Practical Synthesisof Oxepanoprolines

A new, more scalable route for the synthesis of the common oxepanoproline southern fragment of the antibiotic candidates iboxamycin, cresomycin, and BT-33 is presented. A key transformation in the route is a diastereoselective TiCl₄-mediated conjugate addition of an allylsilane to an Evans <i>N</i>-acryloyloxazolidinone, followed by <i>syn</i>-aldol addition of the resultant titanium enolate to (<i>R</i>)-Garner’s aldehyde, which assembles all the stereocenters within the target molecule in a single operation.