The reductive cyclization of o-Nitrobiphenyls and o-Nitrostyrenes to N-Heterocycles by carbon monoxide, catalyzed by Palladium/Phenanthroline Complexes: an experimental and theoretical mechanistic study

Competitive and trapping experiments demonstrated that the reductive cyclization of o-nitrobiphenyl to carbazole using CO as the reductant and a palladium/phenanthroline catalyst proceeds through the formation of free o-nitrosobiphenyl. A kinetic study of its cyclization reaction to N-hydroxycarbazole indicated that the reaction does not require a metal catalyst, but is accelerated by bases, as also observed in the catalytic reaction starting from the nitro compound. Theoretical calculations provided details on the mechanism, including the involvement of DMF (solvent), when no additional base is added. The cyclization reaction is similar in the case of the synthesis of indoles from o-nitrostyrenes, but the two reactions show different sensitivities to air. This was attributed to different rate-determining steps, involving a Pd(II) complex as the resting state for the synthesis of carbazoles and a Pd(0) one for that of indoles. A palladacyclic complex was isolated from a reaction of o-nitrobiphenyl under conditions close to those employed in the catalytic reaction and shown to afford carbazole when reacted with pressurized CO. For the synthesis of indoles, a Pd(0) olefin complex, Pd(Phen)(η2-(E)-3-(5-fluoro-2-nitrophenyl)-1-phenylprop-2-en-1-one), was isolated directly from a catalytic reaction and characterized by single crystal XRD. An analogous complex, Pd(Phen)(η2-methyl (E)-2-nitrocinnamate), was also independently synthesized and structurally characterized, affording 2-carboxymethyl-indole when treated with CO. Some previously reported pieces of evidence apparently in favor of the involvement of metal-imido species as intermediates in cyclization reactions of nitroarenes when CO is employed as a reductant were dismissed. In particular, a compound previously identified as an aziridine was proven to be an allylic amine, whose formation does not require a metal-imido intermediate. Overall, the results strongly indicate that the cyclization occurs outside the metal coordination sphere at the nitrosoarene stage, excluding the involvement of imido (nitrene) complexes.