Photochemically Mediated Ring Expansion of Indoles and Pyrroles with Chlorodiazirines: Synthetic Methodology and Thermal Hazard Assessment

Joynson, Ben W.; Cumming, Graham R.; Ball, Liam Thomas

Abstract

We demonstrate that arylchlorodiazirines serve as photo-activated halocarbene precursors for the selective one-carbon ring expansion of N-substituted pyrroles and indoles to the corresponding pyridinium and quinolinium salts. Preliminary investigations indicate that the same strategy also enables the conversion of N-substituted pyrazoles to pyrimidinium salts. The N-substituent of the substrate plays an essential role in: (1) increasing substrate scope by preventing product degradation, (2) enhancing yields by suppressing co-product inhibition, and (3) activating the azinium products towards subsequent synthetic manipulations. This latter point is illustrated by subjecting the quinolinium salts to four complementary partial reductions, which provide concise access to ring-expanded products with different degrees of increased C(sp3) character. Thermal analysis of the diazirines by differential scanning calorimetry (DSC) provides detailed insight into their energetic properties, and highlights the safety benefits of photolyzing—rather than thermolyzing—these reagents.

Citation

Joynson, B. W., Cumming, G. R., & Ball, L. T. (2023). Photochemically Mediated Ring Expansion of Indoles and Pyrroles with Chlorodiazirines: Synthetic Methodology and Thermal Hazard Assessment. Angewandte Chemie International Edition, 62(31), Article e202305081. https://doi.org/10.1002/anie.202305081

• Journal Article Type: Article
• Acceptance Date: Jun 9, 2023
• Online Publication Date: Jun 9, 2023
• Publication Date: Aug 1, 2023
• Deposit Date: Jun 13, 2023
• Publicly Available Date: Jul 10, 2023
• Journal: Angewandte Chemie International Edition
• Print ISSN: 1433-7851
• Electronic ISSN: 1521-3773
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 62
• Issue: 31
• Article Number: e202305081
• DOI: https://doi.org/10.1002/anie.202305081
• Keywords: General Chemistry; Catalysis
• Public URL: https://nottingham-repository.worktribe.com/output/21906571
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1002/anie.202305081