Bromides cross-coupling

JEl-vinyl bromide, cross-coupling reaction with terminal acetylenes 220... 

Stambuli found that addition of a substoichiometric amount of zinc chloride permits the use of Pd-phosphine catalysts that are typically inactive for crosscoupling of aryl bromides. This system has excellent functional group tolerance, high yields and can even be used for vinyl bromide cross-coupling. 

Organoboranes are reactive compounds for cross-coupling[277]. The synthesis of humulene (83) by the intramolecular cross-coupling of allylic bromide with alkenylborane is an example[278]. The reaction of vinyiborane with vinyl-oxirane (425) affords the homoallylic alcohol 426 by 1,2-addition as main products and the allylic alcohol 427 by 1,4-addition as a minor product[279]. Two phenyl groups in sodium tetraphenylborate (428) are used for the coupling with allylic acetate[280] or allyl chloride[33,28l]. 

The utility of the Suzuki reaction in the challenging arena of natural product total synthesis has been explored. The constitution of bombykol (106) (see Scheme 26), a well-known pheromone, lends itself to a Suzuki coupling. Indeed, in a short stereospecific synthesis of 106, Suginome et al. demonstrated that ( )-vinylboronic acid ( )-104 can be smoothly cross-coupled with (Z)-l-pentenyl bromide [(Z)-105] 44 the configurations of both coupling partners are preserved in the C-C bond forming process. 

The palladium-catalyzed cross-coupling of alkenylsilanols has been extensively studied with respect to the structure of both the silicon component and the acceptor halide. The preferred catalyst for coupling of aryl iodides is Pd(dba)2 and for aryl bromides it is [allylPdCl]2. The most effective promoter is tetrabutylammonium fluoride used as a 1.0M solution in THF. In general the coupling reactions occur under mild conditions (room temperature, in 10 min to 12 hr) and some are even exothermic. 

As complex 67 outperforms the Fe(0)-ate complexes in rate and yield, shown in the reaction of cyclooctenyl bromide with PhMgBr (full conversion complex 67 <20 min, 81% yield, 38 18 h, 39% yield), it was shown that both Fe(0)-ate and Fe (—2)-ate complexes should be intermediates in cross-coupling reactions, but the major contribution should be made by the route emanating from Fe(—2)-com-plexes. The superiority of Fe(—2)-ate complexes was also shown in the stoichiometric insertion of 67 into allylic halides, which proceeded much faster (<5 min) than with any higher valent iron complex (hours or days). 

Recently, Caddick and Cloke have developed an extension of this procedure that allows the use of alkyl bromides as coupling partners. The basic changes consist of a stoichiometric amount of the bulkier KO Bu instead of KOMe to activate the borane, and the addition of AgOTf to the reaction mixture [119]. These results, although poor in terms of yield, clearly confirm that sp -sp Suzuki-Miyaura cross-couplings are possible and should be further developed (Scheme 6.35). 

In the context of NHC/metal catalysed cross-coupling reactions, the only example of a Hiyama reaction was reported by Nolan using an in situ protocol by mixing Pd(OAc)j and IPr HCl for the formation of the catalyst. Activated aryl bromides and chlorides, such as 2-chloropyridine, were coupled with phenyl and vinyl-trimethoxysilane in good yields [123] (Scheme 6.39). 

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