Rigid Scaffold Chemistry

Rigid Scaffolds

The rigid, saturated alkanes cubane, bicyclo[2.2.2]octane and bicyclo[1.1.1]pentane are very attractive as customizable scaffolds for novel drug syntheses and materials applications. These molecules offer precise positioning of covalently linked functionalities in three-dimensional space, in contrast to conventional medicines, which are generally 'flat' molecules. Additionally, saturated alkane molecules often offer lower reactivity than aromatic systems, leading to a potentially longer-lifetime in the body.

Synthetic transformations of cubane and bicyclo[1.1.1]pentane (BCP).

We are exploring the fundamental organic chemistry of these rigid molecules, in order to access new modes of functionalization, and increasing the scope of reactions which can be performed with molecules of this type. Due to the ring strain present in these scaffolds, interesting transannular electronic interactions can be accessed. This ring strain also induces activation of appended moieties and allows for modes of reactivity not observed in alkanes generally, such as the 'breakthrough' metal-catalyzed redox cross coupling on cubane shown.

The Senge group is striving for a complete description of the reactivity and structural characteristics of these rigid, saturated molecules, promoting the use of these subunits in medicine and materials science.