Synthesis of Conformationally Constrained Esters and Amines by Pd-Catalyzed α-Arylation of Hindered Substrates

Abstract

The α-arylation of sterically hindered silyl ketene acetals (SKAs) with sterically hindered aryl bromides occurs efficiently using Pd[P(t-Bu)3]2 as the optimal catalyst and ZnF2 as a promoter. Less sensitive P(t-Bu)3-based catalysts could be also employed but showed a lower activity. The reaction showed a broad scope with regard to both coupling partners, including heteroaryl bromides and cyclic SKAs. It also proved to be scalable to multigram quantities, which allowed us to further transform the ester group and to access conformationally constrained benzyl- and phenethylamines, highly sought-after building blocks for the synthesis of new agrochemicals.