Theoretical study of nickel-catalyzed hydroalkylation of 3-pyrrolines: Origin of ligand-controlled regioselectivity

Xu, Wan; Pei, Guojing; Liu, Yongyin; Song, Guanghui; Li, Juan

doi:10.1016/j.mcat.2022.112238

Cited by 7 publications

(5 citation statements)

References 66 publications

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“…The calculations suggest that under the reaction conditions the Ni(II) salt precatalyst would first convert to the biOx-chelated Ni(II) dihydride complex (biOx)NiH 2 ( IM4 ) in a thermodynamically and kinetically favorable process. This result is consistent with a finding of a previous computational study by Li et al The Ni(II) dihydride complex in that study was further subjected to the reductive elimination of H 2 to form a Ni(0) complex. However, in another earlier computational study by Wang et al, a Ni(II) dihydride complex was considered for alkene insertion into one of its Ni–H bonds to give a Ni(II) alkyl monohydride intermediate, which then undergoes hydrogen–alkyl reductive elimination to form a singlet Ni(0) complex.…”

Section: Resultssupporting

confidence: 93%

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Understanding the Reaction Mechanism of Ni-Catalyzed Regio- and Enantioselective Hydroalkylation of Enamines: Chemoselectivity of (Bi-oxazoline)NiH

Tong,

Su,

Sun

et al. 2023

J. Org. Chem.

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This density functional theory study explores the detailed mechanism of nickel-catalyzed hydroalkylation of the CC bond of N-Cbz-protected enamines (Cbz = benzyloxycarbonyl) with alkyl iodides to give chiral α-alkyl amines. The active catalyst (biOx)NiH, a chiral bioxazoline (biOx)-chelated Ni(I) hydride, exhibits chemoselectivity that favors single electron transfer to the alkyl iodide over CC hydrometalation with the enamine. This generates an alkyl radical and a Ni(II) intermediate, which takes up the enamine substrate CbzNHCHCH2CH3 via a regio- and enantioselective CC insertion into the NiII–H bond. The resulting Ni(II) alkyl complex combines with the alkyl radical, forming a Ni(III) intermediate, from which the alkyl–alkyl reductive elimination delivers the chiral amine product. The regioselectivity arises from a combination of orbital and noncovalent interactions, both of which are induced by the Cbz group. Thus, Cbz plays an additional role in controlling regioselectivity. The enantioselectivity stems from the differing distortion energies of CbzNHCHCH2CH3. The reductive elimination is the rate-determining step (ΔG ⧧ = 18.7 kcal/mol). In addition, the calculations show a noninnocent behavior of the biOx ligand induced by the insertion of CbzNHCHCH2CH3 into the Ni–H bond of (biOx)NiH. These computationally gained insights can have implications for developing new Ni(I)-catalyzed reactions.

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Section: Resultssupporting

confidence: 93%

“…The bromide exchange reactions of IM1/ 3 IM1 with the fluoride additive were computed by approximating fluoride and bromide ions as the entering and leaving ligands, which produce the fluoride complexes IM2/ 3 IM2 with a large thermodynamic driving force. Note that the triplet 3 IM2 is lower than the singlet IM2 in energy by 4.4 kcal/mol.…”

Section: Resultsmentioning

confidence: 99%

Understanding the Reaction Mechanism of Ni-Catalyzed Regio- and Enantioselective Hydroalkylation of Enamines: Chemoselectivity of (Bi-oxazoline)NiH

Tong,

Su,

Sun

et al. 2023

J. Org. Chem.

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“…Based on the above results and previous mechanistic studies of related reactions, [7,15] we propose a Ni I /Ni III catalytic cycle for the C2-selective alkylation as shown in Figure 6. The mixing of a Ni II salt with the ligand gives a Ni II -halide species (A), which would immediately react with a silane in the presence of a base to give a Ni II À H species (B), which is the main resting species of the reaction.…”

Section: Forschungsartikelsupporting

confidence: 64%

“…A previous DFT study suggests that a Ni 0 complex formed by reduction of a Ni II complex with a silane acts as the initial catalytic species. [15] Our data indicates that in our system the formation of a Ni 0 complex is not sufficient to initiate the catalysis.…”

Section: Forschungsartikelmentioning

confidence: 65%

Regiodivergent and Enantioselective Synthesis of Cyclic Sulfones via Ligand‐Controlled Nickel‐Catalyzed Hydroalkylation

Fan,

Dhawa,

Qian

et al. 2024

Angewandte Chemie

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Cyclic sulfones have demonstrated important applications in drug discovery. However, the catalytic and enantioselective synthesis of chiral cyclic sulfones remains challenging. Herein, we develop nickel‐catalyzed regiodivergent and enantioselective hydroalkylation of sulfolenes to streamline the synthesis of chiral alkyl cyclic sulfones. The method has broad scope and high functional group tolerance. The regioselectivity can be controlled by ligands only. A neutral PYROX ligand favors C3‐alkylation whereas an anionic BOX ligand favors C2‐alkylation. This control is kinetic in origin as the C2‐bound Ni intermediates are always thermodynamically more stable. Reactivity study of a wide range of relevant Ni intermediates reveal a NiI/NiIII catalytic cycle with a NiII‐H species as the resting state. The regio‐ and enantio‐determining step is the insertion of this NiII‐H species into 2‐sulfolene. This work provides an efficient catalytic method for the synthesis of an important class of organic compounds and enhances the mechanistic understanding of Ni‐catalyzed stereoselective hydroalkylation.

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“…4 Considering its potential applications, researchers in the fields of organic and medicinal chemistry have shown great interest in developing an efficient and straightforward approach to synthesize 2,5-dihydropyrrole cores. 5 In pursuit of this objective, numerous efforts have been dedicated to the synthesis of 2,5-dihydropyrroles, with various methods being reported. 6 Notably, metal salts or complexes, such as Rh, 7 Pd, 8 Cu, 9 Fe, 10 Ag, 11 Ni, 12 etc.…”

Section: Introductionmentioning

confidence: 99%

A copper-catalyzed annulation reaction of diazo esters with propargyl amines for the synthesis of 2,5-dihydropyrroles

Xie,

Zhao,

Wei

et al. 2024

Org. Chem. Front.

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Theoretical study of nickel-catalyzed hydroalkylation of 3-pyrrolines: Origin of ligand-controlled regioselectivity

Cited by 7 publications

References 66 publications

Understanding the Reaction Mechanism of Ni-Catalyzed Regio- and Enantioselective Hydroalkylation of Enamines: Chemoselectivity of (Bi-oxazoline)NiH

Understanding the Reaction Mechanism of Ni-Catalyzed Regio- and Enantioselective Hydroalkylation of Enamines: Chemoselectivity of (Bi-oxazoline)NiH

Regiodivergent and Enantioselective Synthesis of Cyclic Sulfones via Ligand‐Controlled Nickel‐Catalyzed Hydroalkylation

A copper-catalyzed annulation reaction of diazo esters with propargyl amines for the synthesis of 2,5-dihydropyrroles

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