Asymmetric Organocatalyzed Friedel–Crafts Reaction of Trihaloacetaldehydes and Phenols

Abstract

Abstract 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. magnified image

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