Synlett 2019; 30(13): 1602-1606
DOI: 10.1055/s-0037-1611839
letter
© Georg Thieme Verlag Stuttgart · New York

Copper-Catalyzed Carbene Insertion into the Sulfur–Sulfur Bond of RS–SCF2H/SCF3 under Mild Conditions

Xin Hong
a   Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China   eMail: cnshenql@sioc.ac.cn
,
Long Lu
b   Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China   eMail: lulong@sioc.ac
,
Qilong Shen
a   Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China   eMail: cnshenql@sioc.ac.cn
› Institutsangaben
The authors gratefully acknowledge the financial support from National Natural Science Foundation of China (21572258) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB20000000).
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Publikationsverlauf

Received: 20. März 2019

Accepted after revision: 04. Mai 2019

Publikationsdatum:
03. Juli 2019 (online)


Abstract

A copper-catalyzed carbene insertion into the sulfur–sulfur bond of trifluoromethyl/difluoromethyl/diphenyldisulfides under mild conditions has been developed. Diverse dithioketal derivatives were synthesized in moderate to good yields in an atom-economic process.

Supporting Information

 
  • References

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  • 17 General procedure for copper-catalyzed carbene insertion of disulfides (3ae, 3go, 3rz). In a flame-dried glass tube, under an argon atmosphere, a mixture of disulfide (0.3 mmol) and Cu(OTf)2 (2.7 mg, 0.0075 mmol, 2.5 mol%) was added to DCE (0.6 mL) at room temperature. Diazo compound (0.3 mmol) was then added in one portion. The mixture was stirred for 1 h and then additional diazo compound (0.3 mmol) was added. The mixture was stirred for another 1 h and subsequently filtered through a short plug of Celite and the solvent was evaporated under reduced pressure. The residue was purified by flash chromatography (EtOAc/PE) to give the product. Ethyl 2-((Difluoromethyl)thio)-2-((4-fluorophenyl)thio)-2-phenylacetate (3a). Rf = 0.5 (EtOAc/PE, 1:20); yield: 76 mg (68%); yellow oil. 1H NMR (400 MHz, CDCl3, 293 K, TMS): δ = 7.33–7.20 (m, 5 H), 7.17–7.13 (m, 2 H), 6.93 (dd, J = 56.2, 54.1 Hz, 1 H), 6.89 (t, J = 8.6 Hz, 2 H), 4.35–4.23 (m, 2 H), 1.27 (t, J = 7.1 Hz, 3 H). 19F NMR (375 MHz, CDCl3): δ = –92.72 (dd, J = 252.6, 56.2 Hz, 1 F), –95.60 (dd, J = 252.7, 54.3 Hz, 1 F), –109.87 (s, 1 F). 13C NMR (100.7 MHz, CDCl3): δ = 169.4, 164.2 (d, J = 251.6 Hz), 139.6 (d, J = 8.8 Hz), 136.3, 128.8, 128.3, 127.6, 124.4 (d, J = 3.2 Hz), 122.7 (t, J = 269.9 Hz), 115.7 (d, J = 21.9 Hz), 70.6, 63.5, 13.7. IR (KBr): νmax = 2984, 1728, 1589, 1489, 1446, 1232, 1067, 1041, 864 cm–1. MS (ESI): m/z = 390.0 [M + NH4 +]. HRMS (ESI): m/z calcd for C17H19NF3O2S2 [M + NH4 +]: 390.0809; found: 390.0803. Ethyl 2-((4-Cchlorophenyl)thio)-2-((difluoromethyl)thio)-2-phenylacetate (3b). Rf = 0.5 (EtOAc/PE, 1:20); yield: 100 mg (86%); yellow oil. 1H NMR (400 MHz, CDCl3, 293 K, TMS): δ = 7.30–7.22 (m, 5 H), 7.16 (d, J = 8.4 Hz, 2 H), 7.08 (d, J = 8.6 Hz, 2 H), 6.92 (dd, J = 56.2, 54.1 Hz, 1 H), 4.34–4.22 (m, 2 H), 1.25 (t, J = 7.1 Hz, 3 H). 19F NMR (375 MHz, CDCl3): δ = 92.65 (dd, J = 252.7, 56.2 Hz, 1 F), –95.65 (dd, J = 252.7, 54.1 Hz, 1 F). 13C NMR (100.7 MHz, CDCl3): δ = 169.3, 138.6, 136.8, 136.3, 128.9, 128.8, 128.4, 127.6, 122.6 (t, J = 269.9 Hz), 70.6, 63.5, 13.7. IR (KBr): νmax = 2983, 1728, 1573, 1475, 1301, 1233, 1067, 1042, 796 cm–1. MS (ESI): m/z = 406.0 [M + NH4 +]. HRMS (ESI): m/z calcd for C17H19NF2ClO2S2 [M + NH4 +]: 406.0514; found: 406.0508. Ethyl 2-((4-Bromophenyl)thio)-2-((difluoromethyl)thio)-2-phenylacetate 3c. Rf = 0.5 (EtOAc/PE, 1:20); yield: 107 mg (82%); yellow oil. 1H NMR (400 MHz, CDCl3, 293 K, TMS): δ = 7.25 (d, J = 8.4 Hz, 2 H), 7.23–7.16 (m, 5 H), 6.95 (d, J = 8.4 Hz, 2 H), 6.85 (dd, J = 56.2, 54.1 Hz, 1 H), 4.28–4.16 (m, 2 H), 1.19 (t, J = 7.1 Hz, 3 H). 19F NMR (375 MHz, CDCl3): δ = –92.64 (dd, J = 252.7, 56.3 Hz, 1 F), –95.67 (dd, J = 252.7, 54.1 Hz, 1 F). 13C NMR (100.7 MHz, CDCl3): δ = 169.3, 138.8, 136.2, 131.7, 128.8, 128.4, 128.1, 127.5, 125.2, 122.6 (t, J = 270.1 Hz), 70.5, 65.8, 63.5. IR (KBr): νmax = 2982, 1727, 1473, 1446, 1232, 1068, 1041, 815, 769 cm–1. MS (ESI): m/z = 449.9 [M + NH4 +]. HRMS (ESI): m/z calcd for C17H19NF2BrO2S2 [M + NH4 +]: 450.0009; found: 450.0003