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

• Published in: Tetrahedron Vol. 65; no. 31; pp. 5928 - 5935
• Main Authors: Bhella, Surinderjit Singh, Pannu, Ajay Pal Singh, Elango, Munusamy, Kapoor, Ashish, Hundal, Maninder Singh, Ishar, Mohan Paul S.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.08.2009; Elsevier
• Subjects: 1,3-Dipolar cycloadditions; Bis-indole; Chemistry; Chemistry, Organic; Constrained mimetic scaffolds; DFT analysis; Domino-reorganizations; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Isoxazolidines; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Bis-indole; Constrained mimetic scaffolds; Domino-reorganizations; DFT analysis; 1,3-Dipolar cycloadditions; Isoxazolidines; SECONDARY ORBITAL INTERACTIONS; ROUTE; NITRONES; STRUCTURE ELUCIDATION; REGIOSELECTIVITIES; STEREOSELECTIVITIES; ESTERS; AGENTS; INHIBITORS; 1,3-Dipolar cycloaddition; Nitrogen heterocycle; Orbital interaction; Nitrone; Microwave; Selectivity; Stereoselectivity; Ester; Steric effect; Microwave irradiation; Dipolarophile; Chemical synthesis; Oxygen nitrogen heterocycle; Molecular rigidity; Frontier orbital; Regioselectivity; Biological activity; Olefin; Biomimetic compound; Transition state; Density functional method; Indole derivatives; Allenic compound; Ethylenic compound; Successive reaction
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2009.05.093

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. [Display omitted]