This comprehensive review describes the methodologies reported between 2020 and early 2025 for the synthesis of (hetero)bicyclo[2.1.1]hexane derivatives, organised by mechanisms and the exit vectors achieved.
1,2-Disubstituted bicyclo[2.1.1]hexanes have been synthesized, characterized, and biologically validated as saturated bioisosteres of the ortho-substituted benzene ring.
Identification of rigid counterparts for common flexible scaffolds is crucial to the advancement of medicinal chemistry. Herein, synthesis of new bicyclo[2.1.1]hexanes to act as rigidified cyclopentanes is described.
Herein, we present sp3-rich fragments, that display optimal physicochemical properties and exit vectors ideal for fragment-based lead discovery.
Crossed [2 + 2] cycloaddition yields bicyclo[2.1.1]hexanes with 11 different substitution patterns. ortho-, meta- and polysubstituted benzene bioisosteres, and structures with substituent patterns that go beyond aromatic chemical space can be prepared.