Ni-catalyzed carbamoylation of unactivated alkenes for stereoselective construction of six-membered lactams

Nitrogen-based heterocycles have aroused widespread interest due to their reoccurrence in many pharmaceuticals. Amongst these motifs, the enantioenriched lactams are the ubiquitous scaffolds found in myriad biologically active natural products and drugs. Recently, the transition metal-catalyzed asymmetric carbamoylation has been widely employed as a straightforward arsenal for chiral lactam architecture synthesis, including beta-lactam and gamma-lactam. However, despite the extensive efforts, there still remains no protocol to accomplish the related delta-lactam synthesis. In this manuscript, the Ni-catalyzed enantioselective carbamoylation of unactivated alkenes by the leverage of reductive dicarbofunctionalization strategy allows for the expedient access to two types of mostly common six-membered lactams: 3,4-dihydroquinolinones and 2-piperidinone in high yield and enantioselectivity. This protocol features with good functional group tolerance, as well as broad substrate scope. The newly developed chiral 8-Quinox skeleton ligand is the key parameter for this transformation, which significantly enhances the reactivity and enantioselectivity.

Automated summary

Nitrogen-based heterocycles, particularly enantioenriched lactams, are widely present in pharmaceuticals. Despite extensive efforts, a method for synthesizing delta-lactams remains elusive. In this study, a Ni-catalyzed enantioselective carbamoylation was developed to efficiently access two types of common six-membered lactams. The newly developed chiral 8-Quinox skeleton ligand played a crucial role in enhancing reactivity and enantioselectivity.