Z. Gong et al. / Tetrahedron 70 (2014) 1827e1835
1831
precipitate was removed by filtration, and filtrate was then con-
centrated under reduced pressure. The residue was purified by
column chromatography on silica gel (petroleum ether/EtOAc¼1:1).
(dd, J¼5.7, 11.4 Hz, 1H, eCH2OH), 3.88 (dd, J¼4.8, 11.1 Hz, 1H,
eCH2OH), 4.35 (m, 2H, eSCH2ePh), 4.56e4.64 (m, 1H,
eSCH2CHN]), 7.28e7.38 (m, 5H, ePh); 13C NMR (75 MHz, CDCl3)
d
(ppm) 36.26 (eSCH2CHN]), 37.06 (eSCH2ePh), 64.09 (eCH2OH),
4.2.3.1. (R)-2-((Pyridin-2-ylmethyl)thio)-4-methyloxycarbonyl-
4,5-dihydro-1,3-thiazole (5). Compound 5 was obtained 86% yield
78.33 (eSCH2CHN]), 127.48 (ePh), 128.52 (ePh), 128.89 (ePh),
136.43 (ePh). MS (ESI): m/z 240.1 [MþHþ]. Elemental analysis
calculated for C11H13NOS2: C, 55.20; H, 5.47; N, 5.85. Found: C,
55.26, H, 5.44, N, 5.88.
20
after purification by column chromatography on silica gel, [a]
D
þ27 (c 1.3, CHCl3); 1H NMR (300 MHz, CDCl3)
d (ppm)
3.60e3.74 (m, 2H, eSCH2CHN]), 3.80 (s, 3H, eOCH3), 4.55 (q,
2H, J¼15 Hz, eSCH2epyridine), 5.08 (t, J¼7.5 Hz, 1H, ]NCHe),
7.17e7.21 (m, 1H, epyridine), 7.46e7.49 (m, 1H, epyridine),
7.62e7.68 (m, 1H, epyridine), 8.54e8.56 (m, 1H, epyridine); 13C
4.2.4.4. (R)-2-((Pyridin-2-ylmethyl)thio)-4-hydroxymethyl-4,5-
dihydro-1,3-thiazole (6d). Compound 6d was obtained as light
yellow solid, 88% yield after purification by column chromatogra-
NMR (75 MHz, CDCl3)
(eSCH2CHN]), 52.69 (eOCH3), 77.05 (eSCH2CHN]), 122.35
(epyridine), 123.55 (epyridine), 136.67 (epyridine),
d
(ppm) 37.58 (eSCH2epyridine), 38.82
phy on silica gel (CH3OH/CH2Cl2¼1:20), mp¼60 ꢁC, [
a
]
20 þ62 (c 2.0,
D
CHCl3); 1H NMR (300 MHz, CDCl3)
d
(ppm) 3.31 (dd, J¼7.5, 10.8 Hz,
1H, eSCH2CHN]), 3.45 (dd, J¼8.4, 10.8 Hz, 1H, eSCH2CHN]), 3.62
(dd, J¼5.4, 11.1 Hz, 1H, eCH2OH), 3.86 (dd, J¼4.5, 11.1 Hz, 1H,
eCH2OH), 4.32 (d, J¼13.8 Hz, 1H, eSCH2epyridine), 4.65 (d,
J¼13.8 Hz, 1H, eSCH2epyridine), 4.59e4.68 (m, 1H, eSCH2CHN]),
7.16e7.20 (m, 1H, epyridine), 7.35e7.38 (m, 1H, epyridine),
7.62e7.67 (m, 1H, epyridine), 8.51e8.54 (m, 1H, epyridine); 13C
149.44 (epyridine), 156.62 (epyridine), 168.63 (]NCHe),
170.95 (eC]O). MS (ESI): m/z 269.2 [MþHþ]. Elemental anal-
ysis calculated for C11H12N2O2S2: C, 49.23; H, 4.51; N, 10.44.
Found: C, 49.20, H, 4.50, N, 10.48.
