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

• Unprecedented carbonylative double cyclization leading to indole-fused ε- and ζ-lactones. • Catalytic conditions optimized for a selective N -cyclization ‒ O -cyclocarbonylation pathway. • Previously unknown products obtained in one step in 45–79 % isolated yields. • Structures of three representative products confirmed by SC-XRD analysis. The reactivity of 5-(2-aminophenyl)-4-yn-1-ols and 6-(2-aminophenyl)-5-yn-1-ols under PdI 2 /KI-catalyzed oxidative carbonylation conditions has been studied. It has been found that, with 5 mol% of PdI 2 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-1 H -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.