W-Phos Ligand Enables Copper-Catalyzed Enantioselective Alkylation of N-Sulfonyl Ketimines with Grignard Reagents

Abstract

Catalytic asymmetric addition of reactive Grignard reagents to ketimines poses a considerable challenge. Herein, a PNP-type W-Phos ligand developed recently by our group showed a unique effect toward this end, paving the way to a Cu­(I)-catalyzed asymmetric alkylation reaction of N-sulfonyl ketimines, delivering optically active α-tertiary amines in high enantioselectivities. This catalytic protocol shows an unprecedented substrate scope with more than 80 examples, not only compatible with benzo five- and six-membered cyclic N-sulfonyl ketimines but also suitable for geometrically unstable (E or Z) acyclic N-sulfonyl ketimines. The application potential of the protocol is featured by the extensive presence of α-tertiary amines in natural products and pharmaceutical compounds and also demonstrated by downstream transformations with maintenance of the enantioselectivity.

Photoinduced Metal- and Photosensitizer-Free Decarbonylative C–H Alkylation of Cyclic Sulfamidate Imines

“…Apart from that, cyclic N -sulfonyl ketimines are also privileged skeletons for applications in pharmaceutical chemistry, showing a wide range of biological activities and pharmacological properties such as STS and HCV NS5b inhibitors and antiproliferative agents (Scheme a). Moreover, these skeletons could also be largely acted as versatile synthon in myriad of useful transformation . Despite these significant applications, we note that the synthetic method for the construction of C4 alkyl-substituted sulfonyl ketimines is far less studied at present (Scheme b).…”