The influence of additives on orthogonal reaction pathways in the Mizoroki–Heck arylation of vinyl ethers

Abstract

The Mizoroki–Heck arylation of electron-rich alkenes such as butyl vinyl ether often results in regioisomeric mixtures of products under typical reaction conditions. To discover new catalytic systems for achieving α-selective arylation, an alternative approach to generating aryl methyl ketones, we have combined microscale high-throughput experimentation with mechanistic studies on a model system. A specific combination of catalyst, solvent, base, and additives was found to be crucial for both activity and selectivity, especially when translating screening hits into preparative-scale synthesis.