Nickel Chain-Walking Catalysis: A Journey to Migratory Carboboration of Alkenes

Conspectus Chain-walking offers extensive opportunities for innovating synthetic methods that involve constructing chemical bonds at unconventional sites. This approach provides previously inaccessible retrosynthetic disconnections in organic synthesis. Through chain-walking, transition metal-catalyzed alkene difunctionalization reactions can take place in a 1, n -addition ( n ≠ 2) mode. Unlike classical 1,2-regioselective difunctionalization reactions, there remains a scarcity of reports regarding migratory patterns. Moreover, the range of olefins utilized in these studies is quite limited. About five years ago, our research group embarked on a project aimed at developing valuable migratory difunctionalization reactions of alkenes through chain-walking. Our focus was on carboboration of alkenes utilizing nickel catalysis. The reaction commences with the migratory insertion of an olefin into a Ni–Bpin species. Subsequently, a thermodynamically stable alkyl nickel complex is generated through a chain-walking process. This complex then couples with a carbon-based electrophile, leading to the formation of an alkylboron compound. It is worth highlighting that the success of these transformations relies significantly on the utilization of a bisnitrogen-based ligand and LiOMe as a B 2 pin 2 activator. Synthetically, these migratory carboboration reactions establish a robust platform for the rapid and efficient synthesis of a wide range of structurally diverse organoboron compounds, which are not facially accessed by conventional methods. The incorporation of a versatile boron group introduces a wealth of possibilities for subsequent diversifications, significantly enhancing the value of the resulting products and allowing for the creation of a broader range of valuable derivatives and applications. This Account provides a comprehensive overview of our research efforts and advancements in the field of migratory carboboration of unactivated alkenes using nickel catalysis. We begin by outlining the development of a series of 1,1-regioselective carboboration reactions of terminal alkenes. A significant focus is placed on the initial integration of boronate, which not only triggers the formation of thermodynamically stable metal species but also exerts control over remote stereochemistry in reactions involving substituted methylenecyclohexenes. Continuing our exploration, remarkable success is achieved in 1,3-regio- and cis -stereoselectivity when dealing with cyclic alkenes. Remarkably, nickel chain-walking catalysis enables heterocyclic alkenes to be viable coupling partners within our transformations. Moreover, it grants us the ability to achieve regioselectivity for cyclohexenes that was previously unattainable, thus expanding the horizons of regiochemical control in these reactions. Lastly, we present the evolution of ligand-modulated regiodivergent carboboration of allylarenes. By gaining insights into the underlying mechanisms driving regiodivergence, we lay a strong foundation for tackling challenges related to selecting specific sites in chain-walking reactions, especially when dealing with multiple stable factors. We anticipate that our findings, coupled with the mechanistic insights we’ve gained, will not only advance the realm of nickel chain-walking catalysis but also contribute to the broader understanding of selectivity control in reactions of this nature. This advancement will also catalyze the synthesis of intricate functional molecules, contributing to the creation of complex and valuable compounds in the realm of organic chemistry.