Iridium hydroamination

Fig. 2.14 Rhodium and iridium cataiysts for the intramolecular hydroamination of alkynes...

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. 

The above-mentioned iridium complex, C4, as well as [ lr[bis(l-methylimidazol-2-yl)methane (CO)2][BPh4] (C5), also appeared very efficient in a one-pot tandem hydroamination/hydrosilylation reaction of 4-pentyn-l-amine with HSiEts to form 2-methylpyrroline, and then subsequently l-(triethylsilyl)-2-methylpyrrohdine with an essentially quantitative yield (Equation 14.5) [54]. 

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. 

Ruthenium complexes mediate the hydroamination of ethylene with pyridine.589 The reaction, however, is not catalytic, because of strong complexation of the amine to metal sites. Iridium complexes with chiral diphosphine ligands and a small amount of fluoride cocatalyst are effective in inducing asymmetric alkene hydroamination reaction of norbomene with aniline [the best enantiomeric excess (ee) values exceed 90%].590 Strained methylenecyclopropanes react with ring opening to yield isomeric allylic enamines 591... 

Iridium(ni) hydrides, such as (98), proved to be air-stable active catalysts for intramolecular hydroalkoxylation and hydroamination of internal alkynes with proximate nucleophiles (e.g. 96). The cyclization follows the 6-endo-dig pathway with high preference (when regioselectivity is an issue).125... 

The displacement of cyclooctene or C2H4 from an iridium(I) centre by a variety of chiral phosphines (L) leads to the formation of [ (L)IrCl 2] which, in conjunction with a source of F (phosphazenium fluoride), has been used for catalytic hydroamination of olefins. This combination leads to a 6.5 fold increase in the activity of the system and a total reversal in the enantioselectivity compared to that of the chloride analogue. There is no direct evidence of formation of a metal fluoride complex, but it is proposed that it may well form in situ and that this might explain these interesting results [75]. 

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. 

The diastereoselective addition of aniline to norbornene was accomplished using a catalytic amount of iridium(I). As the intermediate azametallacyclobutane 2 could be isolated its stereochemistry was determined by X-ray analysis both iridium and nitrogen occupy the exo position41. However, the scope of the amination method, with respect to the nature of the amine and the structure of the alkene, was not determined. Conversely, the analogous rhodium(I)-cat-alyzed reactions of norbornene and aromatic amines gave mixtures of hydroamination and hydroarylation products106. 

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

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. 

This chemistry was extended to a number of bicyclic alkenes and dienes utilizing various chelating axially chiral bisphosphine iridium catalysts (Scheme 11.5) [29]. Further synthetic transformations of the chiral hydroamination product 13 provide access to functionally substituted chiral cyclopentylamines with multiple stereocenters, such as 14 and IS. It should be noted that alkylamines, such as octylamine or N methyl aniline, and sterically encumbered aniline derivatives, such as 0 toluidine or o anisidine did not undergo hydroamination reactions under these conditions. 

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

Ebrahimi, D., Kennedy, D. F., Messerle, B. A. Hibbert, D. B. (2008). High throughput screening arrays of rhodium and iridium complexes as catalysts for intramolecular hydroamination using parallel factor analysis. Analyst, Vol. 133,... 

The intermolecialar hydroamination has also received some attention and studies in this area have focussed on the use of iridium and nickel catalysts. Enan-tioselectivities for the intermolecular process are also generally moderate with ees observed between 60 and 70%. The highest enantioselectivities for this reaction have been obtained during the hydroamination of norbornene (2.145) with aniline in the presence of the iridium complex (2.184) and the fluoride ion source... 

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. 

However, others have shown that oxidative additions of much less acidic substrates, such as water, ° alcohols, unactivated anilines and azole heterocycles, " occur to low-valent transition metal complexes. For example, iridium(I) complexes containing tri-ethylphosphine as ligand undergo oxidative addition of water rapidly at room temperature (Equation 7.17). Both [Ir(PEtj)J and [Ir(PEt3)jCl] also add aniline rapidly at room temperature (Equation 7.17). The latter reaction is a step in the catalytic hydroamination of norbornene. These substrates react readily with early metal complexes, but tliese reactions do not occur by oxidative addition. ... 

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