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

Abstract

Several types of C4‐functionalized 4‐alkyl‐2‐aryl‐1,2,3,4‐tetrahydroquinolines underwent rearrangement of their functional groups to C3, with concomitant aromatization, by simple reflux in 1,2‐dichlorobenzene. The functional groups that were shown to undergo the C4 to C3 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/C4 to C3 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.

Mechanochemical Aza-Vinylogous Povarov Reactions for the Synthesis of Highly Functionalized 1,2,3,4-Tetrahydroquinolines and 1,2,3,4-Tetrahydro-1,5-Naphthyridines

“…Yield: 170 mg (81%), as a yellow solid. Characterization data were identical to those described in the literature [ 37 ].…”

“…On the other hand, treatment of 2d with DDQ afforded a quantitative yield of 3d under vibratory ball milling (20 Hz, ZrO 2 ball and jar), and a complex mixture containing only a small amount of 3d when the reaction was performed in methanol solution. It is interesting to note that the formation of compound 4d might have been expected in this experiment, since a C 4 -C 3 rearrangement of the dimethylhydrazono group followed by dehydrogenation was observed when tetrahydroquinolines were employed as starting materials [ 37 ], although these reactions seemed to require a high electron density in the benzene ring of the starting material. Thus, the combination of two mechanochemical steps can be used to synthesize a 2-acyl-1,5-naphthyridine in a high yield from very simple starting materials ( Scheme 4 ).…”