A General Suzuki–Miyaura/[2+2] Photocycloaddition Approach to 2-Oxabicyclo[2.1.1]hexane Biaryl Mimetics
Year: 2026
Type: preprint
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.
Source: ChemRxiv
Institutions: AstraZeneca (Sweden), University of Bath
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7222351093