Metal-catalyzed reactions, covalent

Probably the most common attachment reaction in a late transition metal catalyzed reaction is transmetalation. This reaction, depicted in Figure 1-6, is the reversible exchange of covalently bonded ligands between two metal centres. The placement of the equilibrium is usually determined by the difference between the thermodynamic stability of the sacrificed and the formed bonds. From the practical point of view the placement of the equilibrium is less interesting as long as it is able to provide enough of the transmetalated complex for the follow up reaction. 

Thorn, K. A., Goldenberg, W. S., Younger, S. J., and Weber, E. J. (1996a). Covalent binding of aniline to humic substances—Comparison of nucleophilic addition, enzyme-, and metal-catalyzed reactions by N-15 NMR. ACS Symp. Ser. 651, 299-326. 

The liquid phase NMR spectra comprise the first direct spectroscopic evidence differentiating phenoloxidase- and metal-catalyzed reactions from noncatalyzed nucleophilic addition reactions of aniline with humic substances. The solid state NMR spectra provide the first direct evidence for nucleophilic addition of aniline to quinone and other carbonyl groups in the organic matter of whole soil and peat. The NMR approach has potential for further investigation of the effects of reaction conditions on the incorporation of aromatic amines into naturally occurring organic matter, and for studies on how aromatic amines covalently bound to organic matter may ultimately be re-released or remineralized, either chemically or microbially. 

The application of transition metal-mediated reactions on solid support is an area of supreme interest for both peptide chemistry and the synthesis of nonpeptidic drug-like molecules. Although many metal-catalyzed reactions have been carried out on resin-bound scaffolds, there are scarce examples of metal-mediated solid-phase reactions promoted by a complexing agent that is covalently bound with the resin in close proximity of the scaffold. Dai and Sun have recently proposed an ingenious route toward the microwave-assisted solid-phase synthesis of a small library of 2-(hetero)aryl indoles. The authors demonstrated the strategic use of a tailor-made linker that features the dual function of a normal linker for scaffold attachment as well as of a promoter for the Cu(II)-mediated hetero-annulation of the intermediates (Scheme 8.17). 

Herrmann WA, Brossmer C, Reisinger CP, Riermaier T, Ofele K, Beller M (1997) Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions. Part 10. Palladacycles efficient new catalysts for the Heck vinylation of aryl halides. Chem Eur J 3 1357-1364 Iyer S, Jayanthi A (2001) Acetylferrocenyloxime palladacycle-catalyzed Heck reactions. Tetrahedron Lett 42 7877-7878 Iyer S, Ramesh C (2000) Aryl-Pd covalently bonded palladacycles, novel amino and oxime catalysts di- x-chlorobis(benzaldehydeoxime-6-C,AT)dipalla-dium(II), di- x-chlorobis(dimethylbenzylamine-6-C,A)dipalladium(II) for the Heck reaction. Tetrahedron Lett 41 8981-8984 Jeffery T (1984) Palladium-catalysed vinylation of organic halides under solid-liquid phase transfer conditions. J Chem Soc Chem Commun 1287-1289 (b) idem,... 

With regard to the valence electron count, this number determines whether the transition metal ion is using its full complement of valence shell orbitals— i.e., the five nd s, the (n + l)s, and the three (n + l)p s. If the valence electron count is eighteen, all of the orbitals are fully utilized in bond formation and electron pair storage, the effective atomic number (EAN) rule is fulfilled and the metal ion is said to be saturated. If it is seventeen, the metal ion is covalently unsaturated, and if it is sixteen or less, the metal ion possesses at least one vacant coordination site and is said to be coordinatively unsaturated. The importance of the valence electron count in homogeneously catalyzed reactions has been discussed by Tolman (7). 

Functionalization of superbenzene permits covalent linking leading to, e.g., superbiphenyl 94225 and the supertolane 95,225 prepared by transition-metal-catalyzed coupling reactions starting from the mono-bromo derivatives. Superbenzene as a building block... 

Metal oxide species with acid or basic properties as efficient catalysts for alkylation and related reactions have been discussed in Section 5.2. An alternative approach is based on reactions of covalent metal-to-carbon (M-C) bonds. Transition metals are well-suited for this task, as they form directional bonds using hybrid orbitals, and undergo low-energy electron promotion and transfer processes. There are now many industrial processes involving transition metal-catalyzed carbon-carbon bond formation (for example, carbonylation, metathesis, and polymerization reactions, see Chapters 4, 6 and 7, respectively). In sections 5.3-5.4 we deal with other C-C bond forming reactions that can lead to fine chemicals (see Chapter 1). 

The examples in this section have been chosen to provide an in-depth presentation showing how RSSF currently has been applied to the study of biological systems. These applications include the study of isotope effects on enzyme-catalyzed reactions, the investigation of substrate-metal ion interactions in metalloenzymes, the search for and identification of covalent intermediates in enzyme-catalyzed processes, the analysis of the effects of site-directed mutations on enzyme catalytic mechanism, and the exploitation of natural and artificial chromophores as probes of allosteric processes. 

The catalyzed reaction of enol ethers with carbonyl compounds (Scheme 1) has become an important reaction in synthesis. Compared to the metal enolate reactions (Part 1, Volume 2), the catalyz enol ether reactions offer the following distinct differences. Enol ethers are often isolable, stable covalent compounds, whereas the metal enolates are usually generated and used in situ. Under Lewis acid catalyzed conditions, a number of functional equivalents such as acetals, orthoesters, thioacetals, a-halo ethers and sulfides can participate as the electrophilic components, whereas many of them are normally unreactive towards metal enolates. In synthesis, enol ether reactions now rival and complement the enolate reactions in usefulness. Enol silyl ethers are particularly useful because of their ease of preparation, their reasonable reactivity and the mildness of the desilylation process. 

Lewis acids act as electron pair acceptors. The proton is an important special case, but many other compounds catalyze organic reactions by acting as electron pair acceptors. The most important Lewis acids in organic reactions are metal cations and covalent compounds of metals. Metal cations that function as Lewis acids include the alkali metal monocations Li+, Na+, K+, di- and trivalent ions such as Mg +, Ca, Zn +, Sc, and Bi + transition metal cations and complexes and lanthanide cations, such as Ce + and Yb. Neutral electrophilic covalent molecules can also act as Lewis acids. The most commonly employed of the covalent compounds include boron trifluoride, aluminum trichloride, titanium tetrachloride, and tin(IV)tetrachloride. Various other derivatives of boron, aluminum, titanium, and tin also are Lewis acid catalysts. 

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