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Synlett 2006(19): 3289-3293  
DOI: 10.1055/s-2006-951552
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Lithium 1-Alkynesulfenates by the Mild Oxidation of Thiolates with a Pinacolone-Derived N-Sulfonyloxaziridine

Franck Sandrinellia, Cédric Boudoua, Caroline Caupènea, Marie-Thérèse Averbuch-Pouchotb, Stéphane Perrio*a, Patrick Metznera
a Laboratoire de Chimie Moléculaire et Thio-Organique (UMR CNRS 6507), ENSICAEN, Université de Caen-Basse Normandie, 6 Boulevard du Maréchal Juin, 14050 Caen, France
Fax: +33(23145)2877; e-Mail: perrio@ensicaen.fr;
b LEDSS (UMR CNRS 5616), Université Joseph Fourier, BP 53, 38041 Grenoble 9, France
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Publication History

Received 2 August 2006
Publication Date:
23 November 2006 (online)

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Abstract

Lithium 1-alkynethiolates, generated by a base-induced ring cleavage of 4-substituted 1,2,3-thiadiazoles, were efficiently converted into the corresponding sulfenate salts by mild oxidation using an N-sulfonyloxaziridine derived from pinacolone. In situ S-alkylation with alkyl halides led to α,β-acetylenic sulfoxides.

Key words

oxidation reaction - sulfoxide - sulfenate salt - oxaziridine - heterocycle

    References and Notes

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13

4-(1,1-Dimethylethyl)-1,2,3-thiadiazole (3a):27a R1 = t-Bu; beige powder, (89%); mp 23 °C (Lit.27a 23 °C); 1H NMR (250 MHz, CDCl3): δ = 1.51 (s, 9 H), 8.15 (s, 1 H); 13C NMR (62.9 MHz, CDCl3): δ = 30.9, 34.0, 129.3, 173.6; IR (NaCl): 2964, 2870, 1490, 1462, 1244, 964, 890 cm-1; MS (EI): m/z (%) = 142 (11) [M+], 57 (100), 43 (97), 41 (98). 4-Phenyl-1,2,3-thiadiazole (3b):27b R1 = Ph; orange solid recrystallized from n-hexane (83%); mp 76-78 °C (Lit.27b 77-78 °C); 1H NMR (250 MHz, CDCl3): δ 7.41-7.55 (m, 3 H), 8.02-8.07 (m, 2 H), 8.65 (s, 1 H); 13C NMR (62.9 MHz, CDCl3): δ = 127.8, 129.6, 129.9, 130.4, 131.2, 163.3; IR (NaCl): 3072, 1462, 1442, 1220, 766, 692 cm-1; MS (EI): m/z (%) = 162 (6) [M+], 134 (100), 90 (18).

14

4-Methyl-1,2,3-thiadiazole (3c):27c R1 = Me; white solid which melted rapidly at r.t. (43%); 1H NMR (250 MHz, CDCl3): δ = 2.81 (s, 3 H), 8.17 (s, 1 H); 13C NMR (62.9 MHz, CDCl3): δ = 13.93, 132.6, 160.0; IR (NaCl): 3104, 1494, 1444, 1224 cm-1; MS (CI): m/z (%) = 101 (100) [M + H+], 71 (79).

15

5-Chloro-4-methyl-1,2,3-thiadiazole: Orange oil (8%); 1H NMR (250 MHz, CDCl3): δ = 2.7 (s, 3 H); MS (CI): m/z (%) = 135 (100) [M + H+] 35Cl, 137 (35) [M + H+] 37Cl, 71 (50).

17

N -(1,2,2-Trimethylpropylidene)benzenesulfonamide (4). To a mixture of pinacolone (9.1 mL, 73 mmol) and benzenesulfonamide (5.8 g, 36.5 mmol) in toluene (360 mL), Ti(OEt)4 (25 g, 110 mmol) was added dropwise while stirring. The reaction mixture was slowly heated to reflux (oil bath temperature at 115 °C). After refluxing for 20 h, the yellow mixture was cooled to r.t. and an aq NaOH solution (0.5 M, 350 mL) was added slowly. The white gel of titanium oxides formed was filtered through celite to give a biphasic filtrate. The organic phase was separated and the aq layer extracted with Et2O (2 × 150 mL). The combined organic extracts were washed with sat. aq NaCl solution (100 mL) and dried over MgSO4. Filtration and concen-tration under reduced pressure led to imine 4 (6.5 g, 27 mmol, 75%) as a yellowish solid. The product was used without further purification.

20

trans -3-(1,1-Dimethylethyl)-3-methyl-2-(phenyl-sulfonyl)oxaziridine (1). KF (8.5 g, 146.8 mmol) was dried by heating at 120 °C for 2 h under reduced pressure (1 Torr) and a solution of commercial MCPBA (70%, 18 g, 73.4 mmol) in CH2Cl2 (300 mL) previously dried over MgSO4 was added. A solution of crude imine 4 (11.7 g, 48.9 mmol) was added and the resulting white suspension was stirred at 0 °C for 3 h and then for a further 12 h at r.t. After filtration to remove the insoluble materials and concen-tration, the residue was filtered through SiO2 with CH2Cl2 as eluent to afford oxaziridine 1 (8.77 g, 34.4 mmol, 71%).

