Direct heterobenzylic fluorination, difluorination and trifluoromethylthiolation with dibenzenesulfonamide derivatives.

ABSTRACT: Functionalization of heterocyclic scaffolds with mono- or difluoroalkyl groups provides unique opportunities to modulate drug pK_a, influence potency and membrane permeability, and attenuate metabolism. While advances in the addition of fluoroalkyl radicals to heterocycles have been made, direct C(sp³)-H heterobenzylic fluorination is comparatively unexplored. Here we demonstrate both mono- and difluorination of a range of alkyl heterocycles using a convenient process that relies on transient sulfonylation by the electrophilic fluorinating agent N-fluorobenzenesulfonimide. We also report heterobenzylic trifluoromethylthiolation and ¹⁸F-fluorination, providing a suite of reactions for late-stage C(sp³)-H functionalization of drug leads and radiotracer discovery.

SUBMITTER: Meanwell M 

PROVIDER: S-EPMC6050628 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature