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(kappa(2)-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 (oxyallcyl)lactam products with excellent enantioselectivity.

Automated summary

The article discusses the use of the Cp*Ir(kappa(2)-LX) system as a catalyst for alkene difunctionalization via a nitrenoid-mediated pathway, with a focus on tuning the orbital symmetry of key intermediates to improve catalytic activity. Through systematic engineering, a new catalyst system capable of stepwise nitrenoid transfer was developed, allowing for diastereoselective production of difunctionalized lactams with various nucleophiles. This mechanistic platform also enabled the development of asymmetric methods for introducing two-point chirality in (oxyallcyl)lactam products with excellent enantioselectivity.