title: Evolution of a short route to strychnine by using the samarium-diiodide-induced cascade cyclization as a key step.
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.
authors: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin (Germany).|Leibniz Institute for Natural Product Research and Infection Biology e.V., Hans-Knöll-Institute (HKI), Beutenbergstrasse 11 a, 07745 Jena (Germany).
authors: Christine
authors: C
authors: Beemelmanns
authors: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin (Germany). hans.reissig@chemie.fu-berlin.de.
authors: Hans-Ulrich
authors: HU
authors: Reissig
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D003500:Cyclization; D007454:Iodides / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry; D015394:Molecular Structure; D012493:Samarium / Q000737:chemistry*; D013331:Strychnine / Q000138:chemical synthesis* / Q000737:chemistry; D031451:Strychnos / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D007454:Iodides; D007659:Ketones; D012493:Samarium; D013331:Strychnine; C409809:samarium diiodide
keywords: alkaloids; diastereoselectivity; domino reactions; samarium; total synthesis