Development of a Selective Friedel-Crafts Alkylation Surrogate: Safe Operating Conditions through Mechanistic Understanding

摘要

This article describes a selective one-pot, Friedel-Crafts acylation/ketone reduction protocol, effectively a surrogate for the Friedel桟rafts alkylation reaction with a primary alkyl halide. A potentially dangerous failure mode was identified, resulting in the uncontrolled evolution of hydrogen, A series of mechanistic experiments, including analysis by ~(27)A1 NMR, was undertaken, and the reaction mechanism elucidated. Finally, the use of React IR to ensure real-time reaction safety was demonstrated.