The chain extension of beta-keto phosphonates and the synthesis of polycyclopropanes

A series of beta-keto phosphonates was prepared and their reactivity with the Furukawa-modified Simmons-Smith zinc carbenoid was studied. Various functionality was incorporated into these molecules in efforts to broaden the scope of the zinc-mediated chain extension reaction. The mechanism of the chain extension of dimethyl (2-oxopropyl)phosphonate was probed by nuclear magnetic resonance in efforts to observe key intermediates of these reactions. The stereochemistry of bis-, tris-, and tetrakis-cyclopropanes was confirmed by a one directional asymmetric independent synthesis. Application of an olefin cross-metathesis reaction allowed vinyl tetrakis-cyclopropane to be elaborated into an advanced intermediate toward the preparation of FR-900848, a polycyclopropanated natural product displaying desirable biological activity. The application of olefin metathesis chemistry represents both a novel and efficient means of incorporating both the intervening E-olefin and sequestered cyclopropane contained within these compounds