Gram-scale enantioselective formal synthesis of morphine through an ortho-para oxidative phenolic coupling strategy
Matthieu Tissot1, Robert J Phipps, Catherine Lucas
1Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW (UK) http://www-gaunt.ch.cam.ac.uk/
Abstract:
A gram-scale catalytic enantioselective formal synthesis of morphine is described. The key steps of the synthesis involve an ortho-para oxidative phenolic coupling and a highly diastereoselective "desymmetrization" of the resulting cyclohexadienone that generates three of the four morphinan ring junction stereocenters in one step. The stereochemistry is controlled from a single carbinol center installed through catalytic enantioselective hydrogenation. These transformations enabled the preparation of large quantities of key intermediates and could support a practical and scalable synthesis of morphine and related derivatives.
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