Z-Selective phosphine promoted 1,4-reduction of ynoates and propynoic amides in the presence of water

Abstract

Phosphine-mediated reductions of substituted propynoic esters and amides in the presence of water yield the partially reduced α,β-unsaturated esters and amides with high Z-selectivity. The competitive in situ Z to E-isomerization of the product in some cases lowers the Z to E ratios of the isolated α,β-unsaturated carbonyl products. Reaction time and the amounts of phosphine and water in the reaction mixture are the key experimental factors which control the selectivity by preventing or reducing the rates of Z- to E-product isomerization. Close reaction monitoring enables isolation of the Z-alkenes with high selectivities. The computational results suggest that the reactions could be highly Z-selective owing to the stereoselective formation of the E-P-hydroxyphosphorane intermediate.