Sonogashira reaction quinoxalines

The Sonogashira reaction is of considerable value in heterocyclic synthesis. It has been conducted on the pyrazine ring of quinoxaline and the resulting alkynyl- and dialkynyl-quinoxalines were subsequently utilized to synthesize condensed quinoxalines [52-55], Ames et al. prepared unsymmetrical diynes from 2,3-dichloroquinoxalines. Thus, condensation of 2-chloroquinoxaline (93) with an excess of phenylacetylene furnished 2-phenylethynylquinoxaline (94). Displacement of the chloride with the amine also occurred when the condensation was carried out in the presence of diethylamine. Treatment of 94 with a large excess of aqueous dimethylamine led to ketone 95 that exists predominantly in the intramolecularly hydrogen-bonded enol form 96. 

Likewise, when 98 was refluxed with aqueous KOH in dioxane, the corresponding 2-phenylfurono[2,3-6]quinoxaline was produced in 67% yield [52], The Sonogashira reactions of chloro- and dichloroquinoxalines and trimethylsilylacetylene (56, 57] or but-3-yn-2-ol [58] have also been documented. 

In 1980, Ames et al. reported a related pyrrole formation catalyzed by mer-cury(II) [98], Pyrrole-fused quinoxaline 204 was obtained by treatment of a 2-amino-3-alkynylquinoxaline derivative 203 with a catalytic amount of Hg(OAc)2 (Scheme 19.53). On the other hand, dichloroquinoxaline 205, the precursor of 203, was converted directly to 204 under reaction conditions for Sonogashira coupling with phenylacetylene. A related palladium(II)-catalyzed pyrrole synthesis using 1-aminoalk-3-yn-2-ols 206 was reported by Utimoto, Nozaki and co-workers in 1981 (Scheme 19.54) [99]. It should be noted that PdCl2 showed excellent turnover to produce the corresponding pyrroles 207 in good yields with only 0.1 to 1 mol % catalyst loading. 

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