Rearrangement Reactions in Aza-Vinylogous Povarov Products: Metal-Free Synthesis of C3-Functionalized Quinolines and Studies on their Synthetic Application

Several types of C-4-functionalized 4-alkyl-2-aryl-1,2,3,4-tetrahydroquinolines underwent rearrangement of their functional groups to C-3, with concomitant aromatization, by simple reflux in 1,2-dichlorobenzene. The functional groups that were shown to undergo the C-4 to C-3 migration were -CH=CH-Z (where Z = CO2Et, CN, NO2, COCH3, CH2OH) and -CH=C(Y)-Z (where Y = CN and Z = CO2Et or Y = Z = CN). On the other hand, the dimethylhydrazono group failed to migrate under thermal conditions but was shown to undergo a smooth dehydrogenation/C-4 to C-3 rearrangement/ dehydrogenation sequence at room temperature in the presence of DDQ, with a broad scope that includes 4-alkyl-2-aryl- and 2-acyl-1,2,3,4-tetrahydroquinolines. We also report a computational and experimental study of the mechanism of both reactions, which supports an unusual intramolecular aza-ene pathway. The ready availability by this method of 2,3-difunctionalized quinolines allowed the simple preparation of fused heterocyclic systems derived from the pyrrolo[3,4-b]quinoline framework, using both reductive and non-reductive domino processes.