h was obtained as a yellow oil 2862, 2834, 1681, 1613, 1574, 1549, 1326, 1179, 1156, 996, 827, 791.
(95 mg, 0.232 mmol, 93%). 1H NMR (300 MHz, CDCl3): δ = 7.84 (s, 1H), HRMS (ESI-TOF) calc. [C19H19BrO8Na+] 508.9876, found 508.9883. [α]20D
7.41 – 7.29 (m, 5H), 5.67 (t, J = 3.0, 1.6 Hz, 1H), 5.12 (t, J = 2.9 Hz, 1H), = +36.8 (0.1, CHCl3).
4.59 – 4.47 (m, 1H), 4.41 (dd, J = 12.0, 7.9 Hz, 1H), 4.12 (dd, J = 12.0, 4.4
Hz, 1H), 2.09 – 1.92 (m, 9H). 13C NMR (75 MHz, CDCl3): δ = 186.2, 170.2, (2R,3S,4S)-2-(acetoxymethyl)-5-(((4-nitrophenyl)thio)carbonyl)-3,4-
169.2, 169.1, 155.7, 135.1, 129.5, 129.1, 126.4, 112.2, 75.1, 65.8, 62.0, dihydro-2H-pyran-3,4-diyl diacetate (3n): Product 3n was obtained as a
60.8, 20.7, 20.6, 20.6. IR (, cm−1) = 2961, 2916, 1687, 1611, 1574, 1549, brown solid (41 mg, 0.09 mmol, 36%). 1H NMR (300 MHz, CDCl3): δ = 7.81
1395, 1326, 1173, 1153, 1018, 992. HRMS (ESI-TOF) calc. (s, 1H), 7.18 (d, J = 8.2 Hz, 2H), 6.51 (d, J = 8.5 Hz, 2H), 5.72 – 5.60 (m,
[C19H20O8SNa+] 431.0771, found 431.0767. [α]20D = +38.4 (0.05, CHCl3). 1H), 5.11 (t, J = 3.0 Hz, 1H), 4.60 – 4.48 (m, 1H), 4.47 – 4.34 (m, 1H), 4.19
– 4.01 (m, 1H), 2.07 – 1.91 (m, 9H).13C NMR (75 MHz, CDCl3): δ = 187.9,
(2R,3S,4S)-2-(acetoxymethyl)-5-(((3-methoxyphenyl)thio)carbonyl)- 170.2, 169.3, 169.2, 155.3, 148.0, 136.6, 133.8, 125.7, 115.3, 74.9, 65.9,
3,4-dihydro-2H-pyran-3,4-diyl diacetate (3i): Product 3i was obtained as 62.0, 60.8, 20.7, 20.7, 20.6. IR (, cm−1) = 2820, 1568, 1542, 1685, 1447,
a yellow oil (101 mg, 0.230, 92%). 1H NMR (300 MHz, CDCl3): δ = 7.83 (s, 1192, 1140, 1013, 802. HRMS (ESI-TOF) calc. [C19H19NO10SNa+]
Accepted Manuscript
1H), 7.33 – 7.15 (m, 1H), 7.01 – 6.84 (m, 3H), 5.66 (dd, J = 3.0, 1.6 Hz, 476.0621, found 437.0622. [α]20D = +26.0 (0.05, CHCl3).
1H), 5.12 (t, J = 2.9 Hz, 1H), 4.55 (m, J = 6.0, 2.9, 1.4 Hz, 1H), 4.40 (dd, J
= 12.0, 7.9 Hz, 1H), 4.12 (dd, J = 12.0, 4.5 Hz, 1H), 3.72 (s, 3H), 2.04 – (2R,3S,4S)-2-(acetoxymethyl)-5-((benzylthio)carbonyl)-3,4-dihydro-
1.96 (m, 9H). 13C NMR (75 MHz, CDCl3): δ = 185.1, 169.2, 168.2, 168.1, 2H-pyran-3,4-diyl diacetate (3p): Product 3p was obtained as a yellow oil
158.8, 154.7, 128.9, 126.4, 126.3, 119.3, 114.6, 111.2, 74.1, 64.8, 60.9, (56 mg, 0.13 mmol, 53%). 1H NMR (300 MHz, CDCl3): δ = 7.69 (s, 1H),
59.8, 54.3, 19.7, 19.6, 19.6. IR (, cm−1) = 2916, 2868, 2745, 1685, 1611, 7.22 (d, J = 4.2 Hz, 5H), 5.75 – 5.63 (m, 1H), 5.09 (t, J = 3.1 Hz, 1H), 4.58
1574, 1324, 1169, 1147, 991, 840. HRMS (ESI-TOF) calc. [C20H22O9SNa+] – 4.45 (m, 1H), 4.40 – 4.27 (m, 1H), 4.21 – 4.03 (m, 3H), 2.06 – 1.92 (m,
461.0877, found 461.0883. [α]20D = +37.8 (0.05, CHCl3). 9H). 13C NMR (75 MHz, CDCl3): δ = 187.4, 170.2, 169.3, 169.1, 155.1,
137.4, 128.9, 128.6, 127.3, 112.3, 75.0, 65.8, 62.0, 60.8, 32.5, 20.7, 20.6,
(2R,3S,4S)-2-(acetoxymethyl)-5-(((2- 20.6. IR (, cm−1) = 2931, 1689, 1601, 1575, 1549, 1177, 1153, 1020, 996.
(trifluoromethyl)phenyl)thio)carbonyl)-3,4-dihydro-2H-pyran-3,4-diyl HRMS (ESI-TOF) calc. [C20H22O8SNa+] 445.0927, found 445.0920. [α]20D
diacetate (3j): Product 3j was obtained as a yellow oil (114 mg, 0.240 = +34.0 (0.05, CHCl3).
mmol, 96%). 1H NMR (300 MHz, CDCl3): δ = 7.83 (s, 1H), 7.70 (d, J = 7.1
Hz, 1H), 7.55 – 7.42 (m, 3H), 5.67 (dd, J = 3.2, 1.6 Hz, 1H), 5.14 (t, J = 3.3 (2R,3S,4S)-2-(acetoxymethyl)-5-(((2-hydroxyethyl)thio)carbonyl)-3,4-
Hz, 1H), 4.58 – 4.50 (m, 1H), 4.39 (dd, J = 12.1, 7.6 Hz, 1H), 4.15 (dd, J = dihydro-2H-pyran-3,4-diyl diacetate (3q): Product 3q was obtained as a
12.1, 4.5 Hz, 1H), 2.09 – 1.91 (m, 9H). 13C NMR (75 MHz, CDCl3): δ = coreless oil (40 mg, 0.11 mmol, 42%). 1H NMR (300 MHz, CDCl3): δ =
183.8, 169.2, 168.3, 168.1, 155.1, 138.6, 132.5 (q, J = 30.1 Hz), 131.1, 7.81 (s, 1H), 5.77 – 5.71 (m, 1H), 5.17 (t, J = 3.1 Hz, 1H), 4.64 – 4.56 (m,
129.0, 126.1 (q, J = 5.4 Hz), 124.2, 120.3, 111.3, 74.3, 64.8, 61.2, 59.7, 1H), 4.45 (dd, J = 11.7, 8.2 Hz, 1H), 4.17 (dd, J = 12.0, 4.5 Hz, 1H), 3.79
19.6, 19.5, 19.5. 19F NMR (282 MHz, THF-d8): δ = -61.1. IR (, cm−1) = (t, J = 5.9 Hz, 2H), 3.17 (t, J = 6.2 Hz, 2H), 2.11 – 2.06 (m, 9H). 13C NMR
2972, 2846, 1693, 1622, 1575, 1551, 1272, 1179, 1158, 1002. (75 MHz, CDCl3): δ = 188.3, 170.2, 169.3, 1691, 155.5, 112.4, 77.4, 75.0,
HRMS (ESI-TOF) calc. [C20H19O8F3SNa+] 499.0644, found 499.0625. 65.8, 61.9, 60.8, 31.3, 20.7, 20.6, 20.6. IR (, cm−1) = 3330, 3244, 2844,
[α]20D = +36.8 (0.05, CHCl3). 1687, 1600, 1575, 1547, 1326, 1153, 1177, 1017, 994. HRMS (ESI-TOF)
calc. [C15H20O9SNa+] 399.0720, found 399.0729. [α]20D = +34.8 (0.05,
(2R,3S,4S)-2-(acetoxymethyl)-5-(((4-fluorophenyl)thio)carbonyl)-3,4- CHCl3).
dihydro-2H-pyran-3,4-diyl diacetate (3k): Product 3k was obtained as a
yellow oil (100 mg, 0.235, 94%). 1H NMR (300 MHz, CDCl3): δ = 7.90 (s, (2R,3S,4S)-2-(acetoxymethyl)-5-((((R)-2-((tert-
1H), 7.45 – 7.40 (m, 2H), 7.16 – 7.05 (m, 2H), 5.77 – 5.64 (m, 1H), 5.20 (t, butoxycarbonyl)amino)-3-methoxy-3-oxopropyl)thio)carbonyl)-3,4-
J = 3.0 Hz, 1H), 4.72 – 4.58 (m, 1H), 4.48 (dd, J = 12.0, 7.8 Hz, 1H), 4.20 dihydro-2H-pyran-3,4-diyl diacetate (3r): Product 3r was obtained as a
(dd, J = 12.1, 4.5 Hz, 1H), 2.19 – 1.98 (m, 9H). 13C NMR (75 MHz, CDCl3): yellow oil (113 mg, 0.212 mmol, 85%). 1H NMR (300 MHz, CDCl3): δ =
δ = 186.1, 170.2, 169,2, 169,1, 163.5 (d, J = 250.2 Hz), 155.9, 137.2 (d, J 7.72 (s, 1H), 5.65 (s, 1H), 5.23 (s, 1H), 5.11 (t, J = 3.3 Hz, 1H), 4.59 – 4.31
= 8.6 Hz), 121.7 (d, J = 3.3 Hz), 116.4 (d, J = 22.1 Hz), 112.1, 75.2, 65.7, (m, 3H), 4.11 (m, 1H), 3.68 (d, J = 3.0 Hz, 3H), 3.37 (t, J = 4.3 Hz, 2H),
61.9, 60.7, 20.6, 20.6, 20.5. 19F NMR (282 MHz, THF-d8): δ = 2.02 (m, 9H), 1.37 (m, 9H). 13C NMR (75 MHz, CDCl3): δ = 186.8, 170.8,
-113.2. IR (, cm−1) = 2924, 1685, 1574, 1443, 1324, 1169, 1149, 992, 170.1, 169.2, 169.1, 155.7, 155.0, 112.3, 80.1, 75.1, 65.7, 61.9, 60.7, 53.2,
806. HRMS (ESI-TOF) calc. [C19H19FO8Na+] 449.0676, found 449.0680. 52.5, 30.3, 28.2, 20.6, 20.6, 20.5. IR (, cm−1) = 3267, 2877, 1687, 1661,
[α]20D = +35.2 (0.05, CHCl3). 1587, 1549, 1324, 1153, 1175, 994, 836. HRMS (ESI-TOF) calc.
