Few unexpected results from a Suzuki–Miyaura reaction

Salanouve, Elise; Retailleau, Pascal; Janin, Yves L.

doi:10.1016/j.tet.2012.01.019

Cited by 12 publications

(12 citation statements)

References 37 publications

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“…In a model reaction employing 3b and 2 equivalents of PhZnBr, a mixture of 7b (48%), the desired coupling product 6b (27%) and dehalogenation product 2b (25%) was isolated. Such homocoupling and dehalogenation processes have been also observed in the course of related Pd-catalyzed cross-coupling reactions, such as, for instance, in Suzuki–Miyaura reactions [ 38 ]. In contrast, the corresponding 2-pyridinyl or 2-thienyl organozinc congeners gave much better results with nearly no homocoupling side reactions and only few amounts of dehalogenation products observed.…”

Section: Resultsmentioning

confidence: 93%

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

Jansa¹,

Schmidt²,

Mamuye³

et al. 2017

Beilstein J. Org. Chem.

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A synthesis of tetrasubstituted pyrazoles containing two, three or four pyridinyl substituents is described. Hence, the reaction of 1,3-dipyridinyl-1,3-propanediones with 2-hydrazinopyridine or phenylhydrazine, respectively, affords the corresponding 1,3,5-trisubstituted pyrazoles. Iodination at the 4-position of the pyrazole nucleus by treatment with I2/HIO3 gives the appropriate 4-iodopyrazoles which served as starting materials for different cross-coupling reactions. Finally, Negishi cross-coupling employing organozinc halides and Pd catalysts turned out to be the method of choice to obtain the desired tetrasubstituted pyrazoles. The formation of different unexpected reaction products is described. Detailed NMR spectroscopic investigations (1H, 13C, 15N) were undertaken with all products prepared. Moreover, the structure of a condensation product was confirmed by crystal structure analysis.

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Section: Resultsmentioning

confidence: 93%

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

Jansa¹,

Schmidt²,

Mamuye³

et al. 2017

Beilstein J. Org. Chem.

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“…In the course of our work on the design of chemical libraries with a potential against infectious disease, we were led to synthesize 3‐pyrazolecarboxylic acid derivatives preferably lacking a substituent on carbon 5. From the available synthetic methods reported , three different approaches were used.…”

Section: Methodsmentioning

confidence: 99%

Preparations of 4-Substituted 3-Carboxypyrazoles

Janin

2013

J. Heterocyclic Chem.

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in Wiley Online Library (wileyonlinelibrary.com).The scopes of three synthetic methods reported for the preparation of an array of 3-pyrazolecarboxylates featuring substituents on position 4 were investigated. The first one is based on the potassium permanganate oxidation of methylpyrazoles. The second starts with the condensation between DMF dimethylacetal and ethyl pyruvate and is followed by the addition of hydrazine hydrochloride. The last one makes use of the cycloaddition of diazomethane on acrylate esters followed by a bromine-based oxidative rearrangement into 4-substituted 3-pyrazole esters.In the course of our work [1-7] on the design of chemical libraries with a potential against infectious disease, we were led to synthesize 3-pyrazolecarboxylic acid derivatives preferably lacking a substituent on carbon 5. From the available synthetic methods reported [8-10], three different approaches were used. The controlled oxidation of 3-methylpyrazoles derivatives 1a-e into acids 2a-e using potassium permanganate was first investigated [11-15] (Scheme 1). It appeared that this method is limited by some decarboxylation taking place in refluxing water. Moreover, the lack of solubility of potential reaction substrates, at RT, often prevented less stringent methyl oxidation. Further purification by recrystallization of the rather water-soluble acids was often found necessary and thus led to pure compounds 2a-e in yields no higher than 16%.We then investigated the recently reported preparation of ethyl-3-pyrazolecarboxylate from ethylpyruvate [16]. From the reaction between DMF dimethylacetal and the two pyruvate derivatives 3a-b, followed by addition of hydrazine hydrochloride on the resulting Mannich bases 4a-b, we could extend this original method and prepare esters 5a-b (Scheme 2). The quite low yields obtained are due to the occurrence of many unidentified side compounds. From the benzyl-bearing substrate 3a, we could isolate in 18% yield and fully characterize the furan derivative 6. This side compound, which results from a dimerization of compound 3a under the reaction conditions, illustrates the difficulties we encountered with this synthetic method. A related preparation of such furan derivative has actually been reported [17]. From esters 5a-b, an acidic hydrolysis led to sizable amount (75%) of the target acids 7c but much smaller (5%) amount of the diacid 7d.Far more pyrazole derivatives were made by the welldescribed cycloaddition of diazomethane on a,b-unsaturated esters [18][19][20]. From the acrylates 8a-k, this cycloaddition led to the intermediates 9a-k. No attempts were made to isolate these compounds, and the following oxidative rearrangement into 4-substituted 3-pyrazole esters 10a-k was achieved with bromine. As described in the experimental part, the commercially unavailable a,b-unsaturated esters were prepared by acid-catalyzed esterification of the available acids or by using the greatly optimized condensation of malonic acid monoethylester on aldehydes [21]. To minimize the handling of the c...

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“…This is likely because the main focus of Pd-catalyzed coupling reactions is to form bonds between two different coupling partners, enabling highly productive homocoupling reactions. A handful of papers [ 22 , 23 ] have used the tactical placement of heteroatoms for the coordination of metals in the activation of specific C–H bonds. Other papers [ 24 , 25 ] utilize the possibility of the oxidative addition of Pd into a carbon halogen bond to form di-azole Pd complexes, which can undergo reductive elimination to form desired intermolecular homocoupled products.…”

Section: Recent Advancement Of Bipyrazole Synthesesmentioning

confidence: 99%

“…In 2012, the unexpected discovery of the intermolecular homocoupling between two pyrazoles was made by Salanouve et al ( Scheme 5 ) [ 22 ]. In an effort to study the reaction products obtained under different Suzuki–Miyaura conditions, this group discovered the formation of a C3–C3 intermolecular homocoupled product, resulting from C–H activation.…”

Section: Recent Advancement Of Bipyrazole Synthesesmentioning

confidence: 99%

Homocoupling Reactions of Azoles and Their Applications in Coordination Chemistry

2020

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Pyrazole, a member of the structural class of azoles, exhibits molecular properties of interest in pharmaceuticals and materials chemistry, owing to the two adjacent nitrogen atoms in the five-membered ring system. The weakly basic nitrogen atoms of deprotonated pyrazoles have been applied in coordination chemistry, particularly to access coordination polymers and metal-organic frameworks, and homocoupling reactions can in principle provide facile access to bipyrazole ligands. In this context, we summarize recent advances in homocoupling reactions of pyrazoles and other types of azoles (imidazoles, triazoles and tetrazoles) to highlight the utility of homocoupling reactions in synthesizing symmetric bi-heteroaryl systems compared with traditional synthesis. Metal-free reactions and transition-metal catalyzed homocoupling reactions are discussed with reaction mechanisms in detail.

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Few unexpected results from a Suzuki–Miyaura reaction

Cited by 12 publications

References 37 publications

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

Preparations of 4-Substituted 3-Carboxypyrazoles

Homocoupling Reactions of Azoles and Their Applications in Coordination Chemistry

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