Deprotonative Functionalization of the Difluoromethyl Group

Abstract

The functionalization of 3-(difluoromethyl)pyridine has been developed via direct deprotonation of -CHF 2 with a lithiated base and subsequent trapping with various electrophiles in THF. In situ quenching gives access to 3-pyridyl-CF 2 -SiMe 2 Ph as a new silylated compound, which can be postfunctionalized with a fluoride source to obtain a larger library of 3-(difluoroalkyl)pyridines that could not be accessed via direct deprotonation.

Nucleophilic strategies to construct –CF2– linkages using borazine-CF2Ar reagents

“…[30][31][32] Unlike the -CF 3 group, orthogonal nucleophilic methodologies to install -CF 2 Ar groups remain largely underdeveloped. [33][34][35][36] We anticipated that a Lewis-acidic boron based scaffold could provide broad routes to related compounds with -CF 2 Ar functionality.…”

Asymmetric Defluoroallylation of 4‐Trifluoromethylpyridines Enabled by Umpolung C−F Bond Activation**

“…To realize this design, several challenges remain to be overcome: a) to incorporate 4‐trifluoromethylpyridines into the N ‐boryl pyridyl anion chemistry; b) to avoid decomposition of the difluoromethyl anion by α‐elimination and over‐defluorination; [15] and c) to ensure the compatibility of the fluoroalkyl anion formation with the AAA reaction. Therefore, we set out to test the formation of 4‐pyridyldifluoromethyl anion from 4‐trifluoromethylpyridine ( 1 a ) and trapping of this anion with several simple electrophiles (Scheme 2).…”

New Chemical Transformations Involving SO2F2‐Mediated Alcohol Activation

“…Reported methods for the N ‐polyfluoroalkylation of sulfonamides generally relied on polyfluoroalkyl halides or polyfluoroalkyl sulfonates which typically require an additional step for their synthesis. Therefore, in 2023, our group reported a general method for the SO 2 F 2 ‐mediated N ‐fluoroalkylation of sulfonamides from readily available fluorinated alcohols [70] …”