Modular synthesis of complex benzoxaboraheterocycles through chelation-assisted Rh-catalyzed [2+2+2] cycloaddition

John Halford-McGuff, Marek Varga, David B. Cordes, Aidan McKay, Allan J. B. Watson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Benzoxaboraheterocycles (BOBs) are moieties of increasing interest in the pharmaceutical industry; however, the synthesis of these compounds is often difficult or impractical due to the sensitivity of the boron moiety, the requirement for metalation–borylation protocols, and lengthy syntheses. We report a straightforward, modular approach that enables access to complex examples of the BOB framework through a Rh-catalyzed [2 + 2 + 2] cycloaddition using MIDA-protected alkyne boronic acids. The key to the development of this methodology was overcoming the steric barrier to catalysis by leveraging chelation assistance. We show the utility of the method through synthesis of a broad range of BOB scaffolds, mechanistic information on the chelation effect, intramolecular alcohol-assisted BMIDA hydrolysis, and linear/cyclic BOB limits as well as comparative binding affinities of the product BOB frameworks for ribose-derived biomolecules.
Original languageEnglish
Pages (from-to)1846-1854
Number of pages9
JournalACS Catalysis
Volume14
Issue number3
Early online date24 Jan 2024
DOIs
Publication statusPublished - 2 Feb 2024

Keywords

  • Boron
  • Cycloaddition
  • Heterocycles
  • Mechanism
  • Sensing

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