Mechanisms, Challenges, and Opportunities of Dual Ni/Photoredox-Catalyzed C(sp2)-C(sp3) Cross-Couplings

Abstract

The merging of photoredox and nickel catalysis has revolutionized the field of C-C cross-coupling. However, in comparison to the development of synthetic methods, detailed mechanistic investigations of these catalytic systems are lagging. To improve the mechanistic understanding, computational tools have emerged as powerful tools to elucidate the factors controlling reactivity and selectivity in these complex catalytic transformations. Based on the reported computational studies, it appears that the mechanistic picture of catalytic systems is not generally applicable, but is rather dependent on the specific choice of substrate, ligands, photocatalysts, etc. Given the complexity of these systems, the need for more accurate computational methods, readily available and user-friendly dynamics simulation tools, and data-driven approaches is clear in order to understand at the molecular level the mechanisms of these transformations. In particular, we anticipate that such improvement of theoretical methods will become crucial to advance the understanding of excited-state properties and dynamics of key species, as well as to enable faster and unbiased exploration of reaction pathways. Further, with greater collaboration between computational, experimental, and spectroscopic communities, the mechanistic investigation of photoredox/Ni dual-catalytic reactions is expected to thrive quickly, facilitating the design of novel catalytic systems and promoting our understanding of the reaction selectivity.

Keywords: C-C cross-coupling; Photoredox/nickel dual catalysis; density functional theory; metallaphotoredox catalysis; molecular dynamics; olefin difunctionalization; reaction selectivity.

FIGURE 1

Commonly proposed mechanisms of photoredox/metal dual-catalyzed reactions. (A) Electron transfer events involved in light-irradiated conditions between the electron acceptor/donor and the excited photocatalyst (i.e., via oxidative or reductive quenching, respectively). (B) Proposed mechanism of metallaphotoredox-catalyzed carbon-carbon cross-coupling reactions, where radicals are generated via single-electron transfer between radical precursors and the excited photocatalyst. Sub = substrates; Prod = products. (C) Proposed mechanism of metallaphotoredox-catalyzed carbon-carbon cross-coupling reactions via H-atom abstraction in the presence of electron mediator.

FIGURE 2

Proposed mechanism of photoredox/Ni dual-catalyzed C(sp²)-C(sp³) bond-forming reaction. (A) Photoredox/Ni dual-catalyzed C(sp²)-C(sp³) cross-coupling between aryl bromides and alkyltrifluoroborate salts, including the construction of chiral centers via asymmetric catalysis. (B) Proposed catalytic cycles with calculated energetic values. Photocatalyst [Ir]^III = Ir[dF(CF₃)₂ppy]₂(bpy)PF₆. Relative Gibbs free energy values (kcal/mol;298 K) were calculated with (U)M06/6–311+G(d,p)-SMD(water)//UB3LYP/6–31G(d) level of theory. Both Ni(I)/Ni(II)/Ni(III)/Ni(I) and Ni(I)/Ni(III)/Ni(I) pathways are feasible. (C) Identification of reductive elimination as the stereodetermining step and the origin of stereoselectivity. (D) Comparison of experimental and calculated enantiomeric excess (ee) values for different aryl systems based on the proposed stereocontrol model.

FIGURE 3

Proposed mechanism of photoredox/Ni dual-catalyzed oxetanylation of aryl halides. (A) Experimental condition of photoredox/Ni dual-catalyzed construction of aryl aminooxetanes. (B) Proposed catalytic cycles with calculated energetics. Relative Gibbs free energy values (kcal/mol;298 K) were calculated with M06/6-311+G(d,p)-SDD(Ni)-SMD(DMSO)//B3LYP/6-31G(d)-LANL2DZ(Ni) level of theory.

FIGURE 4

(A) Photoredox/Ni dual-catalyzed single-electron Tsuji-Trost reaction (DHP = 1,4-dihydropyridine). (B) Proposed catalytic cycles with calculated energetics of the allylation of benzyl radical precursor with vinyl epoxide. Relative Gibbs free energy values (kcal/mol;298 K) were calculated with UM06/6-311+G(d,p)-SMD(water)//UB3LYP/6-31G(d) level of theory.

