Mono- and binuclear palladacycles via regioselective C–H bond activation: syntheses, mechanistic insights and catalytic activity in direct arylation of azoles (original) (raw)
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Journal of the American Chemical Society, 2009
Palladium-catalyzed direct arylation reactions are described with a broad range of azine and azole N-oxides. In addition to aspects of functional group compatibility, issues of regioselectivity have been explored when nonsymmetrical azine N-oxides are used. In these cases, both the choice of ligand and the nature of the azine substituents play important roles in determining the regioisomeric distribution. When azole N-oxides are employed, preferential reaction is observed for arylation at C2 which occurs under very mild conditions. Subsequent reactions are observed to occur at C5 followed by arylation at C4. The potential utility of this methodology is illustrated by its use in the synthesis of a potent sodium channel inhibitor 1 and a Tie2 Tyrosine Kinase inhibitor 2.
Molecules
The transition metal-catalyzed C–H bond functionalization of azoles has emerged as one of the most important strategies to decorate these biologically important scaffolds. Despite significant progress in the C–H functionalization of various heteroarenes, the regioselective alkylation and alkenylation of azoles are still arduous transformations in many cases. This review covers recent advances in the direct C–H alkenylation, alkylation and alkynylation of azoles utilizing transition metal-catalysis. Moreover, the limitations of different strategies, chemoselectivity and regioselectivity issues will be discussed in this review.
Regioselective Palladium-Catalyzed Arylation of 4-Chloropyrazoles
Organic Letters, 2010
A highly regioselective Pd-catalyzed arylation of N-methylpyrazoles with aryl bromides is described. This transformation was studied extensively via automated reaction screening. A Design of Experiments (DoE) approach for optimizing the critical parameters was applied, resulting in excellent conditions for preparing selectively 5-arylpyrazoles in moderate to excellent yields under mild conditions. Heteroaryl derivatives, including aryl pyrazoles, are important building blocks in organic synthesis due to their biological properties. 1 Although a number of synthetic methods have been developed to construct pyrazoles possessing an aryl group on the ring, 2 many of these approaches are based on time-consuming multistep procedures or structure-limited ring transformation reactions. Direct introduction of an aryl group onto the pyrazole nucleus via palladium-mediated cross-coupling reaction has been demonstrated via Suzuki, 3 Stille, 4 and Negishi 4,5 reactions. Metal-catalyzed arylation and heteroarylation of C-H bonds have been shown to be a
Palladium-catalyzed coupling reactions for the preparation of concatenated azoles
Arkivoc, 2015
The coupling reactions mediated by sp 2-sp 2 transition metals, mostly Pd, allowed the chemoselective preparation of some synthetic compounds and intermediate structures of great complexity. This work describes the methodology used to obtain several derivatives with bisoxazole and thiazole-oxazole units. The required organozinc reagents were prepared from n-BuLi and ZnCl 2 , and the bimetallic derivative of ethyl oxazole-4-carboxylate was obtained by a second transmetalation with CuI.
“On Water” Palladium Catalyzed Direct Arylation of 1H-Indazole and 1H-7-Azaindazole
Molecules, 2020
The C3 direct arylation of 1H-indazole and 1H-7-azaindazole has been a significant challenge due to the lack of the reactivity at this position. In this paper, we describe a mild and an efficient synthesis of new series of C3-aryled 1H-indazoles and C3-aryled 1H-7-azaindazoles via a C3 direct arylation using water as solvent. On water, PPh3 was effective as a ligand along with a lower charge of the catalyst Pd(OAc)2 (5 mol%) at 100 °C, leading to C3-aryled 1H-indazoles or C3-aryled 1H-7-azaindazoles in moderate to good yields.