Nickel-Catalyzed, Stereospecific C-C and C-B Cross-Couplings via C-N and C-O Bond Activation

Highly enantioenriched benzylic and allylic amines and alcohols are readily available via asymmetric synthesis and in complex natural products. The development of mild, nickel-catalyzed cross-couplings of their derivatives has advanced the tools available for the preparation of a range of highly enantioenriched products, including those with quaternary stereocenters. This perspective focuses on cross-couplings with convenient and functional-group-tolerant organoboron reagents and highlights the discoveries of activating groups and conditions that have led to high-yielding and highly stereospecific reactions. Emphasis is placed on a mechanistic understanding, particularly with regard to controlling inversion vs retention pathways. Limitations and opportunities for future developments are also highlighted.

Automated summary

The development of mild, nickel-catalyzed cross-couplings for the preparation of highly enantioenriched products, including those with quaternary stereocenters, has expanded the synthetic toolbox. This perspective highlights the use of convenient and functional-group-tolerant organoboron reagents, as well as the discoveries of activating groups and conditions that have led to highly stereospecific reactions. Emphasis is placed on mechanistic understanding and controlling inversion vs retention pathways, while also discussing limitations and future development opportunities.