22

Crystal-structure determination of 1: Single crystals of oxaziridine 1, suitable for X-ray crystallographic analysis, were obtained by slow evaporation of n-hexane. X-ray diffraction experiments for the monocrystal of 1 were performed at 293.2 K with graphite-monochromatized Mo Kα radiation on an Enraf-Nonius CAD-4 diffractometer. Formula C12H17NO3S, formula weight 255, crystal system triclinic, space group P-1 (n° 2), a = 9.013 (1) Å, b = 9.169 (4) Å, c = 9.528 (3) Å, α = 108.39 (3)°, β = 108.38 (2)°, γ = 70.09 (2)°, V = 683.2 (4) Å3, Z = 2, density calcd = 1.24 g/cm3, µ = 2.3 cm-1, R = 0.034, wR = 0.0515. Selected bond lengths (Å) and angles (°): O1-C1 1.422 (1), O1-N1 1.484 (1), N1-C1 1.450 (2), S1-N1 1.704 (1), S1-O3 1.421 (1), S1-C7 1.750 (1), C7-C12 1.371 (2), C7-C8 1.374 (2), C1-C2 1.500(2), C1-C3 1.527 (2), C3-C6 1.536 (2), N1-O1-C1 59.90 (7), N1-O1-C1 57.84 (7), O1-C1-N1 62.19 (7), S1-N1-C1 120.27 (9), O2-S1-O3 120.03 (7), O2-S1-N1 102.29 (6), O3-S1-N1 114.31 (6), S1-N1-C1 120.27 (9). Data reduction: TEXSAN (Molecular Structure Corporation). Program(s) used to solve structure: SIR92. Program(s) used to refine structure: TEXSAN. Software used to prepare material for publication: TEXSAN. Crystallographic data for compound 1 have been deposited at the Cambridge Crystallographic Data Centre, CCDC No 615446. Copies of this information may be obtained free of charge from The Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK; +44 (1223)336408; E-mail: deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk.

