Synthesis of α,α-difluoromethylene alkynes by palladium-catalyzed gem-difluoropropargylation of aryl and alkenyl boron reagents

Abstract

gem-Difluoropropargyl bromides are versatile intermediates in organic synthesis, but have rarely been employed in transition-metal-catalyzed cross-coupling reactions. The first palladium-catalyzed gem-difluoropropargylation of organoboron reagents with gem-difluoropropargyl bromides is now reported. The reaction proceeds under mild reaction conditions with high regioselectivity; it features a broad substrate scope and excellent functional-group compatibility and thus provides an attractive approach for the synthesis of complex fluorinated molecules, in particular for drug discovery and development.

Keywords: cross-coupling; difluoropropargyl bromides; fluorine; organoboron reagents; palladium.