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.