Nitrogen hydroamination

Due to its marked atom economy, the intramolecular hydroamination of alkenes represents an attractive process for the catalytic synthesis of nitrogen-containing organic compounds. Moreover, the nitrogen heterocycles obtained by hydroamination/cyclisation processes are frequently found in numerous pharmacologically active products. The pioneering work in this area was reported by Marks et al. who have used lanthanocenes to perform hydroamination/cyclisation reactions in 1992. These reactions can be performed in an intermolecular fashion and transition metals are by far the more efficient catalysts for promotion of these transformations via activation of the... 

Taube, R. Reaction with Nitrogen Compounds Hydroamination. In Applied Homogeneous Catalysis with Organo-metallic Compounds Comils, B. Herrmann, W. A., Eds. VCH Weinheim, Germany, 1996 pp 507-520. 

Transition metal complex-catalyzed carbon-nitrogen bond formations have been developed as fundamentally important reactions. This chapter highlights the allylic amination and its asymmetric version as well as all other possible aminations such as crosscoupling reactions, oxidative addition-/3-elimination, and hydroamination, except for nitrene reactions. This chapter has been organized according to the different types of reactions and references to literature from 1993 to 2004 have been used. 

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. 

Hydroamination of Alkynes The discovery of palladium-catalyzed intramolecular addition of amines to acetylene coupled with the spectacular contribution of Hutchings opened the door for the synthesis of several nitrogen heterocycles. The first study in this field was performed by Utimoto et al., who researched gold catalyzed intramolecular 6-exo-dig hydroamination. Tautomerization of the initial enamines allowed them to obtain imines, which were thermodynamically more stable [111] (Scheme 8.20). 

Ytterbium and lutetium ionic complexes, derived from enantiopure substituted (R)-binaphthylamine ligands of the general formula [Li(THF) ][Ln[(f )C2oHi2(NR)2]2], have been investigated as catalysts for hydroamination/cyclization of several unsatu- rated amines CH2=CH(CH2) C(R2)CH2NH2 (n = 1 or 2). Complexes with isopropyl or cyclohexyl substituents on nitrogen atoms were found to be efficient catalysts for the formation of N-containing heterocycles under mild conditions with enantiomeric excesses up to 78%.124... 

Intramolecular hydroamination of amino alkenes.1 This lanthanide effects cy-clization of amino alkenes in hydrocarbon solvents to five- and six-membered nitrogen heterocycles. 

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]. 

Nitrogen is a prevalent element in naturally occurring molecules, and chemical formation of new carbon-nitrogen bonds has broad applications in both industry and academic research. Despite more recent advances in carbon-nitrogen bond formation, new facile methods are still sought after. Great advances have been made since the late 1990s, particularly in the development of the efficient hydroamination of... 

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... 

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... 

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. ... 

Intramolecular hydroamination/cyclization, the addition of an N-H bond across an intramolecular carbon-carbon unsaturated bond, offers an efficient, atom economical route to nitrogen-containing heterocyclic molecules (Equation 8.37). Numerous organolanthanide complexes were found to be efficient catalysts for this transformation [124, 125]. The real active intermediates are organolanthanide amides, which are formed by the rapid protonolysis reactions of precatalysts with amine substrates. The proposed catalytic cycle of hydroamination/cyclization of aminoalkenes is presented in Figure 8.37 [124]. 

The carbon-carbon unsaturated substrates have now expanded from aminoalkenes to aminoalkynes, aminoallenes, and aminodienes, and the hydroamination/cyclization reactions of these substrates have produced functionalized nitrogen-containing heterocycles. It is worth noting that the aminoallene hydroamination/cyclization reactions are highly diastereoselective, and can provide concise routes to the synthesis of some natural products (Figure 8.38) [126]. 

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. 

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... 

Whereas the catalytic hydrosilylation of alkynes was one of the first methods of controlled reduction and functionalization of alkynes, the ruthenium-catalyzed hydroamination of alkynes has emerged only recently, but represents a potential for the selective access to amines and nitrogen-containing heterocydes. It is also noteworthy that, in parallel, the ruthenium activation of inert C-H bonds allowing alkyne insertion and C-C bond formation also represents innovative aspects that warrant future development. Among catalytic additions to alkynes for the production of useful products, the next decade will clearly witness an increasing role for ruthenium-vinylidenes in activation processes, and also for the development of ruthenium-catalyzed hydroamination and C-H bond activation. 

The scope of the lanthanide-mediated, intramolecular amination/cyclization reaction has been determined for the formation of substituted quinolizidines, indolizidines, and pyrrolizidines,1046 as well as tricyclic and tetracyclic aromatic nitrogen heterocycles.1047 The amide derivative OT ro-[ethylene-bis(indenyl)]ytterbium(m) bis(trimethyl-silyl)amide catalyzes the hydroamination of primary olefins in excellent yields.701 A facile intramolecular hydroamination process catalyzed by [(C5H4SiMe3)2Nd(/r-Me)]2 has also been reported. The lanthanide-catalyzed hydroamination enables a rapid access to 10,1 l-dihydro-5//-dibenzo[tf,rf]cyclohepten-5,10-imines (Scheme 283).1048... 

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