FIGURE 5

(A) Photoredox/Ni dual-catalyzed alkylation of oxa- and azabenzonorbornadienes (4-CzIPN = 2,4,5,6-tetra-9H-carbazol-9-yl-1,3-benzenedicarbonitrile). (B) Proposed catalytic cycles with calculated energetics of the alkylation of oxabenzonorbornadiene with benzyl radical precursor. Relative Gibbs free energy values (kcal/mol;298 K) were calculated with UM06/6-311+G(d,p)-CPCM(acetone)//UB3LYP-D3/6-31G(d)-CPCM(acetone) level of theory.

FIGURE 6

Proposed ligand-dependent mechanisms of photoredox/Ni dual-catalyzed C(sp²)-C(sp³) bond-forming reaction between tertiary alkyltrifluoroborates and aryl bromides. (A) Reported experimental results on the ligand-dependent performance of cross-coupling reactions of tertiary alkyl radicals in bipyridine (blue) and diketonoate (red) systems. (B) Proposed catalytic cycles of neutral bipyridine system. Superscripts indicate the spin state (2S+1) of the corresponding Ni complex. Relative Gibbs free energy values (kcal/mol;298 K) were calculated with UB3LYP-D3/def2-TZVPP-CPCM(THF)//UB3LYP-D3/def2-SVP-CPCM(THF) level of theory. (C) Proposed catalytic cycles of anionic diketonoate system. Relative Gibbs free energy values (kcal/mol;298 K) were calculated with UB3LYP-D3/def2-TZVPP-CPCM(DMA)//UB3LYP-D3/def2-SVP-CPCM(THF) level of theory.

FIGURE 7

Study of the different reactivity of various secondary and tertiary alkyl radicals. (A) The key pathway determining the reactivity of alkyl radicals and the relevant experimental results. (B) Relative Gibbs free energy values (kcal/mol; 298 K) of the generation of Ni(III) intermediate and the following reductive elimination step with respect to the square planar Ni(II)-phenyl-bromo intermediate. Relative Gibbs free energy values (kcal/mol;298 K) were calculated with respect to the sum of separated Ni(II) species and alkyl radical with UB3LYP-D3/def2-TZVPP-CPCM(THF)//UB3LYP-D3/def2-SVP-CPCM(THF) level of theory.

FIGURE 8

Proposed origin of different radical reactivity in the photoredox/Ni dual-catalyzed decarboxylative C(sp²)-C(sp³) bond-forming reaction. Relative Gibbs free energy values (kcal/mol;298 K) were calculated with respect to the sum of separated Ni(II) species and alkyl radical with UB3LYP-D3/def2-TZVPP-CPCM(DMA)//UB3LYP-D3/def2-SVP-CPCM(DMA) level of theory.

FIGURE 9

C-C cross-coupling enabled by C-H activation with the photoredox-Ni-HAT triple catalytic system. (A) Experimental condition and catalytic system (inset) of C(sp²)-C(sp³) and C(sp³)-C(sp³) bond-formation reactions. (B) Proposed catalytic cycles of the photoredox-Ni-HAT triple catalytic system.

FIGURE 10

Enantioselective photoredox/Ni dual-catalyzed dicarbofunctionalization of alkenes. (A) Experimental condition of the catalytic strategy. (B) Proposed catalytic cycles of the operating mechanism. Relative Gibbs free energy values (kcal/mol;298 K) were calculated with UB3LYP-D3(BJ)/def2-SVP-CPCM(THF) level of theory. Superscript indicates the spin state (2S+1) of Ni. (C) Origin of the enantioselectivity of the transformation. Color-filled reduced density gradient surface was created by the VMD program. Relative electronic energy values given were calculated at the same level of theory as structural optimization.

FIGURE 11

Photoredox/Ni dual-catalyzed dicarbofunctionalization of alkenes by photoinduced C-H activation via diaryl ketone hydrogen-atom transfer (HAT) catalysis. (A) Experimental condition of the catalytic strategy. (B) Proposed catalytic cycles of the operating mechanism. (C) Divergent reactivity of alkyl radical is determined by the competition between the metalation of the alkyl radical and the Giese addition processes. (D) Effect of hydrogen bonding in assisting the Giese addition step. Color-filled reduced density gradient surface was obtained via NCI analysis and created by the VMD program.