[C22H31NO12SNa+] 556.1459, found 556.1490. [α]20D = +33.8 (0.05, CHCl3).
(2R,3S,4S)-2-(acetoxymethyl)-5-(((4-chlorophenyl)thio)carbonyl)-3,4-
dihydro-2H-pyran-3,4-diyl diacetate (3l): Product 3l was obtained as a (R)-methyl 3-(((2R,3S,4S)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)-
coreless oil (63 mg, 0.142 mmol, 57%). 1H NMR (300 MHz, CDCl3): δ = 3,4-dihydro-2H-pyran-5-carbonyl)thio)-2-((tert-
7.82 (s, 1H), 7.34 – 7.25 (m, 4H), 5.66 (dd, J = 3.1, 1.7 Hz, 1H), 5.12 (t, J butoxycarbonyl)amino)propanoate (3s): Product 3s was obtained as a
= 3.0 Hz, 1H), 4.60 – 4.52 (m, 1H), 4.41 (dd, J = 12.1, 7.9 Hz, 1H), 4.12 yellow oil (130 mg, 0.192 mmol, 77%). 1H NMR (300 MHz, CDCl3): δ =
(dd, J = 12.1, 4.5 Hz, 1H), 2.06 – 1.95 (m, 9H). 13C NMR (75 MHz, CDCl3): 7.66 (s, 1H), 7.34 – 7.09 (m, 15H), 4.64 – 4.29 (m, 10H), 3.78 – 3.73 (m,
δ = 185.6, 170.2, 169.2, 169.1, 156.0, 136.3, 136.0, 129.4, 124.9, 112.1, 1H), 3.68 – 3.62 (m, 4H), 3.55 – 3.48 (m, 1H), 3.35 (d, J = 4.8 Hz, 2H),
75.2, 65.7, 61.9, 60.7, 20.7, 20.6, 20.6. IR (, cm−1) = 2915, 1689, 1574, 1.37 – 1.32 (m, 9H). 13C NMR (75 MHz, CDCl3): δ = 188.7, 171.1, 155.4,
1549, 1430, 1326, 1173, 1154, 994, 983, 825. HRMS (ESI-TOF) calc. 155.1, 137.8, 137.7, 137.3, 128.5, 128.4, 128.3, 128.0, 127.9, 127.8, 127.7,
[C19H19ClO8SNa+] 465.0381, found 465.0385. [α]20D = +36.2 (0.05, CHCl3). 127.7, 114.4, 80.1, 77.6, 77.3, 73.3, 72.3, 71.5, 71.1, 68.0, 67.8, 53.5, 52.5,
30.3, 28.2. IR (, cm−1) = 3254, 2929, 2853, 2877, 1689, 1657, 1601, 1449,
(2R,3S,4S)-2-(acetoxymethyl)-5-(((4-bromophenyl)thio)carbonyl)-3,4- 1158, 1035, 678. HRMS (ESI-TOF) calc. [C37H43NO9SNa+] 700.2551,
dihydro-2H-pyran-3,4-diyl diacetate (3m):Product 3m was obtained as found 700.2516. [α]20D = +33.4 (0.05, CHCl3).
