Total synthesis of (-)-vindoline and (+)-4-epi-vindoline based on a 1,3,4-oxadiazole tandem intramolecular 4+2 / 3+2 cycloaddition cascade initiated by an allene dienophile

Academic Article
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publication date

  • November 2015

abstract

  • It is reported that an allene dienophile can initiate a tandem intramolecular [4 + 2]/[3 + 2] cycloaddition cascade of 1,3,4-oxadiazoles, that the intermediate cross-conjugated 1,3-dipole (a carbonyl ylide) can participate in an ensuing [3 + 2] dipolar cycloaddition in a remarkably effective manner, and that the reaction can be implemented to provide the core pentacyclic ring system of vindoline. Its discovery improves a previous total synthesis of (-)-vindoline and was used in a total synthesis of (+)-4-epi-vindoline and (+)-4-epi-vinblastine that additionally enlists an alternative series of late-stage transformations.