TOTAL SYNTHESIS OF (+)-PHYLLANTHOCIN - INTRODUCTION OF INTRAMOLECULAR HYDROFORMYLATION FOR COMPLEX MOLECULE FUNCTIONALIZATION

A 17-step total synthesis of (+)-phyllanthocin (la) is described. Application of Sharplessasymmetric epoxidation reaction provided access to the diastereo- and enantiomerically pure epoxy ketone 9, a partner in a crossed aldol construction. A notably rapid and high-yielding spiroketal equilibration leading to the tetracyclic intermediate 2 was effected with HF in acetonitrile. A Rh(I)-catalyzed hydroformylation was used to introduce the C3 functionality. Studies of intramolecular delivery of the rhodium nucleus to the concave face of the C3-C4 olefin led to a substantial improvement in yield and regioselectivity over the intermolecular version. © 1990, American Chemical Society. All rights reserved.