a yellow solid (74 mg, 0.152 mmol, 61%). 1H NMR (300 MHz, CDCl3): δ =
7.89 (s, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.5 Hz, 2H), 5.74 (dd, J (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-(((2R,3S,4S)-3,4-
= 3.2, 1.6 Hz, 1H), 5.23 – 5.15 (m, 1H), 4.69 – 4.61 (m, 1H), 4.48 (dd, J = dimethoxy-2- (methoxymethyl)-3,4-dihydro-2H-pyran-5-
12.1, 7.9 Hz, 1H), 4.18 (dd, J = 12.1, 4.6 Hz, 1H), 2.18 – 2.03 (m, 9H). 13C carbonyl)thio)propanoate (3t): Product 3t was obtained as a yellow oil
NMR (75 MHz, CDCl3): δ = 185.5, 170.2, 169.2, 169.1, 156.0, 136.6, 132.4, (103 mg, 0.230 mmol, 92%). 1H NMR (300 MHz, CDCl3): δ = 7.03 (s, 1H),
COMMUNICATION
5.22 (s, 1H), 4.54 (s, 1H), 4.06 – 3.98 (m, 1H), 3.90 (dd, J = 8.0, 5.0 Hz, (2R,3S,4S)-2-(acetoxymethyl)-5-(((4-
1H), 3.80 – 3.71 (m, 4H), 3.67 – 3.61 (m, 2H), 3.50 – 3.38 (m, 11H), 1.45 methoxyphenyl)selanyl)carbonyl)-3,4-dihydro-2H-pyran-3,4-diyl
– 1.42 (s, 9H).13C NMR (75 MHz, CDCl3): δ = 188.4, 171.1, 170.8, 137.8, diacetate (6a): Product 6a was obtained as a yellow oil (56 mg, 0.116
137.3, 94.7, 80.2, 71.9, 71.1, 68.2, 59.3, 57.1, 56.2, 52.6, 52.5, 41.3, 30.7. mmol, 58%). 1H NMR (300 MHz, CDCl3): δ = 7.77 (s, 1H), 7.47 – 7.32 (m,
IR (, cm−1) = 3226, 2879, 2855, 2736, 1689, 1654, 1618, 1460, 1451, 2H), 6.84 (d, J = 8.7 Hz, 2H), 5.63 (dd, J = 3.1, 1.7 Hz, 1H), 5.11 (t, J = 3.0
1123, 1061, 1017. HRMS (ESI-TOF) calc. [C19H31O9SNa+] 472.1611, Hz, 1H), 4.61 – 4.53 (m, 1H), 4.40 (dd, J = 12.0, 7.8 Hz, 1H), 4.11 (dd, J =
found 472.1618. [α]20D = +25.2 (0.05, CHCl3). 12.1, 4.6 Hz, 1H), 3.75 (s, 3H), 2.09 – 1.91 (m, 9H). 13C NMR (75 MHz,
CDCl3): δ = 188.9, 170.2, 169.2, 169.1, 160.5, 156.6, 137.9, 115.2, 115.1,
(2R,3R,4S,5R,6R)-2-(((2R,3S,4R)-4-acetoxy-2-(acetoxymethyl)-5-(((4- 114.3, 75.3, 65.8, 62.1, 60.7, 55.2, 20.7, 20.7, 20.6. IR (, cm−1) = 2862,
methoxyphenyl)thio)carbonyl)-3,4-dihydro-2H-pyran-3-yl)oxy)-6- 2747, 1685, 1631, 1574, 1443, 1324, 1177, 1154, 1136, 992, 799. HRMS
(acetoxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (3u): (ESI-TOF) calc. [C20H22O9SeNa+] 509.0321, found 509.0316. [α]20D
Product 3u was obtained as a yellow solid (172 mg, 0.237 mmol, 95%). = +33.2 (0.05, CHCl3).
1
H NMR (300 MHz, CDCl3): = 7.85 (s, 1H), 7.29 (d, J = 8.0 Hz, 2H), 6.87
(d, J = 8.4 Hz, 2H), 5.46 (s, 1H), 5.40 – 5.28 (m, 2H), 5.02 – 4.90 (m, 1H), (2R,3S,4S)-2-(acetoxymethyl)-5-(((2-
Accepted Manuscript
4.86 – 4.63 (m, 2H), 4.33 (t, J = 10.3 Hz, 1H), 4.15 – 3.95 (m, 4H), 3.92 (s, methoxyphenyl)selanyl)carbonyl)-3,4-dihydro-2H-pyran-3,4-diyl
1H), 3.75 (s, 3H), 2.08 – 1.92 (m, 18H).13C NMR (75 MHz, CDCl3): = diacetate (6b): Product 6b was obtained as a yellow solid (39 mg, 0.08
187.4, 170.5, 170.2, 170.1, 170.0, 169.6, 169.5, 160.8, 155.3, 136.7, 116.9, mmol, 41%). 1H NMR (300 MHz, CDCl3): δ = 7.82 (s, 1H), 7.49 – 7.44 (m,
114.9, 111.5, 97.0, 75.8, 72.7, 70.1, 69.9, 68.4, 68.2, 61.9, 61.7, 60.8, 55.3, 1H), 7.33 (t, J = 7.8 Hz, 1H), 6.90 (t, J = 7.1 Hz, 2H), 5.68 – 5.60 (m, 1H),
20.7, 20.6, 20.6, 20.6, 20.5, 20.4. IR (, cm−1) = 2864, 1687, 1605, 1572, 5.11 (t, J = 3.1 Hz, 1H), 4.62 – 4.50 (m, 1H), 4.39 (dd, J = 12.1, 7.8 Hz,
1542, 1442, 1184, 1154, 1004, 992. HRMS (ESI-TOF) calc. 1H), 4.12 (dd, J = 12.1, 4.5 Hz, 1H), 3.77 (s, 3H), 2.21 – 1.86 (m, 9H). 13C
[C32H38O17SNa+] 749.1722, found 749.1696. [α]20D = +2.00 (0.05, CHCl3). NMR (75 MHz, CDCl3): δ = 186.2, 169.2, 168.3, 168.1, 158.1, 155.5, 137.3,
130.2, 120.4, 113.6, 113.1, 110.3, 74.3, 64.9, 61.2, 59.8, 55.0, 19.7, 19.7,
(3R,4R)-5-(((4-methoxyphenyl)thio)carbonyl)-3,4-dihydro-2H-pyran- 19.6. IR (, cm−1) = 2877, 2112, 1685, 1564, 1177, 1328, 1197, 1154, 1143,
3,4-diyl diacetate (3v): Product 3v was obtained as a yellow oil (78 mg, 991. HRMS (ESI-TOF) calc. [C20H22O9SeNa+] 509.0321, found 509.0326.
0.215 mmol, 86%). 1H NMR (300 MHz, CDCl3): = 7.90 (s, 1H), 7.28 (d, J [α]20D = +32.6 (0.05, CHCl3).
