Enantioselective α-Arylation of Ketones via a Novel Cu(I)-Bis(phosphine) Dioxide Catalytic System.

Margarita Escudero-Casao,Giulia Licini,Manuel Orlandi

doi:10.1021/jacs.0c13236

Abstract

A novel catalytic system based on copper(I) and chiral bis(phosphine) dioxides is described. This allows the arylation of silyl enol ethers to access enolizable α-arylated ketones in good yields and enantiomeric excess up to 95%. Noncyclic ketones are amenable substrates with this method, which complements other approaches based on palladium catalysis. Optimization of the ligand structure is accomplished via rational design driven by correlation analysis. Preliminary mechanistic hypotheses are also evaluated in order to identify the role of chiral bis(phosphine) dioxides.

Highlights

A novel catalytic system based on copper(I) and chiral bis(phosphine) dioxides is described
The Pd-catalyzed α-arylation of carbonyl compounds is a fundamental reaction in transition metal catalysis, which was first reported by the groups of Buchwald and Hartwig in 1997.1,2 Since this transformation has been successfully employed in academia and industry.[3]
MacMillan demonstrated that aldehydes could be α-arylated via enamine catalysis in the presence of diaryliodonium salts and CuBr (Figure 1C).[15]

Summary

Corresponding Author

Margarita Escudero-Casao − Department of Chemical Sciences and CIRCC−Consorzio Interuniversitario per le Reattività. Chimiche e la Catalisi, University of Padova, 35131 Padova, Italy Giulia Licini − Department of Chemical Sciences and. Chimiche e la Catalisi, University of Padova, 35131 Padova, Italy; orcid.org/0000-0001-8304-0443. Author Contributions †M.E.-C. and M.O. contributed . All authors have given approval to the final version of the manuscript

■ ACKNOWLEDGMENTS

Findings

■ REFERENCES