Transition-metal-catalyzed hydroamination reactions

Earher mechanistic studies by Milstein on a achiral Ir catalyst system indicated that the iridium catalyzed norbornene hydroamination involves amine activation as a key step in the catalytic cycle [27] rather than alkene activation, which is observed for most other late transition metal catalyzed hydroamination reactions [28]. Thus, the iridium catalyzed hydroamination of norbornene with aniline is initiated by an oxidative addition of aniline to the metal center, followed by insertion of the strained olefin into the iridium amido bond (Scheme 11.4). Subsequent reductive elimina tion completes the catalytic cycle and gives the hydroamination product 11. Unfor tunately, this catalyst system seems to be limited to highly strained olefins. 

The hydroamination of alkynes catalyzed by group 4 complexes were some of the first transition-metal-catalyzed hydroamination reactions. One example of these reactions is shown in Equation 16.84. The reactions only occur with hindered amines and are slow. Nevertheless, the reactions occur m high yield and, in the absence of air, the catalysts are stable indefinitely. An early intramolecular reaction catalyzed by CpTiClj to form a cyclic enamine is shown in Equation 16.85. Reactions with internal alkynes occur to form products with Markovnikov regiochemistry. ° As described in more detail below, tliese reactions occur by [2+2] additions of the alkyne to an intermediate metal-imido complex. 

Recently, transition metal-catalyzed hydroamination reaction of alkynes with hydrazines was used to generate aryl hydrazones, highly reactive and versatile intermediates in a subsequent metal-catalyzed Fischer indole synthesis. Thus, Odom first reported a 3 + 2 synthesis of 1,7-fused, di-, and tri-substituted indoles 285 featuring the Ti(IV)-catalyzed hydroamination of various alkynes 283 with... 

I 75 Transition-Metal-Catalyzed Hydroamination Reactions Table 15.4 Group 4 metal-catalyzed intermolecular hydroamination of terminal alkynes. 

Within the field of Au-catalyzed hydroamination, many mechanistic questions remain unaddressed. The role of proton and counterion in these reactions is often unclear and the iruiocence of the Ag(I) halide abstracting agents commonly used has also been called into question [309]. Thus, mechanistic investigations into late-transition-metal-catalyzed hydroamination reactions have much to offer the synthetic community in designing improved catalyst systems. 

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