C‐2 Arylation of Piperidines through Directed Transition‐Metal‐Catalyzed sp<sup>3</sup> CH Activation

Prokopcová, Hana; Bergman, Sheba D.; Aelvoet, Karel; Smout, Veerle; Herrebout, Wouter A.; Veken, B. Van der; Meerpoel, Lieven; Maes, Bert U. W.

doi:10.1002/chem.201001887

Cited by 108 publications

(79 citation statements)

References 38 publications

(31 reference statements)

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“…25 Pd-catalyzed hydrogenation and subsequent treatment with NH 2 NH 2 and HCl furnished 2-aminobiphenyl 14 in good yield (78 %). This demonstrated that pyridine could be considered as the removable directing group and 2-aminobiphenyls were formed from this reaction sequence.…”

Section: Resultsmentioning

confidence: 99%

Palladium(II)‐Catalyzed Regioselective Ortho Arylation of sp² CH Bonds of N‐Aryl‐2‐amino Pyridine Derivatives

et al. 2012

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The direct arylation of N-(2-pyridyl) substituted anilines is described. Arylation takes place in ortho position to the amine functionality and is directed by the pyridine N-substituent. Remarkably, N-arylation was never observed as a competing process even though conditions also suitable for Buchwald–Hartwig reactions were applied. The scope of the reaction was investigated in terms of aryl donors as well as the electronic nature of the substrate. Good yields were obtained for most examples through an operationally simple procedure, which did not require inert conditions or even glove box techniques. Pd(OAc)2 was applied as a cheap catalyst and boronic acids as readily available aryl donors. To obtain full conversion, 1,4-benzoquinone and a silver salt (e.g., Ag2O) were required as additives and reacted at relatively mild temperatures (e.g., 80 °C). Additionally, the pyridine-directing group was cleaved after the reaction to give ortho-arylated aniline derivatives.

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Section: Resultsmentioning

confidence: 99%

Palladium(II)‐Catalyzed Regioselective Ortho Arylation of sp² CH Bonds of N‐Aryl‐2‐amino Pyridine Derivatives

et al. 2012

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“…37 They observed the same problems with competing bisarylation as the group of Sames did on the pyrrolidine system. We wanted to address this shortcoming and hypothesized that a suitable directing group would allow for a selective mono-arylation.…”

Section: Scheme 12mentioning

confidence: 62%

“…37 Initial reduction of the pyridine followed by hydrolysis led to 2-phenyl aniline 14 in 78% yield (Scheme 5).…”

Section: Methodsmentioning

confidence: 99%

Exploiting the C-H bond in metal catalyzed C-C bond forming reactions

Schnürch¹

2015

Arkivoc

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This account summarizes our work in the field of direct C-H bond functionalization. We have explored methods in the area of directing group assisted C(sp 2 )-H and C(sp 3 )-H activation and investigated arylation as well as deuteration reactions. In these transformations either ruthenium or palladium catalysts were applied. In case of C(sp 2 )-H activation, we developed a protocol for the synthesis of ortho arylated anilines and disclosed the first method for a direct arylation in a continuous flow reactor. Additionally, we applied a direct arylation in the synthesis of compounds which can accelerate cell differentiation. In the field of C(sp 3 )-H activation we developed a protocol for the selective mono-arylation of piperidine and three different arylation protocols for acyclic amines employing either aryl chlorides, aryl bromides, aryl iodides, or arylboronic acid esters as the aryl donor.

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“…Sames and co-workers 8 argued that the ketone was important to form an intermediate metal–alkoxy complex that can then undergo transmetalation. Maes and co-workers, 9 on the other hand, reported that an alcohol as solvent is important to trap a formed alkyl–borate species upon concomitant formation of hydrogen. Hence, we investigated the effect of different solvents and atmospheres to check if one of these two mechanisms is operable in our case.…”

Section: Resultsmentioning

confidence: 99%

“…6 A few years later, Kakiuchi et al 7 demonstrated in their pioneering work the arylation of aromatic ketones with arylboronates. Afterward, Sames and co-workers 8 published the arylation of pyrrolidines and piperidine directed by a cyclic imine (Figure 1A), followed by the discovery of Maes and co-workers 9 , where they showed a pyridine-directed arylation of piperidine derivatives (Figure 1B). However, the last two methods were limited to cyclic amines.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic Investigations and Substrate Scope Evaluation of Ruthenium-Catalyzed Direct sp³ Arylation of Benzylic Positions Directed by 3-Substituted Pyridines

et al. 2013

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A highly efficient direct arylation process of benzylic amines with arylboronates was developed that employs Ru catalysis. The arylation takes place with greatest efficiency at the benzylic sp3 carbon. If the distance to the activating aryl ring is increased, arylation is still possible but the yield drops significantly. Efficiency of the CH activation was found to be significantly increased by use of 3-substituted pyridines as directing groups, which can be removed after the transformation in high yield. Calculation of the energy profile of different rotamers of the substrate revealed that presence of a substituent in the 3-position favors a conformation with the CH2 group adopting a position in closer proximity to the directing group and facilitating C–H insertion. This operationally simple reaction can be carried out in argon atmosphere as well as in air and under neutral reaction conditions, displaying a remarkable functional group tolerance. Mechanistic studies were carried out and critically compared to mechanistic reports of related transformations.

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C‐2 Arylation of Piperidines through Directed Transition‐Metal‐Catalyzed sp³ CH Activation

Cited by 108 publications

References 38 publications

Palladium(II)‐Catalyzed Regioselective Ortho Arylation of sp² CH Bonds of N‐Aryl‐2‐amino Pyridine Derivatives

Palladium(II)‐Catalyzed Regioselective Ortho Arylation of sp² CH Bonds of N‐Aryl‐2‐amino Pyridine Derivatives

Exploiting the C-H bond in metal catalyzed C-C bond forming reactions

Mechanistic Investigations and Substrate Scope Evaluation of Ruthenium-Catalyzed Direct sp³ Arylation of Benzylic Positions Directed by 3-Substituted Pyridines

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C‐2 Arylation of Piperidines through Directed Transition‐Metal‐Catalyzed sp3 CH Activation

Cited by 108 publications

References 38 publications

Palladium(II)‐Catalyzed Regioselective Ortho Arylation of sp2 CH Bonds of N‐Aryl‐2‐amino Pyridine Derivatives

Palladium(II)‐Catalyzed Regioselective Ortho Arylation of sp2 CH Bonds of N‐Aryl‐2‐amino Pyridine Derivatives

Exploiting the C-H bond in metal catalyzed C-C bond forming reactions

Mechanistic Investigations and Substrate Scope Evaluation of Ruthenium-Catalyzed Direct sp3 Arylation of Benzylic Positions Directed by 3-Substituted Pyridines

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C‐2 Arylation of Piperidines through Directed Transition‐Metal‐Catalyzed sp³ CH Activation

Palladium(II)‐Catalyzed Regioselective Ortho Arylation of sp² CH Bonds of N‐Aryl‐2‐amino Pyridine Derivatives

Palladium(II)‐Catalyzed Regioselective Ortho Arylation of sp² CH Bonds of N‐Aryl‐2‐amino Pyridine Derivatives

Mechanistic Investigations and Substrate Scope Evaluation of Ruthenium-Catalyzed Direct sp³ Arylation of Benzylic Positions Directed by 3-Substituted Pyridines