Transition-metal-catalyzed hydroamination

The first transition metal-catalyzed hydroamination of an olefin was reported in 1971 by Coulson who used rhodium(I), rhodium(III) or iridium(III) catalysts (Eq. 4.8) [105,106]. 

The cationic imidazolium rhodium complex (56) has been found to catalyze the intramolecular hydroamination of alkynes in refluxing THF. In the case of 2-ethynylaniline, indole is formed in 100% yield over 9h at 55 °C (Scheme 38).173 One of the earliest examples of late transition metal-catalyzed hydroamination involved the use of the iridium(I) complex [Ir(PEt3)2(C2H4)Cl] as... 

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. 

Transition-Metal Catalyzed Hydroamination of Olefins and Alkynes... 

TRANSITION-METAL-CATALYZED HYDROAMINATION OF OLEFINS AND ALKYNES... 

TRANSITION-METAL-CATALYZED HYDROAMINATION OF OLEFINS AND ALKYNES Table 16.6. Effect of catalyst precursor on the intramolecular hydroamlnation In Equation 16.61. 

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. 

Schulte [285, 286] and later Chalk [287] described the Cu(I)-catalyzed synthesis of symmetrical 2,5-diarylpyrroles 261 from conjugated diynes 257 and primary amines 258. The reaction is believed to proceed via the transition metal-catalyzed hydroamination [33, 288-291] leading to tautomeric aminoenyne 259 or homopro-pargylic imine 260 intermediates, which further undergo 5-endo-dig cyclization to furnish pyrrole product 261 (Scheme 8.95). 

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. 

Scheme 15.14 General mechanism of late-transition-metal-catalyzed hydroamination with nucleophilic attack on neutral rt-complexes.

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