Hydroamination reactions

Both heterogeneous and homogeneous catalysts have been found which allow the hydroamination reaction to occur. For heterogeneously catalyzed reactions, it is very difficult to determine which type of activation is involved. In contrast, for homogeneously catalyzed hydroaminations, it is often possible to determine which of the reactants has been activated (the unsaturated hydrocarbon or the amine) and to propose reaction mechanisms (catalytic cycles). 

The same catalytic system has been tested for the hydroamination of 1,3-butadiene with cyclic amines from the three-membered ring aziridine to the seven-mem-bered ring perhydroazepine. Although arizidine does not lead to a hydroamination reaction, all other cyclic amines give rise to a mixture of 1 1 telomers in fair to excellent yields (e.g., Eq. 4.47) [181]. 

Cationic palladium(II) complexes are homogeneous catalysts for both intramolecular and inter-molecular hydroamination reactions.267 Palladium species immobilized on silica can be prepared by the simple addition of alkyl- or hydroxopalladium(II) complexes to partially dehydroxylated silica. The silica-bound species are more stable than their molecular precursors and are efficient catalysts for the cyclization of aminoalkynes.268... 

Organometallic complexes of the /-elements have been reported that will perform both intra-and intermolecular hydroamination reactions of alkenes and alkynes, although these lie outside of the scope of this review.149-155 Early transition metal catalysts are not very common, although a number of organometallic systems exist.156-158 In these and other cases, the intermediacy of a metal imido complex LnM=NR was proposed.159,160 Such a species has recently been isolated (53) and used as a direct catalyst precursor for N-H addition to alkynes and allenes (Scheme 35).161,162... 

Similar to the addition of secondary phosphine-borane complexes to alkynes described in Scheme 6.137, the same hydrophosphination agents can also be added to alkenes under broadly similar reaction conditions, leading to alkylarylphosphines (Scheme 6.138) [274], Again, the expected anti-Markovnikov addition products were obtained exclusively. In some cases, the additions also proceeded at room temperature, but required much longer reaction times (2 days). Treatment of the phosphine-borane complexes with a chiral alkene such as (-)-/ -pinene led to chiral cyclohexene derivatives through a radical-initiated ring-opening mechanism. In related work, Ackerman and coworkers described microwave-assisted Lewis acid-mediated inter-molecular hydroamination reactions of norbornene [275]. 

Scheme 14 Hydroamination reactions catalyzed by CAAC-Au complexes...

The cationic gold complex with CAAC ligand 29 can also catalyze the unprecedented hydroamination reaction of alkynes and allenes using ammonia [59, 60]. It was also demonstrated that it can catalyze the simple hydroamination reaction. It... 

Special dibenzoxazepinones 86, obtained through the general method described in Fig. 16 and containing, as a third additional functionality, a triple bond, have been further cyclized via a palladium-catalysed hydroamination reaction (Fig. 17) [68]. In this way complex polycyclic systems 87 have been assembled in three steps, taking advantage of the three additional functions embedded in the starting component the aryl fluoride, the phenol and the triple bond. 

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>. 

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... 

Several neutral titanium complexes have been shown to catalyse intramolecular hydroamination reactions of alkenes. The corresponding pyrrolidine and piperidine products were formed in up to 97% yields. However, only the geminally disubstituted aminoalkenes were successfully cyclized (Thorpe-Ingold effect).56... 

Several catalytic systems have been investigated for hydroamination of unsaturated bonds [16]. Takahashi et al. reported the telomerization of 1,3-dienes in the presence of an amine leading to octadienylamine or allylic amines when palladium catalysts are used in association with monodentate or bidentate phosphine ligands, respectively [17]. Dieck et al. demonstrated the beneficial effect of addition of an amine hydroiodic salt in the hydroamination reaction of 1,3-dienes in which the allylic amines are produced via an intermediate Jt-allyl palladium complex [18]. Coulson reported the Pd-catalyzed addition of amines to allenes where dimerization is incorporated [4]. This reaction presumably proceeds via a cyclic palladium intermediate in which the Pd activates the olefinic bond for nucleophilic attack the reactions are therefore different from pronucleophilic additions. 

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... 

Finally, though not strictly a hydroamination reaction, the asymmetric addition of alkynes to imines with a copper-bis(oxazoline) complex is worth briefly mentioning.[144] The nature of the ionic liquid cation has a strong effect on the enantioselectivity of the reaction and it appears that a good balance between hydrophobicity and acidity play an important role with best results obtained with [C4Ciim][Tf2N]. 

The complexes were used in catalytic intramolecular hydroamination reactions resulting in the intramolecular cyclisation of aminoalkynes [298,299]. 

Hydroamination of olefins is also possible with gold catalysts. In this reaction, the attack comes Ifom a nitrogen nucleophile as a carbamate,a urea, an amide, or a sulfonamide. In the latter case, the reaction can be carried out intermolecularly. While the carbamates, ureas, and amides give only products of intramolecular anunations, the sulfonamides can perform the intermolecular addition. Only the addition of ureas (equation 146) takes place at room temperature, and in the rest of the additions heating is required. The catalysts of choice in all these reactions are cationic gold(I)-species stabilized by phosphines or NHC ligands. The reaction times have been reduced by the use of microwave irradiation. The mechanism of the hydroamination reaction has been studied in detail theoretically. ... 

Preparation of Amines and /V-Hetero-Substitiited Amines by Hydroamination Reactions Involving Cleavage of the N-H Bond of Ammonia, Amines and /V-Hetero-Substituted Amines (RNHX)... 

A different mechanism again is involved in the hydroamination reaction catalyzed by lanthanide complexes, Cpff.nR which is applied to the cyclization of unsaturated amines. The mechanism involves the formation of a metal amide species from both the catalysts (by different routes), followed by the turnover —limiting intramolecular insertion of the alkene to give a cr-complex, from which the decomplexed cyclic amine is obtained after reaction with a second molecule of the unsaturated amine19,20,107. 

The hydroamination reactions which are assisted or catalyzed by transition metal species can be utilized in the cyclization of unsaturated amines. Palladium(II) is not recommended for such transformations, since low yields were obtained even using stoichiometric amounts of palladium chloride47. Since an enamide is formed by /J-hydride elimination, a reduction step must be performed to obtain the saturated nitrogen heterocycle. A catalytic cyclization reaction, analogous to the Wacker process, was performed from /V-alkenyl tosylamides, such as 1, using... 

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. 

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