3-Methyl-r-butyrolactone has been enployed as a source of Z-methyl-3-hydroxyketones after functioning as a tenplate for the preparation of enantiomerically pure propionate chains. This method is exemplified by the preparation of the C&,-C27 propionate fragment utilized by Kishi in his synthesis of rifamycin S.
The 2-methyl-3-hydroxyketone functionality is prevalent in pclypropionate-derived natural products. of which pikromycin. oleandomycin and erythromycin are representative.2 This functionality also manifests itself in the guise of hemiketals (e.g.. elaiophylin)3 and spiroketals (e.g.. calcimy~in).~ Moreover. Z-methyl-3-hydroxyketones can serve as a source of a-ethyl-1.3-diols by virtue of their stereocontrolled reduction.5
In this Letter we describe a method for the generation of l-methyl-2-hydroxyketones from R-3-methyl-y-butyrolactone. a template that has been shown to provide polypropionate fragme&. and ultimately, natural products7 of high enantiomeric purity. The utility of this method is exemplified by the synthesis of silyl ether 13. an intermediate in Kishi's landmark synthesis' of rifamycin S. through a triple. linear iteration technique.