Asymmetric Organocatalyzed Friedel–Crafts Reaction of Trihaloacetaldehydes and Phenols

Herein we report the asymmetric organocatalyzed method for the Friedel–Crafts reaction between activated phenols and trihaloacetaldehydes. A three‐phase screening including 41 compounds was employed to identify a catalyst structure based on 3,5‐dinitrobenzamide of 9‐amino‐epi‐cinchonidine as the lead catalytic molecule. Under the optimized reaction conditions, the above catalyst offered trihalohydroxyalkylated adducts in yields ranging from 26 to 92% and enantiomeric ratios within 69:31–99:1. The reaction scope was determined on 29 entries and several follow‐up transformations of the enantioenriched products were accomplished.