Sequential Regioselective C-H Functionalization of Thiophenes
Matthew H Daniels1, Jeremy R Armand2, Kian L Tan1
1Global Discovery Chemistry, Novartis Institutes for Biomedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
Abstract:
Herein, the sequential functionalization of 5-membered ring heterocycles is disclosed. By employing a pH sensitive directing group both directed and nondirected C-H activation pathways are available, providing access to 2,3,4- and 2,4,5-substituted thiophenes. The C-H arylation was performed in water, and using a surfactant greatly improved the yield and mass recovery. The use of a directing group with an on/off switch offers a potentially powerful means of generating diversity around medicinally relevant cores.
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