ConspectusMigratory cross-coupling via metal migration is a process of significant academic and industrial interest. It provides an attractive alternative for the selective installation of a functional group at remote C-H positions from simple precursors, thus enabling the direct synthesis of challenging structures not accessible with traditional cross-coupling. In particular, with the merger of 1,n-Ni/H shift and cross-coupling of nickel, the Ni-catalyzed migratory functionalization of simple precursors has undergone particularly intense development and emerged as a valuable field of research in the past few years. This Account will outline the recent progress made in this arena in terms of migration-functionalization modes, diverse functionalizations, and strategies for regio- and stereocontrol. Mechanistic studies and synthetic applications are also discussed.In detail, we systematically categorize our work into two parts based on the migration modes. In the first part, a platform is created for Ni-catalyzed migratory sp3 C-H functionalization of alkenes or alkyl halides via iterative 1,2-Ni/H shift-selective cross-coupling. The key reactive Ni(II)H species for chain-walking could be generated in situ either in a polarity-reversed fashion relying on stoichiometric reductants (X-Ni(II)-H) or in a redox-neutral fashion with the participation of nucleophilic coupling partners (FG-Ni(II)-H). One significant advantage associated with the polarity-reversed NiH system is the use of relatively stable, abundant, and safe olefin surrogates or alkyl halides instead of the sensitive organometallics required in traditional cross-coupling reactions. Another advantage is that diverse functionalizations, including carbonation and more challenging amination and thiolation could be smoothly achieved with suitable electrophiles or their precursors. Finally, to address the challenging multifaceted selectivity and reactivity issues in asymmetric migratory cross-coupling reactions, we have developed a feasible ligand relay catalytic strategy. In this dynamic ligand exchange process, one ligand promotes rapid migration while the other promotes highly regio- and stereoselective coupling. This innovative strategy overcomes the formidable challenge stemming from the difficulty of designing a single ligand to efficiently promote both steps of chain-walking and asymmetric coupling. In the second part, a new platform for Ni-catalyzed migratory sp2 C-H functionalization via 1,4-Ni/H shift-selective cross-coupling has been reported. Starting from readily available aryl or vinyl coupling partners, the in situ-generated aryl- or vinylnickel(II) species could undergo a rapid and reversible 1,4-Ni/H shift along an sp2 backbone, and subsequent selective coupling with various coupling partners would allow regio- and stereoselective access to diverse 1,4-migratory functionalization products. The key to success was the discovery of an appropriate ligand to efficiently promote both migration and subsequent selective cross-coupling. A vinyl-to-aryl 1,4-Ni/H shift successfully enables the modular ipso/ortho difunctionalization of aryl coupling partners, while an aryl-to-vinyl 1,4-Ni/H shift enables regio- and stereoselective access to functionalized trisubstituted alkenes.We hope that this Account will inspire broad interest and future development of migratory cross-coupling reactions. We strongly believe that continued efforts in this fascinating field will overcome many of the remaining challenges, including cutting-edge ligand/catalyst design to enhance reactivity and selectivity, conceptually new migration modes for additional transformations, and in-depth mechanistic studies for rational reaction design.
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