Tuning Orbital Symmetry of Iridium Nitrenoid Enables Catalytic Diastereo- and Enantioselective Alkene Difunctionalizations.

Among the central themes in synthetic chemistry is the establishment of novel strategies that usher in the development of more efficient and mild reactions and also expand the chemical space for asymmetric catalysis. Herein, we present an approach to revitalize the Cp*Ir(κ-LX) system as a catalyst toward alkene difunctionalizations via a nitrenoid-mediated pathway. A key strategy is tuning the orbital symmetry of the key Ir nitrenoid intermediates by ligand modification to impart the desired catalytic activity with the suppression of catalyst deactivation. On the basis of a frontier molecular orbital (FMO) analysis, we systematically engineered a new catalyst system capable of a stepwise nitrenoid transfer to allow for nucleophile incorporation. Using the catalytic protocol, a range of difunctionalized lactams can be produced in a diastereoselective manner with various nucleophiles. Mechanistic investigations revealed that the ligand plays a crucial role in both nitrenoid-delivery and stereoselectivity-determining steps. The current mechanistic platform also enabled the development of new asymmetric methods for introducing two-point chirality in (oxy-alkyl)lactam products with excellent enantioselectivity.