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

The 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.