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

rac-alpha-Amino acids (rac-1a-d) were formally deracemized by a four-step r eaction sequence: (a) protection of the amino function as the phthalimido d erivative; (b) acyl chloride formation; (c) diastereoselective reaction wit h the chiral auxiliaries (R)- or (S)-3-hydroxy-4,4-dimethyl-1-phenyl-2-pyrr olidinone, (R)- or (S)-3; and (d) acid hydrolysis to deprotect both the est er and phthalimido functions. Diastereoselectivities of the intermediate es ters 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, t he (alpha R,3R)-diastereoisomer was the main product, which epimerizes easi ly at the ex-position when at room temperature. Acid hydrolysis of eaters 4 directly gave the deprotected alpha-amino acids, with little or no epimeri zation 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 thei r N,N-dibenzyl derivatives were obtained by dynamic kinetic resolution of d iastereoisomeric mixtures of alpha-bromo esters 5 derived from the chiral a uxiliaries (R)- or (S)-3 during reaction with dibenzylamine. (C) 1999 Elsev ier Science Ltd. All rights reserved.