Copper‐Mediated Late‐Stage Functionalization of Heterocycle‐Containing Molecules
- 10 April 2017
- journal article
- research article
- Published by Wiley in Angewandte Chemie
- Vol. 56 (19), 5317-5321
- https://doi.org/10.1002/anie.201611287
Abstract
One long‐standing issue in directed C−H functionalization is that either nitrogen or sulfur atoms present in heterocyclic substrates may bind preferentially to a transition‐metal catalyst rather than to the desired directing group. This competitive binding has largely hindered the application of C−H functionalization in late‐stage heterocycle drug discovery. Reported here is the use of an oxazoline‐based directing group capable of overriding the poisoning effect of a wide range of heterocycle substrates. The potential use of this directing group in pharmaceutical drug discovery is illustrated by diversification of Telmisartan (an antagonist for the angiotensin II receptor) through copper‐mediated C−H amination, hydroxylation, thiolation, arylation, and trifluoromethylation.Funding Information
- National Science Foundation (CHE-1205646)
This publication has 41 references indexed in Scilit:
- Carboxylate‐Assisted Ruthenium(II)‐Catalyzed Hydroarylations of Unactivated Alkenes through C–H CleavageAngewandte Chemie, 2013
- Carboxylate‐Assisted Ruthenium(II)‐Catalyzed Hydroarylations of Unactivated Alkenes through C–H CleavageAngewandte Chemie, 2013
- Practical and innate carbon–hydrogen functionalization of heterocyclesNature, 2012
- Ruthenium-Catalyzed Direct C–H Bond Arylations of HeteroarenesOrganic Letters, 2011
- Comprehensive Survey of Chemical Libraries for Drug Discovery and Chemical Biology: 2009Journal of Combinatorial Chemistry, 2010
- Pd0/PR3‐Catalyzed Arylation of Nicotinic and Isonicotinic Acid DerivativesAngewandte Chemie, 2010
- Rhodium-Catalyzed C−C Bond Formation via Heteroatom-Directed C−H Bond ActivationChemical Reviews, 2009
- Cu(II)-Catalyzed Functionalizations of Aryl C−H Bonds Using O2 as an OxidantJournal of the American Chemical Society, 2006
- Identification of Telmisartan as a Unique Angiotensin II Receptor Antagonist With Selective PPARγ–Modulating ActivityHypertension, 2004
- Steric and Chelate Directing Effects in Aromatic BorylationJournal of the American Chemical Society, 2000