Studies on organolithium-induced alkylative desymmetrisation of epoxides: synthesis of enantioenriched beta-amino cycloheptenols from 6,7-epoxy-8-azabicyclo[3.2.1]octanes

The synthesis and enantioselective α-deprotonation - double ring opening of 6,7-epoxy-8-azabicyclo[3.2.1]octanes 5 using organolithiums in the presence of (-)-sparteine or (4S)-2,2′-(1-ethylpropylidene)bis-4-(1- methylethyl)-4,5-dihydrooxazole, giving amino cycloheptenols in up to 85% yield and 82% ee is described. The impact of different reaction variables on reaction profiles has been studied, including the nature of organolithium, solvent, ligand, temperature and epoxide structure. The reactions proved to be dependent on all these variables, in particular on the structure of substrate. A mixed organolithium system (PriLi/TMSCH2Li) has been successfully used to introduce potentially versatile allylsilane functionality. © 2004 Elsevier Ltd. All rights reserved