This article investigates a copper-catalyzed alkynyl disulfuration reaction of aryne formed in situ to synthesize o‑alkynyl aryl disulfides. The transformation proceeds through the in situ generation of aryne, followed by alkynylation under copper catalysis and disulfuration with disulfide reagent, which results in the formation of one C-C bond and one C-SS bond in one-pot under mild conditions. The reaction above can be readily employed to facilitate the introduction of a disulfide group and aryl alkynes into an aryne, and thus provide a modular approach to unsymmetrical disulfides.
{"title":"Copper-catalyzed alkynyldisulfuration of arynes: an efficient access to unsymmetrical disulfides","authors":"Shuai Huang, Yumin Zhang, Yuekai Li, Chen-Ho Tung, Xin Li, Zhenghu Xu","doi":"10.1039/d4qo01844c","DOIUrl":"https://doi.org/10.1039/d4qo01844c","url":null,"abstract":"This article investigates a copper-catalyzed alkynyl disulfuration reaction of aryne formed in situ to synthesize o‑alkynyl aryl disulfides. The transformation proceeds through the in situ generation of aryne, followed by alkynylation under copper catalysis and disulfuration with disulfide reagent, which results in the formation of one C-C bond and one C-SS bond in one-pot under mild conditions. The reaction above can be readily employed to facilitate the introduction of a disulfide group and aryl alkynes into an aryne, and thus provide a modular approach to unsymmetrical disulfides.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"16 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The mechanism of the selenium-catalyzed allylic amination reactions with different ligands has been explored with density functional theory calculations. The mechanism consists of the generation of the key active catalyst selenium bis(imide), ene reaction, [2,3]-sigmatropic shift, and ligand-assisted hydrogen transfer. The ene reaction step plays a critical role in determining the regioselectivity of the reaction. Under two different catalytic conditions (Cy3PSe and IMeSe), OPCy3 and OIMe were identified as the most optimal ligands. The computational results indicate that the ene reaction does not occur through a simultaneous ligand dissociation process, but rather proceeds in a stepwise manner where the ligand dissociates before engaging in the ene reaction with the substrate. Furthermore, the regioselectivity mainly originates from the orbital interaction for acyclic trisubstituted alkenes and the distortion energy for cyclic trisubstituted alkenes.
{"title":"Mechanism and Origins of Regioselectivity of Selenium-Catalyzed Allylic Amination Reactions","authors":"Xiaoxiao Hu, Dengmengfei Xiao, Yu Chen, Yi Lu, Zhi-Han Zhang, Peiyuan Yu","doi":"10.1039/d4qo01794c","DOIUrl":"https://doi.org/10.1039/d4qo01794c","url":null,"abstract":"The mechanism of the selenium-catalyzed allylic amination reactions with different ligands has been explored with density functional theory calculations. The mechanism consists of the generation of the key active catalyst selenium bis(imide), ene reaction, [2,3]-sigmatropic shift, and ligand-assisted hydrogen transfer. The ene reaction step plays a critical role in determining the regioselectivity of the reaction. Under two different catalytic conditions (Cy<small><sub>3</sub></small>PSe and IMeSe), OPCy<small><sub>3</sub></small> and OIMe were identified as the most optimal ligands. The computational results indicate that the ene reaction does not occur through a simultaneous ligand dissociation process, but rather proceeds in a stepwise manner where the ligand dissociates before engaging in the ene reaction with the substrate. Furthermore, the regioselectivity mainly originates from the orbital interaction for acyclic trisubstituted alkenes and the distortion energy for cyclic trisubstituted alkenes.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"4 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N-centered radicals mediated remote C(sp3)–H functionalization via HAT processes have been successfully applied in the difunctionalization of alkenes, serving as an elegant and robust method to convert readily available alkenes into various functionalized molecules. However, HAT strategy-enabled difunctionalization of alkenes using electrophiles as functionalizing reagents remains underexplored. In this study, we report a nickel-catalyzed regioselective reductive three-component 1,2-alkylarylation of alkenes with O-oxalate hydroxamic acid esters and aryl iodides. This radical addition/cross-coupling cascade reaction involves amidyl radical-triggered intramolecular 1,5-HAT and nickel-catalyzed reductive coupling processes under mild reaction conditions with good coupling efficiency. Additionally, this approach can be extended to the reductive 1,2-alkylarylation of alkynes, providing an efficient method for the synthesis of multi-substituted alkenes from easily accessible starting materials.
