Palladium-catalyzed carbonylative double cyclization leading to indole-fused ε- and ζ-lactones

Abstract

The reactivity of 5-(2-aminophenyl)-4-yn-1-ols and 6-(2-aminophenyl)-5-yn-1-ols under PdI₂/KI-catalyzed oxidative carbonylation conditions has been studied. It has been found that, with 5 mol% of PdI₂ and 0.5 equiv. of KI, under 60 bar of a 4:1 mixture of CO-air, in MeOH as the solvent at 100 °C for 24 h, a mixture of isomeric indole-fused ε-lactone and pyranoquinolinone derivatives was formed from 5-(2-aminophenyl)-4-yn-1-ols, deriving from divergent 5-endo-dig N-cyclization ‒ 7-O-cyclocarbonylation and 6-endo-dig O-cyclization – 6-N-cyclocarbonylation pathways, respectively. However, the process could be made selective toward the formation of the indole-fused ε-lactone (oxepinoindolone) product when performed in MeCN, thus establishing an unprecedented cyclization – seven-membered cyclocarbonylation process. Under the optimized conditions, a series of previously unknown 6-substituted 3,4,5,6-tetrahydro-1H-oxepino[4,3-b]indol-1-ones could be synthesized in moderate to satisfactory isolated yields (45–79 %) starting from differently substituted 5-(2-aminophenyl)-4-yn-1-ols. Under the same conditions, 6-(2-aminophenyl)-5-yn-1-ols were converted into indole-fused ζ-lactones through an even more challenging cyclization – eight-membered cyclocarbonylation process. The structures of three representative products have been confirmed by XRD analysis.