Fragmentation reactions of optically active trisubstituted cyclopropylcarbinyl radicals

Fragmentation reactions of optically active trisubstituted cyclopropylcarbi nyl radicals and their application to the synthesis of natural products are described. Preparation of the optically pure substrates for radical fragme ntation reactions was efficiently accomplished by lipase-mediated desymmetr ization of a-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 ra dical on the a-carbon of the group and provide the optically pure alkene de rivatives. These derivatives possess three chemically distinct functionalit ies, making them excellent chiral building blocks for the construction of b iologically active molecules. The synthetic usefulness of the procedure dev eloped here has been demonstrated by an application to the enantioselective synthesis of both enantiomers of the key intermediate, 4-(3,4-methylenedio xybenzyl)dihydrofuran-2(3H)-one (54), for the total synthesis of biological ly active lignans.