Samarium Diiodide Induced Cyclizations – Our Way to Strychnine
Professor Hans Reissig
Institut fur Chemie und Biochemie
Free University of Berlin
Monday, August 13, 2012
C2-361 (Reading Room)
Abstract: Application of samarium diiodide as promoter for ketyl cyclizations led to the discovery of several new and synthetically interesting reactions. Starting with smooth 8-endo-trig and 8-endo-dig cyclizations leading to cyclooctanol derivatives we serendipitously discovered the addition of samarium ketyls to aryl groups. This new method stereoselectively provides hexahydronaphthalene derivatives.1
This process is fairly general and was extended to related processes employing naphthyl units and hetaryl moieties as acceptor of the samarium ketyl. In most cases, the cyclization occurs with high diastereoselectivity and delivers dearomatized products with a useful substitution pattern and functional groups (e.g. compounds 1 – 4). Cyclizations with pyrrole and indole moieties as ketyl acceptors are also efficient. Compound 4 was obtained in excellent yield and subsequently converted within few steps into the known strychnine precursor 5, hence establishing one of the shortest and most efficient formal total synthesis of this intriguing natural product.2
1. a) C. U. Dinesh, H.-U. Reissig, Angew. Chem. Int. Ed. 1999, 38, 789-791; b) Reviews: M. Berndt, S. Gross, A. Hölemann, H.-U. Reissig, Synlett 2004, 422-438; C. Beemelmanns, H.-U. Reissig, Chem. Soc. Rev. 2011, 40, 2199-2210.
2. C. Beemelmanns, H.-U. Reissig, Angew. Chem. Int. Ed. 2010, 49, 8021-8025.