O-Allylhydroxyamine: A Bifunctional Olefin for Construction of Axially and Centrally Chiral Amino Alcohols via Asymmetric Carboamidation

Difunctionalization of olefins offers an attractive approach to access complex chiral structures. Reported herein is the design of N-protected O-allylhydroxyamines as bifunctional olefins that undergo catalytic asymmetric 1,2-carboamidation with three classes of (hetero)arenes to afford chiral amino alcohols via C-H activation. The C=C bond in O-allylhydroxyamine is activated by the intramolecular electrophilic amidating moiety as well as a migrating directing group. The asymmetric carboamidation reaction pattern depends on the nature of the (hetero)arene reagent. Simple achiral (hetero)arenes reacted to give centrally chiral beta-amino alcohols in excellent enantioselectivity. The employment of axially prochiral or axially racemic heteroarenes afforded amino alcohols with both axial and central chirality in excellent enantio-and diastereoselectivity. In the case of axially racemic heteroarenes, the coupling follows a kinetic resolution pattern with an s-factor of up to >600. A nitrene-based reaction mechanism has been suggested based on experimental studies, and a unique mode of induction of enantio-and diastereoselectivity has been proposed. Applications of the amino alcohol products have been demonstrated.

Automated summary

This study presents the design of N-protected O-allylhydroxyamines as bifunctional olefins for catalytic asymmetric carboamidation, resulting in the formation of chiral amino alcohols via C-H activation. The reaction pattern is dependent on the nature of the (hetero)arene reagent, with achiral (hetero)arenes giving centrally chiral beta-amino alcohols and axially prochiral or axially racemic heteroarenes yielding amino alcohols with both axial and central chirality. A nitrene-based reaction mechanism has been proposed based on experimental studies. The amino alcohol products show promising applications.