USES OF HYDROXAMIC ACIDS AND OF N-ALKOXYI MIDOYL HALIDES IN ORGANIC-SYNTHESIS

Although N-hydroxyamides (1) have been known for over a century, the c hemistry 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 i ts derivatives, particularly of new chemical reactions having syntheti c utility in organic synthesis developed mainly in our laboratory. The review is divided into two sections. The first section described grea t utility of divalent positively-charged nitrogen species generated fr om 1 in synthesis. Electrophilic intramolecular cyclization with an ac ylnitrenium ion generated from an N-methoxy- or an N-allyloxy-N-chloro amide with anhydrous zinc acetate in nitromethane gave an N-methoxy- o r 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 lacta m with various reagents results in removal of the hydroxy or methoxy f unction and introduction of nucleophiles at the ortho or para position of the aromatic ring. These methodologies were successfully applied b y us for the synthesis of the alkaloid, eupolauramine and for new oxin doles related to the alkaloid, gelsemine, by others. The second sectio n described great utility of N-alkoxyimidoyl halides (2) synthesized f rom 1. Compounds 2 were readily transformed to other functions such as aldehydes, cyanides, and oximes. This methodology was successfully ap plied to the synthesis of omega-N-hydroxy-alpha-amino acids in optical ly pure form which were the key intermediates for the synthesis of hyd roxamate-containing siderophores.