Fragmentation reactions of optically active trisubstituted cyclopropylcarbinyl radicals

Fragmentation reactions of optically active trisubstituted cyclopropylcarbinyl radicals and their application to the synthesis of natural products are described. Preparation of the optically pure substrates for radical fragmentation reactions was efficiently accomplished by lipase-mediated desymmetrization of sigma-symmetrical 3-substituted-1,2-cyclopropanedimethanols. In the presence of a radical stabilizing group, e.g., aryl, ester, or alpha,beta-unsaturated ester, the fragmentation occurs selectively to generate the radical on the alpha-carbon of the group and provide the optically pure alkene derivatives. These derivatives possess three chemically distinct functionalities, making them excellent chiral building blocks for the construction of biologically active molecules. The synthetic usefulness of the procedure developed here has been demonstrated by an application to the enantioselective synthesis of both enantiomers of the key intermediate, 4-(3,4-methylenedioxybenzyl)dihydrofuran-2(3H)-one (54), for the total synthesis of biologically active lignans.