4.2.4. General procedure for preparation of (R)-2-substituted thio-4-
hydroxymethyl-4,5-dihydro-1,3-thiazoles (6ae6d). To a solution of 3
or 5 (5.0 mmol) in methanol (15 mL), NaBH4 (0.57 g, 15.0 mmol)
was added. The solution was then stirred at room temperature for
0.5 h before water was added to quench the excessive NaBH4. The
mixture was then extracted twice with CH2Cl2. The combined or-
ganic phase was washed twice with saturated brine, dried over
anhydrous Na2SO4, and concentrated under reduced pressure. The
crude product was purified by column chromatography on silica gel
to give the alcohol 6ae6d.
NMR (75 MHz, CDCl3) d (ppm) 36.72 (eSCH2epyridine), 38.46
(eSCH2CHN]), 64.36 (eCH2OH), 77.15 (eSCH2CHN]), 122.45
(epyridine), 123.31 (epyridine), 136.91 (epyridine), 149.43
(epyridine), 157.07 (epyridine), 165.95 (]NCHe). HRMS (ESI) m/z
calcd for C10H13N2OS2 [MþHþ]: 241.0464, found 241.0463.
4.2.5. General procedure for preparation of (7ae7d). To a solution of
6 (3 mmol) in dry CHCl3 (10 mL), triethylamine (0.83 mL, 6 mmol)
and p-toluenesulfonyl chloride (0.86 g, 4.5 mmol) were added at
0 ꢁC. The reaction mixture was stirred at room temperature for 60 h.
Then the reaction was quenched by addition of 5% sodium bi-
carbonate solution and extracted with CHCl3 (20 mLꢂ3). The
combined organic phase was washed with brine and dried over
anhydrous Na2SO4. The solvent was then removed under reduced
pressure. The crude product was purified by column chromatog-
raphy on silica gel.
4.2.4.1. (R)-2-Ethylthio-4-hydroxymethyl-4,5-dihydro-1,3-
thiazole (6a). Compound 6a was obtained as colorless oil, 99% yield
after purification by column chromatography on silica gel (petro-
20
leum ether/EtOAc¼1:2), [
a]
þ46.3 (c 2.8, CHCl3); 1H NMR
D
(300 MHz, CDCl3)
d
(ppm) 1.36 (t, J¼7.2 Hz, 3H, eCH3), 2.06 (br, 1H,
eOH), 3.07e3.14 (m, 2H, eSCH2CH3), 3.27 (dd, J¼8.7, 10.8 Hz, 1H,
eSCH2CHN]), 3.42 (dd, J¼8.1, 10.8 Hz, 1H, eSCH2CHN]), 3.69 (dd,
J¼5.7, 11.1 Hz, 1H, eCH2OH), 3.88 (dd, J¼4.8, 11.1 Hz, 1H, eCH2OH),
4.2.5.1. (R)-(2-(Ethylthio)-4,5-dihydrothiazol-4-yl)methyl-4-
methylbenzenesulfonate (7a). Compound 7a was obtained as light
yellow oil, 82% yield after purification by column chromatography
on silica gel (petroleum ether/EtOAc¼5:1); 1H NMR (300 MHz,
4.54e4.63 (m,1H, eSCH2CHN]); 13C NMR (75 MHz, CDCl3)
d (ppm)
14.39 (eCH3), 27.13 (eSCH2CH3), 35.84 (eSCH2CHN]), 63.76
(eCH2OH), 78.39 (eSCH2CHN]). MS (ESI): m/z 179.0 [MþHþ]. El-
emental analysis calculated for C6H11NOS2: C, 40.65; H, 6.25; N,
7.90. Found: C, 40.67, H, 6.23, N, 7.93.
CDCl3)
d
(ppm) 1.31 (t, J¼7.5 Hz, 3H, eSCH2CH3), 2.46 (s, 3H,
ePhCH3), 3.04 (q, J¼7.5 Hz, 2H, eSCH2CH3), 3.27 (dd, J¼6.3, 11.1 Hz,
1H, eSCH2CHN]), 3.46 (dd, J¼8.1, 11.1 Hz, 1H, eSCH2CHN]), 3.99
(dd, J¼8.1, 9.9 Hz, 1H, eCH2OSO2e), 4.21 (dd, J¼4.2, 9.9 Hz, 1H,
eCH2OSO2e), 4.64e4.73 (m, 1H, eSCH2CHN]), 7.36 (d, J¼8.1 Hz,
2H, ePh), 7.80 (d, J¼8.1 Hz, 2H, ePh).
