Benzocarbacephems from quinolines

Abstract

The azetidinones 1, 2 and 3 have been prepared from simple quinoline derivatives. 2,2a,3,4-Tetrahydro-1H-azeto[1,2-a]quinolin-1-one 1 has been synthesised from quinoline N-oxide and, more efficiently, in three steps from 2-methylquinoline. In both routes 1,2,3,4-tetrahydroquinoline-2-acetic acid 7 is prepared as an intermediate and this is then cyclised to the azetidinone 1. The 8-hydroxyazetidinone 3 has been synthesised by analogous routes, the hydroxy group being protected as an isopropyl ether during the intermediate steps. An X-ray crystal structure of compound 3 has been obtained and this reveals intramolecular hydrogen bonding between the hydroxy and carbonyl groups. The unsaturated azetidinone 2 has been prepared from 1 by stereoselective radical bromination at C-4 followed by dehydrobromination with DBU.