5-Functionalized 2-Azahousanes: Synthesis and Core Stability Towards Chemical Transformations

The cyclopropanation of N-Boc-protected parent 1,2-dihydroazete using ethyl diazoacetate was investigated, leading to a preparative protocol for the N-Boc-protected ethyl 2-azahousane-5-carboxylate. The utility of this compound in the synthesis of MedChem-relevant building blocks based on a 5-substituted 2-azahousane core was demonstrated. The locking of the 3-substituted pyrrolidine conformation using the 2-azahousane core was found. Despite the intrinsic instability of 2-azahouzane-5-carboxylic acid derivatives due to the strained azahousane core and donor–acceptor cyclopropane fragment, its incorporation into the peptide chain was developed.