Aryl-substituted five-membered heterocycles

A general and practical method for synthesis of aryl-substituted five-membered heterocycles was developed. In the presence of KOH (30 mol%), l,4-diaryl-l,3-butadiynes undergo a cyclocondensation reaction with water in dimethyl sulfoxide at 80 °C to afford 2,5-diarylfurans in good-to-exceUent yields (14T8252). 

In addition, complexes of P(/-Bu)3 have been shown to catalyze the formation of diaryl heteroarylamines from bromothiophenes.224 Aminations of five-membered heterocyclic halides such as furans and thiophenes are limited because their electron-rich character makes oxidative addition of the heteroaryl halide and reductive elimination of amine slower than it is for simple aryl halides. Reactions of diarylamines with 3-bromothiophenes occurred in higher yields than did reactions of 2-bromothiophene, but reactions of substituted bromothiophenes occurred in more variable yields. The yields for reactions of these substrates in the presence of catalysts bearing P(/-Bu)3 as ligand were much higher than those in the presence of catalysts ligated by arylphosphines. 

Accordingly, whilst five-membered heterocycles exclusively give arylation in a-position toward aryl cations, the Imposition is only arylated in 2,5-dimethyl derivatives. Such selectivity for attacking in the a-position is greater than in other electrophilic substitutions, which indicates that triplet phenyl cations are not localized cations and therefore are more selective electrophiles [53],... 

Aminations of five-membered heterocyclic halides, such as furans and thiophenes, are limited. These substrates are particularly electron-rich. As a result, oxidative addition of the heteroaryl halide and reductive elimination of the amine are slower than for simple aryl halides (see Sections 4.7.1 and 4.7.3). In addition, the amine products can be air-sensitive and require special conditions for their isolation. Nevertheless, Watanabe has reported examples of successful couplings between diarylamines and bromothiophenes [126]. Triaryl-amines are important for materials applications because of their redox properties, and these particular triarylamines should be especially susceptible to electrochemical oxidation. Chart 1 shows the products formed from the amination of bromothiophenes and the associated yields. As can be seen, 3-bromothiophene reacted in higher yields than 2-bromothiophene, but the yields were more variable with substituted bromothiophenes. In some cases, acceptable yields for double additions to dibromothiophenes were achieved. These reactions all employed a third-generation catalyst (vide infra), containing a combination of Pd(OAc)2 and P(tBu)3. The yields for reactions of these substrates were much higher in the presence of this catalyst than they were in the presence of arylphosphine ligands. 

Similar radical cyclizations of other five-membered heterocycles such as furan and thiophene also yielded the expected spirooxindoles as the major product without any evidence of rearrangement [79, 80]. However, when the carboxamide group was substituted with an allyl group, i.e., 117b, cyclization of the initially formed aryl radical onto the allyl group generated the indoline 119 in 20% yield. 

A variety of five-membered heterocycles have been synthesized on solid phase and have been summarized in Figures 6 and 7. Substituted indoles have been prepared by copper/palladium catalyzed coupling of terminal acetylenes with resin bound aryl iodides [61]. Tetramethylguanidine (TMG), which was used as a... 

This may imply that the intermolecular coupling of various aryl halides with other heteroaromatic compounds may proceed. Indeed, it is now known that not only the special heteroaromatic halides but also usual aryl halides can react with a variety of five-membered aromatic heterocycles, including furans, thiophenes, and azole compounds such as M-substituted imidazoles, oxazoles, and thiazoles [133-137]. The arylation of azoles can be carried out using iodobenzoate immobilized on an insoluble polymer support [138]. Related intermolecular reactions of indole [139] and imidazole [140] derivatives have also been reported. 

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