Uses of hydroxamic acids and of N-alkoxyimidoyl halides in organic synthesis

Abstract

Although N-hydroxyamides (1) have been known for over a century, the chemistry of 1 is still relatively unexplored. The scope of the present review is a survey of the recent advances of the chemistry of 1 and its derivatives, particularly of new chemical reactions having synthetic utility in organic synthesis developed mainly in our laboratory. The review is divided into two sections. The first section described great utility of divalent positively-charged nitrogen species generated from 1 in synthesis. Electrophilic intramolecular cyclization with an acylnitrenium ion generated from an N-methoxy- or an N-allyloxy-N-chloroamide with anhydrous zinc acetate in nitromethane gave an N-methoxy- or an N-allyloxy nitrogen heterocyclic compound, deprotection of which led to formation of the corresponding N-hydroxy compound. Treatment of an N-hydroxy- or an N-methoxy-N-arylamide and the corresponding lactam with various reagents results in removal of the hydroxy or methoxy function and introduction of nucleophiles at the ortho or para position of the aromatic ring. These methodologies were successfully applied by us for the synthesis of the alkaloid, eupolauramine and for new oxindoles related to the alkaloid, gelsemine, by others. The second section described great utility of N-alkoxyimidoyl halides (2) synthesized from 1. Compounds 2 were readily transformed to other functions such as aldehydes, cyanides, and oximes. This methodology was successfully applied to the synthesis of omega-N-hydroxy-alpha-amino acids in optically pure form which were the key intermediates for the synthesis of hydroxamate-containing siderophores.