title: A Cascade Strategy Enables a Total Synthesis of (±)-Morphine.
abstract: Morphine has been a target for synthetic chemists since Robinson proposed its correct structure in 1925, resulting in a large number of total syntheses of morphine alkaloids. Here we report a total synthesis of (±)-morphine that employs two key strategic cyclizations: 1) a diastereoselective light-mediated cyclization of an O-arylated butyrolactone to form a tricyclic cis-fused benzofuran and 2) a cascade ene-yne-ene ring closing metathesis to forge the tetracyclic morphine core. This approach enables a short and stereoselective synthesis of morphine in an overall yield of 6.6 %.
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Chu
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Niels
authors.initials: N
authors.lastname: Münster
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Tudor
authors.initials: T
authors.lastname: Balan
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK. martin.smith@chem.ox.ac.uk.
authors.forename: Martin D
authors.identifier: 0000-0002-8849-488X
authors.initials: MD
authors.lastname: Smith
keywords: cascade reactions; metathesis; morphine; photochemistry; total synthesis