Facile and Effective Synthesis of Spirocycloalkanones

Spiroadamantane cyclopentanone and cyclohexanone have been prepared by a simple and effective method, including the synthesis of the key intermediate dinitriles and their intramolecular Thorpe-Ziegler cyclization. In this method, the key step of the dinitriles formation was accomplished by a novel base-induced allylation protocol which involved the treatment of 2-adamantanecarbonitrile precursor with lithium diisopropylamine and allylbromide. Moreover, the cyclization methodology used, allowed to obtain the respective cyanoenamine in high yields, when the respective dinitriles were treated with the previous base. Acidic hydrolysis of enamines led to the desired cycloalkanones, which constitute versatile intermediates in the synthesis of spiroadamantanamines and other bioactive molecules concerning our pharmacological studies.