Single Enantiomer Epoxides by Bromomandelation of Prochiral Alkenes Supporting Information Douglass F. Taber,* and Jiang-Lin Liang Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716 Email:
[email protected] Table of Contents S-3 General Experimental Section
S-27 1H NMR for 3d
S-4 Synthetic procedures and
S-28 13C NMR for 3d
characterization for all new compounds
S-29 1H NMR for 2e
S-13 1H NMR for 2a
S-30 13C NMR for 2e
S-14 13C NMR for 2a
S-31 1H NMR for 3e
S-15 1H NMR for 3a
S-32 13C NMR for 3e
S-16 13C NMR for 3a
S-33 1H NMR for 4a
S-17 1H NMR for 2b
S-34 13C NMR for 4a
S-18 13C NMR for 2b
S-35 1H NMR for 4c
S-29 1H NMR for 3b
S-36 13C NMR for 4c
S-20 13C NMR for 3b
S-37 1H NMR for 9
S-21 1H NMR for 2c
S-38 13C NMR for 9
S-22 13C NMR for 2c
S-39 1H NMR for 10
S-23 1H NMR for 3c
S-40 13C NMR for 10
S-24 13C NMR for 3c
S-41 1H NMR for 6a
S-25 1H NMR for 2d
S-42 13C NMR for 6a
S-26 13C NMR for 2d
S-43 1H NMR for 7a
S- 1
S-44 13C NMR for 7a
S-67 1H NMR for 8
S-45 1H NMR for 6b+7b
S-68 13C NMR for 8
S-46 13C NMR for 6b+7b
S-69 1H NMR for 12
S-47 1H NMR for 6b
S-70 13C NMR for 12
S-48 13C NMR for 6b
S-71 1H NMR for 14
S-49 1H NMR for 7b
S-72 13C NMR for 14
S-50 13C NMR for 7b
S-73 HPLC trace of 4a prepared from 3a
S-51 1H NMR for 6c
S-74 HPLC trace of 4a prepared from 2a
S-52 13C NMR for 6c
S-75 HPLC trace of racemic 12
S-53 1H NMR for 7c
S-76 HPLC trace of 12
S-54 13C NMR for 7c
S-77 X-ray crystal structure of 11
S-55 1H NMR for 6d S-56 13C NMR for 6d S-57 1H NMR for 7d S-58 13C NMR for 7d S-59 1H NMR for 6e S-60 13C NMR for 6e S-61 1H NMR for 7e S-62 13C NMR for 7e S-63 1H NMR for 11 S-64 13C NMR for 11 S-65 1H NMR for 13 S-66 13C NMR for 13
S- 2
General. 1H NMR and 13C NMR were obtained as solutions in deuterochloroform (CDCl3) at 400 MHz and 100 MHz, respectively, with tetramethylsilane = 0.00 as an internal standard. 13C multiplicities were determined with the aid of a JVERT pulse sequence, differentiating the signals for methyl and methine carbons as “d”, from methylene and quaternary carbons as “u”. The infrared (IR) spectra were determined as neat oils. Mass spectra (MS) were obtained by electron impact. Rf values indicated refer to thin layer chromatography (TLC) on 2.5 x 10 cm, 250 µm analytical plates coated with silica gel GF, and developed in the solvent system indicated. Column chromatography was carried out with Merck 35-60 micron grade silica gel or Aldrich TLC mesh silica gel. Solvents are referred as volume/volume mixture. All glassware was dried in the oven. Et2O and THF were distilled from sodium metal/benzophenone under dry nitrogen. Dichloromethane (CH2Cl2) were distilled from calcium hydride under dry nitrogen. MTBE is methyl t-butyl ether. Et2O is diethyl ether. All reaction mixtures were stirred magnetically under a nitrogen atmosphere, unless otherwise noted. Optical rotations were determined as solutions in chloroform, reported in [α]D (c [g/100 mL], CHCl3).
