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.

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.

An unprecedented nickel‐catalyzed 1,1‐alkylboration of electronically unbiased alkenes has been developed, providing straightforward access to secondary aliphatic boronic esters from readily available materials under very mild reaction conditions. The regioselectivity of this reaction is governed by a unique pyridyl carboxamide ligated catalyst, rather than the substrates. Moreover, this transformation shows excellent chemo‐ and regio‐selectivity and remarkably good functional‐group tolerance. We also demonstrate that under balloon pressure, ethylene can also be utilized as a substrate. Additionally, competence experiments indicate that selective bond formation is favored at the α‐position of boron and preliminary mechanistic studies indicate that the key step in this three‐component reaction involves a 1,2‐nickel migration.

An unprecedented nickel-catalyzed 1,1-alkylboration of electronically unbiased alkenes has been developed, providing straightforwarda ccess to secondary aliphatic boronic esters from readily available materials under very mild reaction conditions.T he regioselectivity of this reaction is governed by au nique pyridyl carboxamide ligated catalyst, rather than the substrates.Moreover,this transformation shows excellent chemo-and regio-selectivity and remarkably good functional-group tolerance.W ea lso demonstrate that under balloon pressure,e thylene can also be utilized as as ubstrate. Additionally,c ompetence experiments indicate that selective bond formation is favored at the a-position of boron and preliminary mechanistic studies indicate that the key step in this three-component reaction involves a1 ,2-nickel migration.

As significant pharmacophores, 1,3-disubstituted cyclohexanes are widespread in natural products and synthetic bioactive molecules. In this work, we describe a palladium-catalyzed arylboration of 1,4-cyclohexadienes, which allows expeditious access to an array of functionalized 1,3-disubstituted cyclohexanes from the readily available starting materials. Palladium catalysis enables the arylboration to proceed in a reversed regioselectivity compared with earlier nickel catalysis. The most striking feature of this protocol lies in the 1,3-regioselectivity and exclusive cis-diastereoselectivity. Intriguingly, the success of this three-component reaction does not rely on the application of dative ligands but a cheap ammonium chloride salt instead. The synthetic utility of this method is highlighted by a series of downstream stereospecific transformations and a drug molecule synthesis.