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

rac-alpha-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 (alpha R,3S)- or (alpha S,3R)-, except for 4d: in this case, working at -78 degrees C, the (alpha R,3R)-diastereoisomer was the main product, which epimerizes easily at the ex-position when at room temperature. Acid hydrolysis of esters 4 directly gave the deprotected alpha-amino acids, with little or no epimerization at the alpha-position of the alpha-amino acid and complete recovery of the chiral auxiliary. Only (alpha R,3R)-4d on acid hydrolysis partially epimerized at the alpha-position. Moreover, some alpha-amino acids and their N,N-dibenzyl derivatives were obtained by dynamic kinetic resolution of diastereoisomeric mixtures of alpha-bromo esters 5 derived from the chiral auxiliaries (R)- or (S)-3 during reaction with dibenzylamine. (C) 1999 Elsevier Science Ltd. All rights reserved.