Metal

Catalysis

Coupling reaction

Functional group

Alkyl

Alkene

Physical chemistry

Polymer

Combinatorial chemistry

Organic chemistry

Stoichiometry

Reagent

Reductive elimination

Surface modification

Hydride

Chemistry

Nickel

Accounts of Chemical Research

Transition metal hydride catalyzed functionalization of remote and proximal olefins has many advantages over conventional cross-coupling reactions. It avoids the separate, prior generation of stoichiometric amounts of organometallic reagents and the use of preformed organometallic reagents, which are sometimes hard to access and may compromise functional group compatibility. The migratory insertion of metal hydride complexes generated in situ into readily available alkene starting materials, the hydrometalation process, provides an attractive and straightforward route to alkyl metal intermediates, which can undergo a variety of sequential cross-coupling reactions. In particular, with the synergistic combination of chain-walking and cross-coupling chemistry of nickel, NiH-catalyzed functionalization of remote and proximal olefins has undergone particularly intense development in the past few years. This Account aims to chronicle the progress made in this arena in terms of activation modes, diverse functionalizations, and chemo-, regio-, and enantioselectivity.We first provide a brief introduction to the general reaction mechanisms. Taking remote hydroarylation as an example, the four oxidation states of Ni have allowed us to develop two different reaction strategies to form the final product: a Ni(I)-H/X-Ni(II)-H platform that relies on stoichiometric reductants and a Ni(I/II/III) cycle and a redox-neutral functional group or FG-Ni(II)-H platform that reacts with an alkene substrate and forms the migratory products via a Ni(0/II) pathway. We also demonstrate that diverse functionalization, including general C-C bond-forming reactions and the more challenging C-N/C-S bond-forming reactions could be realized. Moreover, the employment of appropriate chiral ligands has allowed us to successfully realize the corresponding asymmetric hydrofunctionalization reactions of olefins, including hydroalkylation, hydroarylation, hydroalkenylation, hydroalkynylation, and hydroamination. Interestingly, the enantio-determining step could be enantioselective hydronickelation, selective oxidative addition, or selective reductive elimination. To realize more challenging asymmetric migratory hydrofunctionalization, we have developed a general ligand relay catalytic strategy with a combination of two simple ligands, the first for chain-walking and the second for asymmetric coupling. This novel strategy avoids the design of a single, possibly structurally complex chiral ligand to promote both steps of chain-walking and asymmetric coupling. In addition, the success of multicomponent hydrofunctionalization provides a convenient approach to gain simple access to complex molecules. Finally, alkyl halides could be used as olefin precursors to undergo a variety of reductive migratory cross-electrophile coupling reactions. Applications of these remote hydrofunctionalization reactions are also discussed. We hope this Account will inspire future development in the field to overcome key challenges, including conceptually new catalytic strategies, development of high-performance systems with enhanced reactivity and selectivity, cutting-edge catalyst design, and further mechanistic studies.

NiH-Catalyzed Functionalization of Remote and Proximal Olefins: New Reactions and Innovative Strategies