Halogenated heteroaromatic compounds

Aryl halides normally do not react with phosphines. However, under forcing temperature conditions, most frequently at 170-250 °C in the absence of solvents, it is possible to achieve direct arylation of tertiary phosphines by several halogenated aromatic or heteroaromatic compounds, especially when they are activated26 (reactions 20 and 21). New examples of such arylations have been described for nitrogen heterocycles255 256,... 

Trifluoromethylation reactions of heteroaromatic compounds represent a majority of reported nucleophihc perfluoroalkylations. For example, trifluoromethylation of halogenated quinolines, isoquinolines, or pyridines carried out under pressure using CF3X/CU powder system (X = 1 or Br) in DMF or (Me0)3P=0 solvent affords the corresponding trifluoromethylated heterocycles in 22-60% yield (Fig. 7.21). ... 

The standard method for the synthesis of perfluorinated heteroaromatic compounds is most commonly by halogen exchange of the corresponding perchlorinated system using molten potassium fluoride in an autoclave at very high temperature (300-480°C) in the absence of solvent. In many cases, the synthesis of the perchlorinated precursors is the most difficult part of the synthetic sequence and this is usually accomplished by chlorination of the parent hydrocarbon by using a... 

The sUylation of aromatic or heteroaromatic compounds can be performed via magnesiated or lithiated intermediates, which can be accessed by hydrogen-metal or halogen-metal atom exchange. Thus, C-4 silylation of imidazoles is achieved from4-iodo imidazoles (eq 45), while C-2 silylated oxazoles are prepared by addition of TMSOTf to the lithiated oxazole (eq 46) interestingly, for this reaction, the employment of TMSCl as electrophile... 

Iodine in combination with [bis(acyloxy)iodo]arenes is a classical reagent combination for the oxidative iodination of aromatic and heteroaromatic compounds [99], A typical iodination procedure involves the treatment of electron-rich arenes with the PhI(OAc)2-iodine system in a mixture of acetic acid and acetic anhydride in the presence of catalytic amounts of concentrated sulfuric acid at room temperature for 15 min [100,101]. A solvent-free, solid state oxidative halogenation of arenes using PhI(OAc)2 as the oxidant has been reported [102]. Alkanes can be directly iodinated by the reaction with the PhI(OAc)2-iodine system in the presence of f-butanol under photochemical or thermal conditions [103]. Several other iodine(in) oxidants, including recyclable hypervalent iodine reagents (Chapter 5), have been used as reagents for oxidative iodination of arenes [104-107]. For example, a mixture of iodine and [bis(trifluoroacetoxy)iodo]benzene in acetonitrile or methanol iodinates the aromatic ring of methoxy substituted alkyl aryl ketones to afford the products of electrophilic mono-iodination in 68-86% yield [107]. 

A variety of methods for the catalytic direct arylation of aromatic and heteroaromatic compounds via the cleavage of C—H bonds has been developed during recent years. As complementary synthetic tools for conventional cross-couplings in the preparation of biaryls and arylated heteroarenes that require neither stoichiometric metallation nor halogenation, these reactions may be both useful and economical in a variety of situations. Consequently, it is highly likely that a major effort will be made in the near future to enhance the catalytic efficiency and regioselectivity of these reactions. 

One further application of the microwave-assisted Wolff rearrangement of 2-diazo-1,3-dicarbonyl conpounds involves the direct Friedel-Crafts a-ketoacylation of heteroaromatic compounds in the absence of any catalyst or additive and under halogen-free conditions tScheme 3.26k In contrast to standard Friedel-Crafts reactions that are often conplicated by regioselectivity and/or efficiency issues, the microwave-assisted Friedel-Crafts a-ketoacylation via a-oxo-ketenes proceeded cleanly and with high regioselectivity. It should be noted at there are only a few known exanples of formation of carbon-carbon bonds by... 

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