No abstract

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.

Ni­(I)-mediated single-electron oxidative activation of alkyl halides has been extensively proposed as a key step in Ni-catalyzed cross-coupling reactions to generate radical intermediates. There are four mechanisms through which this step could take place: oxidative addition, outer-sphere electron transfer, inner-sphere electron transfer, and concerted halogen-atom abstraction. Despite considerable computational studies, there is no experimental study to evaluate all four pathways for Ni­(I)-mediated alkyl radical formation. Herein, we report the isolation of a series of (Xantphos)­Ni­(I)–Ar complexes that selectively activate alkyl halides over aryl halides to eject radicals and form Ni­(II) complexes. This observation allows the application of kinetic studies on the steric, electronic, and solvent effects, in combination with DFT calculations, to systematically assess the four possible pathways. Our data reveal that (Xantphos)­Ni­(I)-mediated alkyl halide activation proceeds via a concerted halogen-atom abstraction mechanism. This result corroborates previous DFT studies on (terpy)­Ni­(I)- and (py)­Ni­(I)-mediated alkyl radical formation, and contrasts with the outer-sphere electron transfer pathway observed for (PPh3)4Ni­(0)-mediated aryl halide activation. This study of a model system provides insight into the overall mechanism of Ni-catalyzed cross-coupling reactions and offers a basis for differentiating electrophiles in cross-electrophile coupling reactions.

Ni-catalyzed cross-coupling reactions have found important applications in organic synthesis. The fundamental characterization of the key steps in cross-coupling reactions, including C-C bond-forming reductive elimination, represents a significant challenge. Bimolecular pathways were invoked in early proposals, but the experimental evidence was limited. We present the preparation of well-defined (pyridine-pyrrolyl)Ni monomethyl and monophenyl complexes that allow the direct observation of bimolecular reductive elimination to generate ethane and biphenyl, respectively. The sp(3)-sp(3) and sp(2)-sp(2) couplings proceed via two distinct pathways. Oxidants promote the fast formation of Ni(III) from (pyridine-pyrrolyl)Ni-methyl, which dimerizes to afford a bimetallic Ni(III) intermediate. Our data are most consistent with the subsequent methyl coupling from the bimetallic Ni(III) to generate ethane as the rate-determining step. In contrast, the formation of biphenyl is facilitated by the coordination of a bidentate donor ligand.

Natural products containing N-N bonds exhibit important biological activity. Current methods for constructing N-N bonds have limited scope. An advanced understanding of the fundamental N-N bond formation/cleavage processes occurring at the transition-metal center would facilitate the development of catalytic reactions. Herein we present an N-N bond-forming reductive elimination, which proceeds via a mixed-valent Ni(II) -Ni(III) intermediate with a Ni-Ni bond order of zero. The discrete Ni(II) -Ni(III) oxidation states contrast with the cationic dimeric Ni analogue, in which both Ni centers are equivalent with an oxidation state of 2.5. The electronic structures of these mixed-valent complexes have implications for the fundamental understanding of metal-metal bonding interactions.