= 8.9 Hz, 2H), 6.86 (d, J = 8.3 Hz, 2H), 5.61 (t, J = 2.2 Hz, 1H), 4.37 (d, J
= 13.2 Hz, 1H), 3.98 (d, J = 12.6 Hz, 1H), 3.74 (s, 3H), 2.02 (s, 3H), 2.00 (2R,3S,4S)-2-(acetoxymethyl)-5-((phenylselanyl)carbonyl)-3,4-
(s, 3H). 13C NMR (75 MHz, CDCl3): = 187.5, 169.4, 169.0, 160.7, 157.8, dihydro-2H-pyran-3,4-diyl diacetate (6c): Product 6c was obtained as a
136.7, 117.1, 114.8, 112.0, 65.3, 64.7, 61.0, 55.3, 20.9, 20.8. IR (, cm−1) yellow oil (51 mg, 0.112 mmol, 56%). 1H NMR (300 MHz, CDCl3): δ = 7.79
= 2884, 1689, 1605, 1557, 1442, 1174, 1152, 1001, 990. HRMS (ESI- (s, 1H), 7.46 (d, J = 7.5 Hz, 2H), 7.36 – 7.29 (m, 3H), 5.64 (s, 1H), 5.11 (s,
TOF) calc. [C17H18O7SNa+] 389.0665, found 389.0669. [α]20D = -210 (0.05, 1H), 4.56 (d, J = 3.1 Hz, 1H), 4.40 (dd, J = 12.1, 7.9 Hz, 1H), 4.12 (dd, J =
CHCl3). 11.9, 4.4 Hz, 1H), 2.13 – 1.91 (m, 9H). 13C NMR (75 MHz, CDCl3): δ
=188.0, 170.2, 169.2, 169.1, 156.7, 136.3, 129.3, 129.0, 124.9, 114.3, 75.4,
(3S,4R)-5-(((4-methoxyphenyl)thio)carbonyl)-3,4-dihydro-2H-pyran- 65.8, 62.1, 60.7, 20.7, 20.7, 20.6. IR (, cm−1) = 2861, 2827, 2762, 1691,
3,4-diyl diacetate (3x): Product 3x was obtained as a yellow oil (90 mg, 1629, 1574, 1326, 1184, 1158, 1018, 996. HRMS (ESI-TOF) calc.
0.245 mmol, 93%). 1H NMR (300 MHz, CDCl3): = 7.77 (s, 1H), 7.24 (d, J [C19H20O8SeNa+] 479.0216, found 479.0207. [α]20D = +34.0 (0.05, CHCl3).
= 8.2 Hz, 2H), 6.84 (d, J = 8.3 Hz, 2H), 6.04 (d, J = 3.5 Hz, 1H), 5.14 –
5.01 (m, 1H), 4.17 – 4.06 (m, 1H), 4.02 – 3.92 (m, 1H), 3.72 (s, 3H), 2.01 (2R,3S,4S)-2-(acetoxymethyl)-5-((naphthalen-1-ylselanyl)carbonyl)-
(s, 3H), 1.95 (s, 3H). 13C NMR (75 MHz, CDCl3): = 186.8, 169.6, 169.3, 3,4-dihydro-2H-pyran-3,4-diyl diacetate (6d): Product 6d was obtained
160.7, 157.6, 136.4, 117.0, 114.8, 112.7, 65.1, 63.0, 60.8, 55.3, 20.8, 20.5. as a yellow oil (46 mg, 0.09 mmol, 46%). 1H NMR (300 MHz, CDCl3): δ =
IR (, cm−1) = 2949, 2852, 2878, 1686, 1657, 1605, 1447, 1158, 1035. 8.07 (s, 1H), 7.98 – 7.72 (m, 4H), 7.62 – 7.49 (m, 3H), 5.78 – 5.70 (m, 1H),
HRMS (ESI-TOF) calc. [C17H18O7SNa+] 389.0665, found 389.0661. [α]20D 5.25 – 5.16 (m, 1H), 4.73 – 4.60 (m, 1H), 4.49 (dd, J = 12.2, 8.0 Hz, 1H),
= -176 (0.05, CHCl3). 4.20 (dd, J = 12.2, 4.6 Hz, 1H), 2.17 – 2.05 (m, 9H). 13C NMR (75 MHz,
CDCl3): δ = 188.2, 170.2, 169.2, 169.1, 156.8, 136.2, 133.8, 133.2, 132.7,
(2R,3R,4R)-2-(acetoxymethyl)-5-(((4-methoxyphenyl)thio)carbonyl)- 128.7, 127.8, 127.8, 126.9, 126.4, 122.2, 114.4, 75.4, 65.8, 62.1, 60.7,
3,4-dihydro-2H-pyran-3,4-diyl diacetate (3y): Product 3y was obtained 20.7, 20.7, 20.6. IR (, cm−1) = 2862, 2821, 2756, 1689, 1629, 1574. 1326,
as a yellow oil (58 mg, 0.132 mmol, 53%). 1H NMR (300 MHz, CDCl3): = 1182, 1156, 1018, 996. HRMS (ESI-TOF) calc. [C23H22O8SeNa+] 529.0372,
7.73 (s, 1H), 7.25 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 5.99 (d, J = found 529.0378. [α]20D = +32.8 (0.05, CHCl3).
