Use of a Catalytic Chiral Leaving Group for Asymmetric Substitutions at sp3 -Hybridized Carbon Atoms: Kinetic Resolution of β-Amino Alcohols by p-Methoxybenzylation

Abstract

A catalytic strategy was developed for asymmetric substitution reactions at sp³ -hybridized carbon atoms by using a chiral alkylating agent generated in situ from trichloroacetimidate and a chiral phosphoric acid. The resulting chiral p-methoxybenzyl phosphate selectively reacts with β-amino alcohols rather than those without a β-NH functionality. The use of an electronically and sterically tuned chiral phosphoric acid enables the kinetic resolution of amino alcohols through p-methoxybenzylation with good enantioselectivity.

Keywords: Brønsted acid catalysis; asymmetric catalysis; kinetic resolution; substitution reactions; β-amino alcohols.