25

General Procedure for the Synthesis of 1-Alkynyl Sulfoxides 2: A solution of thiadiazole 3 (1.00 mmol) in anhyd THF (5 mL) was cooled to -78 °C and MeLi (0.69 mL of a 1.6 M solution in Et2O, 1.1 mmol) was added dropwise. After stirring at -78 °C for 1 h, a solution of oxaziridine 1 (267 mg, 1.05 mmol) in anhyd THF (2 mL) was slowly added dropwise (exothermic reaction). The reaction mixture was stirred at this temperature for 30 min and treated with the alkyl halide (1-5 equiv). The reaction mixture was then warmed to -20 °C over 1.5 h and then the cold bath was removed. After stirring for a further 1.5 h at r.t., the reaction mixture was treated with sat. aq NaCl solution and the product was extracted with Et2O (3 × 20 mL). The combined organic extracts were washed with sat. aq NaCl solution (3 × 10 mL) and dried over MgSO4. After filtration and concentration under reduced pressure, the residue was purified by column chromatography (PE-EtOAc mixtures) to give the anticipated sulfoxides 2. 1-Benzylsulfinyl-3,3-dimethylbut-1-yne (2a 1 ): Obtained from thiadiazole 3a (R1 = t-Bu, 142 mg, 1 mmol) using benzyl bromide (R2 = Bn, 130 µL, 1.1 mmol) as the electrophile gave 2a 1 as a colorless oil (170 mg, 0.77 mmol, 77%); R f = 0.19 (PE-EtOAc, 4:1); 1H NMR (250 MHz, CDCl3): δ = 1.22 (s, 9 H), 4.25 (s, 2 H), 7.35-7.37 (m, 5 H); 13C NMR (62.9 MHz, CDCl3): δ = 28.8, 30.3, 63.1, 75.8, 113.9, 129.0, 129.1, 129.6, 130.9; IR (NaCl) 3032, 2972, 2928, 2868, 2160 (C≡C), 1454, 1252, 1060 cm-1; MS (EI): m/z (%) = 220 (1) [M+], 91 (100), 65 (14); Anal. Calcd for C13H16OS: C, 70.87; H, 7.32; S, 14.55. Found: C, 70.75; H, 7.47; S, 14.76.
1-Ethylsulfinyl-3,3-dimethylbut-1-yne (2a 2 ). Obtained from thiadiazole 3a (R1 = t-Bu, 142 mg, 1 mmol) using ethyl iodide (R2 = Et, 0.4 mL, 5 mmol) as the electrophile gave 2a 2 as a colorless oil (92 mg, 0,58 mmol, 58%); (R f = 0.3 (PE-EtOAc, 4:1); 1H NMR (250 MHz, CDCl3): δ = 1.29 (s, 9 H), 1.42 (t, J = 7.4 Hz, 3 H), 2.98 and 3.06 (AB part of ABX3, J AB = 13 Hz, J AX = J BX = 7.4 Hz, 2 H); 13C NMR (62.9 MHz, CDCl3): δ = 6.8, 28.8, 30.4, 50.5, 75.7, 112.6; IR (NaCl): 2972, 2932, 2870, 2160 (C≡C), 1456, 1252, 1070 cm-1; MS (EI): m/z (%) = 158 (47) [M+], 142 (33), 130 (68), 115 (100); HRMS m/z calcd for C8H14OS: 158.0765; found: 158.0769.
3,3-Dimethyl-1-methylsulfinylbut-1-yne (2a 3 ). Obtained from thiadiazole 3a (R1 = t-Bu, 142 mg, 1 mmol) using methyl iodide (R2 = Me, 186 µL, 3 mmol) as the electrophile gave 2a 3 as a pale pink oil (123 mg, 0,85 mmol, 85%); R f = 0.32 (PE-EtOAc, 1:1); 1H NMR (250 MHz, CDCl3): δ = 1.29 (s, 9 H), 2.92 (s, 3 H); 13C NMR (62.9 MHz, CDCl3): δ = 28.8, 30.4, 44.1, 77.7, 112.1; IR (NaCl): 2972, 2930, 2870, 2158 (C≡C), 1456, 1252, 1070 cm-1; MS (EI): m/z (%) = 144 (100) [M+], 129 (22), 113 (25), 81 (42); HRMS m/z calcd for C7H12OS: 144.0608; found: 144.0611.
(3,3-Dimethylbut-1-ynylsulfinyl)acetic acid ethyl ester (2a 4 ). Obtained from thiadiazole 3a (R1 = t-Bu, 142 mg, 1 mmol) using 2-bromoacetic acid ethyl ester (R2 = CH2CO2Et, 0.12 mL, 1.1 mmol) as the electrophile gave 2a 4 as a colorless oil (162 mg, 0.75 mmol, 75%); R f = 0.21 (PE-EtOAc, 4:1); 1H NMR (250 MHz, CDCl3): δ = 1.29 (s, 9 H), 1.32 (t, J = 7.1 Hz, 3 H), 3.92 and 4.08 (ΑΒ, J = 13.6 Hz, 2 H), 4.26 (q, J = 7.1 Hz, 2 H); 13C NMR (62.9 MHz, CDCl3): δ = 14.5, 29.0, 30.3, 61.4, 62.6, 75.7, 114.0, 164.6; IR (NaCl): 2974, 2932, 2870, 2160 (C≡C), 1740 (C=O), 1456, 1366, 1252, 1070 cm-1; MS (EI): m/z (%) = 216 (35) [M+], 201 (62), 173 (80), 113 (36), 67 (38), 59 (48), 43 (100); Anal. Calcd for C10H16O3S: C, 55.53; H, 7.46; S, 14.82. Found: C, 55.63; H, 7.46; S, 14,52.
1-Benzylsulfinyl-2-phenylacetylene (2b 1 ). Obtained from thiadiazole 3b (R1 = Ph, 162 mg, 1 mmol) using benzyl bromide (R2 = Bn, 0.130 mL, 1.1 mmol) as the electrophile gave 2b 1 as an orange oil which needed to be purified quickly on SiO2 and stored in a fridge (120 mg, 0.50 mmol, 50%); R f = 0.30 (PE-EtOAc, 4:1); 1H NMR (250 MHz, CDCl3): δ = 4.39 (pseudo s, 2 H), 7.35-7.46 (m, 10 H); 13C NMR (62.9 MHz, CDCl3): δ = 63.1, 85.4, 103.7, 120.1, 128.7, 129.0, 129.1, 129.2, 129.4, 131.0, 132.6; IR (NaCl): 3060, 3030, 2974, 2922, 2164 (C≡C), 1490, 1452, 1246, 1060 cm-1; MS (CI): m/z (%) = 241 (100) [M + H+], 181 (65), 107 (95), 91 (55); HRMS (CI): m/z calcd for C15H13OS: 241.0687; found: 241.0690; Anal. Calcd for C15H12OS: C, 74.97; H, 5.03; S, 13.34. Found: C, 73.15; H, 4.99; S, 13.25.
1-Ethylsulfinyl-2-phenylacetylene (2b 2 ). Obtained from thiadiazole 3b (R1 = Ph, 162 mg, 1 mmol) using ethyl iodide (R2 = Et, 0.4 mL, 5 mmol) as the electrophile gave 2b 2 as an orange oil. The product is highly unstable as previously reported in the literature (31 mg, 0.17 mmol, 17%); R f = 0.10 (PE-EtOAc, 4:1); 1H NMR (250 MHz, CDCl3): δ = 1.51 (t, J = 7.4 Hz, 3 H), 3.07-3.25 (m, 2 H), 7.34-7.92 (m, 5 H).