以 N 为中心的自由基通过 HAT 过程介导的远程 C(sp3)-H 功能化已成功地应用于烯的二官能化，是一种将容易获得的烯转化为各种功能化分子的优雅而稳健的方法。然而，使用亲电体作为官能化试剂，通过 HAT 策略实现烯烃的双官能化仍未得到充分探索。在本研究中，我们报告了一种在镍催化下，烯烃与 O-草酸羟肟酸酯和芳基碘化物发生的具有区域选择性的还原性三组分 1,2-烷基芳基化反应。这种自由基加成/交叉偶联级联反应涉及酰胺基引发的分子内 1,5-HAT 和镍催化的还原偶联过程，反应条件温和，偶联效率高。此外，这种方法还可扩展到炔烃的 1,2-烷基芳基化还原反应，为从容易获得的起始材料合成多取代烯烃提供了一种有效的方法。
{"title":"Nickel-Catalyzed Reductive 1,2-Alkylarylation of Alkenes via a 1,5-Hydrogen Atom Transfer (HAT) Cascade","authors":"Xi Chen, Qiang Wang, Xiao-Ping Gong, Rui-Qiang Jiao, Xue-Yuan Liu, Yong-Min Liang","doi":"10.1039/d4qo01875c","DOIUrl":"https://doi.org/10.1039/d4qo01875c","url":null,"abstract":"N-centered radicals mediated remote C(sp3)–H functionalization via HAT processes have been successfully applied in the difunctionalization of alkenes, serving as an elegant and robust method to convert readily available alkenes into various functionalized molecules. However, HAT strategy-enabled difunctionalization of alkenes using electrophiles as functionalizing reagents remains underexplored. In this study, we report a nickel-catalyzed regioselective reductive three-component 1,2-alkylarylation of alkenes with O-oxalate hydroxamic acid esters and aryl iodides. This radical addition/cross-coupling cascade reaction involves amidyl radical-triggered intramolecular 1,5-HAT and nickel-catalyzed reductive coupling processes under mild reaction conditions with good coupling efficiency. Additionally, this approach can be extended to the reductive 1,2-alkylarylation of alkynes, providing an efficient method for the synthesis of multi-substituted alkenes from easily accessible starting materials.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"65 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yue Wei, Guishun Bai, Jiamin Wu, Yi Hua, Tao Zhang, Congyong Yue, Hong Wang, Xiaoze Bao
The enantioselective reactivity of 3-hydroxyquinolin-2(1H)-ones was developed through their addition to isatin and pyrazole-4,5-dione derived ketimines, affording novel architectures featuring multiple natural products scaffolds in high yield with excellent enantioselectivities. Gram-scale synthesis and synthetic transformations further disclosed the potential of current process.
{"title":"Enantioselective Addition of 3-hydroxyquinolin-2(1H)-one to Isatin and Pyrazole-4,5-dione Derived Ketimines","authors":"Yue Wei, Guishun Bai, Jiamin Wu, Yi Hua, Tao Zhang, Congyong Yue, Hong Wang, Xiaoze Bao","doi":"10.1039/d4qo01895h","DOIUrl":"https://doi.org/10.1039/d4qo01895h","url":null,"abstract":"The enantioselective reactivity of 3-hydroxyquinolin-2(1H)-ones was developed through their addition to isatin and pyrazole-4,5-dione derived ketimines, affording novel architectures featuring multiple natural products scaffolds in high yield with excellent enantioselectivities. Gram-scale synthesis and synthetic transformations further disclosed the potential of current process.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"4 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
An efficient asymmetric cascade allylation/lactonization of methyl salicylates has been achieved. The utilization of chiral-bridged biphenyl phosphoramidite ligand L3 resulted in good yields (up to 85%) and enantioselectivity (up to 95% ee) for the construction of a wide range of chiral benzodioxepinones with tolerance to diverse substituents. This reaction is featured by low catalyst loading, commercially available substrates and a broad substrate scope. Control experiments indicate that a relay catalytic pathway and kinetic resolution of racemic VEC might occur. In this transformation, the chiral-bridged phosphoramidite ligand L3 shows some advantages in enantioselective control compared to its BINOL-derived counterpart.
