Mechanism metal-ligand bifunctional

A monohydride mechanism is not operating in reactions catalyzed by these complexes. Noyori observed that the presence of an NH or NH2 in the auxiliary ligands was crucial for catalytic activity, the corresponding dialkylamino analogs being totally ineffective. These findings indicate a novel metal-ligand bifunctional cycle (Scheme 28) KOH reacts with the pre-catalyst (87)... 

The concerted delivery of protons from OH and hydride from RuH found in these Shvo systems is related to the proposed mechanism of hydrogenation of ketones (Scheme 7.15) by a series of ruthenium systems that operate by metal-ligand bifunctional catalysis [86]. A series of Ru complexes reported by Noyori, Ohkuma and coworkers exhibit extraordinary reactivity in the enantioselective hydrogenation of ketones. These systems are described in detail in Chapters 20 and 31, and mechanistic issues of these hydrogenations by ruthenium complexes have been reviewed [87]. 

Fig. 21. General synthesis of p-CD-linked ruthenium complexes asymmetric transfer hydrogenation is described as a metal-ligand bifunctional mechanism according to 31).

One of the systems was found to be very efficient catalyzing enantioface-selective hydrogen transfer reactions to aromatic and in particular to aliphatic ketones with up to 95% ee. Regarding the latter reaction these are unprecedented ee values. The reaction mechanism of these transformations is best described as a metal-ligand bifunctional catalysis passing through a pericyclic-like transition state. 

The excellent catalytic activity is rationalized by a nonclassical metal-ligand bifunctional mechanism using an NH effect. As shown in Figure 1.18, frani-RuH(ri -BH4)(tolbinap)(dpen) (18A) (TolBINAP see Figure 1.2), a precata-... 

Figure 1.24. Metal-ligand bifunctional mechanism in asymmetric transfer hydrogenation of...

Asymmetric transfer hydrogenation of imines catalyzed by chiral arene-Ru complexes achieves high enantioselectivity (Figure 1.34). Formic acid in aprotic dipolar solvent should be used as a hydride source. The reaction proceeds through the metal-ligand bifunctional mechanism as shown in the carbonyl reduction (Figure 1.24). 

Noyori, R., Yamakawa, M. and Hashiquchi, S. Metal-Ligand Bifunctional Catalysis A Nonclassical Mechanism for Asymmetric Hydrogen Transfer between Alcohols and Carbonyl Compounds. J. Org. Chem. 2001, 66, 7931-7944. 

Other chiral diamine-( -arene)ruthenium catalysts were developed by Noyori where the chirality was centred at the metal (see Figure 3.18). These complexes were effective catalysts for asymmetric transfer hydrogenation of carbonyl compounds and a mechanism involving a metal-ligand bifunctional process was proposed. 

Noyori R, Yamakawa M, Hashiguchi S (2001) Metal-ligand bifunctional catalysis a non-classical mechanism for asymmetric hydrogen transfer between alcohols and carbonyl compounds. J Org Chem 66 7931-7944... 

Core of the mechanism of hydrogenation of ketones by metal-ligand bifunctional catalysts. 

The mechanism of this hydrogenation has not been revealed in detail, but several aspects are noteworthy in the context of the mechanistic discussion earlier in this chapter. First, this reaction almost certainly occurs by the insertion of an imine into a metal hydride (see Chapter 9), rather than by the transfer of a hydride and a proton by a metal-ligand bifunctional system. This iridium catalyst does not contain a protic ligand. Second, acid and iodide are needed as promoters to obtain the fast rates. The iodide is thought to help stabilize an iridium(III) species and the acid is thought to help in the release of the amine product from the metal. 

Outer Coordination Sphere Catalysts. In the classical hydrogenation catalysis shown previously, the substrate must be coordinated to the metal prior to its insertion into a metal-hydrogen bond. However, in recent years, it has been found that unsaturated polar bonds can be hydrogenated without coordination of the substrate to the metal (37). Two well-known, nonclassical possibilities for the hydrogenation of unsaturated polar bonds, such as ketones, are the metal-ligand bifunctional mechanism (38) and the ionic mechanism (39). In the metal-ligand bifunctional mechanism discovered by Noyori (recipient of the Nobel Prize in 2001) for highly efficient ruthenium amine complexes, the hydridic RuH and... 

In the ionic mechanism, the proton and the hydride are sequentially transferred to a substrate, whereas in the metal-ligand bifunctional mechanism, the transfer occurs simultaneously. In both cases, the source of the H is a transition metal hydride, but the source of the proton can be a metal hydride or N—H or 0—H bonds. It seems likely that some previously reported catalysts could follow nonclassical outer-sphere mechanisms... 

In this species, there is no direct coordination of the ketone to the Ru, but rather an outer-sphere association with an orientation of the ketone such that two H atoms can be transferred from the 18-electron hydride, one coming from the hydridic H and the other from the NHj group. This nonclassical mechanistic pathway is now widely accepted for this class of catalysts and is referred to as metal-ligand bifunctional catalysis. Theoretical work of Andersson and co-workers and Noyori et al. provided support for the mechanism and further details are discussed in a review by Noyori et al. ... 

Martin-Matute and coworkers described Cp Ir(III) complexes having hydroxyl-, ether-, and alkoxide-functionahzed NHC ligands, and their application in the N-alkylation of amines with primary and secondary alcohob [66]. In particular, the hydroxyl-functionalized complex dbplayed excellent catalytic outcomes, a broad substrate scope, and allowed amines to be alkylated with alcohob at temperatures as low as 50 °C. Indeed, thb hydroxyl-functionalized complex b one of the best catalysts known to date. The authors proposed a metal-ligand bifunctional mechanism for the iV-alkylation of amines with alcohob using this complex, which involves the formation of alcohol/alkoxide intermediates. Complex 38 (Figure 10.10) proved to be excellent for the A/,N -dialkylation of p-, m-, and 0-phenylenediamine with primary alcohob. The authors observed that the dimetal-lic compound 38 performs better than the monoiridium one, suggesting that a cooperative effect between the two metab may be at play [94]. 

Scheme 1.46 A revised catalytic cycle for the asymmetric transfer hydrogenation of aromatic ketones in propan-2-ol by the Noyori-Ikariya (pre)catalyst 2 demonstrates crossover of the reaction pathways the product is obtained via a H"/H+ outer-sphere hydrogenation mechanism and/or step-wise metal-ligand bifunctional mechanism (see text). Formation of the major enantiomeric product is shown. (Adapted from Dub, P. A. et al., /. Am. Chem. Soc., 135, 2604-2619. Copyright 2013 American Chemical Society.)...

The mechanisms for metal-catalyzed and organocatalyzed direct aldol addition reactions differ one from another, and resemble the mode of action of the type 11 and type I aldolases, respectively. Some metal-ligand complexes, for example, 1-4 and 9 are considered to have a bifunctional character [22], embodying within the same molecular frame a Lewis acidic site and a Bronsted basic site. Whereas base would be required to form the transient enolate species as an active form of the carbonyl donor, the Lewis acid site would coordinate the acceptor aldehyde carbonyl, increasing its electrophilicity. By this means, both transition state stabilization and substrates preorganization would be provided (see Scheme 5 for a proposal). 

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