Rhodium-Catalyzed Stereoselective Access to Polysubstituted Bicyclo[1.1.0]butanes Bearing Quaternary Bridge Carbons
Year: 2026
Type: preprint
Abstract: Bicyclo[1.1.0]butanes (BCBs) are unique strained carbocycles that have emerged as attractive buildingblocks in synthetic and medicinal chemistry owing to their unique reactivity. Despite recent advances in the preparation of polysubstituted BCBs, the stereoselective synthesis of bridge-substituted derivatives remains a significant challenge, particularly when quaternary stereocenters are involved at these positions. Herein, we report a rhodium-catalyzed [2+1] cycloaddition of cyclopropenes and diazo compounds that provides direct access to stereodefined bridge-substituted BCBs. The reaction proceeds with complete diastereocontrol across a broad range of substrates and enables the construction of densely functionalized frameworks bearing up to four stereocenters. The methodology can also be extended to enantioenriched cyclopropenes, providing optically active BCBs with complete enantiospecificity. DFT calculations are consistent with the stereochemical outcome and the synthetic utility of the resulting BCBs is demonstrated by transformations leading to fused tricyclic architectures and polysubstituted cyclobutenes and cyclobutanes.
Source: ChemRxiv
Institution: Universidad de Alcalá
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7213289201