Oxidative cyclization for the synthesis of complex tetrahydrofuran‑containing natural products

Pullin, Robert D. C.; Lipiński, Radosław M.; Donohoe, Timothy J.

doi:10.1351/PAC-CON-12-10-25

Pure Appl. Chem., 2013, Vol. 85, No. 6, pp. 1175-1184

http://dx.doi.org/10.1351/PAC-CON-12-10-25

Published online 2013-03-13

Oxidative cyclization for the synthesis of complex tetrahydrofuran‑containing natural products

Robert D. C. Pullin, Radosław M. Lipiński and Timothy J. Donohoe*

Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK

Abstract: The osmium-catalyzed oxidative cyclization of vicinal diols onto proximal olefins to generate 2,5-cis-substituted tetrahydrofurans (THFs) has been exploited as the key step for the construction of several complex THF‑containing natural products, namely, the annonaceous acetogenins cis‑sylvaticin, sylvaticin, and the excitatory amino acid neo-dysiherbaine A. Recently modified conditions that employ a Lewis acid enable the cyclization to proceed under milder conditions, providing greater tolerance to acid-sensitive functional groups, as demonstrated in two of the syntheses. Flexibility for the construction of 2,5-trans-THFs was demonstrated in the synthesis of sylvaticin by utilization of an intramolecular hydride-shift sequence.