The reaction however suffers from a high activation barrier, perhaps owing to the repulsion of the electron-rich substrate and the amine nucleophile. The intermolecular reaction also is accompanied by highly negative changing entropy, making it unfavorable at higher temperatures. Consequently, catalysts are necessary for this reaction to proceed. As usual in chemistry, intramolecular processes occur at faster rates than intermolecular versions. Thermodynamic vs kinetic product In general, most hydroamination catalysts require elevated temperatures to function efficiently, and as such, only the thermodynamic product is observed. The isolation and characterization of the rarer and more synthetically valuable kinetic allyl amine product was reported when allenes was used at the unsaturated substrate. One system utilized temperatures of 80 °C with a rhodium catalyst and aniline derivatives as the amine. The other reported system utilized a palladium catalyst at room temperature with a wide range of primary and secondary cyclic and acyclic amines. Both systems produced the desired allyl amines in high yield, which contain an alkene that can be further functionalized through traditional organic reactions. Base catalyzed hydroamination Strong bases catalyze hydroamination, an example being the ethylation of piperidine using ethene: Such base catalyzed reactions proceed well with ethene but higher alkenes are less reactive. Hydroamination catalyzed by group (IV) complexes Certain titanium and zirconium complexes catalyze intermolecular hydroamination of alkynes and allenes. Both stoichiometric and catalytic variants were initially examined with zirconocene bis(amido) complexes. Titanocene amido and sulfonamido complexes catalyze the intra-molecular hydroamination of aminoalkenes via a [2+2] cycloaddition that forms the corresponding azametallacyclobutane, as illustrated in the figure below. Subsequent protonolysis by incoming substrate gives the α-vinyl-pyrrolidine (1) or tetrahydropyridine (2) product. Experimental and theoretical evidence support the proposed imido intermediate and mechanism with neutral group IV catalysts. Formal hydroamination The addition of hydrogen and an amino group (NR2) using reagents other than the amine HNR2 is known as a "formal hydroamination" reaction. Although the advantages of atom economy and/or ready available of the nitrogen source are diminished as a result, the greater thermodynamic driving force, as well as ability to tune the aminating reagent are potentially useful. In place of the amine, hydroxylamine esters and nitroarenes have been reported as nitrogen sources. Applications Hydroamination could find applications due to the valuable nature of the resulting amine, as well as the greenness of the process. Functionalized allylamines, which can be produced through hydroamination, have extensive pharmaceutical application, although presently such