Easy Access to Cyclobutane-Based Building Blocks for APIs via Cyclobutane-1,3-dione

Cyclobutane units are increasingly important building blocks in medicinal chemistry, but their scalable synthesis remains challenging. Herein, an efficient modular strategy for accessing functionalized cyclobutane derivatives via cyclobutane-1,3-dione is presented. Central to this approach is an easily isolable dione salt, dicyclohexylammonium 3-oxocyclobut-1-en-1-olate, that is stable in air and at room temperature and enables the controlled generation of cyclobutane-1,3-dione under acidic conditions. From this key intermediate, various derivatization pathways were explored, including amination, reduction as well as O acylation, sulfonylation and -silylation, followed by selective C=C bond hydrogenation and carbonyl reduction.