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Synthesis 2017; 49(13): 2865-2872
DOI: 10.1055/s-0036-1590503
DOI: 10.1055/s-0036-1590503
feature
Copper-Mediated sp 2 C–H Chlorination with Trichloroacetamide Using a Removable Directing Group
Further Information
Publication History
Received: 05 May 2017
Accepted: 08 May 2017
Publication Date:
15 May 2017 (online)
![](https://www.thieme-connect.de/media/synthesis/201713/lookinside/thumbnails/ss-2017-z0219-fa_10-1055_s-0036-1590503-1.jpg)
Dedicated to Prof. David R. Williams at Indiana University
Abstract
2-Aminophenyl-1H-pyrazole was discovered as a removable, bidentate directing group for copper-mediated aerobic oxidative sp 2 C–H bond chlorination employing trichloroacetamide as a new chlorine source. When Cu(OAc)2 was employed as the copper source, 1,1,3,3-tetramethylguanidine (TMG) as an organic base, the reaction, optimally carried out overnight in DMSO at 80 °C in open air, produced a variety of mono- and dichlorinated products in moderate to excellent yields. This directing group can be removed oxidatively with cerium ammonium nitrate (CAN).
Key words
C–H chlorination - copper-mediated - trichloroacetamide - removable directing group - 2-aminophenyl-1H-pyrazoleSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0036-1590503.
- Supporting Information
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A combination of PPh3/CCl3CONH2 was employed to chlorinate alcohols by converting C–OH bonds to C–Cl bonds:
Palladium-catalyzed C–H chlorination:
Reviews on copper-mediated C–H bond activation:
Copper-mediated nucleophilic C–H chlorination:
Copper-mediated electrophilic C–H chlorination: