Recent Developments and Trends in Asymmetric Organocatalysis

Abstract

Asymmetric organocatalysis has experienced a long and spectacular way since the early reports over a century ago by von Liebig, Knoevenagel and Bredig, showing that small (chiral) organic molecules can catalyze (asymmetric) reactions. This was followed by impressive first highly enantioselective reports in the second half of the last century, until the hype initiated in 2000 by the milestone publications of MacMillan and List, which finally culminated in the 2021 Nobel Prize in Chemistry. This short Perspective aims at providing a brief introduction to the field by first looking on the historical development and the more classical methods and concepts, followed by discussing selected advanced recent examples that opened new directions and diversity within this still growing field.

Keywords: Catalyst design; Method development; Organocatalysis; Stereochemistry.

Scheme 1

Selected milestones in the historical development of asymmetric organocatalysis.

Scheme 2

A) Classifications of organocatalysts, and B) established catalytically relevant functional groups.

Scheme 3

Overview about the most classical organocatalytic activation modes.

Scheme 4

A) Combination of activation modes, and B) selected metal‐organocatalysis technology milestones.

Scheme 5

Stepwise one‐pot combination of organocatalysis with metal‐based photoredox catalysis or electrochemical oxidation.

Scheme 6

Chiral organophotocatalytic systems and approaches in enantioselective catalysis.

Scheme 7

Illustrative non‐classical reaction media in organocatalysis.

Scheme 8

Exemplary design‐evolution of chiral Brønsted acids.

Scheme 9

Selected innovative activation approaches: A) Brønsted acid – HB‐donor co‐catalysis, and B) H‐bonding PTC for enrolling KF as nucleophile.

Scheme 10

Different approaches in enantioselective iodine‐based catalysis.