Ti(IV) Promoted Mukaiyam Aldol-Prins Cyclization

University Of California Irvine, Irvine CA

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Abstract

DESCRIPTION (provided by applicant): Facile syntheses of biologically active natural products have often been the motive for development of new methodologies in organic chemistry. The recent development of the Ti(IV) promoted Mukaiyama aldol-Prins cyclization by the Rychnovsky group has allowed entry to complex tetrahydropyran ring systems with concomitant formation of a secondary alcohol. Prins cyclization proceeds stereoselectively to give the 2,4,6-syn-trisubstituted tetrahydropyran in >95:5 diastereoselectivity. The initial aldol adduct proceeds with low diastereoselectivity, which allows for possible asymmetric induction either by introduction of a chiral aldehyde or a chiral Lewis acid. Investigation into the improvement of diastereoselectivity at the exocyclic alcohol center in conjunction with the use of an enantiopure enol ether would provide a methodology that forms two carbon-carbon bonds as well as setting three stereocenters. Application of this methodology to the synthesis of leucascandrolide A would provide a highly efficient synthetic route to a natural product that has shown high activity against cancer cell lines.