Buchler Glossary

Enantioselective Friedel-Crafts

Friedel-Crafts reactions in organic chemistry are referred to two main types of reactions, known as alkylation reactions and acylation reactions. Friedel-Crafts reactions are frequently employed to attach substituents to an aromatic ring. The Friedel-Crafts alkylation (FCA) reaction is one of the most straightforward approaches to the functionalization of aromatic compounds and the introduction of benzylic carbon stereocenters.

Enantioselective Friedel-Crafts-Alkylation

In particularly Cinchona Alkaloid based organocatalysts are widely used to establish the benzylic chiral center. These metal-free organic catalysts offers an economical, less toxic and environmentally friendly alternative to other catalytic systems.

α,β-unsaturated ketones as well as α,β-unsaturated aldehydes are for instance suitable electrophiles for the FCA-type Michael addition of N-unsubstituted pyrroles or indoles using 9-Epiamino Cinchona alkaloid catalysts. The corresponding addition products can be obtained in good to excellent yields and with high enantioselectivity.

On the other hand highly enantioselective aza-Friedel–Crafts (aza-F-C) reaction of cyclic trifluoromethyl ketimines and naphthols/phenols can be obtained with up to 99% yields and up to 99% ee’s using Quinine-squaramide as a catalyst. Also Cinchona alkaloid-urea bifunctional organocatalysts are often applied to synthesize a broad range of Friedel-Crafts adducts with high enantioselectivities. Similarly Cinchona based bifunctional thiourea organocatalysts enable the aza-Friedel–Crafts reaction of 1-naphthol with isatin derived N-Boc ketimines.

A further asymmetric aza-Friedel–Crafts reaction of naphthols with N-sulfonyl imines can be reviewed in our free of charge chiral catalyst search data Base. The cupreine-derived bifunctional organocatalyst BzCPN efficiently catalyzes the formation of aza-Friedel–Crafts products in good to excellent yields (up to 99 %) with high enantioselectivities (up to 99.5:0.5 er) under mild reaction conditions, with a low catalyst loading (2–5 mol-%), and in an aerobic environment.

You will find a lot of enantioselective Friedel-Crafts reactions in our free of charge Chiral Catalyst Search Data Base.

Example from Literature

The origin for highly enantioselective induction of 1-naphthol to isatin-derived N-Boc ketimines catalyzed by quinine thiourea catalyst: an experimental and computational study. (Barik et al.; RSC Adv. 2015, 5, 69493–69501.)

Friedel-Crafts reaction

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