ChemInform Abstract: The Cyanation of Vinyl Halides with Alkali Cyanides Catalyzed by Nickel(0)-phosphine Complexes Generated in situ: Synthetic and Stereochemical Aspects.

One of the most oft-employed methods for C–C bond formation involving the coupling of vinyl-halides with aldehydes catalyzed by Ni and Cr (Nozaki–Hiyama–Kishi, NHK) has been rendered more practical using an electroreductive manifold. Although early studies pointed to the feasibility of such a process those precedents were never applied by others due to cumbersome setups and limited scope. Here we show that a carefully optimized electroreductive procedure can enable a more sustainable approach to NHK, even in an asymmetric fashion on highly complex medicinally relevant systems. The e-NHK can even enable non-canonical substrate classes, such as redox-active esters, to participate with low loadings of Cr when conventional chemical techniques fail. A combination of detailed kinetics, cyclic voltammetry, and in situ UV-vis spectroelectrochemistry of these processes illuminates the subtle features of this mechanistically intricate process.

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(DMP)DAB–Pd–MAH: A Versatile Pd(0) Source for Precatalyst Formation, Reaction Screening, and Preparative-Scale Synthesis

10.26434/chemrxiv.13604777 ◽

2021 ◽

Author(s):

Jingjun Huang ◽

Matthew Isaac ◽

Ryan Watt ◽

Joseph Becica ◽

Emma Dennis ◽

...

Keyword(s):

Room Temperature ◽

Cone Angle ◽

Phosphine Ligands ◽

Coupling Reactions ◽

Preparative Scale ◽

Formation Reaction ◽

Phosphine Complexes ◽

High Throughput Experimentation ◽

Large Cone Angle

We report an easily prepared and bench-stable mononuclear Pd(0) source stabilized by a chelating N,N’-diaryldiazabutadiene ligand and maleic anhydride: DMPDAB–Pd–MAH. Phosphine ligands of all types, including bidentate phosphines and large cone angle biarylphosphines, rapidly and completely displace the diazabutadiene ligand at room temperature to give air-stable Pd(0) phosphine complexes. DMPDAB–Pd–MAH itself is readily soluble and stable in several organic solvents, making it an ideal Pd source for in situ catalyst preparation during reaction screening, as well as solution-dispensing to plate-based reaction arrays for high-throughput experimentation. Evaluation of DMPDAB–Pd–MAH alongside other common Pd(0) and Pd(II) sources in microscale reaction screens reveals that DMPDAB–Pd–MAH is superior at identifying hits across six different C–N, C–C, and C–O coupling reactions. DMPDAB–Pd–MAH, and the phosphine precatalysts derived therefrom, are also effective in preparative-scale cross couplings at low Pd loadings.

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Electrochemical Nozaki–Hiyama–Kishi Coupling: Scope, Applications, and Mechanism

10.26434/chemrxiv.14251787.v1 ◽

2021 ◽

Author(s):

Yang Gao ◽

david hill ◽

wei hao ◽

Brendon J. McNicholas ◽

julien Vantourout ◽

...

Keyword(s):

Cyclic Voltammetry ◽

Bond Formation ◽

Active Esters ◽

Vinyl Halides ◽

Redox Active ◽

Chemical Techniques ◽

Detailed Kinetics ◽

Limited Scope

One of the most oft-employed methods for C–C bond formation involving the coupling of vinyl-halides with aldehydes catalyzed by Ni and Cr (Nozaki–Hiyama–Kishi, NHK) has been rendered more practical using an electroreductive manifold. Although early studies pointed to the feasibility of such a process those precedents were never applied by others due to cumbersome setups and limited scope. Here we show that a carefully optimized electroreductive procedure can enable a more sustainable approach to NHK, even in an asymmetric fashion on highly complex medicinally relevant systems. The e-NHK can even enable non-canonical substrate classes, such as redox-active esters, to participate with low loadings of Cr when conventional chemical techniques fail. A combination of detailed kinetics, cyclic voltammetry, and in situ UV-vis spectroelectrochemistry of these processes illuminates the subtle features of this mechanistically intricate process.

Download Full-text