4.4 Hz, 1H), 5.37 (t, J = 4.0 Hz, 1H), 4.50 – 4.37 (m, 2H), 4.30 – 4.18 (m,
1H), 3.75 (s, 3H), 2.20 – 1.98 (m, 9H). 13C NMR (75 MHz, CDCl3): = (2R,3S,4S)-Se-naphthalen-1-yl 3,4-bis(benzyloxy)-2-
185.5, 169.5, 168.7, 168.3, 159.8, 154.3, 135.7, 115.9, 113.9, 112.3, 73.2, ((benzyloxy)methyl)-3,4-dihydro-2H-pyran-5-carboselenoate (6e):
63.6, 60.3, 60.1, 54.3, 19.7, 19.6, 19.5. IR (, cm−1) = 2948, 2859, 1689, Product 6e was obtained as a yellow oil (56 mg, 0.09 mmol, 43%). 1H NMR
1657, 1607, 1449, 1150, 1001. HRMS (ESI-TOF) calc. [C20H22O9SNa+] (300 MHz, CDCl3): δ = 8.02 (s, 1H), 7.78 (m, 4H), 7.53 (d, J = 8.5 Hz, 1H),
461.0877, found 461.0863. [α]20D = +42.0 (0.05, CHCl3). 7.49 – 7.37 (m, 2H), 7.31 – 7.15 (m, 15H), 4.60 – 4.35 (m, 7H), 3.82 – 3.69
(m, 3H), 3.57 (dd, J = 10.7, 5.0 Hz, 1H). 13C NMR (75 MHz, CDCl3):
(2R,3S,4S)-2-(acetoxymethyl)-5-(((2-(((2R,3S,4S)-3,4-diacetoxy- δ = 189.8, 156.6, 137.8, 137.6, 137.2, 136.2, 133.9, 133.1, 133.0, 128.5,
2- (acetoxymethyl)-3,4-dihydro-2H-pyran-5- 128.5, 128.5, 128.4, 128.4, 128.3, 128.3, 128.0, 127.8, 127.8, 127.7, 127.7,
carbonyl)oxy)ethyl)thio)carbonyl)-3,4- dihydro-2H-pyran-3,4-diyl 126.7, 126.2, 123.1, 116.4, 78.1, 73.3, 72.5, 71.6, 71.3, 68.1, 68.1.
diacetate (4): Product 4 was synthesized according to a previously HRMS (ESI-TOF) calc. [C38H34O5SeNa+] 673.1464, found 673.1466. [α]20D
published procedure1 and was obtained as a yellow solid (97 mg, 0.144 = +34.4 (0.05, CHCl3).
mmol, 72%). 1H NMR (300 MHz, CDCl3): δ = 7.74 (s, 2H), 5.71 – 5.63 (m,
2H), 5.10 (t, J = 3.1 Hz, 2H), 4.60 – 4.48 (m, 2H), 4.38 (dd, J = 12.2, 7.7 (3S,4R)-5-((naphthalen-1-ylselanyl)carbonyl)-3,4-dihydro-2H-pyran-
Hz, 2H), 4.16 – 4.07 (m, 2H), 3.72 (t, J = 5.9 Hz, 2H), 3.10 (t, J = 6.0 Hz, 3,4-diyl diacetate (6f): Product 6f was obtained as a yellow oil (38 mg,
2H), 2.06 – 1.97 (m, 18H). 13C NMR (75 MHz, CDCl3): δ = 188.3, 170.2, 0.09 mmol, 44%). 1H NMR (300 MHz, CDCl3): δ = 8.05 (s, 1H), 7.83 (d, J
169.3, 169.2, 169.1, 155.5, 112.4, 75.0, 65.8, 61.9, 60.8, 31.2, 20.7, 20.6, = 9.4 Hz, 3H), 7.51 (m, 4H), 6.22 – 6.05 (m, 1H), 5.63 (d, J = 4.2 Hz, 1H),
20.6. IR (, cm−1) = 2872, 1685, 1601, 1549, 1326, 1175, 1151, 1015, 992, 4.30 – 4.20 (m, 1H), 4.15 – 3.94 (m, 1H), 2.14 (s, 3H), 2.14 (s, 3H). 13C
836. HRMS (ESI-TOF) calc. [C28H34O17SNa+] 472.1611, found 472.1618. NMR (75 MHz, CDCl3): = 187.8, 169.7, 169.3, 158.5, 150.9, 136.2, 132.7,
[α]20D = +35.6 (0.05, CHCl3). 127.8, 127.7, 127.7, 126.8, 126.5, 126.4, 126.3, 114.9, 68.5, 65.9, 65.1,
COMMUNICATION
20.8, 20.7. IR (, cm−1) = 2876, 2826, 2755, 1689, 1627, 1574. 1321, 1182, 4986-5009; e) A. Brennführer, H. Neumann, M. Beller, Angew. Chem. Int.
1155, 1020, 990. HRMS (ESI-TOF) calc. [C20H18O6SeNa+] 457.0161, Ed. 2009, 48, 4114-4133.
found 457.0164. [α]20D = +4.00 (0.05, CHCl3). [10] a) M. P. Darbem, K. S. Kanno, I. M. de Oliveira, C. H. A. Esteves, D. C.
