Chiral α-Stereogenic Oxetanols and Azetidinols via Alcohol-Mediated Reductive Coupling of Allylic Acetates: Enantiotopic π-Facial Selection in Symmetric Ketone Addition
Nicholas P. Stafford, Melinda J. Cheng, Dương Nguyễn Đình, Katherine L. Verboom, Michael J. Krische
Abstract
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.