ChemInform Abstract: Synthesis of gem‐Difluorocyclopropa(e)nes O‐, S‐, N‐, and P‐Difluoromethylated Compounds with TMSCF₂Br.

Abstract

This is a highly efficient method for the difluoromethylenation of C—C multiple bonds yielding difluorocyclopropane derivatives or the difluoromethylation of heteroatom nucleophiles.

Ring-opening functionalizations of unstrained cyclic amines enabled by difluorocarbene transfer

“…In case of octahydroindolizine (1k), the skeleton was ring-opened exclusively at the 5-membered unit. A dihydropyrrole 1m was readily ring-opened without affecting the olefin moiety (2m, 86%), proving its orthogonality to the previously reported cyclopropanation reactions 58 .…”

“…We envisaged that its highly-electrophilic character would permit an efficient and selective generation of key ammonium salt intermediates from a variety of azacyclic cores, whereby the introduced difluoromethyl (CF 2 H) group would then manipulate the ring properties to eventually enable the deconstructive functionalization of challenging C-N bonds. Difluorocarbene can be readily generated by α-elimination of CF 2 XY-type reagents, among which (bromodifluoromethyl)trimethylsilane (TMSCF 2 Br) stands out as one of the most practical precursors 58 . It is non-toxic, air-and moisture-stable, easy to handle, and can generate the reactive species under mild conditions.…”

Deoxyfluorination of alcohols with 3,3-difluoro-1,2-diarylcyclopropenes

“…During the course of our studies, we noticed that 3,3-difluorocyclopropenes can be hydrolyzed to cyclopropenones upon prolonged storage in a wet atmosphere and that their stability towards water is closely related to their molecular structures353637. On the basis of these findings, we have initiated a program aiming to use the safe and readily available difluorocarbene reagents for deoxyfluorination by virtue of 3,3-difluorocyclopropenes.…”

Pd‐Catalyzed Transfer of Difluorocarbene for Three Component Cross‐Coupling†

“…[ 2 ] Typical difluorocarbene reactions include [2+1] cyclization of alkenes/ alkynes [ 3 ] and difluoromethylation of X—H bonds (X = heteroatom). [ 4 ] Hu disclosed an efficient C—H difluoromethylation by using TMSCF 2 Br, a reagent developed by them recently, [ 5 ] as a difluorocarbene source. [ 6 ] Difluorocarbene can also act as a dipolar CF 2 unit for consecutive bond‐forming reactions, [ 7 ] which were described by Dilman.…”