Rhodium hydroamination

The Rh and Ir complexes 85-88 (Fig. 2.14) have been tested for the intramolecular hydroamination/cyclisation of 4-pentyn-l-amine to 2-methyl-1-pyrroline (n = 1). The reactions were carried out at 60°C (1-1.5 mol%) in THF or CDCI3 The analogous rhodium systems were more active. Furthermore, the activity of 87 is higher than 85 under the same conditions, which was attributed to the hemilabihty of the P donor in the former complex, or to differences in the trans-eSects of the phosphine and NHC ligands, which may increase the lability of the coordinated CO in the pre-catalyst [75,76]. 

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]. 

Study of the mechanism of the rhodium-catalyzed hydroamination of ethylene with secondary amines indicated that the piperidine complex trans-RhCl(C2H4)(piperidine)2 can serve as a catalyst precursor [109, 110]. 

It was elegantly shown later that the hydroamination of ethylene with piperidine or Et2NH can be greatly improved using cationic rhodium complexes at room temperature and atmospheric pressure to afford a high yield of hydroaminated products (Eq. 4.10) [111]. However, possible deactivation of the catalyst can be questioned [17]. 

Although the hydroamination of Michael systems is beyond the scope of this review, it is interesting to note the high yield (98%, TOE = 2 h ) obtained using the above cationic rhodium complexes for the hydroamination of 2-vinylpyridine with morpholine. Indeed, without catalyst, the hydroamination yield is only 5% [167]. 

A range of rhodium complexes have been studied as hydroamination catalysts. Treatment of norbornene with a mixture of aniline and lithium anilide in the presence of [Rh(PEt3)2Cl]2 at 70 °C for over 1 week yields the exo addition product in ca. 15% yield.165... 

Some of the hydroarylation product is also observed substituted anilines afford the two products to varying degrees (Equation (15)). The closely related rhodium complexes [Rh(PCy3)2Cl]2, [Rh(dmpe)Cl]2 (where dmpe= l,2-bis(dimethylphosphino)ethane), and [Rh(C8H14)Cl]2 show essentially no catalytic activity.166 Application of [Rh(PEt3)2Cl]2 to the reaction of aniline with styrene gives a mixture of hydroamination and oxidative amination products, the latter predominating.167 Other related rhodium-catalyzed amination reactions (oxidative amination) have been reported.168 169... 

The first example of anti-Markovnikoff hydroamination of aromatic alkenes has been demonstrated with cationic rhodium complexes.170 A combination of [Rh(COD)2]+/2PPh3 in THF under reflux yields the N-H addition product as the minor species alongside that resulting from oxidative amination (Scheme 37). Hydrogenation products are also detected. 

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... 

Table 13 Rhodium-catalvzed hydroamination of terminal alkynes with anilines (catalyst system = fRh-...

Hydroamination of olefins under most catalytic conditions proceed with Markovnikov addition of the N-H bond across the olefin. Shown below is a rhodium-catalyzed intramolecular, anti-Markovnikov, hydroamination developed for the synthesis of 3-arylpiperidines 167 <06JA6042>. Further evaluation of this reaction as a synthesis of multisubstituted piperidines revealed that substrates with substituents a or y to the amino group did not produce the expected piperidine, however, substrates with a substituent (1 to the amino group produce piperidines in high yield. 

In order to account for the high regioselectivities observed in the rhodium-catalyzed hydroboration of styrenes, Hayashi proposed a modified mechanism which proceeds through 73-benzyl-rhodium complex 22 as a key intermediate (Scheme 7). Reductive elimination from this 73-benzyl-rhodium complex 22 produces the secondary alkylborane regioselectively.12 A related 73-benzyl-palladium complex was recently isolated by Hartwig in studies of hydroamination.75... 

The use of catalytic SILP materials has been reviewed recently [10] covering Friedel-Crafts reactions [33-37], hydroformylations (Rh-catalyzed) [38], hydrogenation (Rh-catalyzed) [39,40], Heck reactions (Pd-catalyzed) [41], and hydroaminations (Rh-, Pd-, and Zn-catalyzed) [42]. Since then, the SILP concept has been extended to additional catalytic reactions and alternative support materials. In this paper we will present results from continuous, fixed-bed carbonylation and hydroformylation reactions using rhodium-based SILP catalysts as reaction examples demonstrating the advantages of the SILP technology for bulk chemical production. 

Optimized reaction conditions call for the use of Wilkinson s catalyst in conjunction with the organocatalyst 2-amino-3-picoline (60) and a Br0nsted add. Jun and coworkers have demonstrated the effectiveness of this catalyst mixture for a number of reactions induding hydroacylation and C—H bond fundionalization [25]. Whereas, in most cases, the Lewis basic pyridyl nitrogen of the cocatalyst ads to dired the insertion of rhodium into a bond of interest, in this case the opposite is true - the pyridyl nitrogen direds the attack of cocatalyst onto an organorhodium spedes (Scheme 9.11). Hydroamination of the vinylidene complex 61 by 3-amino-2-picoline gives the chelated amino-carbene complex 62, which is in equilibrium with a-bound hydrido-rhodium tautomers 63 and 64. 

