Synlett 2018; 29(06): 815-819
DOI: 10.1055/s-0036-1590987
letter
© Georg Thieme Verlag Stuttgart · New York

A Direct Xanthate-Based Route to γ-Thiolactones

Raphaël Simonet-Davin
Laboratoire de Synthèse Organique, CNRS UMR 7652 Ecole Polytechnique, 91128 Palaiseau, Cedex, France   Email: samir.zard@polytechnique.edu
,
Samir Z. Zard*
Laboratoire de Synthèse Organique, CNRS UMR 7652 Ecole Polytechnique, 91128 Palaiseau, Cedex, France   Email: samir.zard@polytechnique.edu
› Author Affiliations
Further Information

Publication History

Received: 03 October 2017

Accepted after revision: 27 November 2017

Publication Date:
02 January 2018 (online)


Abstract

The first examples of direct synthesis of γ-thiolactones by addition of a thiolactone-based radical are described. Mono- and bis-γ-thiolactones can be obtained by a dilauroyl peroxide initiated addition of thiolactone xanthate to various alkenes and α,ω-dienes. The process is modular and exhibits a high functional group tolerance.

Supporting Information

 
  • References and Notes

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  • 11 Typical Experimental Procedures – Synthesis of Thiolactone Xanthate (14) d,l-Homocysteine thiolactone hydrochloride (10.0 g, 65.1 mmol, 1.0 equiv) was suspended in 48% hydrobromic acid (50 mL). The suspension was stirred in an ice-salt bath at –20 °C while NaNO2 (4.87 g, 70.6 mmol, 1.1 equiv) in chilled water (20 mL) was added dropwise. The mixture was stirred for 15 min, warmed up to rt and stirred for 1 h, then extracted with CH2Cl2 (3 × 50 mL), and the organic phase dried over MgSO4. Filtration and concentration in vacuo afforded the crude bromothiolactone 13 as an orange oil. Another batch was made in the same way, and the two crude residues were combined and dissolved in acetone (167 mL). The resulting solution was stirred in an ice bath at 0 °C while KSCSOEt (14.7 g, 91.9 mmol, 0.7 equiv with respect to the starting homocysteine thiolactone hydrochloride; this amount corresponds approximately to 1.1 equiv with respect to the quantity of bromothiolactone 13 estimated by NMR spectroscopy) was slowly added. The solution was allowed to reach rt, stirred for another 45 min, filtered over a plug of silica, and concentrated in vacuo. The residue was purified by flash column chromatography (PE/EtOAc = 90:10) to afford pure 14 (10.5 g, 47.1 mmol; 36%) as an orange oil. Rf = 0.54 (PE/EtOAc = 8:2). 1H NMR (CDCl3, 400 MHz): δ = 4.67 (q, 1 H, J = 7.1 Hz, OCH2CH3), 4.67 (q, 1 H, J = 7.1 Hz, OCH2CH3), 4.62 (d, 0.5 H, J = 7.0 Hz, CHS), 4.59 (d, 0.5 H, J = 7.0 Hz, CHS), 3.48–3.36 (m, 2 H, CH2CH2S), 2.89–2.81 (m, 1 H, CH2CH2S), 2.41–2.31 (m, 1 H, CH2CH2S), 1.43 (t, 3 H, J = 7.1 Hz, OCH2CH3). 13C NMR (CDCl3, 101 MHz): δ = 211.7 (CS2), 202.7 (CO), 71.1 (CH2CH3), 58.3 (CHS), 32.2 (CH2CHS), 30.2 (CH2S), 13.9 (CH2CH3). IR: ν = 1690 (C=O), 1230 (SC–O), 1042 (C=S). COSY, HSQC, and HMBC were consistent with this attribution. HRMS (EI): m/z calcd for C7H10O2S3 [M+]: 221.9843; found: 221.9837. S-[1,1-Diethoxy-3-(2-oxotetrahydrothiophen-3-yl)propan-2-yl] O-Ethyl Carbonodithioate (21) Thiolactone xanthate (14, 222 mg, 1.0 mmol) was dissolved in EtOAc (1 mL) to obtain an