Azole cross-coupling

The synthesis and chemistry of pyrazoles, imidazoles, and 1,2,3-triazoles were actively pursued in 2006. A review on the cross-coupling reactions on azoles with two and more heteroatoms for pyrazoles and imidazoles has been published <06EJO3283>. Publications relating to 1,2,4-triazole and tetrazole chemistry were not particularly well represented this year. The solid-phase and combinatorial chemistry of these ring systems have not been investigated compared to past years. No attempt has been made to incorporate all the exciting chemistry or biological applications that have been published this year. 

The cross-coupling reactions on azoles with two and more heteroatoms including isothiazoles have been reviewed <06EJOC3283>. 

A review concerning the cross-coupling reactions of azoles with two and more heteroatoms was published <06EJOC3283>. 

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. 

As is the case for cross-coupling reactions, arylstannanes and aryltriaUcoxysilanes can be substituted for boronic acids in this method, but would appear to offer few advantages. A number of other, usually Cu(II)-catalysed, reagents can be used to arylate azoles and indoles, of which diaryliodonium salts are the most useful. Aryllead triacetates and triarylbismuth diacetates may find very occasional use, but A-cyclopropylation using tricyclopropylbismuth with cupric acetate is possibly more interesting. ... 

A study of the intermolecular vinylation of azoles (pyrrole, carbazole, and indoles) and phenothiazines was published by I. P. Beletskaya and co-workers.116 This vinylation is catalyzed by Pd(f-Bu)3P and utilizes the lithium amide of various azoles. Various vinyl bromides efficiently undergo the cross-coupling with full retention of their configuration (E or Z). 

Although palladium-catalyzed cross-coupling reactions provide an efficient entry to C-arylated indoles, these reactions require the preparation of functionalized hetero-arenes such as boronates and halides. Therefore, C-arylation reactions of azole and related heteroarenes via direct C-H bond functionalization of the parent heteroar-enes would be much more favorable. In 2004, Sames reported a selective palladium-catalyzed C2-arylation of W-substituted indoles via direct C—H bond arylation [199]. Use CsOAc as the base and low concentration of the substrates proved to be critical for the success of this methodology. 

Scheme 14.50 Ni-catalysed cross-couplings of azoles with arylboronic acids.

The same catalyst as above also catalyses cross-coupling of azoles with styryl pivalate and carbamate to produce alkenylazoles (Scheme 14.58). ... 

Scheme 14.58 Ni-catalysed cross-coupling of azoles with styiyl pivalate or...

In 2011, Ofial succeeded in the C—H/C—H cross-coupling between two very similar reaction partners, such as 1,3-azoles (100 101), thereby overcoming their tendency to undergo homocoupling (Scheme 44) (2011AGE2178). The authors su ested that the presence of Ag ions suppresses the formation of homocoupled reaction products. Furthermore, it is assumed that silver facihtates the proton abstraction of the second C—FI bond of the other 1,3-azole by the (l,3-azole)Pd X complex. The regiose-lectivity is most hkely orchestrated by the acidity of the C2—H bond of the 1,3-azoles, although no clear trend could be identified based on pKa values. 

---