Chiral α‑Stereogenic Oxetanols and Azetidinols via Alcohol-Mediated Reductive Coupling of Allylic Acetates: Enantiotopic π‑Facial Selection in Symmetric Ketone Addition

Iridium-tol-BINAP-catalyzed
reductive coupling of allylic acetates
with oxetanones and azetidinones mediated by 2-propanol provides chiral
α-stereogenic oxetanols and azetidinols. As illustrated in 50
examples, complex, nitrogen-rich substituents that incorporate the
top 10 N-heterocycles found in Food and Drug Administration (FDA)-approved
drugs are tolerated. In addition to 2-propanol-mediated reductive
couplings, oxetanols and azetidinols may serve dually as reductant
and ketone proelectrophiles in redox-neutral C–C couplings
via hydrogen autotransfer, as demonstrated by the conversion of dihydro-1a and dihydro-1b to adducts 3a and 4a, respectively.
The present method delivers hitherto inaccessible chiral oxetanols
and azetidinols, which are important bioisosteres.