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Site‐ and Enantioselective Iridium‐Catalyzed Desymmetric Mono‐Hydrogenation of 1,4‐Dienes
Author(s) -
Wu Haibo,
Su Hao,
Schulze Erik J.,
Peters Bram B. C.,
Nolan Mark D.,
Yang Jianping,
Singh Thishana,
Ahlquist Mårten S. G.,
Andersson Pher G.
Publication year - 2021
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.202107267
Subject(s) - iridium , enantioselective synthesis , catalysis , chemistry , asymmetric hydrogenation , organic chemistry , combinatorial chemistry
The control of site selectivity in asymmetric mono‐hydrogenation of dienes or polyenes remains largely underdeveloped. Herein, we present a highly efficient desymmetrization of 1,4‐dienes via iridium‐catalyzed site‐ and enantioselective hydrogenation. This methodology demonstrates the first iridium‐catalyzed hydrogenative desymmetriation of meso dienes and provides a concise approach to the installation of two vicinal stereogenic centers adjacent to an alkene. High isolated yields (up to 96 %) and excellent diastereo‐ and enantioselectivities (up to 99:1 d.r. and 99 % ee) were obtained for a series of divinyl carbinol and divinyl carbinamide substrates. DFT calculations reveal that an interaction between the hydroxy oxygen and the reacting hydride is responsible for the stereoselectivity of the desymmetrization of the divinyl carbinol. Based on the calculated energy profiles, a model that simulates product distribution over time was applied to show an intuitive kinetics of this process. The usefulness of the methodology was demonstrated by the synthesis of the key intermediates of natural products zaragozic acid A and (+)‐invictolide.