Meerwein arylation radical addition reactions

In comparison to the cyclization reactions shown above, intermolecular Meerwein arylations are often more difficult to conduct. Since the aryl radical addition to the alkene is no longer favored by the close proximity of the reacting centers, the probability for a direct recombination of the aryl radical with scavengers Y is significantly increased (Scheme 17). To maintain the desired reaction course from 44 to 45 including steps (1) and (2) [89, 90], Meerwein arylations have for a long time mostly been conducted with activated alkenes, such as acrylates (R = COOR ), vinylketones (R = COR ), styrenes (R = Ph), or conjugated dienes [91,92]. These types of alkenes are known for fast addition of aryl radicals. 

This synthesis is only one example of a wide range of reactions which involve aryl (or alkyl) radical addition to electron-deficient double bonds resulting in reduction.The corresponding oxidative reaction using aryl radicals is the well known Meerwein reaction, which uses copper(II) salts. 

The chain process of the Meerwein reaction can be visualized as shown in Scheme 10-57. There are at least two likely termination reactions for the chain process, namely the addition of a chlorine atom from CuCl2 to the aryl radical (Scheme 10-58) or reaction of the aryl radical with a hydrogen atom of acetone, followed by the formation of chloroacetone (Scheme 10-59). 

Kochi (1956a, 1956b) and Dickerman et al. (1958, 1959) studied the kinetics of the Meerwein reaction of arenediazonium salts with acrylonitrile, styrene, and other alkenes, based on initial studies on the Sandmeyer reaction. The reactions were found to be first-order in diazonium ion and in cuprous ion. The relative rates of the addition to four alkenes (acrylonitrile, styrene, methyl acrylate, and methyl methacrylate) vary by a factor of only 1.55 (Dickerman et al., 1959). This result indicates that the aryl radical has a low selectivity. The kinetic data are consistent with the mechanism of Schemes 10-52 to 10-56, 10-58 and 10-59. This mechanism was strongly corroborated by Galli s work on the Sandmeyer reaction more than twenty years later (1981-89). 

The addition of aryl radicals, generated by chemical reduction of aryldiazonium salts, onto arenes in the Gomberg-Hey reaction is well established [163]. The addition of these radicals to alkenes in the Meerwein reaction is also well known [164], Aryl o-radicals generated by electrochemical reduction of aryl halides take part in similar reactions. Good yields of the products are obtained when the intermediate phenyl radical can react in an intramolecular manner. The addition step is then fast and competes successfully with further electron transfer to form the phenyl car-banion, followed by protonation. 

This procedure has been used to prepare a variety of substituted a-bromohydrocinnamic acids 2 p-acetyl-a-bromohydro-cinnamic acid was prepared for the first time by this method. The method illustrates a typical application of the Meerwein reaction for the arylation of unsaturated substrates.3 In this reaction a catalytic amount of a copper(I) salt is used to reduce an aryl diazonium salt forming an aryl radical and a copper(II) halide. Addition of the aryl radical to an unsaturated substrate forms an alkyl radical that is reoxidized by the copper(II) halide present forming an alkyl halide and regenerating the copper(I) salt catalyst. In this preparation, the product, an a-bromo acid, is formed in an acidic reaction mixture and dehydro-halogenation does not occur. However, dehydrohalogenation... 

In contrast to classical Meerwein arylations, non-activated alkenes are well suited for this reaction type for two reasons. First, due to the relatively slow formation of azo compounds by addition of aryl radical 49 to 48, this undesired pathway cannot compete successfully with the attack of 49 on the alkene to give radical adduct 50. Second, a nucleophilic alkyl radical 50 arises from the addition step, which is effectively trapped by electrophilic salt 48 to give azo compound 51. As a result of several improvements, the methodology is now applicable for a wide range of polar to non-polar alkenes with almost no restrictions on the substitution pattern of the diazonium salt [101, 102]. Moderate diastereoselectivities have been obtained in first attempts with chiral auxiliaries [103]. The azo compounds accessible, such as 51, can be converted to carboamination products 52 by hydrogenation and to various other heterocycles. 

Meerwein type arylations involving radical additions to carbon-heteroatom multiple bonds such as in isothiocyanates have been further extended to tandem reactions leading to heterocycles [117, 118]. 

The conversion of ArN2 salts into ArH takes place in hexamethyl-phosphoramide (by a long radical chain process), and also by the use of the naphthalene anion radical CioHs" in THF. Alternatively, deamination of ArNH2 can be carried out with Bu ONO in DMF. Unsymmetrical biaryls can be formed in a phase-transfer reaction between the diazonium fluoroborate (in an arene solvent) and KOAc complexed with 18-crown-6 polyether. ° Meerwein aryl-ation of fluorinated olefins with ArN2 and copper(ii) halides has been described, but an alternative procedure for the overall addition of ArHal to an alkene involves the use of ArNH2, Bu ONO, and copper(ii) halides in acetone or... 

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