Halides, aryl solvent effect

Nozaki-Hiyama-Kishi (NHK) reactions215,216 are well known and often employed as a useful method for the synthesis of natural products by coupling of allyl, alkenyl, alkynyl, and aryl halides or triflates with aldehydes. The organochromium reagents are prepared from the corresponding halides or triflates and chromium(ll) chloride, and are employed in polar aprotic solvents (THF, DMF, DMSO, etc.). Subsequently, it was found that nickel salts exhibited a significant catalytic effect on the formation of the C-Cr bond217,218 (Equation (19)). 

Recently, the electrocarboxylations of benzyl and aryl halides and perfluoroalkyl-halides [39] in supercritical mixture or in supercritical carbon dioxide (scC02) and of aryl and benzyl halides in microemulsion [40], were also investigated in order to exploit the possible effect of the use of these solvents on the selectivity of the... 

As to the next step, namely, the reaction of aryl radicals with nucleophiles, we should take into account the fact that air molecular orbital, which initially accommodates the incoming electron, is available in the aryl halide. The electron is subsequently transferred in-tramolecularly from the it to the o molecular orbital of the carbon-halogen bond. Aryl radicals effectively scavenge H atoms. Therefore, an abstraction of a hydrogen atom from the solvent may occur. However, in the case of nucleophiles that can act as effective traps of aryl radicals, the addition of a nucleophile to the phenyl radical takes place. At this point, let us focus on the step of addition of the nucleophile (Y ) to the intermediate radical (Ph). When a new a bond begins to form between the sp3 carbon-centered radical (H5C6) and... 

Substitutions by the SRn 1 mechanism (substitution, radical-nucleophilic, unimolecular) are a well-studied group of reactions which involve SET steps and radical anion intermediates (see Scheme 10.4). They have been elucidated for a range of precursors which include aryl, vinyl and bridgehead halides (i.e. halides which cannot undergo SN1 or SN2 mechanisms), and substituted nitro compounds. Studies of aryl halide reactions are discussed in Chapter 2. The methods used to determine the mechanisms of these reactions include inhibition and trapping studies, ESR spectroscopy, variation of the functional group and nucleophile reactivity coupled with product analysis, and the effect of solvent. We exemplify SRN1 mechanistic studies with the reactions of o -substituted nitroalkanes (Scheme 10.29) [23,24]. 

Various combinations of catalysts, bases, and solvents allow the biaryl coupling of arylboronic acids with aryl halides and triflates if there are no side-reactions such as the hydrolytic B-C bond cleavage or the participation of phosphine-bound aryls [4] (Scheme 29). The representative conditions are summarized in the scheme and the effects of catalysts and bases on yields and side reactions are discussed in sections 3.1 and 3.2. 

The rate is sensitive to solvent and substituent electronic effects, but not to steric effects. The partitioning between the Ni(II) and Ni(I) pathways is dependent on the aryl halide. The Ni(II)/Ni(I) ratio is greatest for aryl chlorides and lowest for aryl iodides. 

Subsequent to his discovery that alkylaluminum compounds in conjunction with suitable alkyl halides are effective initiator systems for synthesizing high molecular weight polyisobutylene (/), Kennedy in 1970 (6) studied the reaction between alkyl and aryl halides with tri-methylaluminum using methyl chloride solvent at —78° C. The results... 

Reduction of an aryl halide at a cadmium-modified nickel cathode in DMF containing TBABF4 leads to a formylation reaction between aryl carbanions and the solvent [186]. Two papers [187,188] have appeared in which reduction of aryl halides gives an aryl carbanion, which, by acting as a base to deprotonate a suitable nitrile, can cause coupling of the nitrile with esters, aldehydes, and ketones. Electrochemical trimethylsilylation of aryl halides can be effected at a stainless-steel or carbon-cloth cathode in THF-HMPA containing TEABF4 and trimethylchlorosilane [189]. 

In a similar attempt to determine the nature of the rate-determining step in the reaction of aryl halides with magnesium, the kinetics of the reaction of substituted aryl bromides with magnesium and with tri-/i-butyltin hydride in ethereal solvents were examined [81c], using competitive kinetics techniques, and were correlated with the substituent effect using Hammett cr parameters. A Hammett plot log iK/K)=f(( x) then provided the value of the Hammett constant p for the reactions of aryl halides with magnesium and with tri-u-butyltin hydride in various solvents (Fig. 4 and Table 11). 

Palladacycles prepared by the addition of furancarbothioamide to a methanol solution of Li2PdCl4 at room temperature are soluble in hexane, chloroform, and moderately soluble in polar solvents DMF and DMSO [187]. These palladacycles are thermally stable, not sensitive to air or moisture, and can be applied effectively in the Heck reaction of aryl halides with terminal olefins and in the Suzuki reaction of aryl halides with arylboronic acids. These reactions were performed under aerobic conditions, leading to turnover numbers... 

The effect of variation of solvent and concentration of reactants in the Sjy l reaction between benzene selenate (PHSe ) and aryl halides has been studied. Evidence was found to suggest that the radical anion derived from combination of the benzene selenate anion and aryl radicals (see scheme 4) is formed reversibly and can also dissociate to generate phenyl radical and aryl selenate anion. 

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