Amines hydroamination give

In 1992, Bergman et al. reported that zirconium bisamides Cp2Zr(NHR)2 catalyze the intermolecular hydroamination of alkynes with sterically hindered primary amines to give enamines or their tautomeric imines (e.g., Eq. 4.77) [126]. 

Schafer found that the bulky bis(amidate) complex is an effective catalyst for intermolecular hydroamination of terminal alkyl alkynes with alkylamines, giving exclusively the anti-Markovnikov aldimine product [309]. The same titanium complexes can also be utilized in the hydroamination of substituted allenes in good yields (Scheme 14.132). Under the catalysis of an imidotitanium complex, the highly strained methylenecyclopropane can undergo hydroamination reaction with either aromatic or aliphatic amines, to give ring-opened imine products in good to excellent yields and chemoselectivities [310]. 

The hydroaminations of electron-deficient alkenes with aniline or small primary alkylamines proceed at high conversions (85-95%, nnder mild conditions, 5 mol%, rt), giving exclnsively the anh-Markovnikov addition product. Secondary dialkyl or bnlky primary amines require longer reaction times. With amines containing P-hydrogens, no imine side-products were observed. 

The first example of acid catalysis appeared in a 1934 patent in which it is claimed that surface catalysts, particularly hydrosilicates of large surface area , known at that time under the trade name Tonsil, Franconit, Granisol, etc. lead to a smooth addition of the olefine to the molecule of the primary aromatic amine . Aniline and cyclohexene were reacted over Tonsil at 230-240°C to give, inter alia, the hydroamination product, N-cyclohexylaniline [47]. 

Hegedus et al. have thoroughly studied the homogeneous hydroamination of olefins in the presence of transition metal complexes. However, most of these reactions are either promoted or assisted, i.e. are stoichiometric reactions of an amine with a coordinated alkene [98-101] or, if catalytic, give rise to the oxidative hydroamination products, as for example in the cyclization of o-allylanilines to 2-alkylindoles [102, 103], i.e. are relevant to Wacker-type chemistry [104]. 

Lithium alkylamides (in situ generated from the amine and either n-BuLi or sec-BuLi) generally give higher yields under milder conditions. Thus, n-BuLi (5%) catalyzes the addition of primary and secondary amines to styrene to afford (-phenethy-lamines in moderate to good yields (e.g., Bq. 4.32) [155]. NH, and PhNHj, however, do not add to styrene under these conditions. a-Methylstyrene and 1,1-diphenyleth-ylene can also be hydroaminated. 

Butadiene and isoprene give rise to mixtures of what are usually called telom-ers, namely 1 1 telomers between the amine and the 1,3-diene (trae hydroamination products), 1 2 telomers and even higher homologs together with oligomers of the diene as exemplified in Eq. (4.41). 

In fact, catalytic systems which effect solely the hydroamination of 1,3-butadiene and isoprene are rare and usually specific to the diene and to the amine. Thus morpholine adds to 1,3-butadiene in the presence of RhCf.lHjO to give a mixture of 1,2-(Markoviiikov) and 1,4-hydroamination products in good overall yield (Eq. 4.42) [171,172). 

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]. 

The hydroamination of phenylacetylene with primary or secondary aromahc amines is also catalyzed by Tl(OAc)3 to give imines or enamines, respectively, in low to good yields (10-89%) with TOF up to 6 h [261]. 

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... 

Summaries of results of hydroamination mediated with Rh(I) amide complexes584 and comprehensive reviews giving detailed information of the field are available.585-587 Therefore, only the more important relatively new findings are presented here. In most of the transformations reported transition metals are applied as catalysts. The feasibility of the use of tcrt-BuOK was demonstrated in the base-catalyzed amination of styrenes with aniline.588... 

Cazes et al. reported the Pd-catalyzed intermolecular hydroamination of substituted allenes using aliphatic amines in the presence of triethylammonium iodide leading to allylic amines [19]. In a way similar to the Pd-catalyzed hydrocarbona-tion reactions we reported that the hydroamination of allenes [20], enynes [21], methylenecyclopropanes [22], and cyclopropene [10] proceeds most probably via oxidative addition of an N-H bond under neutral or acidic conditions to give allylic amines. The presence of benzoic acid as an additive promotes the Pd-medi-ated inter- and intramolecular hydroamination of internal alkynes [23]. Intramolecular hydroamination has attracted more attention in recent years, because of its importance in the synthesis of a variety of nitrogen-containing heterocycles found in many biologically important compounds. The metal-catalyzed intramolecular hydroamination/cyclization of aminoalkenes, aminodienes, aminoallenes, and aminoalkynes has been abundantly documented [23]. 

The direct catalytic reaction of nucleophiles such as amines with 1,3-dienes to give allylic amines is difficult to achieve. A high-throughput assay was used to screen catalysts for the 1 1 hydroamination of aniline to 1,3-cyclohexadiene (equation 44). ... 

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 organolanthanide-catalyzed alkene hydroamination has been reported. With this approach, amino alkenes (not enamines) can be cyclized to form cyclic amines, and amino alkynes lead to cyclic imine. The use of synthesized C-1 and C-2 symmetric chiral organolanthanide complexes give the amino alcohol with good enantioselectivity. 

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. 

The organolanthanide-catalyzed hydroamination of the aminoalkynes 276 gives the nitrogen-containing heterocycles 277 or 278 (in the case of R = H).158 The reaction of primary amines produces the cyclic imines 278, while the reaction of secondary amines gives the cyclic enamines 277 (Scheme 89). The organolan-... 

Hydroamination of olefins is also possible with gold catalysts. In this reaction, the attack comes from 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 aminations, 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. ... 

Cp )2SmCH(TMS)2, giving cyclic imines by a hydroamination/cyclization process. When secondary amines containing two unsaturated bonds are subjected to the reaction conditions, a tandem ring formation process is realized. ... 

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