S- 3
From 233 mg of 1c, method A: Ester 3c (colorless oil, 116 mg, 25%), TLC Rf = 0.49 (25% Et2O/petroleum ether); [α]20D +31.7 (c = 1.15, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 1.22-1.48 (m, 12H), 1.71 (m, 2H), 1.86 (m, 2H), 3.28 (m, 2H), 3.40 (m, 3H), 5.07 (m, 1H), 5.20 (d, J = 6 Hz, 1H), 7.35 (m, 3H), 7.45 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ u 173.3, 138.1, 34.2, 33.1, 32.9, 32.5, 29.4, 29.4, 29.3, 28.8, 28.3, 25.1; d 128.7, 128.7, 126.7, 74.8, 73.1; IR (cm-1) 3451, 1737, 1454, 1181, 1067, 700; HRMS calcd for C19H28Br2NaO3 (M+Na): 385.0303, found: 385.0327. Ester 2c (colorless oil, 125 mg, 27%), TLC Rf = 0.43 (25% Et2O/petroleum ether); [α]20D +41.1 (c = 0.55, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 0.79-1.33 (m, 10H), 1.48 (m, 2H), 1.53 (m, 2H), 1.82 (m, 2H), 3.43 (m, 4H), 3.50 (dd, J = 4.4 and 10.8 Hz, 1H), 5.03 (m, 1H), 5.21 (d, J = 6 Hz, 1H), 7.34 (m, 3H), 7.42 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ u 173.4, 138.4, 34.2, 33.6, 32.9, 32.5, 29.3, 29.2, 29.1, 28.8, 28.2, 24.5; d 128.7, 126.7, 74.7, 73.0; IR (cm-1) 3461, 1738, 1455, 1181, 1067, 700; HRMS calcd for C19H28Br2NaO3 (M+Na): 385.0303, found: 385.0317. The primary esters (1:1) were also eluted. TLC Rf = 0.38 (25% Et2O/petroleum ether). From 260 mg of 1d, method A: Ester 3d (colorless oil, 123 mg, 25%), TLC Rf = 0.36 (25% MTBE/petroleum ether); [α]20D +24.6 (c = 1.1, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 1.22-1.41 (m, 12H), 1.58-1.76 (m, 4H), 3.26 (m, 2H), 3.39 (d, J = 6 Hz, 1H), 3.47 (t, J = 6.8 Hz, 2H), 4.51 (s, 2H), 5.06 (m, 1H), 5.20 (d, J = 6 Hz, 1H), 7.35 (m, 3H), 7.45 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ u 173.3, 138.8, 138.1, 73.0, 70.6, 33.2, 32.5, 29.9, 29.5, 29.4, 29.3, 26.3, 25.1; d 128.7, 128.7, 128.5, 127.8, 127.6, 126.7, 74.8, 73.1; IR (cm-1) 3446, 1738, 1454, 1179, 1097, 733; HRMS calcd for C26H35BrNaO4 (M+Na): 513.1616, found: 513.1638. S- 4
Ester 2d (colorless oil, 128 mg, 26%), TLC Rf = 0.31 (25% MTBE/petroleum ether); [α]20D +43.3 (c = 0.9, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 0.79-1.38 (m, 12H), 1.461.68 (m, 4H), 3.45 (m, 5H), 4.51 (s, 2H), 5.04 (m, 1H), 5.20 (d, J = 5.6 Hz, 1H), 7.35 (m, 3H), 7.45 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ u 173.5, 138.8, 138.4, 73.0, 70.6, 33.6, 32.6, 29.9, 29.5, 29.4, 29.3, 29.1, 26.3, 24.5; d 128.7, 128.5, 127.8, 127.6, 126.7, 74.7, 73.0; IR (cm-1) 3445, 1738, 1454, 1180, 1098, 734; HRMS calcd for C26H35BrNaO4 (M+Na): 513.1616, found: 513.1630. The primary esters (1:1) were also eluted. TLC Rf = 0.25 (25% MTBE/petroleum ether). From 112 mg of 1e, method A: Ester 3e (colorless oil, 89 mg, 26%), TLC Rf = 0.53 (30% MTBE/petroleum ether); [α]20D +37.4 (c = 1.15, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 0.89 (t, J = 6.4 Hz, 3H), 1.28 (m, 8H), 1.70 (m, 2H), 3.28 (m, 2H), 3.39 (d, J = 6 Hz, 1H), 5.07 (m, 1H), 5.20 (d, J = 6 Hz, 1H), 7.35 (m, 3H), 7.45 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ u 173.3, 138.1, 33.2, 32.6, 31.7, 29.0, 25.1, 22.7; d 128.7, 128.7, 126.7, 74.8, 73.1, 14.2; IR (cm-1) 3451, 1736, 1455, 1180, 1067, 700; HRMS calcd for C16H27BrNO3 (M+NH4): 360.1174, found: 360.1159. Ester 2e (white solid, mp 60-61°C, 93 mg, 27%); TLC Rf = 0.48 (30% MTBE/petroleum ether); [α]20D +64.0 (c = 1.35, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 0.82 (t, J = 6.8 Hz, 3H), 0.91 (m, 2H), 1.01-1.20 (m, 6H), 1.54 (m, 2H), 3.45 (m, 2H), 3.50 (dd, J = 4.4 and 11.2 Hz, 1H), 5.04 (m, 1H), 5.20 (d, J = 5.6 Hz, 1H), 7.35 (m, 3H), 7.44 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ u 173.5, 138.4, 33.6, 32.6, 31.5, 28.8, 24.5, 22.5; d 128.7, 126.7, 74.7, 73.0, 14.1; IR (cm-1) 3446, 1732, 1455, 1185, 1068, 736; HRMS calcd for C16H27BrNO3 (M+NH4): 360.1174, found: 360.1158. S- 5
The primary esters were (1:1) also eluted. TLC Rf = 0.43 (30% MTBE/petroleum ether). Epoxide 4c: (method A, colorless oil, 37 mg, 86%), from 80 mg of 3c, TLC Rf = 0.76 (25% Et2O/petroleum ether); [α]20D -5.7 (c = 1.75, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 1.25-1.58 (m, 14H), 1.85 (m, 2H), 2.47 (dd, J = 2.8 and 5.2 Hz, 1H), 2.75 (dd, J = 5.2 and 8.4 Hz, 1H), 2.91 (m, 1H), 3.41 (t, J = 6.8 Hz, 2H); 13C NMR (CDCl3, 100 MHz): δ u 47.3, 34.2, 32.9, 32.6, 29.5, 29.5, 29.4, 28.8, 26.1; d 52.5; IR (cm-1) 1464, 1410, 1259, 1130, 915, 835, 723; HRMS calcd for C11H25BrNO (M+NH4): 266.1120, found: 266.1120. Epoxide 4d: (method A, colorless oil, 47 mg, 87%), from 96 mg of 3d, TLC Rf = 0.65 (25% MTBE/petroleum ether); [α]20D -4.2 (c = 2.25, CHCl3. Data identical with those reported: Chow, S.; Kitching, W. Tetrahedron Asymmetry 2002, 13, 779. [α]20D -4.2 (c = 1.23, CHCl3.). Epoxide 4e: (method B, colorless oil, 240 mg, 94%), from 680 mg of 3e, TLC Rf = 0.71 (25% MTBE/petroleum ether); [α]20D -8.5 (c = 1.5, CHCl3). Data identical with those reported: Paddon-Jones, G. C.; McErlean, C. S. P.; Hayes, P.; Moore, C. J.; Konig, W. A.; Kitching, W. J. Org. Chem. 2001, 66, 7487. [α]20D -8.9 (c = 1.8, CHCl3.). From 136 mg of 5b: Ester 6b and 7b (colorless oil, 503 mg,. 84% yield of 1:1 mixture). These two diastereomers could not be separated by silica gel chromatography. Low temperature differential crystallization The mixture of 6b and 7b (330 mg, 1:1 mixture) was dissolved in 20% CH2Cl2/ petroleum ether (10 mL), and cooled to -78°C. The solution was stirred for 0.5 h, and a white solid was precipitated. The suspension was poured into a filter funnel pre-cooled by S- 6
