N-Heterocyclic Carbene Catalyzed Oxidative Macrolactonization: Total Synthesis of (+)-Dactylolide


  • We are grateful to Duke University for funding this work, to the North Carolina Biotechnology Center (NCBC; Grant No. 2008-IDG-1010) for funding of the NMR instrumentation, and to the National Science Foundation (NSF) MRI Program (Award ID No. 0923097) for funding mass spectrometry instrumentation.


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Three key steps constitute the total synthesis of (+)-dactylolide: the 1,6-oxa conjugate addition reaction of a 2,4-dienal for the facile synthesis of the 2,6-cis-2-(4-oxo-2-butenyl)tetrahydropyran subunit, the umpolung alkylation reaction of a cyanohydrin, and the NHC-catalyzed oxidative macrolactonization reaction for the synthesis of the 20-membered macrocyle. NHC=N-heterocyclic carbene.