Hydroamination ruthenium

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]. 

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... 

Access to more simply substituted azepine derivatives 116 and 117 has also been realized by ruthenium-catalyzed intramolecular hydroamination of the aminoalkyne 115 (Equation 16) <2001JOM(622)149>. The isolated yield of 116 was 21% and of 117 was only 13%. 

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... 

Quinoline and indole derivatives were also synthesized by cyclocondensation reactions of aniline derivatives with alkynes (Eqs. 42,43) [ 108]. These protocols involve the ruthenium-catalyzed inter molecular hydroaminations of terminal alkynes as the initial steps. 

Catalytic hydroamination of imsaturated carbon-carbon bonds has a strong potential for the access to a large variety of amines, enamines or imines [90]. The first addition of a N-H bond to alkynes catalyzed by a ruthenium catalyst was described in 1995 by Watanabe et al. [91], and involved a ruthenium-catalyzed addition of the N-H bond of N-formyl anilines to terminal alkyne (Scheme 8.29). 

Although this mechanism is based on known activation of the N-H bond of aniline by Ru3(CO)i2, a mechanism involving the activation of the carbon-carbon triple bond followed by a nucleophilic attack of the amine carmot be discarded. Indeed, typical Lewis acids such as Zn(II) or Cu(I) salts have been shown to be efficient catalysts for the intramolecular hydroamination of alkyne [93], However, contrary to ruthenium(II) complexes, mthenium(O) catalysts are not expected to electrophili-cally activate alkynes. 

For indole synthesis, the best additive both for yield and regioselectivity was found to be the anilinium hydrochloride (PhNH2- HCl). The formation of the indole product can be explained by the isomerization of the hydroamination product, in which it has been clearly shown that the ruthenium catalyst is not involved. 

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. 

Iron pentacarbonyl and some ruthenium(III) complexes, such as RuCls 3 H2O or Ru(NH3)4(OH)Cl2, are claimed in a patent as catalysts for the hydroamination of ethylene and higher olefins in homogeneous solution [13]. 

Another novel one-pot synthesis of 2-aryl/vinylindoles based on a ruthenium-catalysed hydroamination and a palladium-catalysed Mizoroki-Heck reaction involves terminal or internal alkynes and 2-chloroaniline (Scheme 6.31) [88]. This method is particularly interesting because it uses readily available and relatively cheap chloro-derivatives. The... 

Ackermann, L. and Althammer, A. (2006) One-pot 2-arylAinylindole synthesis consisting of a ruthenium-catalyzed hydroamination and a palladium-catalyzed Heck reaction using 2-choroaniUne. Synlett, 3125-9. 

Ruthenium complexes also catalyze the anti-Markovnikov hydroamination of vinylarenes. In this case, the combination of l,5-bis(diphenylphosphino)pentane (DPPPent), triflic acid, and a ruthenium(II) precursor generates a catalyst for the additions of secondary amines to vinylarenes (Equation 16.72). This mixture of catalyst components has been shown to generate a cationic Ti -arene complex of a PCP pincer ligand generated from the DPPPent ligand. The mechanism of this reaction involves nucleophilic attack of the amine on an Ti -vinylarene complex, as described in more detail in the section on the mechanisms of hydroamination. 

Scheme 15.17 Ruthenium-catalyzed anti-Markovnikov hydroamination of styrene.

Recently, Goopen has reported a new protocol that draws on easily available ruthenium chloride trihydrate (RUCI3 3H2O) as a catalyst precursor instead of the expensive [Ru(cod)(methallyl)2] [189]. In this new protocol, the catalyst is generated in situ, affording comparable yields. Furthermore, in 2007 Kuninobu and Takai reported the synthesis of ( )-enamide by rhenium-catalyzed hydroamination of unactivated terminal alkynes [190]. However, this method proceeds with less efficiency and lower reaction scope with respect to the mthenium one. 

A C=C triple bond of 1,3-diyne 149 was cleaved with 2-aminophenol in the presence of a ruthenium catalyst (Scheme 7.52) [71]. Initially, a ruthenium-catalyzed hydroamination takes place to give alkynyl imine 150. Conjugate addition of 2-aminophenol follows, resulting in the formation of the 1,3-diimine 151, which cyclizes to form the oxazoline 152. Subsequent retro-Mannich reaction cleaves the C-C bond to furnish the oxazole 153 and the imine 154. 

The anti-Markovnikov addition of nitrogen nucleophiles to alkynes has been accomplished using ruthenium catalysts (Scheme 3.125) [137]. During the screening process, the authors discovered that when the reactions were carried out at 80 °C, moderate yields of the hydroamination products were obtained (50%) however, the stereocontrol was poor and a 4 1 ( ratio of the enamines was obtained. When the temperature was increased to 100°C, the Zi-isomer was obtained exclusively. At the higher temperatures, most substrates exclusively generated the E-isomer, although some substrate-specific reactivity was observed. 

SCHEME 3.128 Z-selective anti-Markovnikov hydroamination using ruthenium catalysts [140]. 

Ruthenium and iron compounds have been claimed to catalyze the hydroamination of olefins with NH3, primary and secondary amines (120-190°C, 10-20 bar) [113, 114]. Ethylene is the most reactive olefin either with ruthenium (Eq. 4.11) or with iron catalysts (Eq. 4.12). 

Ruthenium A hydroamination of styrenes ArC(Me)=CH2 with amines, such as piperidine or morpholine, can be catalysed by cationic Ru complexes in combination with chiral diphosphines, for example, [(C6H6)RuCl2]2 and xylylBINAP. The reaction has been reported to be -selective and the products ArC H(Me)CH2NR2 were obtained with <76% ee. ... 

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