SYNTHESIS OF 1,3-DIAZAAZULENE DERIVATIVES OF COLCHICINOIDS AND ISOCOLCHICINOIDS VIA IPSO-SUBSTITUTION-CONDENSATION OR TELE-SUBSTITUTION-CONDENSATION WITH AMIDINES

Condensation of colchicinoids and isocolchicinoids with amidines in dr y benzene affords regioselectively 1,3-diazaazulene derivatives: ipso- substitution-condensation products (e.g. 7) are best obtained from cyc loheptatrienone- ring deactivated substrates (e.g. 4), whereas isomeri c re[e-substitution-condensation products (e.g. 13), are best accessib le from cyctoheptatrienone-ring activated substrates (e.g. 10). Hydrox ylic solvents inhibit tele-substitution-condensation, arguably by unde rgoing protonation in preference of the intermediate sigma adduct. (C) 1998 Elsevier Science Ltd. All rights reserved.