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Gram‐Scale Enantioselective Formal Synthesis of Morphine through an ortho – para Oxidative Phenolic Coupling Strategy
Author(s) -
Tissot Matthieu,
Phipps Robert J.,
Lucas Catherine,
Leon Rafael M.,
Pace Robert D. M.,
Ngouansavanh Tifelle,
Gaunt Matthew J.
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201408435
Subject(s) - enantioselective synthesis , desymmetrization , stereocenter , chemistry , formal synthesis , combinatorial chemistry , catalysis , stereoisomerism , stereochemistry , organic chemistry
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.