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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
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201611006
Subject(s) - chemistry , imidazole , combinatorial chemistry , modular design , serine , alkyl , organic chemistry , computer science , enzyme , programming language
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.