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Short Chemoenzymatic Total Synthesis of ent ‐Hydromorphone: An Oxidative Dearomatization/Intramolecular [4+2] Cycloaddition/Amination Sequence
Author(s) -
Varghese Vimal,
Hudlicky Tomas
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201400286
Subject(s) - intramolecular force , chemistry , amination , dihydroxylation , hydromorphone , cycloaddition , ring (chemistry) , stereochemistry , total synthesis , oxidative phosphorylation , organic chemistry , enantioselective synthesis , catalysis , biochemistry , receptor , opioid
Abstract A short synthesis of ent ‐hydromorphone has been achieved in twelve steps from β‐bromoethylbenzene. The key transformations involved the enzymatic dihydroxylation of the arene to the corresponding cis ‐dihydrodiol, Mitsunobu coupling with the ring A fragment, oxidative dearomatization of the C3 phenol, and the subsequent [4+2] cycloaddition to form ring B of the morphinan. The synthesis was completed by intramolecular amination at C9.