Asymmetric synthesis of (+)- and (–)-dihydropinidines: diastereoselective addition to chiral imine or 1,3-oxazolidine derived from (R)-phenylglycinol as a single starting material with organometallic reagents

Abstract

The asymmetric synthesis of the enantiomeric pair of (+)- and (–)-dihydropinidines has been accomplished. Our strategy was based on the enantioselective construction of both enantiomers of the natural products by using a single chiral source, (R)-phenylglycinol. Both routes were carried out by similar processes, except for either the presence of an imine or 1,3-oxazolidine intermediate. Excellent diastereoselectivity was observed in the reaction of chiral imines and 1,3-oxazolidines with organometallic reagents, to give the chiral amines in high chemical yields. The absolute configuration of both amines was determined by converting each of them into dihydropinidine. The asymmetric synthesis of the (+)- and (–)-dihydropinidine piperidine alkaloids was realized in four steps each and in 46 and 59% overall yield, respectively, from 6 and 11.