4.2.4.2. (R)-2-Butylthio-4-hydroxymethyl-4,5-dihydro-1,3-
thiazole (6b). Compound 6b was obtained as colorless oil, 99% yield
after purification by column chromatography on silica gel (petro-
20
leum ether/EtOAc¼1:2), [
a
]
D
þ28.4 (c 3.9, CHCl3); 1H NMR
4.2.5.2. (R)-(2-(Butylthio)-4,5-dihydrothiazol-4-yl)methyl-4-
methylbenzenesulfonate (7b). Compound 7b was obtained as light
yellow oil, 80% yield after purification by column chromatography on
silica gel (petroleum ether/EtOAc¼5:1); 1H NMR (300 MHz, CDCl3)
(300 MHz, CDCl3)
d
(ppm) 0.93 (t, J¼7.5 Hz, 3H, eCH3),1.37e1.49 (m,
2H, eCH2e), 1.63e1.73 (m, 2H, eCH2e), 1.94 (br, 1H, eOH), 3.12 (t,
J¼7.5 Hz, 2H, eSCH2e), 3.27 (dd, J¼8.7, 10.8 Hz, 1H, eSCH2CHN]),
3.42 (dd, J¼8.4, 10.8 Hz, 1H, eSCH2CHN]), 3.69 (dd, J¼5.7, 11.1 Hz,
1H, eCH2OH), 3.89 (dd, J¼4.8, 11.1 Hz, 1H, eCH2OH), 4.54e4.63 (m,
d
(ppm) 0.91 (t, J¼7.2 Hz, 3H, eCH3), 1.33e1.43 (m, 2H, eCH2e),
1.56e1.68 (m, 2H, eCH2e), 2.46 (s, 3H, ePhCH3), 3.04 (t, J¼7.2 Hz, 2H,
eSCH2CH3), 3.27 (dd, J¼6.3,11.1 Hz,1H,eSCH2CHN]), 3.46(dd, J¼8.1,
11.1 Hz, 1H, eSCH2CHN]), 3.98 (dd, J¼8.4, 9.6 Hz, 1H, eCH2OSO2e),
4.21 (dd, J¼4.2, 9.9 Hz, 1H, eCH2OSO2e), 4.66e4.72 (m, 1H,
eSCH2CHN]), 7.36 (d, J¼8.1 Hz, 2H, ePh), 7.80 (d, J¼8.1 Hz, 2H, ePh).
1H, eSCH2CHN]); 13C NMR (75 MHz, CDCl3)
d (ppm) 13.47 (eCH3),
21.76 (eCH2e), 31.24 (eCH2e), 32.59 (eSCH2e), 35.90
(eSCH2CHN]), 64.04 (eCH2OH), 78.46 (eSCH2CHN]). MS (ESI):
m/z 206.2 [MþHþ]. Elemental analysis calculated for C8H15NOS2: C,
46.79; H, 7.36; N, 6.82. Found: C, 46.75, H, 7.38, N, 6.86.
4.2.5.3. (R)-(2-(Benzylthio)-4,5-dihydrothiazol-4-yl)methyl-4-
methylbenzenesulfonate (7c). Compound 7c was obtained as yellow
oil, 84% yield after purification by column chromatography on silica
gel (petroleum ether/EtOAc¼5:1); 1H NMR (300 MHz, CDCl3)
4.2.4.3. (R)-2-Benzylthio-4-hydroxymethyl-4,5-dihydro-1,3-
thiazole (6c). Compound 6c was obtained as light yellow oil, 98%
yield after purification by column chromatography on silica gel
20
(petroleum ether/EtOAc¼1:2), [
a
]
þ21.6 (c 2.2, CHCl3); 1H NMR
d
(ppm) 2.45 (s, 3H, ePhCH3), 3.28 (dd, J¼6.3, 11.1 Hz, 1H,
D
(300 MHz, CDCl3)
d
(ppm) 1.86 (s, 1H, eOH), 3.29 (dd, J¼8.4, 10.5 Hz,
eSCH2CHN]), 3.47 (dd, J¼8.1, 11.1 Hz, 1H, eSCH2CHN]), 3.98 (dd,
J¼8.1, 9.9 Hz, 1H, eCH2OSO2e), 4.20 (dd, J¼4.2, 9.9 Hz, 1H,
1H, eSCH2CHN]), 3.44 (dd, J¼8.1, 10.5 Hz, 1H, eSCH2CHN]), 3.65