Versatile synthesis of enantiomerically pure 2-alkoxy-1-ethynylcyclopropanes and their application in the synthesis of enantiomerically pure bicyclo-[3.3.0]oct-1-en-3-ones

A variety of chiral, nonracemic 2-alkoxy-1-alkynylcyclopropanes 7 were synthesized in good to very good yields from enantiomerically pure glycidol derivatives (glycidol tosylate, epichlorohydrin) by boron trifluoride promoted addition of lithium trimethylsilylacetylide followed by protection of the secondary hydroxyl group and finally a diastereoselective gamma-elimination. The 2-ethoxy derivative (S,R)-7b was deprotonated with n-butyllithium, and the resulting 1-lithio-2-ethoxy derivative (S,R)-20 functionalized by treatment with oxygen followed by tosyl chloride, Protodesilylation and catalytic hydrogenation smoothly furnished 1-ethenylcyclopropyl sulfonates, which underwent a clean Pd-0-catalyzed S(N)2'-type substitution with dimethyl propargylsodiummalonate to give the (E)-configurated enyne (R,E)-26 with a methylenecyclopropane end group. A diastereoselective Pauson-Khand reaction completed the sequence to give the enantiomerically pure spirocyclopropane-annelated bicyclo[3.3.0]octane derivative 31.