Synthesis of (R)- and (S)-2,3-methanovaline as the hydrochloride salts, through manipulation of the N-phthaloyl group of an (S)-leucine derivative for the recall of stereochemistry

(S)-N-Phthaloyl-4-bromoleucine methyl ester was prepared from (S)-leucine. Treatment of the phthalimide with sodium borohydride in methanol gave the c orresponding diastereomeric alpha-methoxyamides, The new stereochemical cen tre gave rise to diastereoselectivity in the base-induced cyclisation of th e methoxyamides. It was also exploited to distinguish and separate the ster eoisomers of the methanovaline derivatives produced in those reactions. Dep rotection of the cyclised species then completed the synthesis of the hydro chloride salts of the enantiomers of methanovaline, illustrating the way in which an N-phthaloyl protecting group may be manipulated to recall the ste reochemistry of an alpha-amino acid in asymmetric synthesis.