Scope of Hydroaminomethylation

The most important hydroaminomethylations for commodity chemicals woidd be hydroaminomethylations with ammonia, but this reaction remains a challenge. Hydroaminomethylation reactions have more often been conducted between alkenes and secondary aliphatic amines, and these reactions can be useful for fine-chemical s)mthesis. Intramolecular hydroaminomethylations can also be valuable, and many examples of intramolecular hydroaminomethylations to form nitrogen heterocycles have been reported. 

Specific examples of the hydroaminomethylations of olefins with secondary amines are shown in Equations 17.19-17.21. Cyclic and acyclic secondary amines occur in high yield with linear-to-branched ratios exceeding 50 to 1 in most cases when catalyzed by the rhodium complex generated from [Rh(COD)JBF and xantphos. The reaction of pen-tene with piperidine is shown in Equation 17.19. These reactions are also compatible with alcohol (Equation 17.20) and acetal functional groups (Equation 17.21). 

Reactions of internal alkenes can also form terminal amines, and examples of this process are shown in Equation 17.24. These reactions occur in the presence of a rhodium catalyst containing the electron-poor bisphosphine ligand shown in these equations. For example, the reaction of 2-pentene (R = Me in Equation 17.24) with piperidine forms a 4 1 ratio of the linear to branched amines, and the same reaction with a excess of 2-butene (R = H in Equation 17.24) forms a 96 4 ratio of linear to branched products. 

Hydroaminomethylations with ammonia are difficult to develop because the product amine is more nucleophilic than ammonia and preferentially condenses with the aldehyde to form the precursor to the final amine product. Thus, hydroaminomethylations with ammonia tend to form dialkyl- and trialkylamines. To overcome this problem in selectivity, hydroaminomethylations of ammonia have been conducted with a water-soluble catalyst in a biphasic system. Under these conditions, the reaction occurs preferentially with ammonia in the aqueous phase, because it is more soluble than the alkylamine product, and the reactions favor formation of the primary amine. The use of a water-soluble version 

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