Chiral 7-Oxabicyclo[2.2.1]heptane Building Blocks for Prostanoids

Abstract

Methyl (Z)-3-[(2R,3R,4S,5S)-5-(2-methoxy-2-oxoethyl)-3,4-(isopropylidenedioxy)tetrahydrofuran-2-yl]-prop-2-enoate was synthesized, and its intramolecular carbocyclization was studied. This reaction proceeds smoothly and quickly under the action of t-BuOK in THF, leading to three cycles with the methoxy and methoxycarbonylmethyl side substituents trans to each other. A stepwise route for the formation of methyl (1R,2R,6S,7R,8R,9R)-9-(2-methoxy-2-oxoethyl)-4,4-dimethyl-3,5,10-trioxatricyclo[5,2,1,0^2,6]decane-8-carboxylate and methyl (1R,2R,6S,7R,8S,9S)-9-(2-methoxy-2-oxoethyl)-4,4-dimethyl-3.5,10-trioxatricyclo-[5,2,1,0^2,6]decane-8-carboxylate with the trans orientation of the side substituents is proposed. The observed stereochemical result of the reaction is interpreted in terms of epimerization in the C¹ and C⁴ centers of methyl (Z)-3-[(2R,3R,4S,5S)-5-(2-methoxy-2-oxoethyl)-3,4-(isopropylidenedioxy)-tetrahydrofuran-2-yl]prop-2-enoate, which ultimately leads to the cyclized β,β’-cis diastereomer of methyl (Z)-3-[(2R,3R,4S,5S)-5-(2-methoxy-2-oxoethyl)-3,4-(isopropylidenedioxy)-tetrahydrofuran-2-yl]prop-2-enoate and the corresponding α,α’-cis diastereomer, a precursor of methyl (1R,2R,6S,7R,8S,9S)-9-(2-methoxy-2-oxoethyl)-4,4-dimethyl-3,5,10-trioxatricyclo[5,2,1,0^2,6]decane-8-carboxylate.