Enantiocontrolled synthesis of (4S,5S,6S)-6-benzyl-4,5-epoxy-6-hydroxy-2-cyclohexen-1-one, a model compound for the epoxycyclohexenone moiety of scyphostatin

An efficient synthesis of (4S,5S,6S)-6-benzyl-4,5-epoxy-6-hydroxy-2-cyclohexen-1-one (2) representing a model compound for the cyclohexenone moiety of scyphostatin (1) was accomplished; the method features masking of the enone system in 10 in the form of the bromo ether 13 (10→11→12→13), aldol coupling of 13 with benzaldehyde to construct the requisite asymmetric quaternary carbon center at the C-6 position (13→14), and epoxide ring formation (21→2) as the key steps. The key intermediate 10 was prepared from commercially available (−)-quinic acid (3).