En Route to Diastereopure Polycyclic γ-Lactones by Iridium-Catalyzed
Hydride Transfer
Abstract
The reductive lactonization strategy provides an efficient access to
stereoenriched 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 hy-dride
transfer strategy. This method features high levels of stereocontrol,
broad substrate scope, and high catalyst efficiency (S/C = up to 5000).
Mechanistic studies suggested that the iridium hydride formation 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 hydro-gen bonding are critically key
to the diastereocontrol of the hydride transfer process. From the
perspectives of configurational anal-ysis and Duniz angles of attack,
the nature of diastereocontrol is well rationalized. A more general
empirical rule based on facial se-lectivity analysis for explaining and
predicting the stereochemistry is also proposed.