Thioethers heteroaromatic

Liebeskind reported a new method for cross-coupling heteroaromatic thioethers with boronic acids [56]. This required the use of copper(I) thiophene-2-carboxyhc acid (CuTC) but allowed the reaction to be conducted under mild and neutral reaction conditions from readily available starting material. As an example, thiomethylpyridine 161 was cross-coupled to boronic acid 162 to afford the biaryl 163. 

In 2000, Liebeskind and Srogl reported a Pd-catalyzed boronic acid-thioether crosscoupling protocol which was mediated by copper(I)-carboxylate [68]. Recognizing their increased accessibility, this protocol was successfully applied to the Stille-type coupling reactions of organostannanes with heteroaromatic thioethers [69]. Specifically, the Pd-catalyzed reaction of 122 and stannane 123 was promoted by copper(I)-3-methylsalicy-late to provide 124 in excellent yield. 

The classical structures of pyrrole, furan and thiophene (31) suggest that these compounds might show chemical reactions similar to those of amines, ethers and thioethers (32) respectively. On this basis, the initial attack of the electrophile would be expected to take place at the heteroatom and lead to products such as quaternary ammonium and oxonium salts, sulfoxides and sulfones. Products of this type from the heteroaromatic compounds under consideration are relatively rare. 

Trifluoromethylthio-substituted heteroaromatic systems are available by a multistep procedure, namely photochlorination of the corresponding methyl thioether and subsequent halogen exchange on treatment with antimony trifluoride (52ZOB2216 54ZOB887) (Scheme 18). 

The types of organosulfur compound present in petroleum feedstocks are alkyl and aryl thiols (RSH), thioethers (RSR ), disulfides (RSSR ), and thiophenic compounds (Fig. 1). The ease with which sulfur is abstracted depends very much on the nature of the sulfur-containing molecule aliphatic compounds (thiols, thioethers) are usually desulfurized much more easily than heteroaromatic (e.g. thiophenes, benzothiophenes, dibenzothiophenes). Among the latter, reactivity decreases in the order thiophene > benzothiophene > dibenzothiophene. The presence of aliphatic substituent groups can sometimes alter reactivity. The sterically hindered compound 4,6-dimethyldibenzothiophene is, for example, very difficult to desulfurize. 

A soln. of tert-dimy alcohol in DME added to a suspension of Ni(II)-acetate, 2,2 -bi-pyridyl, and NaH in the same solvent at 63° under N2, the mixture stirred for 2 h, a soln. of dibenzothiophene in DME added over 2-3 min, and worked up after 5 h - biphenyl. Y 98%. The reagent efficiently desulfurizes S-heteroaromatics, ar. thioethers, sulfoxides, sulfones and mercaptals (although the efficiency of the last depends on the nature of the substituents on the S atom). F.e.s. S. Becker et al.. Tetrahedron Letters 29, 2963-6 (1988). 

In addition to the success just described with the well-known named processes, a number of other macrocyclization reactions mediated by palladium complexes have been reported. The first of these approaches exploits the established chemistry of palladium Jt-allyl complexes for use in activation towards reaction with nucleophiles. This reaction was employed by Harran et al. as a critical step in the construction of a series of macrocycles such as 116 via 115) designed to significantly reduce the peptidic character of known active peptides (Scheme 11.14). " The approach tolerates a variety of functionality, including alcohols, amides, thioethers and selected heteroaromatics, and was also successfully conducted on solid support. 

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