title: Copper-Mediated Late-Stage Functionalization of Heterocycle-Containing Molecules.
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.
authors.affiliation: State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 LingLing Road, Shanghai, 200032, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shang
authors.affiliation: State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 LingLing Road, Shanghai, 200032, China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Wang
authors.affiliation: The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Tyler G
authors.initials: TG
authors.lastname: Saint-Denis
authors.affiliation: State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 LingLing Road, Shanghai, 200032, China.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Li
authors.affiliation: State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 LingLing Road, Shanghai, 200032, China.
authors.forename: Hui-Xiong
authors.initials: HX
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 LingLing Road, Shanghai, 200032, China.|The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Jin-Quan
authors.identifier: 0000-0003-3560-5774
authors.initials: JQ
authors.lastname: Yu
keywords: C−H activation; amination; copper; heterocycles; hydroxylation