Strain Release [2p+2s]-Cycloadditions for the Synthesis of [2.1.1]-Bicyclohexanes Initiated by Energy Transfer

Abstract

Saturated bicycles are becoming ever more important in the design and development of new pharmaceuticals. In this manuscript, a new strategy for the synthesis of [2.1.1]-bicyclohexanes is described. These bicycles are significant as they have defined exit vectors, yet many substitution patterns are underexplored as building blocks. The process involves sensitization of a [1.1.0]-bicyclobutane followed by cycloaddition with an alkene. The scope and mechanistic details of the methods are discussed.

Beyond Bioisosteres: Divergent Synthesis of Azabicyclohexanes and Cyclobutenyl Amines from Bicyclobutanes**

“…Work is ongoing to explore the mechanistic and synthetic features of cycloaddition to bicyclobutanes, and to apply these techniques toward complex molecule synthesis relevant to the discovery of active pharmaceutical ingredients containing bicyclic scaffolds. [47][48][49][50]…”

“…The resulting products provide a unique platform for chemical space exploration in pursuit of new, C sp 3 ‐rich drug candidates, especially given the functional group compatibility exhibited with respect to heterocycles and diverse synthetic handles. Work is ongoing to explore the mechanistic and synthetic features of cycloaddition to bicyclobutanes, and to apply these techniques toward complex molecule synthesis relevant to the discovery of active pharmaceutical ingredients containing bicyclic scaffolds [47–50] …”