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

This article describes a selective one-pot, Friedel–Crafts acylation/ketone reduction protocol, effectively a surrogate for the Friedel–Crafts 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 ²⁷Al NMR, was undertaken, and the reaction mechanism elucidated. Finally, the use of React IR to ensure real-time reaction safety was demonstrated