dry-ice/ petroleum ether solution, and the white solid was collected and re-dissolved in 20% CH2Cl2/ petroleum ether (4 mL). This solution was cooled to -78°C, and stirred for 0.5 h. The suspension was again filtered through a cold funnel and the white solid collected was taken in ether, dried (Na2SO4) and concentrated to give 6b (100 mg, dr = 19:1) as a colorless oil. All the CH2Cl2/ petroleum ether filtrate was combined and concentrated at high vacuum to give 230 mg of an oil. This oil was dissolved in 30% Et2O/petroleum ether (5 mL), and cooled to-78°C. The solution was stirred for 0.5 h, and again filtered through a cold funnel. The white solid was collected and re-dissolved in 30% Et2O/petroleum ether (5 mL). The solution was cooled to -78°C and stirred for 0.5 h. The suspension was again filtered through a cold funnel, affording 7b as a white solid (80 mg, dr = 9:1). Ester 6b. (dr = 19:1); TLC Rf = 0.48 (30% Et2O/petroleum ether); [α]20D +240.9 (c = 1.05, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 1.73 (m, 2H), 1.93 (m, 3H), 2.35 (m, 1H), 3.44 (d, J = 6 Hz, 1H), 3.91 (m, 1H), 5.14 (d, J = 5.6 Hz, 1H), 5.32 (m, 1H), 7.37 (m, 5H); 13C NMR (CDCl3, 100 MHz): δ u 173.0, 138.2, 34.2, 29.1, 21.5; d 128.8, 128.7, 126.5, 83.7, 72.9, 52.3; IR (cm-1) 3436, 1739, 1454, 1181, 1067, 732; HRMS calcd for C13H19BrNO3 (M+NH4): 316.0548, found: 316.0536. Ester 7b white solid, mp 70-71°C TLC Rf = 0.48 (30% Et2O/petroleum ether); [α]20D +37.8 (c = 0.8, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 1.41 (m, 1H), 1.61 (m, 1H), 1.83 (m, 1H), 2.03 (m, 1H), 2.21 (m, 2H), 3.50 (d, J = 6 Hz, 1H), 4.23 (m, 1H), 5.12 (d, J = 6.0 Hz, 1H), 5.31 (m, 1H), 7.33 (m, 5H); 13C NMR (CDCl3, 100 MHz): δ u 172.9, 138.2, 34.5, 29.2, 21.5; d 128.7, 128.7, 126.5, 83.9, 72.9, 52.2; IR (cm-1) 3443, 1738, 1455, 1181, 1067, 732; HRMS calcd for C13H15O3 (M-Br): 219.1021, found: 219.1026. S- 7
From 192 mg of 5c: Ester 7c (white solid, mp 55-56°C, 286 mg, 44%); TLC Rf = 0.52 (30% Et2O/petroleum ether); [α]20D +35.5 (c = 1.05, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 1.38-1.82 (m, 8H), 2.06 (m, 1H), 2.24 (m, 1H), 3.48 (d, J = 5.6 Hz, 1H), 4.15 (dt, J = 4.0 and 8.0 Hz, 1H), 5.18 (m, 2H), 7.32 (m, 3H), 7.39 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ u 172.8, 138.3, 34.9, 30.5, 27.3, 24.5, 21.8; d 128.7, 128.6, 126.7, 82.1, 73.0, 55.8; IR (cm-1) 3469, 1732, 1456, 1181, 1067, 732; HRMS calcd for C15H19O3 (MBr): 247.1334, found: 247.1334. Ester 6c (white solid, mp 90-91°C, 288 mg, 44%); TLC Rf = 0.42 (30% Et2O/petroleum ether); [α]20D +111.4 (c = 0.7, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 