Photocatalyzed Ring-Opening of Bicyclobutane

Access to 1,2,3-Trisubstituted Bicyclo[1.1.1]pentanes

Bicyclo[1.1.1]pentanes (BCPs) have emerged as valuable bioisosteres for aromatic rings in drug discovery, offering improved solubility, reduced lipophilicity and enhanced metabolic stability. Their rigid, three-dimensional structure enables more effective modulation of biological interactions, supporting improved potency, selectivity and pharmacokinetic performance.

Despite rapid advances in synthetic methodologies, access to 1,2,3-trisubstituted BCPs remains limited due to the lack of efficient and versatile approaches.

Poster Overview

This poster presents a novel single-step photocatalyzed ring-opening approach using bicyclo[1.1.0]butane (BCB) and diazo compounds to provide efficient access to 1,2,3-trisubstituted BCPs.

• Single-step synthesis of complex BCP scaffolds
• Demonstrated across 31 trisubstituted examples
• Broad substrate scope and functional group tolerance
• Use of diazo compounds as versatile carbene precursors
• Improved efficiency vs traditional multistep approaches

This methodology expands accessible chemical space and supports medicinal chemistry programmes targeting next-generation therapeutics.