Volume 20, Issue 22 p. 6795-6800

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Nucleophilic Difluoromethylation of Epoxides with PhSO(NTBS)CF₂H by a Preorganization Strategy^†

Dr. Xiao Shen,

Dr. Xiao Shen

Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032 (P. R. China)

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Qinghe Liu,

Qinghe Liu

Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032 (P. R. China)

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Tao Luo,

Tao Luo

Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032 (P. R. China)

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Prof. Dr. Jinbo Hu,

Corresponding Author

Prof. Dr. Jinbo Hu

[email protected]

Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032 (P. R. China)

Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032 (P. R. China)===Search for more papers by this author

Dr. Xiao Shen,

Dr. Xiao Shen

Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032 (P. R. China)

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Qinghe Liu,

Qinghe Liu

Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032 (P. R. China)

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Tao Luo,

Tao Luo

Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032 (P. R. China)

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Prof. Dr. Jinbo Hu,

Corresponding Author

Prof. Dr. Jinbo Hu

[email protected]

Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032 (P. R. China)

First published: 23 April 2014

https://doi.org/10.1002/chem.201402506

Citations: 25

^†

TBS=tert-butyldimethylsilyl.

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Graphical Abstract

New preorganization strategy: Preorganization of difluoromethyl sulfoximine and epoxide with BF₃ has been found to facilitate the success of the title nucleophilic difluoromethylation. The reaction shows excellent regioselectivity and a broad substrate scope. The facile transformation of the ring-opened products to β-difluoromethyl, γ-difluoromethyl, and β-difluoromethylenyl alcohols (see scheme) demonstrates the synthetic utility of the reaction.

Abstract

Unlike the facile synthesis of β-monofluoromethyl alcohols by nucleophilic monofluoromethylation of epoxides, the synthesis of β-difluoromethyl alcohols by nucleophilic difluoromethylation of epoxides still remains a challenge. Herein, studies on tackling this problem with PhSO(NTBS)CF₂H (2; TBS=tert-butyldimethylsilyl) are reported. The preorganization of 2 and epoxides with BF₃⋅Et₂O was found to be crucial for the reaction. The reaction shows excellent regioselectivity and has a broad substrate scope. The facile transformation of the ring-opened products to β-difluoromethyl, γ-difluoromethyl, and β-difluoromethylenyl alcohols demonstrates the synthetic utility of the reaction.

Supporting Information

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Volume20, Issue22

May 26, 2014

Pages 6795-6800

Nucleophilic Difluoromethylation of Epoxides with PhSO(NTBS)CF₂H by a Preorganization Strategy^†

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Nucleophilic Difluoromethylation of Epoxides with PhSO(NTBS)CF2H by a Preorganization Strategy†

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Nucleophilic Difluoromethylation of Epoxides with PhSO(NTBS)CF₂H by a Preorganization Strategy^†