Fluorine-Labelled Spiro[3.3]heptane-Derived Building Blocks: Is Single Fluorine the Best?

A convergent synthesis of a series of mono- and bifunctional 6-fluoro-spiro[3.3]heptanes-advanced fluorine-labelled conformationally rigid building blocks for medicinal chemistry is developed. The target products were obtained on a multigram scale (up to 302 g), characterized (pK_a, LogP, and S_w), and assessed with the lead-likeness criteria.