En Route to Diastereopure Polycyclic γ-Lactones by Iridium-Catalyzed Hydride Transfer

Abstract

The reductive lactonization strategy provides an efficient access to diastereoenriched polycyclic γ-lactones. However, it is still a formidable challenge to develop an efficient and versatile protocol with excellent levels of diastereocontrol. Herein, we provide a highly diastereoselective and efficient route to diastereopure bi- and polycyclic γ-lactones, by means of an iridium-catalyzed hydride transfer strategy. This method features high levels of diastereocontrol, broad substrate scope, and high catalyst efficiency ( S/ C = up to 5000). Mechanistic studies suggest that the iridium hydride formation might be the rate-determining step, and that the hydride transfer step be the diastereo-determining step. The large steric hindrance of the iridium hydride species and intramolecular hydrogen bonding are critically key to the diastereocontrol of the hydride transfer process. From the perspectives of configurational analysis and Duniz angles of attack, the nature of diastereocontrol is well rationalized. A more general empirical rule based on facial selectivity analysis for explaining and predicting the stereochemistry is also proposed.

Keywords

Iridium catalysis / Hydride transfer / Reductive lactonization / Diastereoselectivity control / Polycyclic γ-lactones / Methodology and reactions / Steric hindrance / Reduction

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2024 SIOC, CAS, Shanghai, & WILEY-VCH GmbH