Diastereoselective schenck ene reaction of singlet oxygen with chiral allylic alcohols; access to enantiomerically enriched 1,2,4-trioxanes

Abstract

A series of antimalarial chiral 1,2,4-trioxanes ( 1– 8) were synthesised in high enantiomeric purities. Enantioselective addition of R 2Zn reagent to 3-methyl-2-butenal catalysed by (+)-MIB or (−)-MIB yielded both the enantiomers of the chiral allylic alcohols 9– 11 (90–98% ee), which were subjected to diastereoselective photooxygenation in the presence of tetraphenylporphine (TPP) to obtain ( R, R)- threo- or ( S, S)- threo-β-hydroperoxy alcohols ( 12– 14). Reaction of β-hydroperoxy alcohols ( 12– 14) with different cyclic ketones produced optically active trioxanes 1– 8.