Pimenta, H. A. Stefani, New J. Chem. 2019, 43, 696-699; b) A. Bordessa,
(2R,3S,4R)-S-(4-methoxyphenyl) 3,4-dihydroxy-2-(hydroxymethyl)- A. Ferry, N. Lubin-Germain, J. Org. Chem. 2016, 81, 12459-12465.
3,4-dihydro-2H-pyran-5-carbothioate (7a): Product 7a was obtained as [11] M. P. Darbem, C. H. A. Esteves, I. M. de Oliveira, J. S. Reis, D. C. Pimenta,
a yellow oil (37 mg, 0.117 mmol, 69%). 1H NMR (300 MHz, CDCl3): δ = H. A. Stefani, RSC Adv. 2019, 9, 9468-9474.
8.15 (s, 1H), 7.45 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 8.9 Hz, 2H), 4.89 (t, 1H), [12] a) M. de Robichon, A. Bordessa, N. Lubin-Germain, A. Ferry, J. Org. Chem.
4.28 (dd, J = 5.9, 3.6 Hz, 1H), 3.99 – 3.93 (m, 2H), 3.90 (s, 3H), 3.78 – 2019, 84, 3328-3339; b) N. Hussain, M. Bhardwaj, A. Ahmed, D.
3.68 (m, 1H). 13C NMR (75 MHz, CDCl3): = 183.0, 159.8, 154.7, 144.5, Mukherjee, Org. Lett. 2019, 21, 3034-3037.
135.4, 113.9, 104.6, 76.0, 67.1, 67.1, 63.8, 54.3. IR (, cm−1) = 3330, 3024, [13] a) G. Lian, X. Zhang, B. Yu, Carbohydr. Res. 20015, 403, 13-22; b) M.
2954, 2910, 2832, 1688, 1615, 1557, 1454, 1190, 1027, 982, 697. Samuni-Blank, I. Izhaki, M. D. Dearing, Y. Gerchman, B. Trabelcy, A. L.
HRMS (ESI-TOF) calc. [C14H16O6SNa+] 335.0560, found 335.0557. [α]20D W. H. Karasov, Z. Arad, Curr. Biol. 2012, 22, 1218-1220.
= +46.0 (0.05, CHCl3). [14] a) N. Yoshikai, R. Iida, E. Nakamura, Adv. Synth. Catal. 2008, 350, 1063–
Accepted Manuscript
1072; b) R. J. Anderson, C. A. Henrick, L. D. Rosenblum, J. Am. Chem.
Soc. 1974, 96, 3654–3655.
(2R,3S,4R)-S-phenyl 3,4-dihydroxy-2-(hydroxymethyl)-3,4-dihydro-
[15] S. Kim and J. I. Lee, J. Org. Chem. 1984, 49, 1712–1716.
2H-pyran-5-carbothioate (7b): Product 7b was obtained as a yellow oil
[16] M. Ueda, K. Seki and Y. Imai, Synthesis 1981, 12, 991–993.
(27 mg, 0.096 mmol, 56%). 1H NMR (300 MHz, CDCl3): δ = 8.03 (s, 1H),
[17] H. Tokuyama, T. Miyazaki, S. Yokoshima, T. Fukuyama, Synlett 2003, 10,
7.42 – 7.30 (m, 5H), 5.22 – 5.13 (m, 1H), 4.35 (d, J = 8.8 Hz, 1H), 3.86 –
1512–1514.
3.77 (m, 2H), 3.61 – 3.56 (m, 1H), 3.44 – 3.38 (m, 2H), 2.72 (s, 1H).13C
[18] a) T. Miyazaki, Y. Han-Ya, H. Tokuyama, T. Fukuyama, Synlett 2004, 3,
NMR (75 MHz, CDCl3): = 185.4, 143.1, 138.4, 134.4, 132.4, 127.1, 126.7,
477-480; b) T. Fukuyama, S. C. Lin, L. Li, J. Am. Chem. Soc. 1990, 112,
103.0, 92.1, 68.1, 65.5, 61.6, 59.7. IR (, cm−1) = 3323, 3015, 2945, 2909,
7050–7051.
2823, 1684, 1615, 1557, 1454, 1192, 1027, 988, 697. HRMS (ESI-TOF)
[19] a) I. M. de Oliveira, C. H. A. Esteves, M. P. Darbem, D. C. Pimenta, J.
calc. [C13H14O5S+Na+] 305.0454, found 305.0449 [α]20D = +46.0 (0.05,
Zukerman-Schpector, A. G. Ferreira, H. A. Stefani, F. Manarin, Adv.
CHCl3).
Synth. Catal., DOI: 10.1002/adsc.201900142; b) I. M. de Oliveira, M. P.
Darbem, C. H. A. Esteves, D. C. Pimenta, J. Zukerman-Schpector, H. A.
Stefani, F. Manarin, Tetrahedron Lett. 2018, 59, 3907-3911; c) I. M. de
Acknowledgements Oliveira, S. N. Vasconcelos, C. S. Barbeiro, T. C. Correra, A. Shamim,
D. C. Pimenta, I. Caracelli, J. Zukerman-Schpector, H. A. Stefani, F.
Manarin, New J. Chem. 2017, 41, 9884-9888; d) M. P. D. Rocha, A. R.
