Asymmetric synthesis of the cis- and trans-stereoisomers of 4-aminopyrrolidine-3-carboxylic acid and 4-aminotetrahydrofuran-3-carboxylic acid

The diastereoselective conjugate addition of lithium (S)-N-benzyl-N-alpha-methylbenzylamide has been successfully applied to the first asymmetric syntheses of cis-(3S,4R)- and trans-(3R,4R)-4-aminotetrahydrofuran-3-carboxylic acids (26% and 25% overall yield respectively, > 98% d.e. and > 97% e. e. in each case). Furthermore, the most efficient asymmetric synthesis to date of cis-( 3R, 4R)- and trans-( 3R, 4S)-4-aminopyrrolidine carboxylic acids is delineated: for cis-( 3R, 4R), four steps, > 98% d.e., 52% overall yield; for trans-( 3R, 4S), five steps, > 98% d.e., 50% overall yield.