Hydroamination late transition metals

The intermolecular hydroamination of alkynes catalyzed by late transition metals was reported for the first time in 1999. Ruthenium carbonyl catalyzes the Markovnikov hydroamination of terminal alkynes with PhNHMe to give enamines (Eq. 4.88) [305]. 

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... 

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 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>. 

Intramolecular addition of amine N-H bonds to carbon-carbon multiple bonds would afford nitrogen heterocycles. To realize catalytic cyclization of a,co-aminoalkenes or aminoalkynes, various catalytic systems have been developed especially with early transition metals such as titanium, zirconium, lanthanide metals, and actinide metals [ 12], Late-transition-metal catalysis based on Ni, Pd, and Rh has also proved to be efficient [ 12], Recently, the ruthenium-catalyzed intramolecular hydroamination of aminoalkynes 15 was reported to afford 5-7-membered ring products 16 in various yields (Eq. 6) [13]. Among... 

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. 

As already mentioned, there has been significant progress in the development of chiral catalysts for asymmetric hydroamination reactions over the last decade. However, significant challenges remain, such as asymmetric intermolecular hydro aminations of simple nonactivated alkenes and the development of a chiral catalyst, which is applicable to a wide variety of substrates with consistent high stereochemical induction and tolerance of a multitude of functional groups as well as air and moisture. Certainly, late transition metal based catalysts show promising leads that could fill this void, but to date, early transition metal based catalysts (in particular, rare earth metals) remain the most active and most versatile catalyst systems. 

Transition metal catalysts from across the periodic table have been investigated for this transformation. [56b, 57] Early transition metal catalysts [58] are of particular interest due to their high reactivities, with reduced air and moisture sensitivity compared with the rare earth metal systems, and lower cost and toxicity compared with the late transition metal catalysts. The A,0-ligands generating tight four-membered metallacycles described above have been studied as precatalysts for hydroamination methodologies that display promising substrate scope and reactivity. 

Catalytic asymmetric hydroamination of alkenes can be achieved using early and late transition metal catalysts and lanthanide-based catalytic... 

Hydroamination is an atom-economical process for the synthesis of industrially and pharmaceutically valuable amines. The hydroamination reaction has been studied intensively, including asymmetric reactions, and a variety of catalytic systems based on early and late transition metals as well as main-group metals have been developed." However, Group 5 metal-catalysed hydroaminations of alkenes had not been reported until Hultzsch s work in 2011. Hultzsch discovered that 3,3 -silylated binaphtho-late niobium complex 69 was an efficient catalyst for the enantioselective hydroaminoalkylation of iV-methyl amine derivatives 70 with simple alkenes 71, giving enantioselectivities up to 80% (Scheme 9.30). Enantiomerically pure (l )-binaphtholate niobium amido complex 69 was readily prepared at room temperature in 5 min via rapid amine elimination reactions between Nb(NMe2)5 and l,l-binaphthyl-2-ol possessing bullqr 3,3 -silyl substituents. Since the complex prepared in situ showed reactivity and selectivity identical... 

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. 

Among the first hydroaminations of alkynes to be published were cyclizations catalyzed by palladium complexes to form indoles. Hydroaminations of alkynes catalyzed by low-valent, late transition metal complexes occur with a narrower scope than the reactions catalyzed by lanathanide complexes. More recently, examples of the hydroaminations of alkynes catalyzed by rhodium complexes have been reported. 

The hydroamination of olefins has been shown to occur by the sequence of oxidative addition, migratory insertion, and reductive elimination in only one case. Because amines are nucleophilic, pathways are available for the additions of amines to olefins and alkynes that are unavailable for the additions of HCN, silanes, and boranes. For example, hydroaminations catalyzed by late transition metals are thought to occur in many cases by nucleophilic attack on coordinated alkenes and alkynes or by nucleophilic attack on ir-allyl, iT-benzyl, or TT-arene complexes. Hydroaminations catalyzed by lanthanide and actinide complexes occur by insertion of an olefin into a metal-amide bond. Finally, hydroamination catalyzed by dP group 4 metals have been shown to occur through imido complexes. In this case, a [2+2] cycloaddition forms the C-N bond, and protonolysis of the resulting metallacycle releases the organic product. 

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

One of the earliest reports for hydroamination by Coulson [86] in 1971 was the hydroamination of ethylene with nucleophilic secondary amines using Rh and Ir salts as the metal catalyst These initial developments sparked intense investigation into this transformation, and while ample well-characterized examples of the stoichiometric addition of amines to ethylene complexes of late transition metals have been disclosed [159], advances in catalytic versions using ethylene as a substrate remains an unsolved problem. 

Alkyne hydroamination has been extensively reviewed [3, 4, 10] and important contributions using late transition metals have been realized to give the Markovnikov-type products most typically. Interestingly, in 2007, Fukumoto reported a tris(pyrazolyl borate)rhodium(l) complex for the anti-Markovnikov hydroamination of terminal aUcynes with both primary and secondary amine substrates, although yields with primary amines are always reduced compared to those with secondary amines (Scheme 15.26). Desirable functional group tolerance is also noteworthy for this regioselective hydroamination catalyst [187]. 

At this stage, the hydroamination of both terminal and internal alkynes with primary and secondary amines can be achieved by judicious choice of substrate and catalyst. Notably, hydroamination with primary aUcylamines using late transition metals is rarely reported [187, 189-191], although the related reaction with anihne derivatives can be mediated by complexes of groups 9-12 metals. Once again, to reduce the nucleophilicity of the amine partner, protected amines are often used as alternative substrates. 

Beller took advantage of simple Zn salts and used Zn(OTf)2 for the hydroamination of terminal aUcynes with arylamines (218). These reactions require similar temperatures as has been reported for other late transition metal catalysts (100-120 °C) and as is most commonly observed for this combination of substrates, the Markovnikov product is preferred (Scheme 15.37). 

Most importantly, this reaction demands control of regioselectivity and can also be carried out asymmetrically (Scheme 15.38). Thus, branched imine or linear allylamine products can be selectively prepared. Diastereoselective and enantiose-lective allene hydroamination can also be targeted with advances in enantioselective catalysis using late transition metals being reviewed in Section 15.3.7. 

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

Key contributions in the development of late transition metal catalysts toward alkene hydroamination, which precede the 2008 comprehensive review [10], focus on contributions using group 9 and 10 metals. Preferred substrates for these transformations include aminoalkenes [230] for intramolecular reactivity or the use of activated alkenes such as styrene [93, 109, 113, 245] or alkenes substituted with electron-withdrawing substituents to generate hydroamination products via aza-Michael-type reactions [246-249]. Au has also been applied to the hydrofunctionalization of alkenes, although these reactions have demanded the use of protected amine substrates such as ureas [250], tosylamides [251], and carbamates [252]. 

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