Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine

Fei Wang; Lingchun Li; Chuanfa Ni; Jinbo Hu

doi:10.3762/bjoc.10.32

Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine

Beilstein J Org Chem. 2014 Feb 6:10:344-51. doi: 10.3762/bjoc.10.32. eCollection 2014.

Authors

Fei Wang¹, Lingchun Li¹, Chuanfa Ni¹, Jinbo Hu¹

Affiliation

¹ Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032, China.

Abstract

Background: 1,1-Difluoroalkenes cannot only be used as valuable precursors for organic synthesis, but also act as bioisosteres for enzyme inhibitors. Among various methods for their preparation, the carbonyl olefination with difluoromethylene phosphonium ylide represents one of the most straightforward methods.

Results: The combination of (chlorodifluoromethyl)trimethylsilane (TMSCF2Cl) and triphenylphosphine (PPh3) can be used for the synthesis of gem-difluoroolefins from carbonyl compounds. Comparative experiments demonstrate that TMSCF2Cl is superior to (bromodifluoromethyl)trimethylsilane (TMSCF2Br) and (trifluoromethyl)trimethylsilane (TMSCF3) in this reaction.

Conclusion: Similar to many other Wittig-type gem-difluoroolefination reactions in the presence of PPh3, the reaction of TMSCF2Cl with aldehydes and activated ketones is effective.

Keywords: (chlorodifluoromethyl)trimethylsilane; Wittig reaction; difluorocarbene; gem-difluoroolefin; organo-fluorine; ylide.