Science of Synthesis

Bernardi, L.; Ricci, A., Science of Synthesis: Multicomponent Reactions, (2014) 1, 154.

The three-component reaction between benzaldehyde, ethanolic ammonia, and 2-naphthol was reported by Betti[‌45‌] a decade before Mannich disclosed the addition of enolates to imines.[‌1‌] Sometimes defined as an aromatic version of the Mannich reaction, the Betti reaction encompasses in a broader sense the addition of different naphthols and phenols to imines and iminium ions, generated in situ from aldehydes and amines (ammonia, primary and secondary amines, anilines) (‌Scheme 33‌). This transformation has gained significant recognition,[‌46‌,‌47‌] as the resulting adducts (Betti bases) possess a broad range of biological activities, and in enantiopure form are very useful as chiral auxiliaries, resolving agents, and ligands for metals in catalytic asymmetric transformations. Nowadays, there exists a plethora of methods for efficiently carrying out the three-component Betti reaction, despite the challenges given by the relatively poor stability of some of the adducts under certain conditions.

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References