The synthesis of bromopyrazines from hydroxypyrazines was successfully effected by the procedure via trimethylsilyloxypyrazines, the sequence of which proceeds under mild conditions and does not require the isolation of intermediate.

Synthesis of acetylpyrazines 3 and propionylpyrazines 5 was achieved by copper-cocatalytic Stille reaction of bromopyrazines 1 with tributyl(1-ethoxyalkenyl)tin and then acidic hydrolysis. The optimal reaction conditions involve the combination of 15 mol% CuI with 5 mol% of PdCl 2 (Ph 3 P) 2 . Similarly, 2-acylpyridines and propionylbenzenes were prepared from the corresponding aryl bromides.The Stille cross-coupling of bromobenzenes with trialkyl(1-ethoxyvinyl)tin followed by acidic hydrolysis has been shown as a convenient method for the synthesis of acetophenones. 2,3 In a preceding paper, we reported this methodology to be also effective in the dehalogenative acylation of electron-deficient nitrogen heteroaromatics, thus high yields of 1,3-dihydro-6-propionylpterin-2,4-diones were synthesized via Pd-catalyzed reaction of the 6-bromopteridines with tributyl(1-ethoxyprop-1-enyl)tin. 1 The key for the successful transformation was the use of CuI under the traditional Stille conditions, in other words the cross-coupling did not proceed at all without the additive. The cocatalytic effect of CuI in the Stille coupling was first reported by Liebeskind and Fengl, 4 and the many subsequent applications have stimulated a considerable development in this chemistry. 5 Much less is known, however, about the couplings of aryl halides with trialkyl(1-ethoxyalkenyl)tin in the presence of CuI. 6 On the other hand, acylpyrazines are of interest as the constituents in foodstuffs or pheromones, which have been often prepared by the Minisci-type radical reaction of pyrazines 7 or lithiation followed by reaction of the resultant lithiopyrazines with N,N-dialkylamides. 8 These methods suffer from some drawbacks, especially the regioselectivity of aromatic substitution. In this respect, acylation via displacement of halogeno substituent is a promising synthetic route to the desired acylpyrazines. We are currently investigating the acylation of bromopyrazines through copper-cocatalytic Stille reaction with 1-ethoxyvinyl or 1-ethoxypropenyl tin compounds (Scheme 1). Additionally, the cross-coupling of halogenopyridines and bromobenzenes was carried out under similar conditions for comparison of reactivity with pyrazine series.We first examined Pd-catalysts in the cross-coupling of 2-bromo-5-phenylpyrazine (1a) 9 with tributyl(1-ethoxyvinyl)tin (2), in which 5 mol% each of Pd catalyst and CuI were employed in refluxing MeCN containing triethylamine (Table 1, entries 1-3) according to our previous procedure. 1 Consequently, PdCl 2 (Ph 3 P) 2 induced the best yield (81%) of 2-acetyl-5-phenylpyrazine (3a). When toluene 2 was used as the solvent instead of MeCN, the yield of 3a decreased to 72%. The effects of Pd-catalyst, CuI and triethylamine can be realized from the experiments lacking each additive (entries 4-9). Without the Pdcatalyst, the coupling proceeded only slightly. The addition of CuI unexpectedly led to an appreciable increase in the yield of acetylpyrazine 3a. Our previous cross-coupling of bromopteridines necessitated cat...

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ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.