( R)- and ( S)-3-Hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone as chiral auxiliaries in the enantioselective preparation of α-amino acids

Abstract

rac-α-Amino acids ( rac- 1a– d) were formally deracemized by a four-step reaction sequence: (a) protection of the amino function as the phthalimido derivative; (b) acyl chloride formation; (c) diastereoselective reaction with the chiral auxiliaries ( R)- or ( S)-3-hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone, ( R)- or ( S)- 3; and (d) acid hydrolysis to deprotect both the ester and phthalimido functions. Diastereoselectivities of the intermediate esters 4 were good (82–96% d.e.), except for the case of 4b (41% d.e.), the precursor of valine. The main diastereoisomer of esters 4 was (α R,3 S)- or (α S,3 R)-, except for 4d: in this case, working at −78°C, the (α R,3 R)-diastereoisomer was the main product, which epimerizes easily at the α-position when at room temperature. Acid hydrolysis of esters 4 directly gave the deprotected α-amino acids, with little or no epimerization at the α-position of the α-amino acid and complete recovery of the chiral auxiliary. Only (α R,3 R)- 4d on acid hydrolysis partially epimerized at the α-position. Moreover, some α-amino acids and their N, N-dibenzyl derivatives were obtained by dynamic kinetic resolution of diastereoisomeric mixtures of α-bromo esters 5 derived from the chiral auxiliaries ( R)- or ( S)- 3 during reaction with dibenzylamine.