Iron-Catalysed Carbene Transfer to Isocyanides as a Platform for Heterocycle Synthesis.

An iron-catalysed carbene transfer reaction of diazo compounds to isocyanides has been developed. The resulting ketenimines are trapped in situ with various bisnucleophiles to access a range of densely functionalized heterocycles (pyrimidinones, dihydropyrazolones, 1H-tetrazoles) in a one-pot process. The electron-rich Hieber anion ([Fe(CO)3 NO]- ) facilitates efficient catalytic carbene transfer from acceptor-type α-diazo carbonyl compounds to isocyanides, providing a cost-efficient and benign alternative to similar noble metal-catalysed processes. Based on DFT calculations a plausible reaction mechanism for activation of the α-diazo carbonyl carbene precursor and ketenimine formation is provided.

How Solvation Influences the SN2 versus E2 Competition.

We have quantum chemically investigated how solvation influences the competition between the SN2 and E2 pathways of the model F- + C2H5Cl reaction. The system is solvated in a stepwise manner by going from the gas phase, then via microsolvation of one to three explicit solvent molecules, then last to bulk solvation using relativistic density functional theory at (COSMO)-ZORA-OLYP/QZ4P. We explain how and why the mechanistic pathway of the system shifts from E2 in the gas phase to SN2 upon strong solvation of the Lewis base (i.e., nucleophile/protophile). The E2 pathway is preferred under weak solvation of the system by dichloromethane, whereas a switch in reactivity from E2 to SN2 is observed under strong solvation by water. Our activation strain and Kohn-Sham molecular orbital analyses reveal that solvation of the Lewis base has a significant impact on the strength of the Lewis base. We show how strong solvation furnishes a weaker Lewis base that is unable to overcome the high characteristic distortivity associated with the E2 pathway, and thus the SN2 pathway becomes viable.