An Expedient and Practical Approach to Functionalized 3-Aza-, 3-Oxa-, and 3-Thiabicyclo[3.3.1]nonane Systems

The synthesis of a number of heterobicyclo[3.3.1]nonane derivatives possessing carbonyl, amino, or carboxyl groups is reported. The synthetic scheme is concise and practical, based on optimized reaction conditions for each step and an orthogonal protection group strategy. Procedures for the key synthetic steps (double annulation of α-bromomethyl acrylates to enamines and a Caglioti reaction) were improved significantly. This makes the compounds attractive for medicinal chemistry as potential chemically diverse 3D-scaffolds applicable in drug design.