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Palladium‐Catalyzed Enantioselective Desymmetrizing Aza‐Wacker Reaction: Development and Application to the Total Synthesis of (−)‐Mesembrane and (+)‐Crinane
Author(s) -
Bao Xu,
Wang Qian,
Zhu Jieping
Publication year - 2018
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.201712521
Subject(s) - enantioselective synthesis , catalysis , phosphoric acid , palladium , chemistry , ligand (biochemistry) , wacker process , combinatorial chemistry , total synthesis , organic chemistry , receptor , biochemistry
Reported is an unprecedented catalytic enantioselective desymmetrizing aza‐Wacker reaction. In the presence of a catalytic amount of a newly developed Pd(CPA) 2 (MeCN) 2 catalyst (CPA=chiral phosphoric acid), a pyrox ligand, and molecular oxygen, cyclization of properly functionalized prochiral 3,3‐disubstituted cyclohexa‐1,4‐dienes afforded enantioenriched cis ‐3a‐substituted tetrahydroindoles in good yields with excellent enantioselectivities. A cooperative effect between the phosphoric acid and the pyrox ligand ensured efficient transformation. This reaction was tailor‐made for Amaryllidaceae and Sceletium alkaloids as illustrated by its application in the development of the concise and divergent total synthesis of (−)‐mesembrane and (+)‐crinane.