Asymmetric Organocatalysis: A Critical Review of Mechanistic Frameworks, Emerging Methods and Applications
DOI:
https://doi.org/10.37022/jcls.v9i2.232Keywords:
asymmetric organocatalysis, enantioselectivity, enamine and iminium catalysis, chiral Brønsted acids, photoredox catalysis, green chemistryAbstract
Asymmetric organocatalysis, the acceleration of enantioselective reactions by small chiral organic molecules, has developed within two decades from a set of isolated observations into a mature and independent branch of catalysis. Its appeal rests on a combination of practical advantages: the catalysts are metal-free, frequently derived from the chiral pool, tolerant of air and moisture, and compatible with the aims of green chemistry. This review examines the mechanistic basis of the field and the methodological developments that have shaped it, with emphasis on the period from 2018 to 2025. The two governing activation regimes, covalent (enamine, iminium and N-heterocyclic carbene catalysis) and non-covalent (hydrogen-bond donation, Brønsted acid catalysis and ion pairing), are treated in terms of the frontier-orbital and non-covalent-interaction arguments that rationalise stereocontrol. Attention then turns to five areas in which the field has moved most rapidly: dual and cooperative catalysis, in which organocatalysts are combined with transition metals or with one another; the merger of chiral amine catalysis with visible-light photoredox catalysis, which has made enantioselective radical chemistry a practical proposition; enantioselective hydrogen atom transfer and related open-shell manifolds; electrochemical and mechanochemical implementations; and confined Brønsted acids such as the imidodiphosphorimidates, whose enzyme-like active sites have brought previously intractable substrates within reach. Applications in pharmaceutical process chemistry, natural product total synthesis and sustainable manufacture are surveyed, and the outstanding limitations of the field, principally catalyst loading, substrate generality and catalyst incompatibility in multicatalytic systems, are assessed. Data-driven catalyst design and continued convergence with photochemical, electrochemical and enzymatic catalysis are identified as the developments most likely to determine the next phase of the discipline.
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