Practical Synthesis of (S)-3-(p-Nitrobenzyloxycarbonylamino)pyrrolidine and Its Related Compounds from L-Aspartic Acid

Abstract

An efficient method for the preparation of (S)-3-aminopyrrolidine derivatives was developed starting from L-aspartic acid, which involves an efficient formation of a pyrrolidine-ring from allylamine and a practical PdIC-catalyzed cleavage of N-ally1 protective group.This method affords the enantiomerically pure desired compounds ( I ) in high overall yields.A widespread occurrence of (S)-3-amino-1-pyrrolidinyl moiety in biologically active compounds such as Ip-methylcarbapenem antibiotic^,^ new quinolone antibacterials,2.3 and antitumor agents4 has stimulated the development of numerous methods for the synthesis of (S)-3-aminopyrrolidine~.~~~~~Among these, the methods that use L-aspartic acid as a starting ~n a t e r i a l ~~.~ are considered to be the most promising entry because of its commercial availability.Our attention was focused on the synthesis of (S)-3-@-nitrobenzyloxycarbonylamino)pyrrolidine ( l a ) and (S)-3-(benzy1oxycarbonylamino)pyrrolidine (1 b), which are imperative in manufacturing the potent antibiotic agents with a wide range of antibacterial spectrum.'In this paper, we describe a practical method for preparing 1 a and 1 b.The retrosynthesis is as follows: A key intermediate (B) possessing two leaving groups at both termini, derived from natural L-aspartic acid, can react with a synthetic equivalent of ammonia to give a N1-protected 1 (A), and the selective N1deprotection of A should give the target compound.A key to our success is to develop an efficient PdICcatalyzed deallylation procedure, which realizes the selective deprotection of A to provide a practical route