approximately 1 M solution. The solution was warmed up to 80 °C with acrolein diethyl acetal (318 μL, 2.0 mmol, 2.0 equiv). After 15 min at reflux under nitrogen, DLP (40 mg, 0.1 mmol, 0.1 equiv) was added, and the solution was stirred under reflux for 1 h with monitoring by TLC. The addition of DLP was repeated 3 times. The reaction mixture was then concentrated in vacuo and purified by flash column chromatography (PE/EtOAc = 90:10) to afford pure 21 (245 mg, 0.7 mmol, 69%) as a pale yellow oil and as a 1:1 mixture of diastereoisomers. Rf (PE/EtOAc = 8:2) = 0.76. 1H NMR (CDCl3, 400 MHz): δ = 4.66–4.60 (m, 2 H, CSOCH2CH3), 4.55–4.52 (m, 1 H, CH(OCH2CH3)2) 4.34–4.29 (m, 0.5 H, CHS), 4.06–4.03 (m, 0.5 H, CHS), 3.78–3.47 (m, 4 H, CH(OCH2CH3)2), 3.27–3.24 (m, 2 H, CH2S), 2.75–2.66 (m, 1 H, CHCOS), 2.62–2.47 (m, 1 H, CH2CH2S), 2.42–2.35 (m, 0.5 H, CHCH2CH), 2.27–2.19 (m, 0.5 H, CHCH2CH), 2.02–1.92 (m, 0.5 H, CHCH2CH), 1.92–1.83 (m, 1 H, CH2CH2S), 1.64–1.57 (m, 0.5 H, CHCH2CH), 1.41 (t, 1.5 H, J = 7.0 Hz, CSOCH2CH3), 1.40 (t, 1.5 H, J = 7.0 Hz, CSOCH2CH3), 1.24–1.16 (m, 6 H, CH(OCH2CH3)2). 13C NMR (CDCl3, 101 MHz): δ = 215.1 (CS2), 214.2 (CS2), 210.0 (COS), 209.7 (COS), 104.2 (CH(OCH2CH3)2), 104.0 (CH(OCH2CH3)2), 70.6 (CSOCH2CH3), 70.3 (CSOCH2CH3), 65.0 (CH(OCH2CH3)2), 64.8 (CH(OCH2CH3)2), 64.0 (CH(OCH2CH3)2), 63.8 (CH(OCH2CH3)2), 53.0 (CHS), 51.7 (CHS), 49.5 (CHCOS), 49.1 (CHCOS), 33.0 (CH2CH2S), 32.5 (CH2CH2S), 30.3 (CH2CH2S), 30.2 (CH2CH2S), 28.7 (CHCH2CH), 28.3 (CHCH2CH), 15.4 (CH(OCH2CH3)2), 15.3 (CH(OCH2CH3)2), 15.3 (CH(OCH2CH3)2), 15.2 (CH(OCH2CH3)2), 13.9 (CSOCH2CH3), 13.8 (CSOCH2CH3). IR: ν = 1695 (C=O), 1220 (SC–O), 1053 (C=S). COSY, HSQC, and HMBC were consistent with this attribution. HRMS (EI): m/z calcd for C14H24O4S3 [M+]: 352.0837; found: 352.0843. 3,3′-(Octane-1,8-diyl)bis[dihydrothiophen-2(3H)-one] (37) To a solution of adduct 32 (525 mg, 0.9 mmol) in dioxane (9.5 mL) was added Et3N (870 μL, 6.2 mmol, 6.6 equiv) followed by H3PO2 (as a 50% solution in water; 294 μL, 5.7 mmol, 3.0 equiv), and the resulting mixture was heated under reflux for 15 min under nitrogen. AIBN (31 mg, 0.2 mmol, 0.2 equiv) was added, and the solution was stirred under reflux for 1 h and monitored by TLC. The addition of AIBN was repeated twice. The reaction mixture was concentrated in vacuo and the residue dissolved in EtOAc (15 mL). The organic phase was washed with water (3 × 15 mL) and dried over MgSO4. Filtration, concentration in vacuo, and recrystallization from EtOAc afforded pure bis-thiolactone 37 (228 mg, 0.7 mmol, 77%) as a white solid (1:1 mixture of meso and d,l-diastereoisomers); mp ca. 73 °C. 1H NMR (CDCl3, 400 MHz): δ = 3.25–3.21 (m, 4 H, CH2S), 2.46–2.34 (m, 4 H, CHCH2CH2S), 1.90–1.80 (m, 2 H, CHCH2CH2S), 1.79–1.71 (m, 2 H, CH2CHCOS), 1.29–1.23 (br, 14 H, CH2CH2CH2CH2CHCOS). 13C NMR (CDCl3, 101 MHz): δ = 210.6 (COS), 51.6 (CHCOS), 31.8 (CH2CHS), 30.4 (CH2CH2S), 29.8 (CH2CHCOS), 29.4 (CH2CH2CHCOS), 29.3 (CH2CH2CH2CHCOS), 27.3 (CH2CH2CH2CH2CHCOS). IR: ν = 1693 (SC=O). COSY, HSQC, and HMBC were consistent with this attribution. HRMS (EI): m/z calcd for C16H26O2S2 [M+]: 314.1374; found: 314.1377.
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