Recent Advances in Catalytic Asymmetric Transformations of Bicyclobutane: A Versatile Building Block for Enantiopure Bioisosteric Molecules

Bridged bicyclic scaffolds such as bicyclo[2.1.1]hexanes (BCHs) and bicyclo[3.1.1]heptanes (BCHeps) have emerged as valuable bioisosteres for ortho- and meta-substituted arenes in contemporary drug design. These three-dimensional frameworks offer enhanced conformational rigidity and superior physicochemical properties compared to their planar aromatic counterparts. The precise control of stereochemistry in these scaffolds is paramount, as chirality profoundly influences biological activity and pharmacokinetic profiles. Strain-release transformations of bicyclo[1.1.0]butanes (BCBs) represent particularly efficient and atom-economical synthetic approaches to access these architectures. Despite significant…

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  Institute for Basic Science

  Award: IBS-R010-A2