Asymmetric Three-Component Reaction of Two Diazo Compounds and Hyrdroxylamine Derivatives for the Access to Chiral α-Alkoxy-β-amino-carboxylates

Hydroxylamine derivatives are commonly used as both nitrogen and oxygen sources in the aminohydroxylation of alkenes, which is a powerful and practical method for the rapid assembly of synthetically useful 1,2-aminoalcohols. In this work, we disclose an unprecedented asymmetric formal aminohydroxylation of two diazo compounds with O-benzyl hydroxylamines, which involves a N-O bond activation, fragment modification, and reassembly cascade process. This cascade reaction forms multiple bonds in one-pot, including C=N, C-O, and C-C bonds, providing a potent complement for the aminohydroxylation using alkenes to that using two different diazo compounds, and leading to chiral alpha-alkoxy-beta-amino-carboxylate derivatives with two adjacent tertiary chiral centers in generally good yields and high to excellent enantioselectivity.

Automated summary

In this study, an asymmetric aminohydroxylation method using hydroxylamine derivatives was developed. This method involves N-O bond activation, fragment modification, and reassembly cascade process, forming multiple bonds in one reaction. The resulting chiral compounds have two adjacent tertiary chiral centers.