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1. Impact of Oxidation State on Reactivity and Selectivity Differences between Nickel(III) and Nickel(IV) Alkyl Complexes

   https://doi.org/10.1002/anie.201903638  

   Roberts, Courtney C. ; Camasso, Nicole M. ; Bowes, Eric G. ; Sanford, Melanie S. ( May 2019 , Angewandte Chemie International Edition)

   Described is a systematic comparison of factors impacting the relative rates and selectivities of C(sp³)−C and C(sp³)−O bond‐forming reactions at high‐valent Ni as a function of oxidation state. Two Ni complexes are compared: a cationic octahedral Ni^IVcomplex ligated by tris(pyrazolyl)borate and a cationic octahedral Ni^IIIcomplex ligated by tris(pyrazolyl)methane. Key features of reactivity/selectivity are revealed: 1) C(sp³)−C(sp²) bond‐forming reductive elimination occurs from both centers, but the Ni^IIIcomplex reacts up to 300‐fold faster than the Ni^IV, depending on the reaction conditions. The relative reactivity is proposed to derive from ligand dissociation kinetics, which vary as a function of oxidation state and the presence/absence of visible light. 2) Upon the addition of acetate (AcO⁻), the Ni^IVcomplex exclusively undergoes C(sp³)−OAc bond formation, while the Ni^IIIanalogue forms the C(sp³)−C(sp²) coupled product selectively. This difference is rationalized based on the electrophilicity of the respective M−C(sp³) bonds, and thus their relative reactivity towards outer‐sphere S_N2‐type bond‐forming reactions.

    

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2. Impact of Oxidation State on Reactivity and Selectivity Differences between Nickel(III) and Nickel(IV) Alkyl Complexes

   https://doi.org/10.1002/ange.201903638  

   Roberts, Courtney C. ; Camasso, Nicole M. ; Bowes, Eric G. ; Sanford, Melanie S. ( May 2019 , Angewandte Chemie)

   Described is a systematic comparison of factors impacting the relative rates and selectivities of C(sp³)−C and C(sp³)−O bond‐forming reactions at high‐valent Ni as a function of oxidation state. Two Ni complexes are compared: a cationic octahedral Ni^IVcomplex ligated by tris(pyrazolyl)borate and a cationic octahedral Ni^IIIcomplex ligated by tris(pyrazolyl)methane. Key features of reactivity/selectivity are revealed: 1) C(sp³)−C(sp²) bond‐forming reductive elimination occurs from both centers, but the Ni^IIIcomplex reacts up to 300‐fold faster than the Ni^IV, depending on the reaction conditions. The relative reactivity is proposed to derive from ligand dissociation kinetics, which vary as a function of oxidation state and the presence/absence of visible light. 2) Upon the addition of acetate (AcO⁻), the Ni^IVcomplex exclusively undergoes C(sp³)−OAc bond formation, while the Ni^IIIanalogue forms the C(sp³)−C(sp²) coupled product selectively. This difference is rationalized based on the electrophilicity of the respective M−C(sp³) bonds, and thus their relative reactivity towards outer‐sphere S_N2‐type bond‐forming reactions.

    

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3. Nickel‐Catalyzed Enantioselective Reductive Alkyl‐Carbamoylation of Internal Alkenes

   https://doi.org/10.1002/anie.202207536  

   Wu, Xianqing ; Turlik, Aneta ; Luan, Baixue ; He, Feng ; Qu, Jingping ; Houk, K. N. ; Chen, Yifeng ( July 2022 , Angewandte Chemie International Edition)

   Herein, we leverage the Ni‐catalyzed enantioselective reductive dicarbofunctionalization of internal alkenes with alkyl iodides to enable the synthesis of chiral pyrrolidinones bearing vicinal stereogenic centers. The application of newly developed^1‐NapQuinim is critical for formation of two contiguous stereocenters in high yield, enantioselectivity, and diastereoselectivity. This catalytic system also improves both the yield and enantioselectivity in the synthesis of α,α‐dialkylated γ‐lactams. Computational studies reveal that the enantiodetermining step proceeds with a carbamoyl‐Ni^Iintermediate that is reduced by the Mn reductant prior to intramolecular migratory insertion. The presence of thet‐butyl group of the Quinim ligand leads to an unfavorable distortion of the substrate in the TS that leads to the minor enantiomer. Calculations also support an improvement in enantioselectivity with^1‐NapQuinim compared to^p‐tolQuinim.

