Nickel-Catalyzed Enantioselective Reductive Cross-Coupling Reactions

Nickel-catalyzed reductive cross-coupling reactions have emerged as powerful methods to join two electrophiles. These reactions have proven particularly useful for the coupling of sec-alkyl electrophiles to form stereogenic centers; however, the development of enantioselective variants remains challenging. In this Perspective, we summarize the progress that has been made toward Ni-catalyzed enantioselective reductive cross-coupling reactions

Nickel-Catalyzed Asymmetric Reductive Cross-Coupling To Access 1,1-Diarylalkanes

An asymmetric Ni-catalyzed reductive cross-coupling of (hetero)aryl iodides and benzylic chlorides has been developed to prepare enantioenriched 1,1-diarylalkanes. As part of these studies, a new chiral bioxazoline ligand, 4-heptyl-BiOX (L1), was developed in order to obtain products in synthetically useful yield and enantioselectivity. The reaction tolerates a variety of heterocyclic coupling partners, including pyridines, pyrimidines, indoles, and piperidines

Nickel-Catalyzed Enantioselective Cross-Coupling of N-Hydroxyphthalimide Esters with Vinyl Bromides

An enantioselective Ni-catalyzed cross-coupling of N-hydroxyphthalimide esters with vinyl bromides is reported. The reaction proceeds under mild conditions and uses tetrakis(N,N-dimethylamino)ethylene as a terminal organic reductant. Good functional group tolerance is demonstrated, with over 20 examples of reactions that proceed with >90% ee

Nickel-Catalyzed Conversion of Enol Triflates into Alkenyl Halides

A Ni‐catalyzed halogenation of enol triflates was developed and it enables the synthesis of a broad range of alkenyl iodides, bromides, and chlorides under mild reaction conditions. The reaction utilizes inexpensive, bench‐stable Ni(OAc)_2⋅4 H_2O as a precatalyst and proceeds at room temperature in the presence of sub‐stoichiometric Zn and either 1,5‐cyclooctadiene or 4‐(N,N‐dimethylamino)pyridine

Nickel-Catalyzed Asymmetric Reductive Cross-Coupling of a-Chloroesters with (Hetero)Aryl Iodides

An asymmetric reductive cross-coupling of alpha-chloroesters and (hetero)aryl iodides is reported. This nickel-catalyzed reaction proceeds with a chiral BiOX ligand under mild conditions, affording alpha-arylesters in good yields and enantioselectivities. The reaction is tolerant of a variety of functional groups, and the resulting products can be converted to pharmaceutically-relevant chiral building blocks. A multivariate linear regression model was developed to quantitatively relate the influence of the alpha-chloroester substrate and ligand on enantioselectivity

Nickel-catalyzed asymmetric reductive cross-couplings with vinyl bromide electrophiles

Nickel-catalyzed reductive cross-coupling reactions allow for the use of bench-stable electrophiles as both cross-coupling partners. In an effort to broaden the range of viable substrates in asym. transformations, two new cross-coupling reactions using vinyl bromide electrophiles were developed. The cross-coupling of vinyl bromides with chlorobenzyl silanes in the presence of a chiral nickel bis(oxazoline) catalyst and stoichiometric manganese reductant delivers chiral allyl silane products with excellent enantioselectivity. These products are known to participate in diastereoselective allylation reactions that form addnl. stereocenters, building mol. complexity. Application of the same catalyst-ligand system to the cross-coupling of vinyl bromides with N-hydroxyphthalimide esters gives rise to chiral allylic stereocenters in the presence of tetrakis(dimethylamino)ethylene as a terminal org. reductant

Correction to “Nickel-Catalyzed Asymmetric Reductive Cross-Coupling To Access 1,1-Diarylalkanes”

Correction to “Nickel-Catalyzed Asymmetric Reductive Cross-Coupling To Access 1,1-Diarylalkanes

Correction to “Nickel-Catalyzed Asymmetric Reductive Cross-Coupling To Access 1,1-Diarylalkanes”

Correction to “Nickel-Catalyzed Asymmetric Reductive Cross-Coupling To Access 1,1-Diarylalkanes