Mechanistic Investigations of the Asymmetric Hydrogenation of Enamides with Neutral Bis(phosphine) Cobalt Precatalysts

The mechanism of the asymmetric hydrogenation of prochiral enamides by well-defined, neutral bis(phosphine) cobalt(0) and cobalt(II) precatalysts has been explored using(R,R)-iPrDuPhos ((R,R)-iPrDuPhos = (+)-1,2-bis[(2R,5R)-2,5-diisopropylphospholano]benzene) as a representative chiral bis(phosphine) ligand. A series of (R,R)-(iPrDuPhos)Co(enamide) (enamide = methyl-2-acetamidoacrylate (MAA), methyl(Z)-α-acetamidocinnamate (MAC), and methyl(Z)-acetamido(4-fluorophenyl)acrylate (4FMAC)) complexes (1-MAA, 1-MAC, and 1-4FMAC), as well as a dinuclear cobalt tetrahydride, [(R,R)-(iPrDuPhos)Co]2(μ2-H)3(H) (2), were independently synthesized, characterized, and evaluated in both stoichiometric and catalytic hydrogenation reactions. Characterization of (R,R)-(iPrDuPhos)Co(enamide) complexes by X-ray diffraction established the formation of the pro-(R) diastereomers in contrast to the (S)-alkane products obtained from the catalytic reaction. In situ monitoring of the cobalt-catalyzed hydrogenation reactions by UV–visible and freeze-quench electron paramagnetic resonance spectroscopies revealed (R,R)-(iPrDuPhos)Co(enamide) complexes as the catalyst resting state for all the three enamides studied. Variable time normalization analysis kinetic studies of the cobalt-catalyzed hydrogenation reactions in methanol established a rate law that is first order in (R,R)-(iPrDuPhos)Co(enamide) and H2 but independent of the enamide concentration. Deuterium-labeling studies, including measurement of an H2/D2 kinetic isotope effect and catalytic hydrogenations with HD, established an irreversible H2 addition step to the bound enamide. Density functional theory calculations support that this step is both rate and selectivity determining. Calculations, as well as HD-labeling studies, provide evidence for two-electron redox cycling involving cobalt(0) and cobalt(II) intermediates during the catalytic cycle. Taken together, these experiments support an unsaturated pathway for the [(R,R)-(iPrDuPhos)Co]-catalyzed hydrogenation of prochiral enamides

Mechanistic Studies of Ethylene Hydrophenylation Catalyzed by Bipyridyl Pt(II) Complexes

This article discusses mechanistic studies of ethylene hydrophenylation catalyzed by bipyridyl Pt(II) complexes

Mechanistic Studies of Ethylene Hydrophenylation Catalyzed by Bipyridyl Pt(II) Complexes

This article discusses mechanistic studies of ethylene hydrophenylation catalyzed by bipyridyl Pt(II) complexes

Bis(phosphine)cobalt Dialkyl Complexes for Directed Catalytic Alkene Hydrogenation

Planar, low-spin cobalt­(II) dialkyl complexes bearing bidentate phosphine ligands, (P–P)­Co­(CH₂SiMe₃)₂, are active for the hydrogenation of geminal and 1,2-disubstituted alkenes. Hydrogenation of more hindered internal and endocyclic trisubstituted alkenes was achieved through hydroxyl group activation, an approach that also enables directed hydrogenations to yield contrasteric isomers of cyclic alkanes

Platinum(II)-Catalyzed Ethylene Hydrophenylation: Switching Selectivity between Alkyl- and Vinylbenzene Production

Article discussing platinum(II)-catalyzed ethylene hydrophenylation and the influence of dipyridyl chelate ring size on catalyst activity and longevity

Cobalt-Catalyzed Enantioselective Hydrogenation of Minimally Functionalized Alkenes: Isotopic Labeling Provides Insight into the Origin of Stereoselectivity and Alkene Insertion Preferences

The asymmetric hydrogenation of cyclic alkenes lacking coordinating functionality with a <i>C</i>₁-symmetric bis­(imino)­pyridine cobalt catalyst is described and has been applied to the synthesis of important substructures found in natural products and biologically active compounds. High activities and enantioselectivities were observed with substituted benzo-fused five-, six-, and seven-membered alkenes. The stereochemical outcome was dependent on both the ring size and exo/endo disposition. Deuterium labeling experiments support rapid and reversible 2,1-insertion that is unproductive for generating alkane product but accounts for the unusual isotopic distribution in deuterated alkanes. Analysis of the stereochemical outcome of the hydrogenated products coupled with isotopic labeling, stoichiometric, and kinetic studies established 1,2-alkene insertion as both turnover limiting and enantiodetermining with no evidence for erosion of cobalt alkyl stereochemistry by competing β-hydrogen elimination processes. A stereochemical model accounting for the preferred antipodes of the alkanes is proposed and relies on the subtle influence of the achiral aryl imine substituent on the cobalt catalyst

Platinum(II)-Catalyzed Ethylene Hydrophenylation: Switching Selectivity between Alkyl- and Vinylbenzene Production

The series of Pt^II complexes [(^xbpy)­Pt­(Ph)­(THF)]­[BAr′₄] (^xbpy =4,4′-X-2,2′-bipyridyl, X = OMe, ^tBu, H, Br, CO₂Et, NO₂; Ar′ = 3,5-bis­(trifluoromethyl)­phenyl) are catalyst precursors for ethylene hydrophenylation. The bipyridyl substituent provides a tunable switch for catalyst selectivity that also has significant influence on catalyst activity and longevity. Less electron donating 4,4′-substituents increase the propensity toward styrene formation over ethylbenzene

Nickel-Catalyzed Asymmetric Alkene Hydrogenation of α,β-Unsaturated Esters: High-Throughput Experimentation-Enabled Reaction Discovery, Optimization, and Mechanistic Elucidation

A highly active and enantioselective phosphine-nickel catalyst for the asymmetric hydrogenation of α,β-unsaturated esters has been discovered. The coordination chemistry and catalytic behavior of nickel halide, acetate, and mixed halide-acetate with chiral bidentate phosphines have been explored and deuterium labeling studies, the method of continuous variation, nonlinear studies, and kinetic measurements have provided mechanistic understanding. Activation of molecular hydrogen by a trimeric (Me–DuPhos)₃Ni₃(OAc)₅I complex was established as turnover limiting followed by rapid conjugate addition of a nickel hydride and nonselective protonation to release the substrate. In addition to reaction discovery and optimization, the previously unreported utility high-throughput experimentation for mechanistic elucidation is also described