No abstract

Ni-catalyzed cross-electrophile coupling reactions have emerged as appealing methods to construct organic molecules without the use of stoichiometric organometallic reagents. The mechanisms are complex: plausible pathways, such as "radical chain" and "sequential reduction" mechanisms, are dependent on the sequence of the activation of electrophiles. A combination of kinetic, spectroscopic, and organometallic studies reveals that a Ni-catalyzed, reductive 1,2dicarbofunctionalization of alkenes proceeds through a "sequential reduction" pathway. The reduction of Ni by Zn is the turnover-limiting step, consistent with Ni(II) intermediates as the catalyst resting-state. Zn is only sufficient to reduce (phen)Ni(II) to a Ni(I) species. As a result, commonly proposed Ni(0) intermediates are absent under these conditions. (Phen)Ni(I)-Br selectively activates aryl bromides via two-electron oxidation addition, whereas alkyl bromides are activated by (phen)Ni(I)-Ar through single-electron activation to afford radicals. These findings could provide insight into achieving selectivity between different electrophiles.

Conspectus Nickel complexes exhibit distinct properties from other group 10 metals, including a small nuclear radius, high paring energy, low electronegativity, and low redox potentials. These properties enable Ni catalysts to accommodate and stabilize paramagnetic intermediates, access radical pathways, and undergo slow β-H elimination. Our research program investigates how each of these fundamental attributes impact the catalytic properties of Ni, in particular in the context of alkene functionalization. Alkenes are versatile functional groups, but stereoselective carbofunctionalization reactions of alkenes have been underdeveloped. This challenge may derive from the difficulty of controlling selectivity via traditional two-electron migratory insertion pathways. Ni catalysts could lead to different stereodetermining steps via radical mechanisms, allowing access to molecular scaffolds that are otherwise difficult to prepare. For example, an asymmetric alkene diarylation reaction developed by our group relies upon the radical properties of Ni­(III) intermediates to control the enantioselectivity and give access to a library of chiral α,α,β-triarylethane molecules with biological activity. Mechanistic studies on a two-component reductive 1,2-difunctionalization reaction have shed light on the origin of the cross-electrophile selectivity, as C sp2 and C sp3 electrophiles are independently activated at Ni­(I) via two-electron and radical pathways, respectively. Catalyst reduction has been identified to be the turnover-limiting step in this system. A closer investigation of the radical formation step using a (Xantphos)­Ni­(I)Ar model complex reveals that Ni­(I) initiates radical formation via a concerted halogen-abstraction pathway. The low redox potentials of Ni have allowed us to develop a reductive, trans-selective diene cyclization, wherein a classic two-electron mechanism operates on a Ni­(I)/Ni­(III) platform, accounting for the chemo- and stereoselectivity. This reaction has found applications in the efficient synthesis of pharmaceutically relevant molecules, such as 3,4-dimethylgababutin. The tendency of Ni to undergo one-electron redox processes prompted us to explore dinuclear Ni-mediated bond formations. These studies provide insight into Ni–Ni bonding and how two metal centers react cooperatively to promote C–C, C–X, and N–N bond forming reductive elimination. Finally, isolation of β-agostic Ni and Pd complexes has allowed for X-ray and neutron diffraction characterization of these highly reactive molecules. The bonding parameters serve as unambiguous evidence for β-agostic interactions and help rationalize the slower β-H elimination at Ni relative to Pd. Overall, our research has elucidated the fundamental properties of Ni complexes in several contexts. Greater mechanistic understanding facilitates catalyst design and helps rationalize the reactivity and selectivity in Ni-catalyzed alkene functionalization reactions.

α,β-Unsaturated carbonyl compounds are versatile intermediates in the synthesis of pharmaceuticals and biologically active compounds. Here, we report the discovery and application of Pd(DMSO)2(TFA)2 as a catalyst for direct dehydrogenation of cyclohexanones and other cyclic ketones to the corresponding enones, using O2 as the oxidant. The substrate scope includes heterocyclic ketones and several natural-product precursors.

The aryl-substituted bis(imino)pyridine cobalt methyl complex, ((Mes)PDI)CoCH3 ((Mes)PDI = 2,6-(2,4,6-Me3C6H2-N═CMe)2C5H3N), promotes the catalytic dehydrogenative silylation of linear α-olefins to selectively form the corresponding allylsilanes with commercially relevant tertiary silanes such as (Me3SiO)2MeSiH and (EtO)3SiH. Dehydrogenative silylation of internal olefins such as cis- and trans-4-octene also exclusively produces the allylsilane with the silicon located at the terminus of the hydrocarbon chain, resulting in a highly selective base-metal-catalyzed method for the remote functionalization of C-H bonds with retention of unsaturation. The cobalt-catalyzed reactions also enable inexpensive α-olefins to serve as functional equivalents of the more valuable α, ω-dienes and offer a unique method for the cross-linking of silicone fluids with well-defined carbon spacers. Stoichiometric experiments and deuterium labeling studies support activation of the cobalt alkyl precursor to form a putative cobalt silyl, which undergoes 2,1-insertion of the alkene followed by selective β-hydrogen elimination from the carbon distal from the large tertiary silyl group and accounts for the observed selectivity for allylsilane formation.