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 hydride 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 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.
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