1.41-1.83 (m, 7H), 2.01 (m, 3H), 3.43 (d, J = 6 Hz, 1H), 3.98 (dt, J = 3.6 and 7.6 Hz, 1H), 5.16 (m, 2H), 7.31 (m, 3H), 7.39 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ u 172.8, 138.1, 34.5, 30.9, 27.4, 24.5, 22.1; d 128.7, 126.9, 81.9, 73.3, 55.2; IR (cm-1) 3453, 1735, 1452, 1207, 1068, 738; HRMS calcd for C15H19O3 (M-Br): 247.1334, found: 247.1336. From 220 mg of 5d: Ester 7d (colorless oil, 285 mg, 42%); TLC Rf = 0.63 (30% Et2O/petroleum ether); [α]20D +15.0 (c = 1.4, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 1.51 (m, 9H), 1.85 (m, 1H), 2.06 (m, 1H), 2.25 (m, 1H), 3.48 (d, J = 5.6 Hz, 1H), 4.27 (m, 1H), 5.21 (d, J = 5.6 Hz, 1H), 5.28 (dt, J = 2.0 and 8.0 Hz, 1H), 7.32 (m, 3H), 7.38 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ u 172.9, 138.3, 31.8, 31.6, 25.5, 25.4, 25.3, 24.9; d 128.7, 128.6, 126.8, 81.5, 73.0, 56.7; IR (cm-1) 3472, 1732, 1452, 1183, 1067, 734; HRMS calcd for C16H21O3 (M-Br): 261.1491, found: 261.1481. Ester 6d (white solid, mp 87-88°C, 310 mg, 45%); TLC Rf = 0.45 (30% Et2O/petroleum ether); [α]20D +107.5 (c = 0.8, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 1.31-1.91 (m, 10H), 1.96 (m, 1H), 2.21 (m, 1H), 3.43 (d, J = 6 Hz, 1H), 4.14 (m, 1H), S- 8
5.15 (d, J = 6 Hz, 1H), 5.23 (dt, J = 2.0 and 7.6 Hz, 1H), 7.32 (m, 3H), 7.39 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ u 172.8, 138.0, 32.3, 31.4, 26.1, 25.4, 25.3, 24.6; d 128.6, 128.6, 127.0, 81.6, 73.4, 56.3; IR (cm-1) 3403, 1722, 1463, 1182, 938, 730; HRMS calcd for C16H21O3 (M-Br): 261.1491, found: 261.1484. From 168 mg of 5e: Ester 6e (white solid, mp 93-94°C, 170 mg, 27%); TLC Rf = 0.32 (2% MTBE/CH2Cl2); [α]20D +12.0 (c = 0.3, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 1.39 (m, 1H), 1.98 (m, 2H), 2.23 (m, 1H), 3.29 (m, 1H), 3.42 (d, J = 5.6 Hz, 1H), 3.52 (m, 1H), 4.06 (dd, J = 4.0 and 8.6 Hz, 1H), 5.22 (d, J = 5.6 Hz, 1H), 6.01 (d, J = 3.2Hz, 1H), 7.36 (m, 5H); 13C NMR (CDCl3, 100 MHz): δ u 172.1, 138.1, 63.2, 28.4, 21.5; d 128.9, 128.9, 126.9, 95.1, 73.0, 46.4; IR (cm-1) 3452, 1747, 1176, 1064, 738; HRMS calcd for C13H15O4 (M-Br): 235.0970, found: 235.0968.
Ester 7e (colorless oil, slightly decomposed on chromatography, 180 mg, 28%).; TLC Rf = 0.27 (2% MTBE/CH2Cl2); [α]20D +98.5 (c = 0.3, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 1.53 (m, 1H), 1.89 (m, 1H), 2.03 (m, 2H), 3.38 (d, J = 5.2Hz, 1H), 3.76 (m, 2H), 3.93 (m, 1H), 5.24 (d, J = 5.2 Hz, 1H), 5.95 (d, J = 4.0Hz, 1H), 7.36 (m, 5H); 13C NMR (CDCl3, 100 MHz): δ u 172.1, 137.9, 64.1, 28.9, 22.1; d 128.9, 128.8, 126.8, 95.8, 73.0, 46.1; IR (cm-1) 3450, 1748, 1177, 1065, 700; HRMS calcd for C13H15O4 (M-Br): 235.0970, found: 235.0961.
