Chemo- and Enantioselective Insertion of Furyl Carbene into the N-H Bond of 2-Pyridones

Asymmetric carbene insertion reactions represent one of the most important protocols to construct carbon-heteroatom bonds. The use of donor-acceptor diazo compounds bearing an ester group is however a prerequisite for achieving high enantioselectivity. Herein, we report a chemo and enantioselective formal N-H insertion of 2-pyridones that has been accomplished for the first time with enynones as the donor-donor carbene precursors. DFT calculations indicate an unprecedented enantioselective 1,4-proton transfer from O to C. The rhodium catalyst provides a chiral pocket in which the steric repulsion and the pi-pi interaction of the propeller ligand play a critical role in determining the selectivities.

Automated summary

Asymmetric carbene insertion reactions are crucial for constructing carbon-heteroatom bonds, but high enantioselectivity typically requires the use of donor-acceptor diazo compounds with an ester group. This study presents the first chemo and enantioselective formal N-H insertion of 2-pyridones using enynones as donor-donor carbene precursors, with DFT calculations revealing an unprecedented enantioselective 1,4-proton transfer from O to C. The rhodium catalyst's chiral pocket, along with steric repulsion and pi-pi interactions of the propeller ligand, play essential roles in determining the selectivities.