Diastereotopic Group-Selective Intramolecular Aldol Reactions Initiated by Enantioselective Conjugate Silylation: Diastereodivergence Controlled by the Silicon Nucleophile

A reaction sequence consisting of enantioselective copper-catalyzed conjugate silylation and diastereotopic group-selective aldol cyclization is reported. The diastereoselectivity of the intramolecular aldol reaction depends on the silicon nucleophile used, either Me2PhSiZnX·2LiX (trans) or Me2PhSiBpin (cis). The more basic zinc reagent and as such the very basic reaction medium also enable thermodynamically driven cis-to-trans isomerization by a retro-aldol–aldol process. A broad range of electron-withdrawing groups including electron-deficient heterocycles is compatible with the different procedures developed.