One-Pot, Multistep Synthesis of Pyrano[3,2‑b]indol-2-ones

Significance

One-pot synthesis is a strategy to improve the efficiency of a chemical reaction and is frequently based on a cascade process. The approach is broadly employed in medicinal chemistry and drug discovery research for the synthesis of heterocyclic compounds. In the present discovery, pyrano[3,2‑b]indol-2-ones were accessed from simple starting materials, namely o‑nitroynones and β‑keto esters, using a one-pot, telescoped synthesis. Initially, a pyrone intermediate was formed through base-mediated Michael addition followed by cyclization, generating C–C and C–O bonds. In a second step, (EtO)₃P facilitated the Cadogan–Sundberg reductive cyclization, producing a C–N bond. The pyrano[3,2‑b]indol-2-ones were further diversified for the synthesis of various substituted carbazoles using cycloaddition chemistry.

Comment

The reaction was optimized using 0.5 equivalents of NaH as a base and 1,2-dichlorobenzene (1,2-DCB) as a solvent at room temperature for the first step, followed by Cadogan–Sundberg reductive cyclization at 160 °C using 4 equivalents of (EtO)₃P. The substrate scope included various substituents on the o‑nitroynone as well as on the β‑keto ester producing products in moderate to good yields. Product A was engaged in cycloadditions with various dienophiles to demonstrate its usability in synthesis of variety of substituted synthetic as well as natural carbazoles, for example hyellazole. In general, this approach could be used to access fused carbazole heterocycles in an easy and rapid manner.

Publication History

Article published online:
23 June 2025

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