Why does the synthesis of N-phenylbenzamide from benzenesulfinate and phenylisocyanate via the palladium-mediated Extrusion-Insertion pathway not work? A mechanistic exploration

The gas-phase extrusion-insertion (ExIn) reactions of the palladium complexes [(phen)(n)Pd (O2SC6H5)](+) (phen = 1,10-phenanthroline, n = 1 or 2), were investigated in the gas phase by multistage mass spectrometry (MSn) experiments consisting of electrospray ionisation and a linear ion trap combined with density functional theory (DFT) calculations. Desulfination of palladium sulfinate cations under collision-induced dissociation (CID) generates the organopalladium intermediates [(phen)(n)Pd(C6H5)](+). Of these two organometallic cations, only [(phen)Pd(C6H5)](+) reacts with phenyl isocyanate via insertion to yield [(phen)Pd(NPhC(O)C6H5)](+). The formation of a coordinated amidate anion is supported by DFT calculations. In exploring this reactivity in the solution phase, we found that heating a mixture of benzenesulfinic acid, phenylisocyanate and palladium trifluoroacetate under a range of different conditions (ligand free versus with ligand, different solvents, addition of acid or base) failed to lead to the formation N-phenyl-benzamide in all cases. Instead, biphenyl was formed and could be isolated in a yield of 46%. DFT calculations using a solvent continuum reveal that the barrier associated with the insertion reaction lies above the competing sequential reactions of desulfination of a second phenyl sulfinate followed by reductive elimination of biphenyl.

Automated summary

The gas-phase and solution-phase reactions for the synthesis of N-phenyl-benzamide were investigated. In the gas-phase experiments, only specific organometallic cations were found to react with phenyl isocyanate via insertion. In the solution-phase experiments, the desired product was not formed, instead, biphenyl was obtained.