Fluorinated alcohol directed formation of dispiro-1,2,4,5-tetraoxanes by hydrogen peroxide under acid conditions

Abstract

The oxidative system MTO/30%H 2O 2/HBF 4/fluorous alcohol is promising for the selective synthesis of biologically important antimalarial dispiro-1,2,4,5-tetraoxanes by direct acid-catalysed cyclisation of various 4-substituted cyclohexanones ( 1 , R=Me, Et, tBu, Ph, COOEt, CF 3). The role of the substitutent at the 4-position was important in the selectivity of formation of tetraoxane ( 2 , TO) with respect to hexaoxonane ( 3 , HO). By the use of fluorinated alcohols and under the right reaction conditions, tetraoxanes 2 were selectively formed and synthesised in 46–86% isolated yield from 4-substituted cyclohexanones 1 .