Solid Phase Asymmetric Benzylation Using 5,5-Dimethyl-2-Phenylamine-2-Oxazoline Chiral Auxiliary

摘要

Solid phase synthesis has emerged as a versatile and powerful method in modern organic synthesis.1 However, the application of solid-supported chiral auxiliaries is still relatively underdeveloped. Such solid-supported chiral auxiliaries offer some advantages as compared to their application in the solution phase, including a simple filtration procedure for the isolation of the desired compounds or the recovery of the expensive chiral auxiliaries, and their possible extension to a continuous flow system. In addition, the microenvironment of the polymeric backbone could lead to an improvement in the stereoselectivity for a given trans-formation. Recently, we have investigated 2-phenylamino-2-oxazolines as effective chiral auxiliaries for asymmetric alkylation, which provided some beneficial effects for the removal problem as well as stereoselectivity. As a part of our interest in solid-supported chiral auxiliaries, we herein wish to introduce 5,5-dimethyl-2-phenylamino-2-oxazoline chiral auxiliary in solid phase as a good leaving group in the final cleavage step. Asymmetric benzylation as a model alkylation reaction using this chiral auxiliary with different cleavage conditions for the parallel synthesis of several kinds of chiral products will be discussed.