Mechanistic Interrogation of Co/Ni-Dual Catalyzed Hydroarylation

Abstract

Cobalt/nickel-dual catalyzed hydroarylation of terminal olefins with iodoarenes builds complexity from readily available starting materials, with a high preference for the Markovnikov (branched) product. Here, we advance a mechanistic model of this reaction through the use of reaction progress kinetic analysis (RPKA), radical clock experiments, and stoichiometric studies. Through exclusion of competing hypotheses, we conclude that the reaction proceeds through an unprecedented alkylcobalt to nickel direct transmetalation. Demonstration of catalytic alkene prefunctionalization, via spectroscopic observation of an organocobalt species, distinguishes this Csp²-Csp³ cross-coupling method from a conventional transmetalation process, which employs a stoichiometric organometallic nucleophile, and from a bimetallic oxidative addition of an organohalide across nickel, described by radical scission and subsequent alkyl radical capture at a second nickel center. A refined understanding of the reaction leads to an optimized hydroarylation procedure that excludes exogenous oxidant, demonstrating that the transmetalation is net redox neutral. Catalytic alkene prefunctionalization by cobalt and engagement with nickel catalytic cycles through direct transmetalation provides a new platform to merge these two rich areas of chemistry in preparatively useful ways.

Figure 1.

Electron-neutral alkenes and electron-deficient aryl iodides couple efficiently in Co/Ni-catalyzed cross-coupling.

Figure 2.

Different excess experiments varying initial concentrations of iodoarenes, olefin, and silane. Standard condition concentrations are [ArI]₀ = 0.32 M, [olefin]₀ = 0.42 M, and [silane]₀ = 0.64 M.

Figure 3.

Burés graphical rate analysis for (A) cobalt and (B) nickel.

Figure 4.

Different excess experiments with NFTPB. An induction period is observed at 20 mol % loading, but the rate is parallel to the standard conditions (a line has been added as a visual aid). Higher loadings of oxidant led to deleterious effects on the yield and rate, possibly due to off-pathway reactions with the nickel catalyst.

Figure 5.

(A) Evidence for stability of sec-alkyl-Co(Sal^t-Bu,t-Bu) organometallic complexes at room temperature: the active catalyst appears to be sequestered;^5d and (B) observation of two diastereotopic methyls at –0.4 and –0.5 ppm from Co(I) S_N2 and Co(III)/PhSiH₃/alkene combination.

Figure 6.

Hydroarylation with d₂-alkene indicates an irreversible HAT under catalytic conditions.

Figure 7.

(A) The coupling reaction with radical clock substrate (E)-1,6-octadiene and varying concentrations of nickel can indicate whether a radical chain mechanism is operative. (B) A comparative graph of relative U/R increase as a function of relative nickel precatalyst loading in nickel-radical cross-coupling mechanistic studies (see refs 18 and 19). The lack of a direct relationship in our work effectively excludes a radical chian mechanism (mechanism C).

Figure 8.

(A) An alkyl radical is generated and captured by cobalt, not nickel, in the reaction. The unrearranged and rearranged alkyl cobalt species directly transfer an alkyl ligand to nickel. The ratio of product displays a positive, albeit nonlinear, relationship to the concentration of salenCo(II) precatalyst. (B) Alkyl radical chain mechanisms using primary hexenyl-Co(salen) complexes elucidated by Kochi and coworkers.

Figure 9.

(A) Oxidation of Co^II(Sal^t-Bu,t-Bu) by NFTPT. (B) X-ray crystal structure of oxidized cobalt(III) product shown with 50% thermal ellipsoids. Two molecules of DMPU stabilize a coordinated water molecule.

Figure 10.

Low yield of o-tolyl hydroarylation product observed in catalytic reaction when using 2 as the nickel precatalyst.

Figure 11.

Dual catalytic cycles of cobalt/nickel-catalyzed branch-selective hydroarylation.

Figure 12.

Proposed mechanism of direct transmetalation between an alkyl cobalt and aryl nickel species (L = DMPU).

Scheme 1.

Observed Reactivity of Metal–Hydrides (M = Co, Mn, Fe) with Unactivated Olefins

Scheme 2.

Possible Mechanisms of the Cobalt/Nickel-Dual Catalyzed Hydroarylation

Scheme 3.

Standard Hydroarylation Conditions

Scheme 4.

Literature Precedent for Alkyl Ligand Transfer from Organocobalt to Nickel Chelates Relevant to the Wood–Ljungdahl Pathway

Scheme 5.

Coupling Reaction with a Radical Clock Substrate to Differentiate Mechanisms C and D

Scheme 6.. Stoichiometric Transmetalation Experiments

^a The reaction of i-Pr-Co(Salt-Bu,tBu)(pyr) (1) and dtbbpyNi(o-Tol)I (2) led to coupled product, o-cymene, in only 10% yield. 2-iodotoluene and biaryl (2,2’-dimethyl-1,1’-biphenyl) were also observed