Ed desulfitative direct arylations of heteroarenes making use of difluorobenzenesulfonyl chlorides because the arylating agents. i) PdCl2(CH3CN)2 (5 mol ), Li2CO3 (3 equiv), 1,4-dioxane, 140 , 48 h.With C2-(difluorophenyl)heteroarenes 194 in hands, we studied their reactivity in Pd-catalyzed direct arylations utilizing PdCl(C3H5)(dppb) as catalyst within the presence of KOAc because the base and aryl bromide as coupling partners (Scheme six). On 2-(3,4-difluorophenyl)menthofuran (23), the two C bonds atScheme 4: Pd-catalyzed direct regioselective arylation of 3-(two,three,4-trifluorophenyl)thiophenes. i) PdCl(C3H5)(dppb) (2 mol ), KOAc (2 equiv), DMA, 150 , 16 h.Beilstein J. Org. Chem. 2015, 11, 2012020.Scheme 6: Pd-catalyzed second direct regioselective arylation of difluorophenylheteroarenes 19-23. i) PdCl(C3H5)(dppb) (two mol ), KOAc (2 equiv), DMA, 150 , 16 h. [a] C5/C2 regioisomers ratio determined on crude 1H NMR ; [b] C3’/C3/C5′ regioisomers ratio determined on crude 1H NMR.ortho-position to a fluorine atom may be arylated beneath this reaction circumstances.4-Fluoro-7-azaindole Data Sheet Using 4-bromobenzaldehyde as coupling partner, a mixture of two regioisomers in 82:18 ratio was obtained, plus the C5 arylation solution 25 (big regioisomer) was isolated after flash chromatography in 53 yield as pure item. It is actually important to note that 25 benefits in the activation on the less hindered C bond. When the reaction was performed with 2-(two,4-difluorophenyl)menthofuran (21), the position flanked by two fluorine atoms was essentially the most reactive. Only the regioisomer 26 was observed in crude GC S and 1H NMR and was isolated in 68 yield. Making use of the far more difficult substrate 2-butyl-5-(two,4-difluorophenyl)furan (19) with 4-bromobenzonitrile, a mixture of three regioisomers was formed inside a 61:32:7 ratio. Only the important regioisomer 27, inwhich the arylation happend in the C bond flanked by the two fluorine atoms, has been isolated in pure kind. The other regioisomers may outcome in the activation of a C bond around the furan ring and from the other C bond at ortho-position for the fluorine atom. In contrast to (2,three,4-trifluorophenyl)benzofuran 2 in which the benzofuryl C bond is the most reactive 2-(2,4-difluorophenyl)benzofuran (20) only reacted through the activation from the electron-deficient phenyl ring to afford the heteroaryl triad 28 in 56 yield.(S)-Tetrahydrofuran-3-carboxylic acid Chemical name We imputed this shift of regioselectivity for the higher acidity of your C bond flanked by the two fluorine atoms.PMID:23290930 Then, the regioselectivity of Pd-catalyzed second direct arylation was investigated with 2-(two,4-difluorophenyl)-5-(4-methoxyphenyl)-1-methylpyrrole (22) and 2-(3,4-difluorophenyl)-5-(4-methoxyphenyl)-1-Beilstein J. Org. Chem. 2015, 11, 2012020.methylpyrrole (24). As anticipated, in the presence from the 2,4difluorophenyl motif, the arylation exclusively took place involving the two fluorine atoms to let the formation of tetramer 29 in 51 yield. We also investigated iterative direct arylations for the building of (hetero)aryl triads or tetrads containing a mono-fluorinated phenyl motif (Scheme 7). In 2006, it has been currently demonstrated that the palladium-catalyzed direct arylation of fluorobenzene proceeds in quite low yield [26]. Based on our prior works, in which we’ve got demonstrated that a halogen atom for example chlorine or bromine at the C3 or C4 position enhances its reactivity [65], we decided to utilize 2-chloro-4fluorobenzenesulfonyl chloride because the first arylating agent. We firstly chosen menthofuran as starting material for the syn.