Chiral Magnesium Complex-Catalyzed Asymmetric Cyclization of Vinyl Diazo Compounds with Phenol Derivatives via Noncarbene Pathways

Abstract

Vinyl diazo compounds are of great interest since they can both serve as carbene precursors to react with nucleophiles and act as nucleophiles to react with electrophiles via the noncarbene pathway. However, due to the competing metal carbene reactivity and weak nucleophilicity, it is challengeable but useful to get the diazo-preserved chiral products with structural complexity from simple vinyl diazo compounds, especially in metal-catalyzed conditions. Herein, we report the first asymmetric reaction of vinyl diazo compounds via a noncarbene process enabled by a low-cost magnesium(II)-N,N′-dioxide complex, which successfully suppressed the metal-carbene reactivity in a chiral environment. This work exhibits good functional group tolerance and enables rapid synthesis of enantioenriched diazo-containing chromane derivatives with high enantioselectivity and full diastereoselectivity. Control experiments demonstrate the significance of dibenzylamino on the ortho-quinone methide precursors in a ligand exchange process to ensure the reactivity and stereocontrol of the real catalyst. Computational studies elucidate the origin of enantioselectivity and suggest an ionic stepwise mechanism for the Mg II -catalyzed asymmetric cyclization reaction, in which the nucleophilicity of the vinyl motif is largely enhanced by the adjacent diazo group.