Stille coupling imidazoles

Arylstannanes reacted with 2-iodoimidazole under Stille conditions gave rise to cross-coupled products. The imidazole modified tetrathiafulvalene 362, synthesized via Stille coupling, formed a charge transfer complex with chloranil, which displayed metal like conductivity for the first time in a purely organic material (Scheme 85) <2004AGE6343>. 

Using the Stille reaction similar to the one described immediately above, a new synthetic route to imidazo[4,5-c]pyridines has been delineated [46]. Following the coupling reaction to provide alkenyl imidazole 79b, an electrocyclic reaction was employed to provide 80 after aromaticity was attained by the elimination of methanol. The flexibility of this process is demonstrated by the fact that nearly identical yields are possible regardless of whether the Stille coupling reaction is done on compound 79a or the aldehyde compound that immediately precedes it in the synthetic sequence. 

Tin Derivatives Treatment of Af-protected 4-iodoimidazole with ethylmagnesium bromide in anhydrous dichloromethane followed by quenching with trimethyltin chloride will give the 4-stannylated imidazole 110 (Scheme 47). Subsequent Stille coupling has been effected with p-bromostyrene or the bromovinyl-dioxole lll.t i... 

The Stille reaction is arobust choice for the synthesis of biaryls, including heteroaryl systems (Scheme 2.61). Despite trying Suzuki, Hiyama and Kumada couplings and others, only Stille coupling (M = -BusSn) proved reliable on a large scale (302 g) for the synthesis of a heteroaryl-substituted imidazole 2.180, needed for the synthesis of an angiogenesis inhibitor (Scheme 2.62). ... 

In a similar approach, Stelzer and coworkers [114] prepared a range of phosphines bearing Al-methyl imidazolium groups placed close or remote from the phosphorus (Scheme 2.32). Aryl rings could be linked to the imidazol part via a Kosugi-Stille coupling. Additional abundant functional groups like in compound I may furthermore enhance the solubility in ILs [115]. 

Triorganostannyl imidazoles can also be synthesized via 2,5-diUthiation using excess n-BuLi. Treatment with tributyltin chloride, followed by aqueous workup to cleave the labile 2-stannyl substituent gives 5-(tributylstannyl)-A(-methylimidazole (eq 16). This substrate was then applied in a Stille coupling with 2-iodothienop)uidine in the scale-up synthesis of a VEGFR kinase inhibitor. ... 

Process chemists at Pfizer took advantage of the Stille coupling reaction between an iodothienopyridine 61 and 5-(tributylstannyl)-l-imidazole 62 to produce 63, an intermediate in the synthesis of a cGMP bulk lot of VEGFR kinase inhibitor 64. ... 

Nonetheless, to make imidazole-containing molecules, haloimidazoles may serve as electrophilic coupling partners for the Suzuki reaction. As described in section 9.1, regioselective bromination at the C(4) position could be achieved for a 1,5-dialkylimidazole using NBS in CH3CN. The Suzuki coupling of l-benzyl-4-bromo-5-methylimidazole with phenylboronic acid assembled the unsymmetrical heterobiaryl in 93% yield, whereas the corresponding Stille reaction with phenyltrimethyltin proceeded in only moderate yield (51%) [8]. 

Analogously, 5-tributylstannylimidazole 29 was easily obtained from the regioselective deprotonation of 1,2-disubstituted imidazole 28 at C(5) followed by treatment with tributyltin chloride [24]. In the presence of 2.6 equivalents of LiCl, the Stille reaction of 29 with aryl triflate 30 afforded the desired 1,2,5-trisubstituted imidazole 31 with 2,6-di-tert-butyl-4-methylphenol (BHT) as a radical scavenger. Reversal of the nucleophile and electrophile of the Stille reaction also provided satisfactory results. For example, the coupling reaction of 5-bromoimidazole 33, derived from imidazole 32 via a regioselective bromination at C(5), and vinylstannane 34 produced adduct 35 [24],... 

In 1956 our laboratory, in collaboration with Beiser and Lieberman, became interested in preparing steroid-protein conjugates that were to be used to elicit antisteroid antibodies. An examination of the literature at that time showed that the azo coupling techniques of Landsteiner were still dominant. Like him, we chose to use the serum albumins because they were inexpensive and likely to yield soluble conjugates. However, an examination of the amino acid content of bovine serum albumin (BSA) (Fig. 1) convinced us that substitution by such relatively complex haptens as steriods should be attempted by reaction with the more plentiful c-amino groups of the lysine residues rather than by an azo coupling reaction with tyrosine, tryptophan, and imidazole residues. This meant forma-... 

The mechanism of alkylation of AT-unsubstituted imidazoles and benzimidazole was discussed in CHEC(1984). Both CHEC(1984) and CHEC-II(1996) had extensive reviews on the topic, which are still relevant. A summary of improved Ullman coupling reactions is given in Table 9. 

Sometimes, the role of the coupling partner is important for the success of a coupling reaction. Imidazole stannane 367 reacted with iodoimidazolopyridine 366 under the common Stille conditions to give product 368 in good yields. However, under the same conditions, iodoimidazole 370 and stannane 369 only produced traces of the desired product 368 (Scheme 87) <2003HCA3461>. 

The imidazole, benzoxazole, and benzthiazole derivatives in Table 7-3 are rather moisture-sensitive.92 On the whole, however, the heteroarylstannanes show the same reactions that characterise the homoarylstannanes. With a palladium catalyst, they undergo coupling112 and cross-coupling reactions68 and indeed much of the recent interest in the heteroarylstannanes stems from their applications in the Stille reaction (see Section 22.2). One aspect of this is the synthesis of oligomers and polymers or copolymers, for example by the cross-coupling of 2,5-distannylthiophene with a 1,4-diiodo-arene.113,114... 

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