organocascade

Organocascade refers to cascade reactions in organic synthesis that are catalyzed by organocatalysts—small organic molecules that do not contain metals. In an organocascade, a single catalytic event initiates a sequence of two or more bond-forming transformations occurring in one pot, producing complex molecules with high efficiency and minimal workup. The reactions leverage organocatalysis modes such as enamine catalysis, where a secondary amine forms an enamine with a carbonyl to enable nucleophilic additions, and iminium catalysis, where an iminium ion activates an electrophile toward nucleophilic attack. Other modes include N-heterocyclic carbene (NHC) catalysis and hydrogen-bonding catalysis. Organocascade sequences often build up stereochemistry and complexity rapidly, offering metal-free conditions, mild temperatures, and compatibility with sensitive functional groups.

Typical organocascade designs combine two or more reaction steps such as aldol, Michael, cyclization, and Mannich-type additions in a domino sequence, leading to formation of rings, polycyclic frameworks, or densely functionalized motifs. They are widely used in natural product synthesis and medicinal chemistry for rapid access to complex architectures and enantioenriched products.

Challenges include precise control of chemo-, regio-, and enantioselectivity across several steps, optimizing catalysts and solvents for compatibility, and potential competing side reactions. Ongoing research continually expands the repertoire of organocascade reactions, their substrate scope, and their applicability to scalable synthesis.