Palladium-catalyzed Cross-coupling Ractions of Chloropyrazines with Aromatic Heterocycles

Abstract

&&&----In the presence of tetakis(mphenylphosphine)palladium, chloropyrazines were treated with aromatic heterocycles such as fwan, thiophene, pyrrole, N-substituted pyrroles, benzo[blfuran, benzo[b]thiophene, oxazole,thiazole, N-methylimidazoles, benz[bloxazole and benzo[b]thiazole.The corresponding coupling products were obtained in moderate to good yields.The smctures of the coupling products were determined.Palladium-catalyzed moss-coupling reactions of aryl halides with organometallics, ethylenes or acetylenes proceeded easily and efticiently during carbon-carbon bond formation.lSome biaryls are important pharmaceutical agents,2.3but nowadays, they of interest mainly 6vm the standpoint of theu physical properties in liquid crystals.'fHowever, little is known in regard to the coupling reactions of aromatic heterocyclic halides with aromatic heterocycles.In previous papers, palladium-mediated cross-coupling reactions of Zchlompyrazines with indoles,5.6ethylenes,'l acetylenes,8.9and organometallics 10-12 were ported and in which the reactions of aryl bromides with n-sufficient aromatic heterocycles in the presence of Pd(0) catalyst were also discussed13 These coupling reactions proceeded regioselectively without conversion of aromatic heterocycles such as indoles, furan, thiophene, benzo[blfuran and benzo[b]thiophene to the corresponding organometallic reagents.In this study, we repon the palladiumsatalyzed cross-coupling reactions between 2-chloropyradnes and aromatic heterocycles.258 HETEROCYCLES.Yo1 33.Na. 1. 1992 3,6-Dialkyl-2-chl01opyrazines (la-c) were reacted with n-sufficient aromatic heterccycles such as furan (2).thiophene (3), pyrroles (11,12 and 16), benzo[b]furan (22) and benzo[b]thiophene (23) to give the corresponding coupling products in moderate to g a d yields (Schemes 1,4, 5 and 7, Tables 1-4).Scheme 1 AcOK Scheme 2 Scheme 3 IBu Raney Ni (W-6) 6c 92 % 10In the reactions of chloropyrazines with fnran (2), thiophene (3) and pyrrole (I]), disubstituted hetemycles (Sb, c, 7c and 14 a-c) were also obtained though in low yields.These coupling reactions occurred almost regioselectively.However, on using N-phenylsulfonylpyrrole (16) as the reaction substrate, a mixture of regioisomers (17 and 18) which could not be separated, was obtained.The ratio of 17 to 18 was determined by l ~-n r n r spectroscopy.The hydrolysis of a mixture of 17 and 18 with 5N aq.NaOH afforded 13 and 19, which