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Oxalyl Boronates Enable Modular Synthesis of Bioactive Imidazoles
Author(s) -
Lee C. Frank,
Holownia Aleksandra,
Bennett James M.,
Elkins Jonathan M.,
St. Denis Jeffrey D.,
Adachi Shinya,
Yudin Andrei K.
Publication year - 2017
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.201611006
Subject(s) - imidazole , chemistry , combinatorial chemistry , serine , modular design , organic chemistry , computer science , programming language , enzyme
Described herein is the preparation of oxalyl boronate building blocks and their application for the construction of heterocycles. The oxalyl unit, readily accessible through commercially available starting materials, enables a modular approach for the synthesis of imidazoles. A variety of aromatic, heteroaromatic, and alkyl carboxaldehydes were condensed with oxalyl boronates to afford substituted boryl imidazoles in a regiocontrolled fashion. Subsequent palladium‐catalyzed cross‐coupling with haloarenes furnished the desired trisubstituted imidazole scaffolds. To demonstrate the utility of these scaffolds, potent inhibitors of the serine/threonine‐protein kinase STK10 were synthesized.