Chiral N‐Heterocyclic Carbene Ligands Bearing a Pyridine Moiety for the Copper‐Catalyzed Alkylation of N‐Sulfonylimines with Dialkylzinc Reagents

Amino acid‐derived chiral imidazolium salts, each bearing a pyridine ring, were developed as N‐heterocyclic carbene ligands. The copper‐catalyzed asymmetric alkylation of various N‐sulfonylimines with dialkylzinc reagents in the presence of these chiral imidazolium salts afforded the corresponding alkylated products with high enantioselectivity (up to 99 % ee). The addition of HMPA to the reaction mixture as a co‐solvent is critical in terms of chemical yield and enantioselectivity. A wide range of N‐sulfonylimines and dialkylzinc reagents were found to be applicable to this reaction.     

An Iridium(I) N‐Heterocyclic Carbene Complex Catalyzes Asymmetric Intramolecular Allylic Amination Reactions

A chiral iridium(I) N‐heterocyclic carbene complex was reported for the first time as the catalyst in the highly enantioselective intramolecular allylic amination reaction. The current method provides facile access to biologically important enantioenriched indolopiperazinones and piperazinones in good yields (74–91 %) and excellent enantioselectivities (92–99 % ee). Preliminary mechanistic investigations reveal that the C?H activation occurs at the position ortho to the N‐aryl group of the ligand.     

Copper‐Catalyzed Enantioselective Allyl–Allyl Coupling between Allylic Boronates and Phosphates with a Phenol/N‐Heterocyclic Carbene Chiral Ligand

Copper‐catalyzed enantioselective allyl–allyl coupling between allylboronates and either Z‐acyclic or cyclic allylic phosphates using a new chiral N‐heterocyclic carbene ligand, bearing a phenolic hydroxy, is reported. This reaction occurs with exceptional S_N2′‐type regioselectivities and high enantioselectivities to deliver chiral 1,5‐diene derivatives with a tertiary stereogenic center at the allylic/homoallylic position.     

Catalytic Asymmetric Hydroalkenylation of Vinylarenes: Electronic Effects of Substrates and Chiral N‐Heterocyclic Carbene Ligands

An asymmetric tail‐to‐tail cross‐hydroalkenylation of vinylarenes with terminal olefins was achieved by catalysis with NiH complexes bearing chiral N‐heterocyclic carbenes (NHCs). The reaction provides branched gem‐disubstituted olefins with high enantioselectivity (up to 94 % ee) and chemoselectivity (cross/homo product ratio: up to 99:1). Electronic effects of the substituents on the vinylarenes and on the N‐aryl groups of the NHC ligands, but not a π,π‐stacking mechanism, assist the steric effect and influence the outcome of the cross‐hydroalkenylation.     

Enantioselective Synthesis of All‐Carbon Quaternary Stereogenic Centers via Copper‐Catalyzed Asymmetric Allylic Alkylation of (Z)‐Allyl Bromides with Organolithium Reagents

A copper/phosphoramidite catalyzed asymmetric allylic alkylation of Z trisubstituted allyl bromides with organolithium reagents is reported. The reaction affords all‐carbon quaternary stereogenic centers in high yields and very good regio‐ and enantioselectivity. This systematic study illustrates the crucial role of the olefin geometry of the allyl substrate on the outcome of the reaction and provides a viable alternative to access these important structural motifs.     

N‐Heterocyclic Carbene Catalyzed Enantioselective α‐Fluorination of Aliphatic Aldehydes and α‐Chloro Aldehydes: Synthesis of α‐Fluoro Esters,Amides, and Thioesters

The asymmetric fluorination of azolium enolates that are generated from readily available simple aliphatic aldehydes or α‐chloro aldehydes and N‐heterocyclic carbenes (NHCs) is described. The process significantly expands the synthetic utility of NHC‐catalyzed fluorination and provides facile access to a wide range of α‐fluoro esters, amides, and thioesters with excellent enantioselectivity. Pyrazole was identified as an excellent acyl transfer reagent for catalytic amide formation.     

A Cooperative N‐Heterocyclic Carbene/Chiral Phosphate Catalysis System for Allenolate Annulations

The highly enantioselective NHC‐catalyzed [3+2] annulation reaction with α,β‐alkynals and α‐ketoesters has been developed. A new mode of cooperative catalysis involving the combination of a chiral Brønsted acid and a C₁‐symmetric biaryl saturated‐imidazolium precatalyst was required to generate the desired γ‐crotonolactones in high yields and levels of enantioselectivity.     

Cu‐Catalyzed Asymmetric Allylic Alkylation of Phosphonates and Phosphine Oxides with Grignard Reagents

An efficient and highly enantioselective copper‐catalyzed allylic alkylation of phosphonates and phosphine oxides with Grignard reagents and Taniaphos or phosphoramidites as chiral ligands is reported. Transformation of these products leads to a variety of new phosphorus‐containing chiral intermediates.