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Enantioselective Electrophilic Aromatic Nitration: A Chiral Auxiliary Approach
Author(s) -
Campbell Joseph P.,
Rajappan Sinu C.,
Jaynes Tyler J.,
Sharafi Mona,
Ma YongTao,
Li Jianing,
Schneebeli Severin T.
Publication year - 2019
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.201811517
Subject(s) - enantioselective synthesis , nitration , stereocenter , regioselectivity , chemistry , electrophile , enantiomer , chirality (physics) , axial chirality , combinatorial chemistry , electrophilic aromatic substitution , stereochemistry , computational chemistry , organic chemistry , catalysis , physics , nambu–jona lasinio model , chiral symmetry breaking , quantum mechanics , quark
Enantioselective electrophilic aromatic nitration methodology is needed to advance chirality‐assisted synthesis (CAS). Reported here is an enantioselective aromatic nitration strategy operating with chiral diester auxiliaries, and it provides an enantioselective synthesis of a C 3 v ‐symmetric tribenzotriquinacene (TBTQ). These axially‐chiral structures are much sought‐after building blocks for CAS, but they were not accessible prior to this work in enantioenriched form without resolution of enantiomers. This nitration strategy controls the stereochemistry of threefold nitration reactions from above the aromatic rings with chiral diester arms. Dicarbonyl‐to‐arenium chelation rigidifies the reaction systems, so that remote stereocenters position the ester‐directing groups selectively over specific atoms of the TBTQ framework. Closely guided by computational design, a more selective through‐space directing arm was first predicted with density functional theory (DFT), and then confirmed in the laboratory, to outperform the initial structural design. This enantio‐ and regioselective TBTQ synthesis opens a new pathway to access building blocks for CAS.