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Enantioselective Desymmetrization of Prochiral Cyclohexanones by Organocatalytic Intramolecular Michael Additions to α,β‐Unsaturated Esters
Author(s) -
Gammack Yamagata Adam D.,
Datta Swarup,
Jackson Kelvin E.,
Stegbauer Linus,
Paton Robert S.,
Dixon Darren J.
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201411924
Subject(s) - enantioselective synthesis , desymmetrization , stereocenter , chemistry , moiety , intramolecular force , bicyclic molecule , stereochemistry , organocatalysis , cyclohexanone , michael reaction , organic chemistry , catalysis
A new catalytic asymmetric desymmetrization reaction for the synthesis of enantioenriched derivatives of 2‐azabicyclo[3.3.1]nonane, a key motif common to many alkaloids, has been developed. Employing a cyclohexanediamine‐derived primary amine organocatalyst, a range of prochiral cyclohexanone derivatives possessing an α,β‐unsaturated ester moiety linked to the 4‐position afforded the bicyclic products, which possess three stereogenic centers, as single diastereoisomers in high enantioselectivity (83–99 % ee ) and in good yields (60–90 %). Calculations revealed that stepwise CC bond formation and proton transfer via a chair‐shaped transition state dictate the exclusive endo selectivity and enabled the development of a highly enantioselective primary amine catalyst.