Confronting the Challenging Asymmetric Addition of Vinyl Arene Pronucleophiles into Ketones: Ligand-Controlled Regiodivergent Processes Through a Dearomatized Allyl-Cu Species
Year: 2021
Type: preprint
Abstract: The selective reductive coupling of vinyl arenes and ketones represents a versatile approach for the rapid construction of enantiomerically enriched tertiary alcohols. Herein, we demonstrate a CuH-catalyzed regiodivergent coupling of vinyl arenes and ketones, in which the selectivity is controlled by the ancillary ligand. This approach leverages an in situ generated benzyl- or dearomatized allyl-Cu intermediate, yielding either the dearomatized or exocyclic addition products, respectively. The method exhibits excellent regio-, diastereo- and enantioselectivity, and tolerates a range of common functional groups and heterocycles. Computational studies suggest that the regio- and enantioselectivity are controlled by the ancillary ligand, while the diastereoselectivity is enforced by steric interactions between the alkyl-Cu intermediate and ketone substrates in a six-membered cyclic transition state.
Source: ChemRxiv
Authors: Yuyang Dong, Alexander Schuppe, Binh Khanh Mai, Peng Liu, Stephen Buchwald
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Awards: G1742171491, G2206590661, G3226045097, XSEDE 2.0: Integrating, Enabling and Enhancing National Cyberinfrastructure with Expanding Community Involvement, G9000100211, G9000350156, Metal-Catalyzed Methods for Organic Synthesis, Computational Models for Reactivity and Selectivity in Catalytic Olefin Functionalization
OpenAlex ID: W4226113607