1,1-Diarylalkanes are important structural frameworks which are widespread in biologically active molecules. Herein, we report a reductive relay cross-coupling of alkyl bromides with aryl bromides by nickel catalysis with a simple nitrogen-containing ligand. This method selectively affords 1,1diarylalkane derivatives with good to excellent yields and regioselectivity.

The direct difunctionalization of alkenes, a cheap and abundant feedstock, represents one of the most attractive strategies for increasing molecular complexity in synthetic organic chemistry. In contrast with the 1,2‐difunctionalization of alkenes, recent advances showcase alkene 1,n‐difunctionalizations (n≠2) involving metal migration is an emerging and rapidly growing area of research. This promising strategy not only opens a novel avenue for future development of alkene transformations, but also significantly expands upon the bond disconnections available in modern organic synthesis. This Minireview summarizes recent progress in the migratory difunctionalization of alkenes, with an emphasis on the driving force for metal migration.

Cross-coupling reactions have developed into powerful approaches for carbon-carbon bond formation. In this work, a Ni-catalyzed migratory Suzuki-Miyaura cross-coupling featuring high benzylic or allylic selectivity has been developed. With this method, unactivated alkyl electrophiles and aryl or vinyl boronic acids can be efficiently transferred to diarylalkane or allylbenzene derivatives under mild conditions. Importantly, unactivated alkyl chlorides can also be successfully used as the coupling partners. To demonstrate the applicability of this method, we showcase that this strategy can serve as a platform for the synthesis of terminal, partially deuterium-labeled molecules from readily accessible starting materials. Experimental studies suggest that migratory cross-coupling products are generated from Ni(0/II) catalytic cycle. Theoretical calculations indicate that the chain-walking occurs at a neutral nickel complex rather than a cationic one. In addition, the original-site cross-coupling products can be obtained by alternating the ligand, wherein the formation of the products has been rationalized by a radical chain process. 1 1234567890():,; Reductive conditions Redox-neutral conditions Redox-neutral conditions Alkyl reagents Metal migration a Migratory cross-coupling of alkyl electrophiles Ni-catalyzed reductive migratory cross-coupling (Zhu and our group): Pd-catalyzed migratory suzuki-miyaura cross-coupling (Sigman): Ni-catalyzed migratory suzuki-miyaura cross-coupling (this work): b c d Fig. 1 Transition metal-catalyzed migratory cross-coupling. a Migratory cross-coupling of alkyl electrophiles. b Ni-catalyzed reductive migratory crosscoupling. c Pd-catalyzed migratory Suzuki-Miyaura cross-coupling. d The approach developed in this study. ARTICLE NATURE COMMUNICATIONS | https://doi.

Chiral phosphine-containing skeletons are important motifs in bioactive natural products, pharmaceuticals, chiral catalysts, and ligands. Herein, we report a general and modular platform to access chiral α-aryl phosphorus compounds via a Ni/photoredox-catalyzed enantioconvergent reductive cross-coupling between α-bromophosphates and aryl iodides. This dual catalytic regime exhibited high efficiency and good functional group compacity. A wide variety of substrates bearing a diverse set of functional groups could be converted into chiral phosphates in good to excellent yields and enantioselectivities. The utility of the method was also demonstrated by the development of a new phosphine ligand and the synthesis of enzyme inhibitor derivatives. The detailed mechanistic studies supported a radical chain process and revealed a unique distinction compared with traditional reductive cross-coupling.

Substituted six-membered cyclic hydrocarbons are common constituents of biologically active compounds. Although methods for the synthesis of thermodynamically favored, disubstituted cyclohexanes are well established, a reliable and modular protocol for the synthesis of their stereoisomers is still elusive. Herein, we report a general strategy for the modular synthesis of disubstituted cyclohexanes with excellent kinetic stereocontrol from readily accessible substituted methylenecyclohexanes by the implementation of chain-walking catalysis. Mechanistically, the initial introduction of a sterically demanding boron ester group adjacent to the cyclohexane is key to guiding the stereochemical outcome. The synthetic potential of this methodology has been highlighted in late-stage modification of complex bioactive molecules and in comparison with current cross-coupling techniques.