Ketone 11. To the mixture of 7a (200 mg, 0.64 mmol) in CH2Cl2 (4 mL) was added Dess-Martin reagent (407 mg, 0.96 mmol). After stirring for 2 h, the suspension was filtered and the filtrate was concentrated. The residue was chromatographed to afford 11 S- 9
(white solid, mp 78-79°C, 199 mg, 98%); TLC Rf = 0.48 (5% Et2O/petroleum ether); [α]20D -41.7 (c = 1.9, CHCl3); The absolute configuration of 11 was established by X-ray analysis. 1H NMR (CDCl3, 400 MHz): δ 1.40-1.65 (m, 3H), 1.73-2.04 (m, 3H), 2.39 (m, 1H), 2.44 (m, 1H), 4.06 (m, 1H), 5.22 (dt, J = 4.4 and 9.4 Hz, 1H), 7.52 (m, 2H), 7.67 (m, 1H), 8.06 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ u 186.5, 163.2, 132.4, 36.0, 31.5, 25.7, 23.5; d 135.1, 130.3, 129.0, 78.3, 52.1; IR (cm-1) 1728, 1688, 1595, 1449, 1300, 1198, 1006, 986; HRMS calcd for C14H16BrO3 (M+H): 311.0283, found: 311.0268.
O
O Ph
O Br
11
O
Ph
O SPh
O 13
Sulfide 13: A mixture of 11 (100 mg, 0.32 mmol), Na2CO3 (136 mg, 1.28 mmol) and benzenethiol (131 µL, 1.28 mmol) in dry DMF (1 mL) was heated to 85°C for 14 h. The cooled mixture was partitioned between water and Et2O. The combined organic extract was dried (Na2SO4) and concentrated. The residue was chromatographed to give the sulfide 13 (colorless oil, 73 mg, 0.21 mmol, 67%), TLC Rf = 0.42 (5% Et2O/petroleum ether); [α]20D -113.3 (c = 0.4, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 1.38-1.95 (m, 7H), 2.13 (m, 1H), 3.40 (m, 1H), 5.45 (m, 1H), 7.27 (m, 3H), 7.46 (m, 2H), 7.53 (m, 2H), 7.67 (m, 1H), 8.12 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ u 186.8, 163.8, 134.7, 132.6, 30.0, 28.7, 24.8, 20.7; d 135.0, 132.7, 130.4, 129.2, 129.0, 127.6, 74.1, 51.0; IR (cm-1) 1738, 1689, 1597, 1450, 1203, 1175, 1002, 986, 700; HRMS calcd for C20H20BrO3S (M): 340.1133, found: 340.1130.
S- 10
O
O Ph
O Br
O
11
Ph
O N3
O
12
Azide 12: To a mixture of 11 (100 mg, 0.32 mmol) and NaN3 (208 mg, 3.2 mmol) in dry DMF (1 mL) was added one drop of 15-crown-5. The mixture was heated to 95°C for 14 h. The cooled mixture was partitioned between water and Et2O. The combined organic extract was dried (Na2SO4) and concentrated. The residue was chromatographed to give the azide 12 (colorless oil, 51 mg, 0.19 mmol, 58%), TLC Rf = 0.31 (5% Et2O/petroleum ether); [α]20D +24.4 (c = 1.15, CHCl3); The enantiomeric excess was measured to be > 99.0% by HPLC using a CHIRALPAK IA column, eluting at 1 mL/min with 99.4/0.6 hexane/isopropanol, monitored at 254 nm, retention time: 21.05 min (1R,2S-enantiomer), 22.83 min (1S,2R-enantiomer). 1H NMR (CDCl3, 400 MHz): δ 1.47 (m, 2H), 1.63-1.84 (m, 4H), 1.91 (m, 1H), 2.06 (m, 1H), 3.80 (m, 1H), 5.32 (m, 1H), 7.53 (m, 2H), 7.67 (m, 1H), 8.03 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ u 186.3, 163.5, 132.4, 27.9, 27.4, 22.0, 21.4; d 135.1, 130.2, 129.1, 74.6, 60.5; IR (cm-1) 2103, 1738, 1690, 1596, 1450, 1268, 1197, 1176, 990; HRMS calcd for C14H19NO3 (M+H): 291.1457, found: 291.1456. O Ph
