Catalytic asymmetric conjugate addition reactions represent a powerful strategy to access chiral molecules in contemporary organic synthesis. However, their applicability to conjugated alkenyl-N-heteroaromatic compounds, of particular interest in medicinal chemistry, has lagged behind applications to other substrates. We report a highly enantioselective and chemoselective catalytic transformation of a wide range of β-substituted conjugated alkenyl-N-heteroaromatics to their corresponding chiral alkylated products. This operationally simple methodology can introduce linear, branched, and cyclic alkyl chains, as well as a phenyl group, at the β-carbon position. The key to this success was enhancement of the reactivity of alkenyl-heteroaromatic substrates via Lewis acid activation, in combination with the use of readily available and highly reactive Grignard reagents and a copper catalyst coordinated by a chiral chelating diphosphine ligand.

BACKGROUND Ring‐closing metathesis (RCM) for the synthesis of macrocycles has been used more and more often over recent years, including some interesting applications on industrial scale. However, like all macrocyclization strategies RCM is plagued by the traditional issue of low volume efficiency. To‐date this is typically addressed in a molecule specific manner with varying degrees of success. Here we report a process intensification method of metathesis macrocyclization that reduces the solvent load required for the reaction significantly. RESULTS Metathesis macrocylizations were successfully carried out in a solvent volume of upto 82% lower than an equivalent batch reaction, with only minimal impact upon the reaction outcome. A switch of reaction solvent to ethyl acetate renders the process more benign and applicable to large scale. CONCLUSION A membrane‐assisted processing method that relies upon organic solvent nanofiltration permitting an internal solvent recycling and concumittent in situ product removal. The method is also designed to be applicable to a wide range of metathesis cyclizations. © 2019 Society of Chemical Industry

We present our design of a cross-catalytic system based on organocatalysis. The system features two organic reactions, namely a deprotection reaction of Fmoc protected proline and a Mannich reaction between...

A highly enantioselective and chemoselective catalytic transformation of a wide range of β‐substituted conjugated alkenyl‐N‐heteroaromatics to their corresponding chiral alkylated products is reported.