Steering selective stereochemistry from racemic alkyls

Abstract

Making carbon-carbon bonds is hard. Linking racemic mixtures of two alkyls while simultaneously controlling the stereochemistry of both ends of the product is nigh impossible. Gregory Fu, together with his colleagues at the California Institute of Technology, has found a way to make it easy. Using a chiral nickel catalyst, Fu coupled a racemic mixture of electrophiles and nucleophiles with up to 82% yield and 95% stereoselectivity (Science 2020, DOI: 10.1126/science.aaz3855). What’s more, this unlikely reaction is compatible with 19 functional groups. Most substitution reactions for forming the C–C bonds critical to pharmaceutical manufacturing have major limitations. They work for only some alkyl compounds and often lead to side reactions, especially with bulky substituents. Plus, these reactions tend to form a racemic mixture of products. But usually only one isomer of a pharmaceutical compound is biologically active. For the catalyst to be stereoselective, its ligand needs to discern between the