Preparation of new nitrogen-bridged heterocycles. XXII. A new approach to the syntheses of thienoindolizine derivatives.

Abstract

Ethyl 2-[(2-substituted ethyl)thio]-3-indolizinecarboxylates (1a-f and 5a-f) were deprotected with potassium tert-butoxide in N, N-dimethylformamide and the resulting potassium 2-indolizinethiolates were alkylated with various alkylating agents such as chloroacetone (3a), phenacyl bromides (3b-d), and nitrobenzyl bromides (3e, f) to afford smoothly the corresponding S-functinoalized indolizine derivatives (4a-r and 6a-r) in considerable yields. On the other hand, the similar reactions of 3-acetyl-2-[(2-substituted ethyl)thio]indolizines (7a-f) provided 3-metylthieno[2, 3-b]indolizine derivatives (8a-o), formed via the further intramolecular cyclization of the initially generated S-alkylated indolizines under the reaction conditions employed here. The functionalized indolizines (4a-r and 6a-r) obtained above could also be transformed to the corresponding thieno[3, 2-α]-(10a-r, 14a-d, and 15a, b) and thieno[2, 3-b]indolizine derivatives (11a-h and 12a-d) under various alkaline conditions.