O SPh
O 13
OH SPh
8
Cis-hydroxy Sulfide 8: To a solution of sulfide 13 (44 mg, 0.13 mmol) in methanol (1.5 mL) was added K2CO3 (72 mg, 0.52 mmol), and the mixture was stirred at r.t. for 20 min. When the reaction was complete (monitored by TLC), methanol was removed at reduced S- 11
pressure and the residue was filtered with Et2O. The combined filtrate was concentrated, and the residue was chromatographed to provide 8 (colorless oil, 23 mg, 85%), TLC Rf = 0.33 (10% Et2O/petroleum ether); [α]20D -25.2 (c = 1.15, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 1.33-1.56 (m, 3H), 1.64-1.90 (m, 5H), 2.45 (dd, J = 1.0 and 4.0 Hz, 1H), 3.35 (dt, J = 2.4 and 9.6 Hz, 1H), 3.78 (ddd, J = 2.4 Hz, 1H), 7.26 (m, 3H), 7.44 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ u 134.4, 31.9, 27.9, 25.0, 20.5; d 132.3, 129.2, 127.4, 67.3, 54.6; IR (cm-1) 3450, 1583, 1480, 1438, 1254, 1067, 993, 970, 750, 700; HRMS calcd for C12H16OS (M+): 208.0922, Found: 208.0921 (1H NMR spectrum is identical to reference: Ritter, R. H.; Cohen, T. J. Am. Chem. Soc. 1986, 108, 3718 trans methines δ 2.80, 3.33; cis methines δ 3.35, 3.78) O Ph
O N3
OH
O
N3
12
14
Cis-azido alcohol 14: To a solution of sulfide 12 (56 mg, 0.21 mmol) in methanol (2.0 mL) was added K2CO3 (138 mg, 1.0 mmol), and was stirred at r.t. for 20 min. When the reaction was complete (monitored by TLC), methanol was removed at reduced pressure and the residue was filtered with Et2O. The combined filtrate was concentrated, and the residue was chromatographed to provide 14 (colorless oil, 26 mg, 90%), TLC Rf = 0.22 (15% Et2O/petroleum ether); [α]20D +14.3 (c = 1.3, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 1.35 (m, 2H), 1.67 (m, 4H), 1.87 (m, 2H), 3.66 (m, 1H), 3.80 (m, 1H); 13C NMR (CDCl3, 100 MHz): δ u 30.8, 26.9, 22.1, 21.4; d 69.9, 63.7; IR (cm-1) 3391, 2106, 1448, 1073, 977, 914, 847; HRMS calcd for C6H11N3O (M+): 141.0902, found: 141.0897 (1H NMR spectrum is identical to reference: Ami, E.; Ohrui, H. Biosci. Biotechnol. Biochem. 1999, 63, 2150 trans methines δ 2.19, 3.39; cis methines δ 3.66, 3.80). S- 12
S- 13
S- 14
S- 15
S- 16
S- 17
S- 18
S- 19
S- 20
S- 21
S- 22
S- 23
S- 24
S- 25
S- 26
S- 27
S- 28
S- 29
S- 30
S- 31
S- 32
S- 33
S- 34
S- 35
S- 36
S- 37
S- 38
S- 39
S- 40
S- 41
S- 42
S- 43
S- 44
S- 45
S- 46
S- 47
S- 48
S- 49
S- 50
S- 51
S- 52
S- 53
S- 54
S- 55
S- 56
S- 57
S- 58
S- 59
S- 60
S- 61
S- 62
S- 63
S- 64
S- 65
S- 66
S- 67
S- 68
S- 69
S- 70
S- 71
S- 72
S- 73
S- 74
S- 75
S- 76
C10 Br
C11 C9
C2 O1
C1 C3
H6A H1A
C7 C8
C6 O2
C4 C5
O3
a
Molecular b structure of compound 11 Cc H O Br
S- 77
C12
C14 C13
