Straightforward access toward previously unreported substituted, heterocyclic spiro[3.3]heptanes is disclosed. These spirocyclic systems may be considered as alternatives to 1,3-heteroatom-substituted cyclohexanes, which are otherwise insufficiently stable to allow their use in drug discovery. Conformational details are discussed on the basis of X-ray crystallographic structures.

The preparation of versatile azaspiro[3.3]heptanes carrying multiple exit vectors is disclosed. Expedient synthetic routes enable the straightforward access to these novel modules that are expected to have significance in drug discovery and design.

The syntheses of a variety of novel angular azaspiro[3.3]heptanes are reported. gem-Difluoro and gem-dimethyl variants of the angular 1,6-diazaspiro[3.3]heptane module were prepared in high yields using efficient sequences. Additionally, a practical one-pot synthesis of 5-oxo-2-azaspiro[3.3]heptanes and subsequent conversions into functionalized derivatives are described. The methods reported are amenable to the synthesis of these building blocks for drug discovery as members of a library or individually on a preparative scale.