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 F...

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Veröffentlicht in:ACS catalysis 2022-05, Vol.12 (10), p.6172-6179
Hauptverfasser: Stafford, Nicholas P., Cheng, Melinda J., Dinh, Duong Nguyen, Verboom, Katherine L., Krische, Michael J.
Format: Artikel
Sprache:eng
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Zusammenfassung: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.
ISSN:2155-5435
2155-5435
DOI:10.1021/acscatal.2c01647