Synthesis of noradamantane building blocks

Abstract

The carbon scaffold of noradamantane, a ring contracted adamantane derivative, is notoriously difficult to selectively oxidise and functionalise, which limits the hydrocarbon's use as a building block for preparing noradamantyl decorated targets. In this research we disclose the use of Burgess reagent in a ring-contraction of pre-functionalised 2-amino-adamantan-1-ols to noradamantyl carbaldehydes in a pinacol-type rearrangement, that can be readily post-functionalised and further derivatised. To showcase their potential applicability, we performed structural analysis and their comparison to ortho- and meta-substituted benzene together with the synthesis of bioisosteric analogues of known drug molecules. We also report a new C12 parent cage hydrocarbon that was prepared by the same method from a diamantane precursor. This work may prompt further implementation of noradamantane as a sacffold for new molecular frameworks and help recognizing its utility in the space of chemical synthesis.