Evolution of a Short Route to Strychnine by Using the Samarium‐Diiodide‐Induced Cascade Cyclization as a Key Step |
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| Authors: | Dr Christine Beemelmanns Prof Hans‐Ulrich Reissig |
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| Affiliation: | 1. Institut für Chemie und Biochemie, Freie Universit?t Berlin, Takustrasse?3, 14195 Berlin (Germany);2. Leibniz Institute for Natural Product Research and Infection Biology e.V., Hans‐Kn?ll‐Institute (HKI), Beutenbergstrasse 11?a, 07745 Jena (Germany) |
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| Abstract: | This comprehensive report accounts the development of a highly diastereoselective samarium diiodide‐induced cascade reaction of substituted indolyl ketones. The complexity‐generating transformation with SmI2 allows the diastereoselective generation of three stereogenic centers including one quaternary center in one step. The obtained tetra‐ or pentacyclic dihydroindole derivatives are structural motifs of many monoterpene indole alkaloids, and their subsequent transformations gave way to one of the shortest approaches towards strychnine (14 % overall yield in ten steps, or 10 % overall yield in eight steps). During the course of this report we discuss the influence of substituents on the cyclization step, plausible mechanistic scenarios for the SmI2‐induced cascade reaction, diastereoselective reductive amination, and regioselective dehydratization protocols towards the pentacyclic core structure of strychnos alkaloids. |
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| Keywords: | alkaloids diastereoselectivity domino reactions samarium total synthesis |
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