Asymmetric Synthesis of Goniodiol Intermediates

Abstract

Enantioselective formal syntheses of both the Goniothalamus amuyon metabolite (+)-goniodiol-8-monoacetate 1 and its enantiomer were achieved. Access to the Goniothalamus metabolites (+)-goniotriol 2 and (+)-goniofufurone 5 and their enantiomers was accomplished by the same route. A method was developed to transform threo diols into their erythro counterparts with complete retention of enantiopurity by selective inversion of one stereocentre using the Prévost solvolysis reaction. The meso problem inherent in the Sharpless asymmetric dihydroxylation of Z-alkenes was thereby circumvented. This method was demonstrated using enantioenriched diols derived from Sharpless asymmetric dihydroxylation of several alkenes. Menthyl cinnamate 135 was investigated as a substrate with pre-existing chirality to determine the merits of double diastereoselection for application in the synthesis of Goniothalamus metabolites. A mechanistic insight allowed simplification of the Prévost solvolysis method to a one-pot procedure requiring only mild reaction conditions.