A Stereoselective Approach to Both 3,4-trans-Disubstituted Pyrrolidin-2-ones and Pyrrolidines. A Convenient Synthesis of (3R,4R)-4-Benzyl-3-pyrrolidinecarboxylic Acid

Abstract

Chiral 4-alkyloxymethyl- and silyloxymethylpyrrolidin-2-ones, (10a-c), underwent alkylation to give the corresponding 3,4-trans-disubstituted pyrrolidin-2-ones, (lla-g), in good yield and total stereoselection, as shown by 'H NMR spectral data and n.O.e. experiments. Moreover compounds (lla-c) were converted into the corresponding 3,4-trans-disubstituted pyrrolidines, (12a-c). Removal of the chiral auxiliary from 12a, followed by protection of the nitrogen with t-Boc group, led to the corresponding derivative (13). Cleavage of the benzyl ether and subsequent oxidation of the hydroxy function afforded (3R,4R)-4-benzyl-3-pyrrolidinecarboxylic acid (4).