Chatani s proposed mechanism bears some similarity to that of Jun s reaction (Scheme 9.12). They both begin with hydroamination of the C=C 7t-bond of a rhodium vinylidene. The resultant aminocarbene complexes (71 and 62) are each in equilibrium with two tautomers. The conversion of 71 to imidoyl-alkyne complex 74 involves an intramolecular olefin hydroalkynylation. Intramolecular syn-carbome-tallation of intermediate 74 is thought to be responsible for ring closure and the apparent stereospecificity of the overall reaction. In the light of the complexity of Chatani and coworkers mechanism, the levels of chemoselectivity that they achieved should be considered remarkable. For example, 5 -endo-cyclization of intermediate 72 was not observed, though it has been for more stabilized rhodium aminocarbenes bearing pendant olefins [27]. 

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. 

Hydroamination of allenes and 1,3-dienes in the presence of Ni(II), Pd(II), and Rh(III) complexes yields product mixtures composed of simple addition products and products formed by addition and telomerization.288 Nickel halides308 and rhodium chloride309 in ethanol [Eq. (6.51)] and Pd(n) diphosphine complexes310 are the most selective catalysts in simple hydroamination, while phosphine complexes favor telomerization 288... 

The intramolecular anti-Markovnikov hydroamination of l-(3-aminopropyl)vinyl-arenes (71 R = H, Me, CH2OMe, CH2OTBS) in the presence of a rhodium catalyst to form 3-arylpiperidines (72) has been reported. In contrast to intermolecular hydroamination of vinylarenes, which occurs in high yields in the presence of rhodium catalysts... 

The aziridination of olefins, which forms a three-membered nitrogen heterocycle, is one important nitrene transfer reaction. Aziridination shows an advantage over the more classic olefin hydroamination reaction in some syntheses because the three-membered ring that is formed can be further modified. More recently, intramolecular amidation and intermolecular amination of C-H bonds into new C-N bonds has been developed with various metal catalysts. When compared with conventional substitution or nucleophilic addition routes, the direct formation of C-N bonds from C-H bonds reduces the number of synthetic steps and improves overall efficiency.2 After early work on iron, manganese, and copper,6 Muller, Dauban, Dodd, Du Bois, and others developed different dirhodium carboxylate catalyst systems that catalyze C-N bond formation starting from nitrene precursors,7 while Che studied a ruthenium porphyrin catalyst system extensively.8 The rhodium and ruthenium systems are... 

A series of rhodium and platinum compounds have been tested in the hydroamination of norbomene with aniline, as shown in Scheme 9.36.[141] Selectivity and activity were highly dependent on the nature of the ionic liquid, but were always superior to those observed in THF. Solvents with chloride anions led to essentially no catalytic activity, whereas [PF6] or Br afforded some catalysis. Nonetheless, even with the best solvent/catalyst combination, less than 40 turnovers are achieved after 6 days at 140°C. 

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. 

As the first transition metal-based homogeneous catalysis of hydroamination, in the early 1970s Coulson from the Du Pont laboratories had described the addition of secondary aliphatic amines to ethylene in the presence of various rhodium compounds [15, 16]. Definite results were reported with RhCl3 3 H2O as pre-catalyst in tetrahydrofuran as solvent under starting ethylene pressures of 5-14 MPa at 180-200 °C for different secondary amines (Table 3). 

Quite stable catalytic reaction solutions were obtained in THF with the starting pressure for ethylene of 6-6.5 MPa at a reaction temperature of 120 °C. Under these conditions and with the ratios piperidine/rhodium of 100 1 and 1000 1 in 36 and 72 h, yields of 70 and 50 % ethylpiperidine were reached, which correspond to TONs of 2 and 7 mol amine/(mol Rh) per h, respectively. Total conversion is also possible if the reaction time is prolonged further. As a side reaction, ethylene dimerization to butene was observed. This indicates the formation of a hydrido rhodium(III) complex in the hydroamination reaction, as formulated in Scheme 3, route (b). Hydrido rhodium(III) complexes are known as catalysts for ethylene dimerization [19], and if the reductive elimination of ethylpiperidine from the hydrido-y9-aminoethyl rhodium(III) complex is the rate-limiting step in the catalytic cycle of hydroamination, a competitive catalysis of the ethylene dimerization seems possible. In the context of these mechanistic considerations, an increase of the catalytic activity for hydroamination requires as much facilitation of the reductive elimination step as possible. 

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,... 

Examples of the insertions of alkenes or alk5mes into metal-amido bonds are also rare. Examples of the insertions of alkenes into tihe M-N bonds of isolated amido complexes include the reaction of a rhodium anilide complex with alkenes to form imines witii kinetic behavior that is consistent with migratory insertion,and the formal insertion of the strongly electrophilic acrylonitrile into a platinum anilide. Additional examples include reactions of a lanthanide-amido complex generated in situ, a catalytic carboamination process in which the stereochemistry implies insertions of olefins into amides, and a catalytic hydroamination that appears to occur through an aminoalkyl complex generated by S3m addition of the iridium and amido groups across the C=C bond of norbomene. 

One of the best-characterized examples of intramolecular hydroamidation of an alkene with the tethered activated nitrogen of amide and carbamate groups is shown in Equations 16.66a and 16.66b. This reaction is catalyzed by a dicationic palladium complex ligated by a PNP pincer ligand. Like the rhodium-catalyzed hydroamination, this process occurs to form five- and six-membered rings with or without substituents to bias the system toward cyclization.. 

Hydroamination of Alkynes Catalyzed by Rhodium and Palladium Complexes... 

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. 

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. 

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]. 

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