{"title":"Iridium-catalyzed asymmetric cascade allylation/lactonization of methyl salicylates: enantioselective construction of chiral benzodioxepinones","authors":"Bendu Pan, Yunru Wu, Yaqi Zhang, Xiaobo He, Long Jiang, Liqin Qiu","doi":"10.1039/d4qo01771d","DOIUrl":"https://doi.org/10.1039/d4qo01771d","url":null,"abstract":"An efficient asymmetric cascade allylation/lactonization of methyl salicylates has been achieved. The utilization of chiral-bridged biphenyl phosphoramidite ligand L3 resulted in good yields (up to 85%) and enantioselectivity (up to 95% ee) for the construction of a wide range of chiral benzodioxepinones with tolerance to diverse substituents. This reaction is featured by low catalyst loading, commercially available substrates and a broad substrate scope. Control experiments indicate that a relay catalytic pathway and kinetic resolution of racemic VEC might occur. In this transformation, the chiral-bridged phosphoramidite ligand L3 shows some advantages in enantioselective control compared to its BINOL-derived counterpart.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"87 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tobias B. Tischer, Zulema Fernandez, Lorenz Borsdorf, Constantin Daniliuc, Shigehiro Yamaguchi, Soichiro Ogi, Gustavo Fernandez
Supramolecular polymers are often investigated for highly symmetric and planar molecules, such as typically explored BF2-substituted BODIPY dyes . However, it is surprising that the possibility of desymmetrizing the sp3 hybridized boron centre of BODIPY dyes has remained unexplored in the context of supramolecular polymerization. Herein, we synthesized a new BODIPY derivative 2 with two different substituents at the boron (fluorine and phenyl), resulting in a system with two different π-surfaces, and analyzed its supramolecular polymerization in non-polar media. Notably, this symmetry reduction increases the complexity of the self-assembly by enabling the formation of an intermediate assembled state, which can not be found in the symmetrical model BODIPY 1 with a BF2 group. Different experimental and theoretical studies suggest that significant steric effects together with multiple potential intermolecular stacking modes of the BODIPY dyes lead to discrete nanoparticle intermediates that ultimately transform into more-ordered H-type supramolecular polymers at lower temperatures. Our results introduce a new design strategy for controlled supramolecular polymerization.
{"title":"Impact of boron desymmetrization on supramolecular polymerization of BODIPY dyes","authors":"Tobias B. Tischer, Zulema Fernandez, Lorenz Borsdorf, Constantin Daniliuc, Shigehiro Yamaguchi, Soichiro Ogi, Gustavo Fernandez","doi":"10.1039/d4qo01848f","DOIUrl":"https://doi.org/10.1039/d4qo01848f","url":null,"abstract":"Supramolecular polymers are often investigated for highly symmetric and planar molecules, such as typically explored BF2<small><sub></sub></small>-substituted BODIPY dyes . However, it is surprising that the possibility of desymmetrizing the sp3<small><sup></sup></small> hybridized boron centre of BODIPY dyes has remained unexplored in the context of supramolecular polymerization. Herein, we synthesized a new BODIPY derivative 2 with two different substituents at the boron (fluorine and phenyl), resulting in a system with two different π-surfaces, and analyzed its supramolecular polymerization in non-polar media. Notably, this symmetry reduction increases the complexity of the self-assembly by enabling the formation of an intermediate assembled state, which can not be found in the symmetrical model BODIPY 1 with a BF2<small><sub></sub></small> group. Different experimental and theoretical studies suggest that significant steric effects together with multiple potential intermolecular stacking modes of the BODIPY dyes lead to discrete nanoparticle intermediates that ultimately transform into more-ordered H-type supramolecular polymers at lower temperatures. Our results introduce a new design strategy for controlled supramolecular polymerization.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"27 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A totally controlled regiodivergent azidation of activated N-allenamides is presented. Using TMSN3/TBAF, β-azidation of N-allenamides occurs exclusively, yielding vinyl azides. Conversely, employing a TFA/TMSN3 mixture results solely in the formation of γ-azides. A subsequent formal Winstein rearrangement of the latter with DBU produces α-amido vinyl azides. Additionally, δ-difluorinated azides featuring an ynamide are selectively synthesized from ene-ynamides. The practical applicability of these transformations is demonstrated through the formation of cyanide derivatives, trifluoromethyl ketones and primary enamines.