The authors thank the São Paulo Research Foundation, FAPESP
Oliveira, T. B. Albuquerque, C. D. G. da Silva, R. Katla N. L. C.
for financial support (grant 2017/24821-4 to HAS, 2016/24396-9
Domingues, RSC Adv. 2016, 6, 4979–4982.
to MPD, 2017/26673-2 to HAE, 2016/04289-3 to IMO). We are [20] H. Maeda, S.-i. Fujiwara, T. S.-I., N. Kambe, N. Sonoda, J. Am. Chem. Soc.
also thankful for the financial support provided by The National 1996, 118, 8160-5161.
Council for Scientific and Technological Development (CNPq) for [21] Y. Nishiyama, K. Tokunaga, H. Kawamatsu, N. Sonoda, Tetrahedron Lett.
the fellowship 306119/2014-5 to HAS. 2002, 43, 1507-1509.
[22] a) A. Temperini, F. Piazzolla, L. Minuti, M. Curini, C. Siciliano, J. Org. Chem.
2017, 82, 4588-4603; b) L. Sancineto, J. P. Vargas, B. Monti, M. Arca, V.
Keywords: Thiocarbonylation, selenocarbonylation,
Lippolis, G. Perin, E. J. Lenardao, C. Santi, Molecules 2017, 22, 953; c)
C2-Branched sugars, glycals, molybdenum hexacarbonyl. P. A. Grieco, Y. Yokoyama, E. Williams, J. Org. Chem. 1978, 43, 1283–
1285; d) H.-J. Gais and T. Lied, Angew. Chemie Int. Ed. 1978, 17, 267-
268.
[1] a) Y. Yang, B. Yu, Chem. Rev. 2017, 117, 12281-12356; b) D.-C. Xiong, C. [23] M. N. Burhardt, A. Ahlburg, T. Skydstrup, J. Org. Chem. 2014, 79, 11830-
Gao, W. Li, Y. Wang, Q. Li, X.-S. Ye, Org. Chem. Front. 2014, 1, 798- 11840.
806. [24] a) B. C. Hamann, J. F. Hartwig, J. Am. Chem. Soc. 1998, 120, 7369-7370;
[2] a) S. Colombel, N. Van Hijfte, T. Poisson, E. Lecler, X. Pannecoucke, Chem. b) B. C. Hamann, J. F. Hartwig, J. Am. Chem. Soc. 1998, 120, 3694-
Eur. J. 2013, 19, 12778-12787; b) A. M. Gomez, M. Casillas, S. .Valverde, 3703.
J. C. Lopez, Tetrahedron: Asymmetry 2001, 12, 2175-2183. [25] a) S. Bharti, M. Choudhary, B. Mohan, S. P. Rawat, S. R. Sharma, J. Mol.
[3] K. Pachamuthu, A. Gupta, J. Das, R. R. Schmidt, Y. D. Vankar, Eur. J. Org. Struct. 2018, 1164, 137-154; b) R. Lertlapwasin, N. Bhawawet, A. Imym,
Chem. 2002, 1479-1483 S. Fuangswasdi, Sep. Pur. Tech. 2010, 72, 70-76.
[4] a) S. Barroso, S. Lemaire, V. Farina, A. K. Steib, R. Blanc, P. Knochel, J. [26] S. Durand, G. Jugie, J.-P. Laurent, Transition Met. Chem. 1982, 7, 310-312.
Org. Chem. 2016, 81, 2804-2816; b) S. Lemaire, I. N. Houpis, T. Xiao, J. [27] P. Zhong, M.-P. Guo, Synth. Commun. 2001, 31, 1507-1510.
Li, E. Digard, C. Gozlan, R. Liu, A. Gavryushin, C. Diene, Y. Wang, V.
Farina, P. Knochel, Org. Lett. 2012, 14, 1480-1483; c) D. Mukherjee, S.
K. Sarkar, U. S. Chowdhury, S. C. Taneja, Tetrahedron Lett. 2007, 48,
663-667.
[5] I. Cobo, M. I. Matheu, S. Castillon, O. Boutureira, B. G. Davis, Org. Lett.
2012, 14, 1728-1731.
[6] S. Dharuman, Y. D. Vankar, Org. Lett. 2014, 16, 1172-1175.
[7] A. Shamim, S. N. Vasconcelos, B. Ali, L. S. Madureira, J. Zukerman-
Schpector, H. A. Stefani, Tetrahedron Lett. 2015, 56, 5836-5842.
[8] R. A. A. AL-Shuaeeb, D. Montoir, M. Alami, S. Messaoudi, J. Org. Chem.
2017, 82, 6720-6728.
[9] a) J.-B. Peng, F.-P. Wu, X.-F. Wu, Chem. Rev. 2019, 119, 4, 2090-2127; b)
B. Gabriele, R. Mancuso, G. Salerno, Eur. J. Org. Chem. 2012, 6825-
6839; c) Q. Liu, H. Zhang, A. Lei, Angew. Chem. Int. Ed. 2011, 50, 10788-
10799; d) X.-F. Wu, H. Neumann, M. Beller, Chem. Soc. Rev. 2011, 40,
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 1:
COMMUNICATION
Text for Table of Contents Mariana P. Darbem,[a] Henrique A.
Esteves,[a] Isadora M. de Oliveira,[b]
Daniel C. Pimenta,[c] Hélio A. Stefani[a]*
Accepted Manuscript
Page No. – Page No.
Layout 2:
COMMUNICATION
Author(s), Corresponding Author(s)*
Title