Stille Coupling of α-Alkoxybenzylstannanes: Optimization Study and Stereochemical Outcome

Abstract

In order to make the stereospecific palladium-catalyzed cross-coupling of α-alkoxybenzyl-stannanes a useful synthetic methodology, optimization was undertaken to improve the coupling yields between these stannanes and benzoyl chloride as a model electrophilic substrate. Efforts were put into synthesizing and screening of a number of protecting groups for α-hydroxystannane, followed by optimization of reaction parameters for the Stille coupling reaction of different racemic α-alkoxybenzylstannanes. These protecting groups were chosen based on the principle of “complexation-induced proximity effect” to guide the metal catalyst. Upon obtaining an optimized reaction condition, the stereochemical outcome for the cross-coupling of enantiomerically enriched α-(trimethylacetoxy)benzylstannane with benzoyl chloride will be unambiguously presented. Influences by both the palladium ligand and the electronic property of the substituted-benzoyl chloride will be discussed.