{"title":"Regio-and Stereoselective Azidation of Activated N-allenamides: an entry to , , and -amido-azides.","authors":"Dorian Schutz, Maxime Hourtoule, Laurence Miesch","doi":"10.1039/d4qo01802h","DOIUrl":"https://doi.org/10.1039/d4qo01802h","url":null,"abstract":"A totally controlled regiodivergent azidation of activated N-allenamides is presented. Using TMSN3/TBAF, β-azidation of N-allenamides occurs exclusively, yielding vinyl azides. Conversely, employing a TFA/TMSN3 mixture results solely in the formation of γ-azides. A subsequent formal Winstein rearrangement of the latter with DBU produces α-amido vinyl azides. Additionally, δ-difluorinated azides featuring an ynamide are selectively synthesized from ene-ynamides. The practical applicability of these transformations is demonstrated through the formation of cyanide derivatives, trifluoromethyl ketones and primary enamines.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"195 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Photoclick chemistry represents an integration of photo- and click chemistry, enabling spatiotemporal control, high selectivity, and efficient conjugation. Photo-induced defluorination acyl fluoride exchange (photo-DAFEx), as a novel photoclick reaction, has emerged as a promising tool for the flourishing field of photoaffinity labeling (PAL) for drug discovery and the exploration of protein interactions. Currently, the first-generation photo-DAFEx reaction relies on the photo-defluorination of a monocyclic m-trifluoromethylaniline, and consequently the excitation wavelength (λex.) falls within the UV-B band (311 nm), limiting its widespread applications. Therefore, there is a high demand for the discovery of innovative cores that can expedite visible-light-induced photo-DAFEx reactions and for the exploration of their crosslinking capabilities. Herein, we report that the combination of phenoxazine chromophores with dialkylated amine auxochromes expands the excitation wavelength (λex.) of the photo-DAFEx into the visible region (405 nm), enabling the multifunctional design of photoaffinity probes for in-situ identification of drug-target interactions. By employing the phenoxazine-based photo-DAFEx reagent, we successfully developed potent PAL probes targeting hCA-II and BRD4, which can be activated with controllability using a 405 nm LED, thereby underscoring the potential of photo-DAFEx in advancing our understanding of protein-ligand interactions.
{"title":"Visible-light Responsive Defluorination-Acyl Fluoride Exchange for Photoclick Labeling Based on Phenoxazine Chromophore","authors":"Lijun Deng, Sitong Li, Cefei Zhang, Yuqiao Zhou, Zhishan Su, Changwei Hu, Xiaohu Zhao, Zhipeng Yu","doi":"10.1039/d4qo01870b","DOIUrl":"https://doi.org/10.1039/d4qo01870b","url":null,"abstract":"Photoclick chemistry represents an integration of photo- and click chemistry, enabling spatiotemporal control, high selectivity, and efficient conjugation. Photo-induced defluorination acyl fluoride exchange (photo-DAFEx), as a novel photoclick reaction, has emerged as a promising tool for the flourishing field of photoaffinity labeling (PAL) for drug discovery and the exploration of protein interactions. Currently, the first-generation photo-DAFEx reaction relies on the photo-defluorination of a monocyclic m-trifluoromethylaniline, and consequently the excitation wavelength (λ<small><sub>ex.</sub></small>) falls within the UV-B band (311 nm), limiting its widespread applications. Therefore, there is a high demand for the discovery of innovative cores that can expedite visible-light-induced photo-DAFEx reactions and for the exploration of their crosslinking capabilities. Herein, we report that the combination of phenoxazine chromophores with dialkylated amine auxochromes expands the excitation wavelength (λ<small><sub>ex.</sub></small>) of the photo-DAFEx into the visible region (405 nm), enabling the multifunctional design of photoaffinity probes for <em>in-situ</em> identification of drug-target interactions. By employing the phenoxazine-based photo-DAFEx reagent, we successfully developed potent PAL probes targeting hCA-II and BRD4, which can be activated with controllability using a 405 nm LED, thereby underscoring the potential of photo-DAFEx in advancing our understanding of protein-ligand interactions.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"16 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Imidates have enormous applications in the synthesis of natural products and nitrogen-containing heterocyclic compounds, as well as in drug development. However, there is currently a lack of green and efficient synthesis methods for imidate compounds. We present a novel one-pot synthesis of multifunctional organic fluorescent imidates from quinolinium salt derivatives, nitrosoarenes and alcohols. This method has the advantages of operational simplicity, mild reaction conditions, metal-free catalysis, a wide substrate scope (43 examples) and excellent isolated yields (up to 93%). Meanwhile, quinolinium-imidates exhibit good fluorescence intensity and excellent chemical stability, which makes them suitable for application in living cells, and in particular, imidate 4v can target the endoplasmic reticulum with high selectivity.
