Access to Silylated Pyrazole Derivatives by Palladium-Catalyzed C-H Activation of a TMS group.
A simple and efficient approach to new silylated heterocycles of potential interest in medicinal chemistry is presented. A set of bromophenyl trimethylsilyl pyrazole intermediates can be transformed by direct organometallic routes into two families of regioisomeric iodoaryl substrates; using either arylzinc or aryllithium chemistry, the TMS group remains on the pyrazole ring or translocates to the aryl moiety. These two families can then be efficiently transformed into benzo silino pyrazoles thanks to a single-step cyclization relying on the Pd-catalyzed activation of a non-activated C(sp(3) )-H bond alpha to a silicon atom. The experimental conditions used, which are fully compatible with the pyrazole ring, suggest that this reaction evolves through a concerted metalation-deprotonation (CMD) mechanism.
Laboratoire COBRA, CNRS UMR 6014 & FR 3038, Univ. Rouen; INSA Rouen, 76821, Mt St Aignan Cedex, France.
Laetitia
L
Mistico
Janssen Research & Development, Division of Janssen-Cilag, Chaussée du Vexin, BP615, 27106, Val de Reuil, France.
Olivier
O
Querolle
Janssen Research & Development, Division of Janssen-Cilag, Chaussée du Vexin, BP615, 27106, Val de Reuil, France.
Lieven
L
Meerpoel
Janssen Research & Development, Division of Janssen-Cilag, Chaussée du Vexin, BP615, 27106, Val de Reuil, France.
Patrick
P
Angibaud
Laboratoire COBRA, CNRS UMR 6014 & FR 3038, Univ. Rouen; INSA Rouen, 76821, Mt St Aignan Cedex, France. muriel.durandetti@univ-rouen.fr.
Muriel
http://orcid.org/0000-0002-5136-9655
M
Durandetti
Laboratoire COBRA, CNRS UMR 6014 & FR 3038, Univ. Rouen; INSA Rouen, 76821, Mt St Aignan Cedex, France. jmaddalu@crihan.fr.
Jacques
J
Maddaluno
C−H activation; cyclization; heterocycles; pyrazole; silicon