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Catalytic and Enantioselective Control of the C–N Stereogenic Axis via the Pictet–Spengler Reaction
Author(s) -
Kim Ahreum,
Kim Aram,
Park Sunjung,
Kim Sangji,
Jo Hongil,
Ok Kang Min,
Lee Sang Kook,
Song Jayoung,
Kwon Yongseok
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202100363
Subject(s) - stereocenter , chemistry , pictet–spengler reaction , enantioselective synthesis , kinetic resolution , aryl , catalysis , phosphoric acid , chirality (physics) , ring (chemistry) , hydrogen bond , combinatorial chemistry , axial chirality , stereochemistry , organic chemistry , molecule , alkyl , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
An unprecedented example of a chiral phosphoric acid‐catalyzed atroposelective Pictet–Spengler reaction of N ‐arylindoles is reported. Highly enantioenriched N ‐aryl‐tetrahydro‐β‐carbolines with C−N bond axial chirality are obtained via dynamic kinetic resolution. The hydrogen bond donor introduced on the bottom aromatic ring, forming a secondary interaction with the phosphoryl oxygen, is essential to achieving high enantioselectivity. A wide variety of substituents are tolerable with this transformation to provide up to 98 % ee . The application of electron‐withdrawing group‐substituted benzaldehydes enables the control of both axial and point stereogenicity. Biological evaluation of this new and unique scaffold shows promising antiproliferative activity and emphasizes the significance of atroposelective synthesis.