Synthesis of indole substituted dihydro- and tetrahydro-isoxazoles via 1,3-dipolar cycloadditions of C-(1-methylindol-2-yl)-N -methylnitrone with unsaturated carbonyl derivatives and a study of their acid-induced intramolecular cyclizations

Abstract

C-(1-Methylindol-2-yl)-N-methylnitrone 4 reacts with carbonyl-substituted dipolarophiles to afford the isoxazolidines 6–9 and the 3,4-dihydroisoxazole 10 in high yields and with low to moderate regio- and stereo-selectivity. The indolyl-isoxazolidines 6a–c,e,f bearing a 5-methoxycarbonyl or a 5-carboxy substituent in a cis relationship to the 3-indolyl group undergo acid-induced intramolecular acylation to afford the bridged indole derivatives 11a–d. The acid-induced intramolecular cyclization products of the isoxazolidines 7a,b that lack a cis 5-methoxycarbonyl substituent or the isoxazolidines 8c,f that have no 5-methoxycarbonyl substituent are the enamine (→ imine) 12 and/or the diketone 13 depending on the reaction conditions. The spectral elucidation of the products is discussed and mechanistic schemes to explain the formation of the products are suggested. An X-ray structure determination has been carried out on product 11a.