Synthesis of (-)-morphine: application of sequential Claisen/Claisen rearrangement of an allylic vicinal diol.

Masato Ichiki, Hiroki Tanimoto, Shohei Miwa, Ryosuke Saito, Takaaki Sato, Noritaka Chida

Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.

Chemistry (Weinheim an der Bergstrasse, Germany) 2013 Jan 2

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A detailed exploration of the synthesis of (-)-morphine based on sequential [3,3]-sigmatropic rearrangements is described. The sequential Claisen/Claisen rearrangements of an allylic vicinal diol resulted in the stereoselective formation of the two contiguous carbon centers, including a sterically encumbered quaternary carbon, in a single operation. The two ethyl esters generated in this reaction were successfully differentiated during a subsequent Friedel-Crafts-type cyclization. The (-)-morphine double bond was introduced at a late stage in our first-generation synthesis, but was formed at an earlier stage in the second-generation synthesis, resulting in a more efficient route to the end product. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Citation

Masato Ichiki, Hiroki Tanimoto, Shohei Miwa, Ryosuke Saito, Takaaki Sato, Noritaka Chida. Synthesis of (-)-morphine: application of sequential Claisen/Claisen rearrangement of an allylic vicinal diol. Chemistry (Weinheim an der Bergstrasse, Germany). 2013 Jan 2;19(1):264-9