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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 mechanistic understanding, particularly with regards to controlling inversion vs. retention pathways. Limitations and opportunities for future developments are also highlighted.

The identification of Yb(OTf)3 through a multivariable high-throughput experimentation strategy has enabled a unified protocol for the direct conversion of enantioenriched N-acyloxazolidinones to the corresponding chiral esters, amides, and carboxylic acids. This straightforward and catalytic method has shown remarkable chemoselectivity for substitution at the acyclic N-acyl carbonyl for a diverse array of N-acyloxazolidinone substrates. The ionic radius of the Lewis acid catalyst was demonstrated as a key driver of catalyst performance that led to the identification of a robust and scalable esterification of a pharmaceutical intermediate using catalytic Y(OTf)3.

Cross couplings between simple allylic alcohols and aryl and vinyl boronic acids are efficiently catalyzed by nickel(0) catalysts and bidentate N-heterocyclic carbene/phosphine ligands. The bidentate nature of the ligand is shown to extend catalyst lifetime and enable high yields of the corresponding cross coupling products. X-ray crystallography confirms the bidentate nature of the ligand scaffold. Multistep cross coupling-alkene/alkyne insertions reactions are also conducted and the bidentate nature of the substrate makes the pendant phosphine of the ligand unnecessary.

A nickel-catalyzed reductive cross-coupling of alkylpyridinium salts and aryl bromides has been developed using Mn as the reductant. Both primary and secondary alkylpyridinium salts can be used, and high functional group and heterocycle tolerance is observed, including for protic groups. Mechanistic studies indicate the formation of an alkyl radical, and controlling its fate was key to the success of this reaction.

In situ formation of heterobimetallic Pt–Ti catalysts enables rapid room temperature catalysis in enyne cycloisomerization reactions. The Lewis acidic titanium atom in the ligand framework is shown to be essential for fast catalysis. A range of enyne substrates are efficiently cyclized to carbocycles and heterocycles in high yield.