Synthesis of Chiral Spirocyclopropanepenicillanates via [2 + 1] Annulation of 6-Alkylidenepenicillanates and Sulfur Ylides

An unexplored reactivity of 6-(Z)-alkylidenepenicillanates was unveiled, describing the synthesis of compounds having a cyclopropane ring spiro-fused to the penicillanic core. This was achieved via the in situ generation of sulfur ylide intermediates from the corresponding sulfur salts, which react with 6-(Z)-alkylidenepenicillanates, leading to spirocyclopropanepenicillanates. The formal [2 + 1] cycloaddition, which involved the creation of three new chiral centers, proved to be diastereoselective, affording the new chiral spiropenicillanates in good yields. Notably, one spiro-β-lactam exhibited excellent anti-HIV-1 activity.