Optically active diethyl N-(p-toluenesulfonyl)-aziridine 2-phosphonates as chiral synthons for the synthesis of beta-substituted alpha-amino phosphonates

摘要

A versatile approach for the synthesis of both protected enantiomers of aziridine 2-phosphonates for use as chiral synthons has been developed. The aziridines arise from either (R)- or (S)-phosphonoserine diethyl esters followed by N-tosylation, O-mesylation and cyclization with sodium hydride. These highly enantio-enriched aziridine 2-phosphonates have been shown to react with carbon, nitrogen, sulfur, hydride, fluoride, and phosphorus nucleophiles allowing for the rapid production of a variety of beta-substituted alpha-amino phosphonates in either the (R)- or (S)-configurations. In the case of thiol nucleophiles, use of a stoichiometric amount of tri-n-butylphosphine was necessary to cleanly produce the corresponding sulfide products. Chiral HPLC methods were utilized to monitor the synthetic processes to evaluate the enantiomeric excess of the products obtained when possible. (C) 2004 Elsevier Ltd. All rights reserved.