Azoles oxidative cross-coupling

The groups of Hu and You reported a remarkable palladium-catalyzed oxidative cross-coupling of Af-containing heteroarenes 62 with diversely substituted thiophenes 47 to afford products 63A-D (Scheme 10.19). The Af-containing heteroarenes included electron-rich heterocycles such as xanthines and azoles as weU as electron-poor heterocycles such as pyridine IV-oxides. In cases where heteroarenes demonstrated sluggish reactivity, CuBr was used as an additive to assist C—H bond activation. A computational study provided support for a two-fold C—H activation pathway via a CMD mechanism. 

One of the most frequently studied transition metal catalyzed transformations of azoles and indole is their participation in cross-coupling reactions. Due to the abundance of examples in this field we only present some representative examples of the different reaction classes. In this chapter reactions where a halogenated azole is used to introduce the five membered ring onto the palladium in the oxidative addition and processes,... 

Gillmann et al. (94SC2133) (Scheme 148) found a convenient method to prepare methyl 2-bromo-2,3-butadienoate 540 via oxidative ring cleavage of 4-bromopyr-azol-3-one 539 using lead tetraacetate and boron trifluoride etherate in 59% yield. Compounds such as 540 are valuable building blocks for the synthesis of 2-aryl and 2-alkenyl substituted alka-2,3-dienoates via palladium-catalyzed cross-coupling reactions. 

Bao et al. report an efficient and convenient air oxidative biaryl coupling reaction of azoles." The authors did not find significant differences in the yields when comparing pure oxygen and air, and catalytic Cu(OAc)2 in xylene provided the best conversions. The method was not only successfully applied to homo-coupling of various azoles (imidazoles, benzimidazoles, thiazoles. Table 7.1) but also to cross-coupling... 

There were a couple of reports of cross-coupling reactions of pyrazoles published. Palladium-catalyzed cross-coupling between 3,4-, and 5-halopyr-azoles 32 and H-phosphonates, H-phosphinates, and secondary phosphine oxides to give pyrazoles 33 was accomplished in moderate-to-good yields (13OL5550). 1,3,5-Triarylaminopyrazoles 35 were prepared by Ullmann coupling firom l,3-diaryl-5-aminopyrazoles 34 and aryl halides in the presence ofcopper(I) iodide (13T570). 

A Cu-catalyzed dehydrogenative cross-coupling between azoles employed Ag2C03 as an oxidant. Benzothiazole could be cross-coupled with various oxazoles as the C2IC2 products in good yields with minor amounts of homocoupling products (10-13% for benzothiazole, <5-18% for azoles) (eq 41). 

Copper(I) complexed with 1,10-phenanthroline has been used in the arylation of imidazo[l,2-a]pyridines by aryl bromides, iodides, and triflates to give products, (139), substituted at the 3-position. The mechanism is likely to involve initial deprotonation at the 3-position followed by cupration and oxidative addition of the aryl halide. The copper-mediated cross-coupling of indoles with 1,3-azoles is assisted by chelation of a, readily removed, 2-pyrimidyl group and leads to products such as (140). In this reaction, two carbon-hydrogen substitutions are required and it is likely that initial cupration of the 1,3-azole is followed by chelation-assisted formation of a bis(heteroaryl) copper species before oxygen-promoted reductive elimination... 

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