Modern Synthetic Approaches to Cubebene and Related Sesquiterpene Frameworks

Abstract

Cubebenes and related sesquiterpenes, featuring a tricyclo[4.4.0.0¹,⁵]decane framework, exhibit notable structural complexity and diverse bioactivity. This review highlights key synthetic approaches toward these molecules, including diazo-mediated cyclopropanation, metal-catalysed enyne cyclisation, bicycloannulation cascades, and photochemical rearrangements. Mechanistic and stereochemical aspects are discussed, highlighting progress in diastereo- and enantioselective methodologies. Although substantial advances have been achieved, efficient access to higher cubebene analogues remains a synthetic challenge. Integration of bioinspired design, modern synthetic methods, and asymmetric catalysis is expected to further advance concise and stereoselective synthesis of these complex architectures.