(E)-Selective Weinreb Amide–type Horner–Wadsworth–Emmons Reaction: Effect of Reaction Conditions, Substrate Scope, Isolation of a Reactive Magnesium Phosphonoenolate, and Applications

An iPrMgCl-deprotonating Weinreb amide–type Horner–Wadsworth–Emmons (HWE) reaction was developed, and the effects of diverse reaction conditions, including the base, cation, solvent, and concentration, were investigated to broaden the substrate scope and achieve high (E)-selectivity. The Weinreb amide–type phosphonoenolate generated from iPrMgCl was found to be isolable, stable for at least over a half year, and applicable in the HWE reaction keeping high productivity and selectivity compared with the in situ generated phosphonoenolate. The results prompted us to perform an application study including successive elongation, synthesis of a biscyclopropane, and Weinreb ketone syntheses.