Synthesis of cycl[3.2.2]azine and benzo[g]cycl[3.2.2]azine derivatives by use of the [2 + 8] cycloaddition reaction of indolizines and dimethyl acetylenedicarboxylate

Abstract

AbstractThe reaction of 1‐ethoxycarbonylmethylpyridinium bromides 5a‐k with nitro ketene dithioacetal, 1,1‐bis‐(methylthio)‐2‐nitroethylene (2), in the presence of triethylamine in ethanol gave the desired ethyl 2‐methyl‐thioindolizine‐3‐carboxylates 3a‐k in good yields, along with ethyl 2‐methylthio‐1‐nitroindolizine‐3‐carboxyl‐ates 4a‐d. Deesterification of 3 using sodium hydroxide in methanol followed by treatment with polyphosphoric acid gave the corresponding 2‐methylthioindolizines 5a‐d in good yields. The desulfurization of 5 with Raney‐nickel in ethanol occurs smoothly to give the 1,2,3‐unsubstituted indolizines 6a‐c (a, parent indolizine; b, 8‐methylindolzine; c, 6,8‐dimethylindolizine). Similarly, pyrrolo[2,1‐a]isoquinoline (19) was also synthesized.These indolizine and pyrrolo[1,2‐a]isoquinoline derivatives were allowed to react with dimethyl acetylene to give the corresponding cycl[3.2.2]azine and benzo[g]cycl[3.2.2]azine derivatives in good results.