Formal Synthesis of Borrelidin: A Highly Enantio- and Diastereoselective Access to the Morken’s C2–C12 Intermediate

Abstract

In contrast to methyl and isobutyl phenyl sulfone, condensing under basic conditions higher alkyl sulfones and trans-2,3-epoxy-butanol 13c (or its O-benzyl and O-silyl derivatives) proved unfeasible, a difficulty that was overcome by using mono ethers of trans-2,3-epoxy-butane-1,4-diol 35c as the electrophilic reagents. Thus, adding excess BuLi to a mixture of the benzyl ether 35b and sulfone ent-12a, a stereodiad sulfone prepared in pure state from the R-Roche ester, via the O-trityloxy-sulfone ent-12c (X-ray), gave, after elimination by column chromatography of the side-formed regioisomer, a diol-sulfone that was next converted to sulfone 20 by means of conventional functional-group modifications. Reacting likewise this sulfone with the parent O-PMB derivative 35a, and then proceeding to the same purification process and function adjustment, delivered the title fragment in virtually pure state.