Environmentally‐Safe Conditions for a Palladium‐Catalyzed Direct C3‐Arylation with High Turn Over Frequency of Imidazo[1,2‐b]pyridazines Using Aryl Bromides and Chlorides

Abstract

Pd(OAc)2 was found to catalyze very efficiently the direct arylation of imidazo[1,2-b]pyridazine at C3-position under a very low catalyst loading and phosphine-free conditions. The reaction can be performed in very high TOFs and TONs employing as little as 0.1-0.05 mol % catalyst using a wide range of aryl bromides. In addition, some electron-deficient aryl chlorides were also found to be suitable substrates. Moreover, 31 examples of the cross couplings were reported using green, safe, and renewable solvents, such as pentan-1-ol, diethylcarbonate or cyclopentyl methyl ether, without loss of efficiency.

Reactivity of antipyrine and haloantipyrines in Pd-catalyzed C H bond arylations

“…We have previously shown that DMA can be replaced in some cases by greener solvents in Pd-catalyzed C-H bond arylation. 29,30 Therefore, we investigated the outcome of this reaction using water, pentan-1-ol, CPME [= cyclopentyl methyl ether], and DEC [= diethyl carbonate] (Table 1, entries 8-11). Among them, DEC, which is a polar, aprotic, non-toxic, biodegradable, and biosourced solvent, [31][32][33][34][35][36] proved to be the best choice to replace DMA, as the arylated antipyrine 1 was isolated in 78% yield.…”

Palladium‐Catalyzed Regioselective Direct Arylation of Benzofurazans at the C‐4 Position

“…Under these conditions, the excess of benzofurazan can be decreased up to 1.15 equivalents, as the desired product 1 was isolated in 89% yield (Table 1, entry 10). Then, we employed greener solvents than DMA such as cyclopentylmethyl ether, 1-pentanol or diethylcarbonate, [15] but no reaction occurred (Table 1, entries [11][12][13]. No reaction occurred when 4-chlorobenzonitrile was used as aryl source (Table 1, entry 14).…”

Quinoxaline as an integrated directing group in palladium-catalyzed ortho-C–H bond arylation of the aryl unit of 2-arylquinoxalines

“…We had already observed that lower catalyst loadings often gave better results in C-H bond arylation of heteroarenes due to a reduction of the formation of homocoupling side-product of the aryl bromide. 18 Indeed, when we employed lower Pd(OAc)2 loadings, higher yields in 1 were obtained. The best result was obtained using as little as 0.5 mol% of Pd(OAc)2, and the arylated product 1 was isolated in 68% yield ( entries 14 and 15).…”