Iridium-Catalyzed Hydroamination

From a historic point of view, metal-catalyzed or metal-promoted hydroamina-tions were first achieved with alkali metals [4]. The use of soluble transition-metal complexes as catalysts for the OHA reaction was pioneered by DuPont workers during the 1970s, the best results being obtained with Rh and Ir salts [5], Later, the finding that electron-rich Ir(I) species cleanly activated N—H bonds to form Ir-amido-hydrido species [6] opened the way to study the reactivity of these amides 

Iridium Complexes in Organic Synthesis. Edited by Luis A. Oro and Carmen Claver Copyright 2009 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim Tf RN 97R-h 27.HQQfi.1 

In 1971, Coulson at DuPont reported the first example of an OHA reaction catalyzed by soluble Rh and Ir complexes [5]. Secondary amines such as dimethyl-amine, pyrrolidine and piperidine were effectively added to ethylene, while primary amines, ammonia and heavier olefins were essentially unreactive (see Equation 6.3). IrCl3-3H20 proved to be an equally effective catalyst precursor in these reactions. It is probable that, under the conditions employed in this study, the Rh(III) and Ir(III) salts are reduced to monovalent, electron-rich species such as 3 (see Equation 6.6). 

The first example of a catalytic OHA reaction that was shown to proceed via N—H activation, was published by Casalnuovo, Calabrese and Milstein (CCM) in 

1988 [7], and represents a milestone in iridium-catalyzed OHA. The best catalytic system for the model reaction of norbornene with aniline to form exo-2-phenylaminonorbornane (1) [10] was found to be a combination of the electron-rich complex lrCl(PEt3)2(C2H4)2 and the Lewis acid ZnCl2 (see Equation 6.4). Exo selectivity in the C—N bond-formation step was almost complete. A continuous flow of inert gas was apparently necessary to remove ethylene from the catalyst precursor. TIPF as cocatalyst instead of ZnCh was also effective. The mechanistic and structural details of this reaction are described in Sections 6.4.1 and 6.5. 

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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. 

Scheme 11.4 Proposed mechanism for iridium catalyzed hydroamination of norbomene via amine activation.

In other cases, the properties of fluoride ligands have been exploited to generate more active catalysts than are obtained in the absence of added fluoride or with other halogen ligands. As described in Chapter 16, added fluoride accelerates the rate of the iridium-catalyzed hydroamination of norbomene with aniline. The origin of this effect has not been revealed. 

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... 

Iridium-Catalyzed Olefin Hydroamination (OHA) 151 Table 6.2 Widening the synthetic scope of the CMM system. 

Equation 11.6. Iridium catalyzed asymmetric hydroamination of norbornene [26]. 

Examples of palladium- and rhodium-catalyzed hydroaminations of alkynes are shown in Equations 16.90-16.92 and Table 16.9. The reaction in Equation 16.90 is one of many examples of intramolecular hydroaminations to form indoles that are catalyzed by palladium complexes. The reaction in Equation 16.91 shows earlier versions of this transformation to form pyrroles by the intramolecular hydroamination of amino-substituted propargyl alcohols. More recently, intramolecular hydroaminations of alkynes catalyzed by complexes of rhodium and iridium containing nitrogen donor ligands have been reported, and intermolecular hydroaminations of terminal alkynes at room temperature catalyzed by the combination of a cationic rhodium precursor and tricyclohexylphosphine are known. The latter reaction forms the Markovnikov addition product, as shown in Equation 16.92 and Table 16.9. These reactions catalyzed by rhodium and iridium complexes are presumed to occur by nucleophilic attack on a coordinated alkyne. 

A few examples are known using homogeneous transition-metal-catalyzed additions. Rhodium(III) and iridium(III) salts catalyze the addition of dialkylamines to ethylene.302 These complexes are believed to activate the alkene, thus promoting hydroamination. A cationic iridium(I) complex, in turn, catalyzes the addition of aniline to norbornene through the activation of the H—N bond.303 For the sake of comparison it is of interest to note that dimethylamino derivatives of Nb, Ta, and Zr can be used to promote the reaction of dialkylamines with terminal alkenes.304 In this case, however, C-alkylation instead of /V-alkylation occurs. 

A different catalytic cycle for alkene hydroamination is initiated by the oxidative addition of the N-H bond to the metal, followed by insertion of the alkene into the metal-nitrogen bond and reductive elimination to form the amine. The oxidative addition of unactivated N-H bonds to platinum(O) complexes is thermodynamically unfavorable, so the catalytic cycle cannot be completed17, but the successful iridium(I)-catalyzed amination of norbornene with aniline has been reported18. 

As discussed in Chapter 9, the insertion of olefins and alk)nes into metal-amido complexes is limited to a few examples. Such insertion reactions are proposed to occur as part of the mechanism of the hydroamination of norbomene catalyzed by an iridium(I) complex and as part of the hydroamination of alkenes and alkynes catalyzed by lanthanide and actinide metal complexes. This reaction was clearly shown to occur with the iridium(I) amido complex formed by oxidative addition of aniline, and this insertion process is presented in Chapter 9. The mechanism of the most active Ir(I) catalyst system for this process involving added fluoride is imknown. 

As an alternative, iridium complexes show exciting catalytic activities in various organic transformations for C-C bond formation. Iridium complexes have been known to be effective catalysts for hydrogenation [1—5] and hydrogen transfers [6-27], including in enantioselective synthesis [28-47]. The catalytic activity of iridium complexes also covers a wide range for dehydrogenation [48-54], metathesis [55], hydroamination [56-61], hydrosilylation [62], and hydroalkoxylation reactions [63] and has been employed in alkyne-alkyne and alkyne - alkene cyclizations and allylic substitution reactions [64-114]. In addition, Ir-catalyzed asymmetric 1,3-dipolar cycloaddition of a,P-unsaturated nitriles with nitrone was reported [115]. 

Li X, Chianese AR, Vogel T, Crabtree RH (2005) Intramolecular alkyne hydroalkoxylation and hydroamination catalyzed by iridium hydrides. Org Lett 7 5437-5440... 

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