Asymmetric Synthesis of Cyanohydrins and α-Aminonitriles

The asymmetric synthesis of cyanohydrins and α-aminonitriles occupies a central position in modern organic chemistry owing to the wide utility of these motifs as chiral building blocks for pharmaceuticals, agrochemicals and natural products. Cyanohydrins, formed by addition of hydrogen cyanide to carbonyl compounds, and their protected derivatives enable divergent elaboration into α-hydroxy acids, β-hydroxy ketones and other functionalised scaffolds. α-Aminonitriles, accessible via the Strecker reaction or direct C–H cyanation, serve as precursors to enantiomerically pure amino acids and heterocyclic frameworks. Achieving high enantioselectivity in these processes demands precise control of catalyst architecture and reaction conditions. Over the past decade, strategies have evolved from classical metal-based Lewis acid catalysis towards organocatalytic and photocatalytic approaches, often leveraging chiral Schiff bases, cinchona alkaloids or bespoke bifunctional catalysts. Concurrent efforts in flow chemistry and green metrics have further reduced waste and enhanced safety by employing milder cyanide sources and continuous-processing protocols. This integrative landscape underscores the ongoing challenge of balancing reactivity, selectivity and sustainability in asymmetric cyanosynthesis.

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Asymmetric Synthesis of Cyanohydrins and α-Aminonitriles publication trend

The graph below shows the total number of articles in asymmetric synthesis of cyanohydrins and α-aminonitriles across all publications each year (not limited to Nature Index journals).

Technical terms

Cyanohydrin: A compound formed by addition of cyanide to a carbonyl, bearing both hydroxyl and nitrile groups.

α-Aminonitrile: A molecule featuring adjacent amino and nitrile functionalities, commonly accessed via the Strecker reaction.

Enantioselectivity: The preference of a catalytic process to form one enantiomer over its mirror image.

Strecker reaction: A multicomponent synthesis of α-aminonitriles from aldehydes, amines and cyanide sources.

Organocatalysis: The use of small, non-metal organic molecules to promote chemical transformations with stereocontrol.

Lewis acid: A species capable of accepting an electron pair to activate electrophilic substrates in asymmetric catalysis.

References

1. Organocatalytic Synthesis of α-Aminonitriles: A Review. Catalysts (2022).
2. Enantioselective catalytic Strecker reaction on cyclic (Z)-aldimines in flow: reaction optimization and sustainability aspects. Journal of Flow Chemistry (2023).
3. Waste-Minimized Cyanosilylation of Carbonyls Using Fluoride on Polymeric Ionic Tags in Batch and under Continuous Flow Conditions. ACS Sustainable Chemistry & Engineering (2021).