Theoretical study of intramolecular aldol condensation of 1,6-diketones: Trimethylsilyl substituent effect

Diastereoselective intramolecular aldol condensations are investigated in a n experimental and computational study of 1,6-diketones. Ab initio results show the importance of the acid medium and disapprove the possibility of a spontaneous cyclization, even for silylated compounds. The combination of b oth experimental and computational approaches brings valuable information o n the mechanism and on the selectivity of the aldol reaction. It is found t hat the enolization of the diketone is a key step in acid-catalyzed mechani sm. The cyclization step bears a very small activation energy. The dehydrat ion of the aldols are discussed.