A3 coupling reaction

The A³ coupling, coined by Prof. Chao-Jun Li of McGill University, is a type of multicomponent reaction involving an aldehyde, an alkyne and an amine which react to give a propargyl amine.
The reaction proceeds via direct dehydrative condensation and requires a metal catalyst, typically based on ruthenium/copper, gold or silver. Chiral catalyst can be used to give an enantioselective reaction, yielding a chiral amine. The solvent can be water. In the catalytic cycle the metal activates the alkyne to a metal acetylide, the amine and aldehyde combine to form an imine which then reacts with the acetylide in a nucleophilic addition. The reaction type was independently reported by three research groups in 2001 -2002; one report on a similar reaction dates back to 1953.
If the amine substituents have an alpha hydrogen present and provided a suitable zinc or copper catalyst is used, the A³ coupling product may undergo a further internal hydride transfer and fragmentation to give an allene in a Crabbé reaction.

Decarboxylative A3 reaction

One variation is called the decarboxylative A³ coupling. In this reaction the amine is replaced by an amino acid. The imine can isomerise and the alkyne group is placed at the other available nitrogen alpha position. This reaction requires a copper catalyst. The redox A³ coupling has the same product outcome but the reactants are again an aldehyde, an amine and an alkyne as in the regular A³ coupling.