    

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4. Nickel‐Catalyzed Enantioselective Reductive Alkyl‐Carbamoylation of Internal Alkenes

   https://doi.org/10.1002/ange.202207536  

   Wu, Xianqing ; Turlik, Aneta ; Luan, Baixue ; He, Feng ; Qu, Jingping ; Houk, K. N. ; Chen, Yifeng ( July 2022 , Angewandte Chemie)

   Herein, we leverage the Ni‐catalyzed enantioselective reductive dicarbofunctionalization of internal alkenes with alkyl iodides to enable the synthesis of chiral pyrrolidinones bearing vicinal stereogenic centers. The application of newly developed^1‐NapQuinim is critical for formation of two contiguous stereocenters in high yield, enantioselectivity, and diastereoselectivity. This catalytic system also improves both the yield and enantioselectivity in the synthesis of α,α‐dialkylated γ‐lactams. Computational studies reveal that the enantiodetermining step proceeds with a carbamoyl‐Ni^Iintermediate that is reduced by the Mn reductant prior to intramolecular migratory insertion. The presence of thet‐butyl group of the Quinim ligand leads to an unfavorable distortion of the substrate in the TS that leads to the minor enantiomer. Calculations also support an improvement in enantioselectivity with^1‐NapQuinim compared to^p‐tolQuinim.

    

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5. Scope and Mechanistic Probe into Asymmetric Synthesis of α-Trisubstituted-α-Tertiary Amines by Rhodium Catalysis

   https://doi.org/10.1021/jacs.3c04211  

   Arachchi, Madhawee K. ; Schaugaard, Richard N. ; Schlegel, H. Bernhard ; Nguyen, Hien M. ( September 2023 , Journal of the American Chemical Society)

   Asymmetric reactions that convert racemic mixtures into enantioenriched amines are of significant importance due to the prevalence of amines in pharmaceuticals, with about 60% of drug candidates containing tertiary amines. Although transition metal catalyzed allylic substitution processes have been developed to provide access to enantioenriched α-disubstituted allylic amines, enantioselective synthesis of sterically demanding α-tertiary amines with a tetrasubstituted carbon stereocenter remains a major challenge. Herein, we report a chiral diene-ligated rhodium catalyzed asymmetric substitution of racemic tertiary allylic trichloroacetimidates with aliphatic secondary amines to afford α-trisubstituted-α-tertiary amines. Mechanistic investigation is conducted using synergistic experimental and computational studies. Density functional theory calculations show that the chiral diene-ligated rhodium promotes the ionization of tertiary allylic substrates to form both anti and syn π-allyl intermediates. The anti π-allyl pathway proceeds through a higher energy than the syn π-allyl pathway. The rate of conversion of the less reactive π-allyl intermediate to the more reactive isomer via π−σ−π interconversion was faster than the rate of nucleophilic attack onto the more reactive intermediate. These data imply that the Curtin−Hammett conditions are met in the amination reaction, leading to dynamic kinetic asymmetric transformation. Computational studies also show that hydrogen bonding interactions between β-oxygen of allylic substrate and amine-NH greatly assist the delivery of amine nucleophile onto more hindered internal carbon of the π-allyl intermediate. The synthetic utility of the current methodology is showcased by efficient preparation of α-trisubstituted-α-tertiary amines featuring pharmaceutically relevant secondary amine cores with good yields and excellent selectivities (branched−linear >99:1, up to 99% enantiomeric excess). 

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