Asymmetric Total Synthesis of Vindoline
- 26 February 2010
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 132 (11), 3685-3687
- https://doi.org/10.1021/ja910695e
Abstract
A concise asymmetric total synthesis of (−)-vindoline (1) is detailed based on a tandem intramolecular [4+2]/[3+2] cycloaddition cascade of a 1,3,4-oxadiazole inspired by the natural product structure, in which the tether linking the initiating dienophile and oxadiazole bears a chiral substituent that controls the facial selectivity of the initiating Diels−Alder reaction and sets absolute stereochemistry of the remaining six stereocenters in the cascade cycloadduct. This key reaction introduces three rings and four C−C bonds central to the pentacyclic ring system setting all six stereocenters and introducing essentially all the functionality found in the natural product in a single step. Implementation of the approach also required the development of a unique ring expansion reaction to provide a six-membered ring suitably functionalized for introduction of the Δ(6, 7)-double bond found in the core structure of vindoline and defined our use of a protected hydroxymethyl group as the substituent used to control the stereochemical course of the cycloaddition cascade.Keywords
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