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Synthesis of Aryl Tri‐ and Difluoromethyl Thioethers via a CH‐Thiocyanation/Fluoroalkylation Cascade
Author(s) -
Jouvin Kévin,
Matheis Christian,
Goossen Lukas J.
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201502914
Subject(s) - trifluoromethylation , aryl , reagent , regioselectivity , trifluoromethyl , chemistry , steric effects , cascade , sulfur , medicinal chemistry , combinatorial chemistry , organic chemistry , catalysis , alkyl , chromatography
Abstract An AlCl 3 ‐catalyzed CH thiocyanation was discovered and combined with a Langlois‐type trifluoromethylation to afford aryl trifluoromethyl thioethers directly from arenes, N ‐thiocyanatosuccinimide (NTS) and Ruppert–Prakash reagent. An analogous combination with a copper‐mediated difluoromethylation gives access to aryl difluoromethyl thioethers. Both processes proceed with exceptional regioselectivity for the most electron‐rich, sterically least hindered position of the arene. The sulfur and fluoroalkyl groups originate from different sources, so that the use of expensive, preformed fluoroalkylthiolation reagents is avoided.