N-H activation

Although a maximum of 6 turnovers in 3 days (TOP = 0.08 h ) were reached before loss of activity, this is the first successful demonstration of hydroamination of an alkene via a transition metal-catalyzed N-H activation process. 

The experimental evidence, first based on spectroscopic studies of coadsorption and later by STM, indicated that there was a good case to be made for transient oxygen states being able to open up a non-activated route for the oxidation of ammonia at Cu(110) and Cu(lll) surfaces. The theory group at the Technische Universiteit Eindhoven considered5 the energies associated with various elementary steps in ammonia oxidation using density functional calculations with a Cu(8,3) cluster as a computational model of the Cu(lll) surface. At a Cu(lll) surface, the barrier for activation is + 344 k.I mol 1, which is insurmountable copper has a nearly full d-band, which makes it difficult for it to accept electrons or to carry out N-H activation. Four steps were considered as possible pathways for the initial activation (dissociation) of ammonia (Table 5.1). 

A molecular oxygen state is the most likely to be involved, it would require a barrier of only 67 k.f mol 1 and is exothermic a hydroperoxide state is formed together with NH2(a). When the heats of adsorption of ammonia and oxygen are taken account of, then according to Neurock44,45 there is no apparent activation barrier to N-H activation. 

The first example of a catalytic OHA reaction that was shown to proceed via N—H activation, was published by Casalnuovo, Calabrese and Milstein (CCM) in... 

An understanding of N—H activation via oxidative addition to Ir(I) fragments - and of its microscopic reverse, reductive elimination - is of fundamental importance... 

The first successful catalytic animation of an olefin by transition-metal-catalysed N—H activation was reported for an Ir(I) catalyst and the substrates aniline and norbornene 365498. The reaction involves initial N—FI oxidative addition and olefin insertion 365 - 366, followed by C—FI reductive elimination, yielding the animation product 367. Labelling studies indicated an overall. vyw-addition of N—FI across the exo-face of the norbornene double bond498. In a related study, the animation of non-activated olefins was catalysed by lithium amides and rhodium complexes499. The results suggest different mechanisms, probably with /5-arninoethyl-metal species as intermediates. 

The transition metal catalyzed synthesis of arylamines by the reaction of aryl halides or tri-flates with primary or secondary amines has become a valuable synthetic tool for many applications. This process forms monoalkyl or dialkyl anilines, mixed diarylamines or mixed triarylamines, as well as N-arylimines, carbamates, hydrazones, amides, and tosylamides. The mechanism of the process involves several new organometallic reactions. For example, the C-N bond is formed by reductive elimination of amine, and the metal amido complexes that undergo reductive elimination are formed in the catalytic cycle in some cases by N-H activation. Side products are formed by / -hydrogen elimination from amides, examples of which have recently been observed directly. An overview that covers the development of synthetic methods to form arylamines by this palladium-catalyzed chemistry is presented. In addition to the synthetic information, a description of the pertinent mechanistic data on the overall catalytic cycle, on each elementary reaction that comprises the catalytic cycle, and on competing side reactions is presented. The review covers manuscripts that appeared in press before June 1, 2001. This chapter is based on a review covering the literature up to September 1, 1999. However, roughly one-hundred papers on this topic have appeared since that time, requiring an updated review. 

The cleavage of allcylamine N-H bonds by late transition metals to form metal amido complexes is also rare [69, 70]. When the transition metal is a low valent, late metal, the resulting amido complexes are highly reactive [71, 72]. It appears that the amination of aryl halides can involve an unusual N-H activation process by a palladium alkoxide to form a highly reactive palladium amide [65, 73]. 

The complex resulting from triple C-H/N-H activation can be heterobifunc-tionalized by successive addition of CO2 (carboxylation of the hexamethylbenzene ligand) and water (acidic hydrolysis of the imine to the aldehyde on the Cp substituent). This heterobifunctional complex is very useful for the branching to nano-scopic substrates and yet keep the solubility in aqueous media by means of the carboxylate group. Use of this functionalized electron-reservoir system in redox catalysis is promising. Thus, from the starting 18-electron complex, the overall heterobifunctionalization can be carried out in one pot as shown in Scheme 16 [177, 178]. 

Butadiene complexes display a wealth of interesting reactivity including G-H and N-H activation,160 use in the synthesis of metal-bound enamines,178 oxidative addition of hypervalent organosulfur compounds to yield... 

