Transition-metal-catalyzed hydroamination catalysts

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]. 

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 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. 

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. 

Consequently, the late transition metal-catalyzed hydroamination is focused in this chapter. In general, the late transition metal catalysts are relatively stable in air and tolerant of most of the polar functional groups. Accordingly, the catalysts are convenient to handle and perhaps applicable to many industrial syntheses. 

In the above sections, the mechanisms of the late transition metal-catalyzed hydroamination have been discussed mainly. In this section, the scope of the reaction is summarized concisely with selected examples. Due to space limitation, not all the examples are covered and the detailed reaction sequences/processes are not shown, but the catalysts used in the reactions are shown attached with reference number (the attached references report enantio-/diastereo-selective or chirality transfer reactions). We hope that readers may understand what types of catalysts are used in the hydroamination, in addition to what type of molecular transformation is feasible in the hydroamination. 

Late transition-metal hydroamination is the method of choice for the atom economical and functional group-tolerant construction of C—N bonds, and in this context Ir plays a central role (indeed, homogenous transition-metal-catalyzed OHA was discovered with Rh and Ir). However, there is a strong need for the development of better OHA catalyst systems that are applicable to a wider range of substrates and conditions. The characteristics of current Ir based catalyst systems to function via N—H bond activation, though, is a potential handicap to achieve this goal, since it implies highly reactive Ir intermediates that are prone... 

The hydroamination of alkenes and alkynes has been of longstanding interest in organometallic chemistry [26]. Much of the early work in this area focused on early transition metal or lanthanide metal catalyst systems. However, much recent progress has been made in late-metal catalyzed hydroamination chemistry, and several interesting hydroamination reactions that afford nitrogen heterocycles have been developed using palladium catalysts. 

The excellent ability of late transition metal complexes to activate alkynes to nucleophilic attack has made them effective catalysts in hydroamination reactions. The gold(l)-catalyzed cyclizations of trichloroacetimidates 438, derived from homopropargyl alcohols, furnished 2-(trichloromethyl)-5,6-dihydro-4f/-l,3-oxazines 439 under exceptionally mild conditions (Equation 48). This method was successfully applied to compounds possessing aliphatic and aromatic groups R. With R = Ph, cyclization resulted in formation of 439 with complete (Z)-stereoselectivity <2006OL3537>. 

Summaries of results of hydroamination mediated with Rh(I) amide complexes584 and comprehensive reviews giving detailed information of the field are available.585-587 Therefore, only the more important relatively new findings are presented here. In most of the transformations reported transition metals are applied as catalysts. The feasibility of the use of tcrt-BuOK was demonstrated in the base-catalyzed amination of styrenes with aniline.588... 

This section focuses on hydroamination catalyzed by transition metal complexes, but many studies on hydroamination catalyzed by acid, base, - main group metals such as mercury and copper, and heterogeneous catalysts have been reported. Because the elementary steps of the mechanisms of these reactions lie outside the scope of this text, this chapter does not present details of the hydroaminations conducted with these t5q>es of catalysts. This material has been presented in many reviews. - ... 

Intermolecular additions of primary amines to alkenes have also been reported using lanthanide catalysts. These reactions, although slow, do occur to high conversion. Similar to hydroaminations catalyzed by late transition metal complexes, these reactions form the products from Markovnikov addition of the N-H bond across the olefin. One example of such a reaction is shown in Equation 16.59. ... 

Catalysts for tfie additions of amines to vinylarenes have also been developed. These catalytic reactions include some of the first hydroaminations of unstrained olefins catalyzed by late transition metals, as well as examples catalyzed by lanthanide complexes. These additions occur with Markovrukov selectivity with one set of catalysts and with anti-Markovnikov selectivity with several others. These additions occur by several different mechanisms that are presented in Section 16.5.3.2. 

Late Transition Metal Catalysts 11191 Table 15.19 Au-NHC-catalyzed allene hydroamination of carbamates. 

Many transition metals and lanthanide-based complexes have been shown to catalyze (5.7.2)-type hydroamination reactions. In many cases the catalysts based on lanthanides are found to have significant activity. Structures 5.70 and 5.71 are two typical examples of transition metaland lanthanide-based precatalysts. 

The inteimolecular hydroamination of allenes is readily catalyzed by early transition metal complexes to yield imines. An addition of aromatic and ahphatic amines to aUene requires high reaction temperatures (90-135°C) and long reaction times (1-6 days) when mediated by zirconocene- [41] and tantalum-imido [178] catalysts. The more efficient titanium half-sandwich imido-amide complex 42 operates under significantly milder reaction conditions (27) [179], Because the metal-imido species are prone to dimerization, sterically more hindered aliphatic and aromatic amines are more reactive. Simple, sterically unencumbered aliphatic amines add to aUenes in the presence of the bis(amidate) titanium complex 43 (28), although higher reaction temperatures are required [180]. 

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