Application of (3,3)-sigmatropic rearrangements to the rapid elaboration of complex molecules including natural products

Two approaches have been developed to the total synthesis of (+)-acetoxycrenulide. First, the fully functionalized tricyclic system, (7R,7aS,8aS)-4,6,7,7a,8,8a-hexahydro-7-methyl-1H-cyclopropa(3,4) cycloocta(1,2-c) furan-1,5(3H)-dione, corresponding to the ring framework of crenulide diterpenes has been synthesized in optically active form from L-glutamic acid. The enantiospecific synthesis includes an aldol condensation, an intramolecular selenonium ion-promoted cyclization with participation by a neighboring hydroxyl group, a selenoxide elimination, a stereocontrolled thermal Claisen ring expansion, and a Simmons-Smith cyclopropanation. Second, the precursor to acetoxycrenulide, (4S)-4-((1R,2S)-2,6-dimethyl-1-vinyl-5-heptenyl) dihydro-2(3H)-furanone, has been enantiospecifically produced from (S)-citronellol. The key reactions involve an asymmetric alkylation, a selective hydroboration, a lactonization, cuprate 1,4-addition, and a Wittig olefination.;The diastereoselectivity in the 1,2-addition of four chiral organocerates to two ;A general strategy featuring Dieckman condensation, carbomethoxylation, Favorskii ring contraction, and radical bromo-decarboxylation has been developed in an enantiospecific fashion for the preparation of (S)-(+)-1-bromo-3-(1-methylethyl)cyclopentene. This vinyl bromide is an important precursor to the synthesis of three natural products via (3,3) -sigmatropic rearrangements. From (R)-(-)-carvone it has been synthesized in its enantiomerically pure form without any isomeric contamination for the first time.