Metal complexes containing the anionic pyn olyl ligands are much more frequent throughout the periodic table, and the Tj N and Tj binding modes are dominant in the coordination chemistry of such anions [1, 13]. ri N-Pyrrolyl complexes may be synthesized by in situ N-H activation of Pyr by a low-valent metal fragment as in Eq. 

The propensity for C-N vs. N-H activation correlates well with substituent Hammet parameters groups that increase the basicity of aniline increase the relative rate of N-H activation, suggesting that nucleophilic attack by the amine at an empty d /dy orbital of Ta(silox)3 preceeds oxidative addition. On the other hand, electron-withdrawing substituents decrease the rate of N-H activation and increase the rate of C-N activation, similarly to the effects observed on electrophilic aromatic substitution. Nucleophilic attack by the filled d a orbital of Ta(silox)3 is expected to occur at the arylamine ipso carbon preceding C-N oxidative addition. The carbon-heteroatom cleavages can be accomodated by mechanisms using both electrophilic and nucleophilic sites on the metal center. 

Ru(Tp)(Ph)(NCMe)CO] reacts with the electron-rich olefins, ethyl vinyl sulfide and 2,3-dihydrofuran, yielding [Ru(Tp)(CO)( x-SEt)]2 and [Ru(Tp)(CO)(NCMe)(C=CCH2CH2OH)] through a transformation that involves stoichiometric C-S and C-H/C-O bond cleavage, respectively.326 [Ru(Tp)(Me)(CO)(NCMe)] reacts with pyrrole forming [Ru(Tp)(CO) K2- V, V-(H)N=C(Me)(NC4H3) ]. Mechanistic studies indicate that the most likely reaction pathway involves metal-mediated N-H activation of pyrrole to form [Ru(Tp)(CO)(A/-pyrrolyl)(NCMe)], followed by C-C bond formation and proton transfer (Fig. 2.71).327... 

The calculated free energies of the reactions AG° (298.15 K) and the sum of the key barriers can approximately measure the yield of products. As Table 10 shows, the loss of HD from C-H and N-H activation is the most favored both... 

The aminolysis of esters catalyzed by complex 8 is possibly initiated by N-H activation of the amine by metal-ligand cooperation involving 8. Ester coordination followed by intramolecular nucleophilic attack by the amido ligand at the acyl functionality is thought to be a key step [15]. Overall, in one catalytic cycle, two... 

DFT studies of the N-H activation chemistry mediated by (PSiP)Ir species have been carried out. An initial report calculated the relative stabilities of the amido hydride compleffis 71 and 73 and the corresponding amine complejKS that would result from N-H reductive ehmination [71]. AG was determined to be 33.4kcalmol for 71 and 29.0kcalmol for 73 in the gas phase at 298 K. 

The synthesis of phthalimides has also been achieved using the Rh(III)-catalyzed oxidative addition of aromatic amides via C-H/N-H activation. The reaction was carried out using RhCp (MeCN)3(C104)2, KH2PO4 as an additive under 1 atmosphere of carbon monoxide in the presence of an oxidizing agent. Various phthalimides were obtained in up to 94% yield. 

Anion displacement of halides with azolyl anions is one common route to azolyl complexes. One example of such a synthesis is shown in Equation 4.21. In other cases, azolyl complexes have been prepared by proton transfer between the free azole and a metal alkox-ide or hydroxide. An example involving the synthesis of palladium-azolyl complexes is shown in Equation 4.22. In some rare cases, reactions of pyrrole and d early metal alkyls also lead to the formation of a metal-nitrogen bond via o-bond metathesis, as shown in Equation 4.23. Finally, several late-transition-metal-azolyl complexes possessing accompanying hydride Hgands have been prepared by N-H activation of pyrrole and other azoles. 

Table 2.1 lists some of the mechanistic studies of organic and organometallic reactions reported in the literature by ESI-MS. All sorts of reactions have been successfully explored in the gas phase, such as the Baylis-Hillman reaction [211-213], C-H or N-H activation [214—219], cydopropanation reaction [220], Diels-Alder reactions [221], displacement reactions [222], electrophilic fluorination [223, 224], Fischer indole synthesis [225], Gilman reaction [226, 227], Grubbs metathesis reaction [228-231], Heck reaction [194], methylenation [232], oxidation [233, 234], Petasis olefination reaction [235], Raney Nickel-catalyzed coupling [236], ruthenium... 

In an effort to address the role of PCET in the initial N-H activation step, we turned to luminescence quenching experiments using acetanilide as a model... 

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