Abstract

The Friedel–Crafts (F–C) reaction has been a fundamental pillar of both academic and industrial synthetic organic chemistry since its discovery in 1873. Its success is based on the versatility and applicability of F–C reactions for a wide range of substrates, and there have been an impressive number of publications and patents describing catalytic F–C reaction methods. The asymmetric version of the reaction was discovered about 100 years after the seminal work by Friedel and Crafts and has become a major area of research. While chemical methods with much-improved efficacies and scopes have been discovered, F–C reactions still suffer from limitations. Biocatalysis has the potential to be the best solution to this challenge because of the excellent selectivity (enantio-, chemo-, and regioselectivity) displayed by enzymes. In the last two decades, advancements in molecular biology techniques, bioinformatics, high-throughput screening, directed evolution, and process scale-up have led to biocatalysis becoming a mature field. It is therefore not surprising that researchers around the globe have developed several biocatalysts for asymmetric F–C reactions. Herein, we review recent developments in the design and use of catalytic and stereoselective strategies for performing the asymmetric F–C reactions.

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