Palladium-Catalyzed Cyclization of 6-Aminohex-1-yne

Mechanistic details and limiting factors for the palladium-catalyzed addition of amines to alkynes (hydroamination) were studied, using the cyclization of 6-aminohex-1-yne to 2-methyl-1,2-dehydropiperidine as a specific example. The complex [Pd(Triphos)](CF3SO3)2 showed the highest catalytic activity of a series of structurally and electronically distinct palladium complexes. Several methods, such as calorimetry and in situ IR and NMR spectroscopy, were used to obtain evidence for a possible reaction cycle. It seems likely that (i) the substrate initially coordinates via the amine group and (ii) an intermediate is formed which is the product of a nucleophilic attack of the amine on a coordinated alkyne. Addition of an acid to the reaction mixture led to a strong increase in the reaction rate, probably by accelerating protolytic cleavage of the palladium−carbon bond in the intermediate complex.