Ligand-Enabled NiH-Catalyzed Migratory Hydroamination: Chain Walking as a Strategy for Regiodivergent/Regioconvergent Remote sp ³ C–H Amination

Abstract

Direct and positionally selective aliphatic C-H functionalization is an attractive means with which to streamline chemical synthesis. With many possible reaction sites, most traditional methods need a polar-directing group nearby to achieve high regioand chemoselectivity and are often restricted to a single site of functionalization. Here, we report a nondirected, remote sp 3 C-H amination process with predictable and switchable regioselectivity. This reaction uses a nickel hydride-catalyzed remote relay hydroamination strategy in which an aliphatic amino group is installed at a position far from the original C=C bond present in all unsaturated hydrocarbon substrates. Depending on the choice of ligand, either terminal or benzylic functionalization products can be obtained with excellent levels of regioselectivity.We also show that an alkyl bromide could also be used as an olefin precursor when using Mn 0 as a reductant. The utility of this transformation is further highlighted by the regioconvergent migratory hydroamination of isomeric mixtures of olefins forming single isomers of value-added benzylic or linear amines.

Nickel‐Catalyzed Switchable Site‐Selective Alkene Hydroalkylation by Temperature Regulation**

“…Based on precedents, Lu and Fu reported an aminoquinoline directed nickel‐catalyzed alkene hydroalkylation, and adjustments to the reaction ligands resulted in the switching on and off of alkylnickel chain‐walking [11] . In addition, regiodivergent alkene hydroamination/hydroamidation by the chain‐walking of a nickel‐hydride species has also been realized, and ligand‐controlled regiodivergence is state of the art [5b, 12] …”

Ligand‐Controlled NiH‐Catalyzed Regiodivergent Chain‐Walking Hydroalkylation of Alkenes

“…Notwithstanding recent advances, the protocol predominantly promotes functionalization at terminal [3] or α‐carbon adjacent to electron‐withdrawing groups such as aryl, [4] boryl, [5] and other moieties [6] (Scheme 1A). Moreover, the protocol generally incorporates functional groups only at a single position; functionalization of multiple sites within the same alkene starting material to produce either regioisomer remains elusive [7] . Therefore, it is highly significant and desirable to develop catalytic remote functionalization reactions with predicable and switchable regioselectivity to prepare structurally diverse functionalized branched molecules, which are difficult to access in a conventional chain‐walking regime.…”

Temperature-Regulated Regiodivergent Synthesis via Alkene Migratory Hydroalkylation

“…[13][14][15][16][17] In addition, carbon-carbon bond formation on remote and unfunctionalized sites enabled by the chain-walking process, a formal translocation of the original active site to a nonspecific position along with the carbon skeletons, allows for the synthesis of complex structures that would otherwise be difficult to prepare. [18][19][20][21][22][23][24][25] In the context of alkene functionalization, both catalysts and ligands could regulate the regiodivergence of hydrofunctionalization [26][27][28][29] and difunctionalization process [30][31][32][33][34] . In consideration of the essential problem that to achieve switchable selectivity using easily changed and controlled physical variables, switching reaction temperatures to provide the regiodivergent products starting from a single alkene substrate would be an ideal choice.…”