Synthesis of trihydroxy quinolizidine alkaloids: 1,3-addition reaction of allylmagnesium bromide to a sugar nitrone

The synthesis of (1R,2R,3S,9aR) and (1R,2R,3S,9aS) trihydroxy quinolizidine alkaloids and from d-glucose derived nitrone is described. The key transformation involves the 1,3-addition of allylmagnesium bromide to nitrone that afforded high diastereoselectivity in the presence of TMSOTf. The N–O bond reductive cleavage, N-Cbz protection, ozonolysis, Wittig olefination, lactum formation and reductive amination cascade afforded the target compounds and in good overall yield.