Annulated and spiro-molecular systems from cycloheptane-based β-ketoesters: Synthesis, reactivity, and biological applications

The β-ketoesters are versatile intermediates that are widely used in the field of organic chemistry, especially in the synthesis of annulated heterocyclic derivatives. These intermediates have two electrophilic and two nucleophilic sites, allowing for multi-coupling reactions. Due to their excellent synthetic potential, several reports were dedicated to exploring the reactivity of β-ketoesters. To the best of our knowledge, the current review explores, for the first time, the reactivity of cycloheptane-based β-ketoesters in producing annulated and spiro-molecular systems. They are regarded as effective chemical reagents capable of generating a diverse range of heterocyclic derivatives with potential biological applications. This review includes all reports where cycloheptane-based β-ketoesters are annulated, resulting in carbocycles or heterocycles with bi-, tri-, and tetracyclic rings. The review is divided into sections according to the type of annulation system and the number of heteroatoms in each system. We also reviewed all available papers on the synthesis of spiro-molecular systems using cycloheptane-based β-ketoesters. The biological applications of annulated derivatives are covered in this review.