Modes of hydrogen activation

Figure 4. Possible modes of hydrogen activation on transition metal sulfur sites.

Heterolytic cleavage. This leads to formation of a metal hydride with release of a proton (equation 1). The formal oxidation state of the metal does not change. This mode of hydrogen activation is common in hydrogenation by complexes of ruthenium(II). 

Both modes of hydrogen activation, heterolytic and homolytic, may be achieved either directly or through a two-step mechanism involving the intermediate formation of ri -H2 complexes. 

The three basic modes of hydrogen activation by a transition metal complex (M, ML, M2, or MX) are illustrated by reactions A m-oxidative addition of H2 to the metal center(s) occurs in (43)-(45), whereas (46) is... 

Scheme 1.7 Three possible modes of hydrogen activation in Rh-catalyzed asymmetric hydrogenation of activated olefins. For the clarity reasons here and further the coordinated molecules of solvent completing square planar for Rh(I) or octahedral for Rh(III) configuration are not shown.

Hydrogen bonding to substrates such as carbonyl compounds, imines, etc., results in electrophilic activation toward nucleophilic attack (Scheme 3.1). Thus, hydrogen bonding represents a third mode of electrophihc activation, besides substrate coordination to, for example, a metal-based Lewis acid or iminium ion formation (Scheme 3.1). Typical hydrogen bond donors such as (thio)ureas are therefore often referred to as pseudo-Lewis-acids. ... 

Significant levels of syn diastereoselectivities (5 1 to 16 1) were observed for all substrates, with the exception of an ortho-chloro-substituted aryl imine, which provided only 2 1 syn selectivity. The catalyst was viable for a variety of nitroalkanes, and afforded adducts in uniformly high enantioselectivities (92-95% ee). The sense of enantiofacial selectivity in this reaction is identical to that reported for the thiourea-catalyzed Strecker (see Scheme 6.8) and Mannich (see Tables 6.18 and 6.22) reactions, suggesting a commonality in the mode of substrate activation. The asymmetric catalysis is likely to involve hydrogen bonding between the catalyst and the imine or the nitronate, or even dual activation of both substrates. The specific role of the 4 A MS powder in providing more reproducible results remains unclear, as the use of either 3 A or 5 A MS powder was reported to have a detrimental effect on both enantioselectivities and rates of reaction. 

The use of chiral Brpnsted acid catalysis as a mode of asymmetric activation burgeoned dramatically in the early part of the twenty first century [35]. The role of hydrogen in this process is, in essence, similar to that of Lewis acid catalysts - i.e. activation of the C=X bond (X=0, NR, CR ) by decreasing the LUMO energy and ultimately leading to promotion of nucleophilic addition to the C=X bond (Fig. 1.5). 

The phonon frequencies Vpho on in proteins have the following characteristic values at acoustic modes they lie between 10" and 10" s" ( 0.0004-0.004 eV) in a polypeptide chain the acoustic modes are generated by vibrations, which cause changes in the relative distances and orientations of the side chains. The upper limit is given by the high-frequency intramolecular vibrational modes of hydrogen atoms with a frequency of 10 s" ( 0.4 eV). At body temperatures (k T ks 310 K 0.03 eV), the acoustic modes will be most active in the scattering of electrons. Therefore for the subsequent considerations Vphonon = 10 s has been taken as the characteristic value. 

The third approach to activation involves pyridoxal-mediated conversion of the endiyne to an eneyne-allene [26, 344]. Acyclic enediynyl amine 3.756, upon treatment with pyridoxal in the presence of a base (EtsN), undergoes isomerization to the eneyne-allene 3.757 following imine formation. The allene then reacts at room temperature to generate the products 3.759 and 3.760 (Scheme 3.89) via diradical intermediate 3.758 A or B depending on the mode of hydrogen abstraction [26, 344]. 

Diphenyl derivatives. Gschwind and co-workers have demonstrated that NMR spectroscopy was the method of ehoice to clearly distinguish between the activation modes of hydrogen bonding and ion pairing in the Bronsted acid (190) catalysis reaction of imines with nucleophiles. ... 

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