Experimental and Computational Study of 6-exo and 7-endo Cyclization of Aryl Radicals Followed by Tandem S RN 1 Substitution

• Published in: Journal of organic chemistry 2013-05, Vol.78 (10), p.4719-4729
• Main Authors: Peisino, Lucas E, Pierini, Adriana B
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo4001788

The reaction of N-allyl-N-(2-halobenzyl)-acetamides and derivatives was investigated in liquid ammonia under irradiation with the nucleophiles Me3Sn–, Ph2P– and O2NCH2 –. Following this procedure, novel substituted 2-acetyl-1,2,3,4-tetrahydroisoquinolines and substituted 2-acetyl-2,3,4,5-tetrahydro-1H-benzo[c]azepines were obtained in good yields. These reactions are proposed to occur through the intermediacy of aryl radicals, which by intramolecular 6-exo or 7-endo attack to a double bond cyclize to give aliphatic radicals, which react along the propagation steps of the S RN 1 chain cycle to afford the cyclic substituted compounds as main products. The reactions were modeled with DFT methods, which provide a rational understanding that relates the product distribution to the structure of the aliphatic radicals proposed as intermediates and the kinetic of their formation.