Ruthenium(II)-Catalyzed sp<sup>3</sup> C–H Bond Arylation of Benzylic Amines Using Aryl Halides

Dastbaravardeh, Navid; Schnürch, Michael; Mihovilovic, Marko D.

doi:10.1021/ol301680v

Cited by 46 publications

(27 citation statements)

References 32 publications

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“…Also, when the reaction mixtures were analyzed, no imine was detected in any case (GC-MS analysis) from either the substrate or the product. This is in contrast to our previously reported Ru(II)-catalyzed arylation protocol, 12 where we detected the arylated imine in most cases. Additionally, the reaction also proceeds in H 2 atmosphere, where imine formation is certainly disfavored.…”

Section: Resultscontrasting

confidence: 99%

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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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Section: Resultscontrasting

confidence: 99%

“…In subsequent work we could develop a method for the reaction with aryl halides as well by using a Ru(II) catalyst with the same directing group. 12 …”

Section: Resultsmentioning

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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“…N ‐(Diphenylmethylene)‐3‐methylpyridin‐2‐amine (4): 7 The reaction was carried out according to general procedure III with N ‐benzylidene‐3‐methylpyridin‐2‐amine ( 12 , 98 mg, 0.5 mmol, 1 equiv. ), 1‐bromobenzene (118 mg, 0.75 mmol, 1.5 equiv.…”

Section: Methodsmentioning

confidence: 99%

“…However, this protocol was limited to boronic acid esters, and other aryl sources, most importantly aryl halides, were not tolerated. Hence, we were interested in the investigation of alternative methods suitable for aryl halides, and we developed a Ru II ‐catalyzed method that enabled the use of aryl bromides and aryl iodides as arylation reagents 7. Aryl chlorides were not suitable for this kind of transformation.…”

Section: Introductionmentioning

confidence: 99%

Aryl Bromides and Aryl Chlorides for the Direct Arylation of Benzylic Amines Mediated by Ruthenium(II)

2013

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The ruthenium(II)-catalyzed sp3 C–H bond arylation of benzylic amines with aryl halides is reported. In the present method, aryl iodides and, more importantly, also the cheaper aryl bromides and aryl chlorides can be applied as aryl sources. Additionally, the method does not require elaborate manipulations in a glove box and can be carried out in simple screw cap vials. Potassium pivalate proved to be beneficial for the transformation with aryl bromides or iodides as aryl source, but was not required for aryl chlorides. In the latter case, the addition of PPh3 led to high conversion. 3-Methyl and 3-phenyl pyridine were established as directing groups, and the substituent in the 3-position represents a key structural feature for high conversion. The directing group can be cleaved after the transformation, which allows access to diarylmethylamines. Mechanistic studies were carried out and critically compared to mechanistic reports of related transformations.

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“…Ruthenium (II) catalyzed arylation of acyclic amines using aryl bromides and aryl iodides. 70,71 To use neutral conditions for a direct arylation is certainly very attractive. However, one little flaw of that protocol is that boronic acid esters are used as aryl source.…”

Section: Scheme 20mentioning

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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Ruthenium(II)-Catalyzed sp³ C–H Bond Arylation of Benzylic Amines Using Aryl Halides

Cited by 46 publications

References 32 publications

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

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

Aryl Bromides and Aryl Chlorides for the Direct Arylation of Benzylic Amines Mediated by Ruthenium(II)

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

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Ruthenium(II)-Catalyzed sp3 C–H Bond Arylation of Benzylic Amines Using Aryl Halides

Cited by 46 publications

References 32 publications

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

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

Aryl Bromides and Aryl Chlorides for the Direct Arylation of Benzylic Amines Mediated by Ruthenium(II)

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

Contact Info

Product

Resources

About

Ruthenium(II)-Catalyzed sp³ C–H Bond Arylation of Benzylic Amines Using Aryl Halides

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

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