Modular synthesis of complex benzoxaboraheterocycles through chelation-assisted Rh-catalyzed [2+2+2] cycloaddition
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.
Citation
Halford-McGuff , J , Varga , M , Cordes , D B , McKay , A & Watson , A J B 2024 , ' Modular synthesis of complex benzoxaboraheterocycles through chelation-assisted Rh-catalyzed [2+2+2] cycloaddition ' , ACS Catalysis , vol. 14 , no. 3 , pp. 1846-1854 . https://doi.org/10.1021/acscatal.3c05766
Publication
ACS Catalysis
Status
Peer reviewed
ISSN
2155-5435Type
Journal article
Description
Funding: J.M.H.-M. and M.V. thank the EaSI-CAT Centre for Doctoral Training for PhD studentships. A.J.B.W. thanks the Leverhulme Trust for a research fellowship (RF-2022-014) and the EPSRC Programme Grant “Boron: Beyond the Reagent” (EP/W007517/1) for support.Collections
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