Synlett 2021; 32(01): 91-94
DOI: 10.1055/s-0040-1707311
letter

Synthesis of gem-Difluoroalkenes via a Sequence of Hydroboration and 1,2-Elimination of α,β-Unsaturated Carbonyls

Shiyun An
a   State Key Laboratory for Oxo Synthesis and Selective Oxidation, Center for Excellence in Molecular Synthesis, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000, P. R. of China   Email: gxjiang@licp.cas.cn
b   University of Chinese Academy of Sciences, Beijing 100049, P. R. of China
,
Jinlong Zhang
a   State Key Laboratory for Oxo Synthesis and Selective Oxidation, Center for Excellence in Molecular Synthesis, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000, P. R. of China   Email: gxjiang@licp.cas.cn
,
Gaoxi Jiang
a   State Key Laboratory for Oxo Synthesis and Selective Oxidation, Center for Excellence in Molecular Synthesis, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000, P. R. of China   Email: gxjiang@licp.cas.cn
› Author Affiliations
Financial support from the Natural Science Foundation of Jiangsu Province (BK20191197) is gratefully acknowledged.


Abstract

We reported a simple protocol for the synthesis of gem-difluoroalkenes via a reaction sequence of hydroboration and 1,2-elimination of α,β-unsaturated carbonyl substrates under mild conditions. Two steps of this method could be executed in one pot. The β-CF2H- and β-CFH2-α,β-unsaturated carbonyls can be obtained smoothly from the α,β-unsaturated gem-difluoroamide with NaH as the base and via a boration–1,2-elimination sequence.

Supporting Information



Publication History

Received: 26 August 2020

Accepted after revision: 03 September 2020

Article published online:
14 October 2020

© 2020. Thieme. All rights reserved

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  • 11 Typical Procedure for the Synthesis of 4,4,4-Trifluoro-N-phenyl-3-(4,4,5-trimethyl-1,3,2-dioxaborolan-2-yl)butanamide (3a) The reaction mixture of α,β-unsaturated carbonyl substrate 1a (0.2 mmol), B2pin2 (2, 0.3 mmol, 1.5 equiv), CuCl (10 mol%), t-BuOLi (15 mol%), and i-PrOH (0.4 mol, 2.0 equiv) was stirred in THF (2.0 mL) at room temperature for 12 h. After the reaction was accomplished, the solvent was evaporated, and the crude mixture purified by flash chromatography on silica gel to afford the desired compound 3a in 92% yield. 1H NMR (300 MHz, CDCl3): δ = 8.15 (br, 1 H), 7.53–7.40 (m, 2 H), 7.33–7.18 (m, 2 H), 7.15–7.03 (m, 1 H), 2.80 (qd, J = 16.4, 7.9 Hz, 2 H), 2.23 (dd, J = 17.3, 10.1 Hz, 1 H), 1.26 (d, J = 7.6 Hz, 12 H). 13C NMR (75 MHz, MeOD): δ = 176.83, 137.86, 130.42 (d, J = 273.8 Hz), 130.25, 127.21, 121.97, 83.04, 33.17, 33.12, 25.41, 25.15. 19F NMR (282 MHz, CDCl3): δ = –63.10. HRMS (ESI): m/z [M + H]+ calcd for C16H22BF3NO3: 344.1642; found: 344.1647.