Gram‐Scale Enantioselective Formal Synthesis of Morphine through an ortho–para Oxidative Phenolic Coupling Strategy |
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Authors: | Dr Matthieu Tissot Dr Robert J Phipps Dr Catherine Lucas Dr Rafael M Leon Dr Robert D M Pace Dr Tifelle Ngouansavanh Prof Matthew J Gaunt |
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Institution: | Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW (UK) http://www‐gaunt.ch.cam.ac.uk/ |
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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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Keywords: | alkaloids asymmetric synthesis oxidative coupling total synthesis |
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