Investigations on synthesis of indole based constrained mimetic scaffolds through 1,3-dipolar cycloadditions of the C-(3-indolyl)- N-phenylnitrone with a variety of olefinic and allenic dipolarophiles under microwave irradiation

Abstract

Monomode microwave assisted regio- and stereo-selective 1,3-dipolar cycloadditions of C-(3-indolyl)- N-phenylnitrone ( 19) with a number of olefinic dipolarophiles ( 20a– f) afford isoxazolidines ( 21– 26) in high yields, which are conformationally constrained mimetics of indole-3-propionic acid of biological significance. Similar cycloadducts derived from addition of nitrone ( 19) to allenic esters ( 27a– c) undergo domino reorganization to afford potentially biologically active bis-indole derivatives ( 28, 29). The observed regio- and stereo-selectivities are analysed, inter alia, in terms of HOMO-dipole–LUMO-dipolarophile and involved secondary orbital/steric interactions in the transition states intervening these cycloadditions.