Organocatalyse

Organocatalyse, or organocatalysis, is a form of catalysis that uses small organic molecules as catalysts to accelerate chemical reactions. Unlike many traditional catalysts, organocatalysts are typically metal-free and can be used under relatively mild, sometimes environmentally friendlier conditions. The field emerged prominently in the early 2000s with the demonstration that chiral organocatalysts could induce highly enantioselective transformations, building on earlier work with simple amino acids such as proline.

The catalytic modes in organocatalysis are diverse. Enamine catalysis involves secondary amines forming reactive enamine intermediates with carbonyl compounds, enabling nucleophilic attack at the activated α,β-unsaturated partners. Iminium catalysis employs chiral iminium ions to activate enals and related substrates toward electrophilic addition. Hydrogen-bond-donor catalysis uses ureas or thioureas to organize transition states and stabilize charged intermediates. N-heterocyclic carbene (NHC) catalysis enables umpolung of aldehydes, generating acyl anion equivalents. Acid- and base-catalysis with Brønsted acids or bases also play important roles in many transformations. These modes can be used independently or in combination, and many catalysts are designed to be highly modular and tunable for enantioselectivity.

Applications of organocatalysis span carbon–carbon and carbon–heteroatom bond formations, including aldol, Mannich, and Michael additions, as well as cycloadditions and oxidations. The approach is particularly valued for metal-free conditions, operational simplicity, and compatibility with sensitive substrates, contributing to its prominence in pharmaceutical synthesis and natural product construction. Limitations include sometimes modest activity or narrower substrate scope compared with metal catalysis, and ongoing efforts aim to broaden applicability and improve efficiency.