A General Suzuki–Miyaura/[2+2] Photocycloaddition Approach to 2-Oxabicyclo[2.1.1]hexane Biaryl Mimetics
4 affiliations
- 1Oncology R&D
- 2Discovery Centre, AstraZeneca
- 3Small Molecule Product Discovery & Development, Astra-Zeneca, Pepparedsleden 1, Mölndal, Sweden
- 4Department of Chemistry, University of Bath, Claverton Down, Bath, UK
Abstract
Herein, we report a modular approach to monosubstituted, (hetero)arylated 2-oxabicyclo[2.1.1]hexanes (oxa-BCHs). The strategy combines facile Suzuki–Miyaura cross-couplings to assemble suitable diene precursors that can undergo [2+2] photocycloadditions. Nineteen novel (hetero)aromatic building blocks and fragments are constructed from their respective (hetero)aryl boronates, conveniently accessed from commercial sources. Next, a high-throughput enabled synthetic sequence is performed, demonstrating the gram-scale conversion of 6-quinoline bromide to the corresponding 4-(quinolyl)oxa-BCH adduct. Finally, the physicochemical properties and aqueous stability of the new oxa-BCH biaryl mimetic was compared with those of other medicinally relevant substituents, demonstrating its promise as a robust, three-dimensional, polarity-enhancing motif for medicinal-chemistry applications.
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BibTeX
@misc{whalley2026general,
title = {{A General Suzuki–Miyaura/[2+2] Photocycloaddition Approach to 2-Oxabicyclo[2.1.1]hexane Biaryl Mimetics}},
author = {David M. Whalley and Olivier Lorthioir and Niall Anderson and Ioannis Asproudis and Erin Braybrooke and Susannah Coote and James Middleton and Okky Dwichandra Putra and Philip J. Rushworth and Sam Staniland},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010496/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010496/v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A General Suzuki–Miyaura/[2+2] Photocycloaddition Approach to 2-Oxabicyclo[2.1.1]hexane Biaryl Mimetics
AU - David M. Whalley
AU - Olivier Lorthioir
AU - Niall Anderson
AU - Ioannis Asproudis
AU - Erin Braybrooke
AU - Susannah Coote
AU - James Middleton
AU - Okky Dwichandra Putra
AU - Philip J. Rushworth
AU - Sam Staniland
PY - 2026
DA - 2026/10/15
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010496/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010496/v1
AB - Herein, we report a modular approach to monosubstituted, (hetero)arylated 2-oxabicyclo[2.1.1]hexanes (oxa-BCHs). The strategy combines facile Suzuki–Miyaura cross-couplings to assemble suitable diene precursors that can undergo [2+2] photocycloadditions. Nineteen novel (hetero)aromatic building blocks and fragments are constructed from their respective (hetero)aryl boronates, conveniently accessed from commercial sources. Next, a high-throughput enabled synthetic sequence is performed, demonstrating the gram-scale conversion of 6-quinoline bromide to the corresponding 4-(quinolyl)oxa-BCH adduct. Finally, the physicochemical properties and aqueous stability of the new oxa-BCH biaryl mimetic was compared with those of other medicinally relevant substituents, demonstrating its promise as a robust, three-dimensional, polarity-enhancing motif for medicinal-chemistry applications.
ER -