title: gem-Difluoroolefination of diaryl ketones and enolizable aldehydes with difluoromethyl 2-pyridyl sulfone: new insights into the Julia-Kocienski reaction.
abstract: The direct conversion of diaryl ketones and enolizable aliphatic aldehydes into gem-difluoroalkenes has been a long-standing challenge in organofluorine chemistry. Herein, we report efficient strategies to tackle this problem by using difluoromethyl 2-pyridyl sulfone as a general gem-difluoroolefination reagent. The gem-difluoroolefination of diaryl ketones proceeds by acid-promoted Smiles rearrangement of the carbinol intermediate; the gem-difluoroolefination is otherwise difficult to achieve through a conventional Julia-Kocienski olefination protocol under basic conditions due to the retro-aldol type decomposition of the key intermediate. Efficient gem-difluoroolefination of aliphatic aldehydes was achieved by the use of an amide base generated in situ (from CsF and tris(trimethylsilyl)amine), which diminishes the undesired enolization of aliphatic aldehydes and provides a powerful synthetic method for chemoselective gem-difluoroolefination of multi-carbonyl compounds. Our results provide new insights into the mechanistic understanding of the classical Julia-Kocienski reaction.
authors.affiliation: Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032 (P.R. China), Fax: (+86) 21-6416-6128.
authors.forename: Bing
authors.initials: B
authors.lastname: Gao
authors.forename: Yanchuan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Mingyou
authors.initials: M
authors.lastname: Hu
authors.forename: Chuanfa
authors.initials: C
authors.lastname: Ni
authors.forename: Jinbo
authors.initials: J
authors.lastname: Hu
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry*; D013237:Stereoisomerism; D013450:Sulfones / Q000737:chemistry*
chemical_list: D000447:Aldehydes; D007659:Ketones; D011725:Pyridines; D013450:Sulfones; C550215:difluoromethyl 2-pyridyl sulfone
keywords: Julia-Kocienski reaction; chemoselectivity; difluoromethyl 2-pyridyl sulfone; olefination; rearrangements