Covalent arylation

The reaction of aryllead triacetate with 3,5-di-tert-butylphenol has been shown to yield very hindered di-arylated products (Scheme 13.20) [22a]. The favored pathway must involve the occurrence of covalent aryl(aryloxy)lead(IV) diacetate intermediates, although they have not been detected. 

Substrate binding and activation are followed by attack of the carboxylate side chain of Asp-145 at the benzoyl C-4 atom to give an enzyme-stabilized Meisenheimer intermediate (EMc) (Figure 8). Indeed, a site-directed mutant in which Asp-145 has been replaced by an alanine is catalytically inactive." Ketonization of the EMc results in rearomatization of the benzoyl ring and expulsion of the chloride. This nucleophilic addition-elimination mechanism (SNAr-type reaction) results in a second covalent (aryl-enzyme) intermediate, which is subsequently hydrolyzed by a water molecule that is activated by His-90 to give the free enzyme and the product. The existence of a covalent aryl-enzyme intermediate has been inferred from 0-labeling studies (similar to those described for haloalkane and haloalcohol dehalogenase) and from the direct measurement of the aryl-enzyme... 

RTIX2 derivatives are covalent compounds, generally soluble in organic solvents. The aryl and vinyl derivatives are more stable than the corresponding alkyl compounds. This type of compound has been postulated to be an intermediate in many organic synthetic reactions involving thaUium(III) species. 

CovalentISPoncycIopentadienyl Compounds. The general synthesis of covalent non-Cp compounds, R TiX where R = alkyl or aryl... 

Pyridinium salts, l-aryl-4-methoxy-2,6-dimethyl-synthesis, 3, 762 Pyridinium salts, N-aryloxy-rearrangements, 2, 354 Pyridinium salts, 1-benzyl-covalent amination, 2, 239 Pyridinium salts, N-benzyl-reactions... 

The UV spectra suggest that the equilibrium between the diazonium ion and the solvent, on the one hand, and an electron donor-acceptor complex (8.58) on the other, lies on the side of the complex. The latter may possibly exist also as a radical pair (8.60) or a covalent compound (8.59). Dissociation of this complex within a cage to form an aryl radical, a nitrogen molecule, and the radical cation of DMSO is slow and rate-determining. Fast subsequent steps lead to the products observed. 

A similar case is the catalysis of Gomberg-Bachmann arylations by A,A-diphenyl-hydroxylamine, which was discovered by Cooper and Perkins (1969). As Scheme 8-46 shows, the covalent adduct cation 8.62 first loses a proton. This facilitates the homolytic dissociation, as a stable radical, A/,A-diphenylnitroxide (8.63), is formed. This... 

The experiments with 2-(3-butenyloxy)benzenediazonium ions (10.55, Z = 0, n = 2, R=H) and benzenethiolate showed a significant shift of the product ratio in favor of the uncyclized product 10.57. They also indicated that the covalent adduct Ar — N2 — SC6H5 is formed as an intermediate, which then undergoes homolytic dissociation to produce the aryl radical (Scheme 10-83). Following the bimolecular addition of the aryl radical to a thiolate ion (Scheme 10-84), the chain propagation reaction (Scheme 10-85) yielding the arylphenylsulfide is in competition with an alternative route leading to the uncyclized product 10.57. 

Organotin(rV) compounds are characterized by the presence of at least one covalent C-Sn bond. The compounds contain tetravalent Sn centers and are classified as mono-, di-, tri-, and tetraorganotin(IV), depending on the number of alkyl (R) or aryl (Ar) moieties bound. The anions are usually CP, F , 0 , OH , -COO , or -S . It seems that the nature of the anionic group has only secondary importance in biological activity. 

When the tritium (half-life 12.26 years) decays it is converted to the helium-3 isotope, which, of course, does not form covalent bonds, and so immediately departs, leaving behind the alkynyl cation. When this was done in the presence of benzene, RC CCgHs was isolated. The tritium-decay technique has also been used to generate vinylic and aryl cations. 

In each case the mechanism involves generation of an aryl radical from a covalent azo compound. In acid solution diazonium salts are ionic and their reactions are polar. When they cleave, the product is an aryl cation (see p. 852). However, in neutral or basic solution, diazonium ions are converted to covalent compounds, and these cleave to give free radicals ... 

Ru—C(carbene) bond distances are shorter than Ru—P bond lengths, but this can simply be explained by the difference in covalent radii between P and The variation of Ru—C(carbene) bond distances among ruthenium carbene complexes illustrates that nucleophilic carbene ligands are better donors when alkyl, instead of aryl, groups are present, with the exception of 6. This anomaly can be explained on the basis of large steric demands of the adamantyl groups on the imidazole framework which hinder the carbene lone pair overlap with metal orbitals. Comparison of the Ru—C(carbene) bond distances among the aryl-substituted carbenes show... 

As the cation becomes progressively more reluctant to be reduced than [53 ], covalent bond formation is observed instead of electron transfer. Further stabilization of the cation causes formation of an ionic bond, i.e. salt formation. Thus, the course of the reaction is controlled by the electron affinity of the carbocation. However, the change from single-electron transfer to salt formation is not straightforward. As has been discussed in previous sections, steric effects are another important factor in controlling the formation of hydrocarbon salts. The significant difference in the reduction potential at which a covalent bond is switched to an ionic one -around -0.8 V for tropylium ion series and —1.6 V in the case of l-aryl-2,3-dicyclopropylcyclopropenylium ion series - may be attributed to steric factors. 

The most fundamental issues of the structures of heavier group 14 element-centered anionic derivatives R3EM (R = alkyl, aryl, silyl E = Si, Ge, Sn, Pb M = alkali or alkaline earth metals) turned out to be the questions of their aggregation states (monomeric, dimeric, or oligomeric), nature of the E-M bond (covalent or ionic), and configuration of the anionic centers E (tetrahedral, pyramidal, or planar). The most important experimental techniques that are widely used to clarify these questions are NMR spectroscopy and X-ray diffraction analysis. 

Aida and Jiang recently reported an iron(II) porphyrin 1-methylimidazole complex covalently encapsulated within a large aryl ethereal dendrimer cage, as... 

The importance of protonated N-hydroxy arylamines as ultimate carcinogens has been suggested for some time (28,40,139). From studies on their reactivity with nucleic acids at different pH s (2,15,16,63,130,131), the pK for protonation of the N-hydroxy group appears to be between pH 5a and 6 thus, a significant proportion (1-10%) of the N-hydroxy derivative exists as the protonated form even under neutral conditions. This would account for the significant levels of covalent modification of DNA observed in vitro by reaction with N-hydroxy arylamines at neutral pH. Consequently, it has been proposed that in vivo formation of non-acetylated aryl... 

Aryl halide compounds such as fluorobenzene derivatives can be used to form covalent bonds with amine-containing molecules like proteins. The reactivity of aryl halides, however, is not totally specific for amines. Other nucleophiles such as thiol, imidazolyl, and phenolate groups of amino acid side chains also can react (Zahn and Meinhoffer, 1958). Conjugates formed with sulfhydryl groups are reversible by cleaving with an excess of thiol (Shaltiel, 1967). 

Primary amine-containing polymeric particles are available from a number of manufacturers and have either aliphatic or aryl amine groups on their surface. Occasionally, a particle type may have secondary or tertiary amines present, but these should be avoided for covalent coupling, as primary amines typically give better reaction yields than secondary amines and tertiary amines are unreactive. 

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