{"title":"Facile one-pot synthesis of novel imidates as multifunctional organic fluorescent materials","authors":"Feng-Ting Liu, Shuo Wang, Yong-Shun Chen, Jun-Ying Miao, Bao-Xiang Zhao, Zhao-Min Lin","doi":"10.1039/d4qo01628a","DOIUrl":"https://doi.org/10.1039/d4qo01628a","url":null,"abstract":"Imidates have enormous applications in the synthesis of natural products and nitrogen-containing heterocyclic compounds, as well as in drug development. However, there is currently a lack of green and efficient synthesis methods for imidate compounds. We present a novel one-pot synthesis of multifunctional organic fluorescent imidates from quinolinium salt derivatives, nitrosoarenes and alcohols. This method has the advantages of operational simplicity, mild reaction conditions, metal-free catalysis, a wide substrate scope (43 examples) and excellent isolated yields (up to 93%). Meanwhile, quinolinium-imidates exhibit good fluorescence intensity and excellent chemical stability, which makes them suitable for application in living cells, and in particular, imidate <strong>4v</strong> can target the endoplasmic reticulum with high selectivity.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"5 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cintya Pinilla, Mario García-Zarza, Ana Carmen Albeniz
The use of Pd(OAc)2 and a mixture of the cooperating ligand [2,2′-bipyridin]-6(1H)‐one (bipy-6-OH) and PCy3 in an optimal mol ratio Pd:bipy-6-OH:PCy3 = 1: 0.5:1 leads to a more active system for the non-chelate assisted direct arylation of simple arenes. The system operates at a temperature 30 ˚C lower than that for the Pd/bipy-6-OH system and it is active for aryl chlorides as arylating partners. Mechanistic experiments support the operation of a bimetallic pathway via two connected catalytic cycles: a Pd/PCy3 system responsible for the oxidative addition and reductive elimination steps and a Pd/bipy-6-OH system that enables the C–H activation. Both cycles are connected by a transmetalation step. The phosphine ligand is not directly involved in the C–H activation but, hea compared to the monoligand system, the occurrence of the bimetallic route changes the nature of the key intermediate species in the C–H activation favoring this turnover limiting step and the overall reaction rate.
{"title":"Metal-Ligand Cooperation and Synergistic Palladium Catalysis for the Dual Ligand System [2,2′-bipyridin]-6(1H)‐one/PCy3: Milder conditions for the Undirected C–H Arylation of Arenes","authors":"Cintya Pinilla, Mario García-Zarza, Ana Carmen Albeniz","doi":"10.1039/d4qo01877j","DOIUrl":"https://doi.org/10.1039/d4qo01877j","url":null,"abstract":"The use of Pd(OAc)<small><sub>2</sub></small> and a mixture of the cooperating ligand [2,2′-bipyridin]-6(1H)‐one (bipy-6-OH) and PCy<small><sub>3</sub></small> in an optimal mol ratio Pd:bipy-6-OH:PCy<small><sub>3</sub></small> = 1: 0.5:1 leads to a more active system for the non-chelate assisted direct arylation of simple arenes. The system operates at a temperature 30 ˚C lower than that for the Pd/bipy-6-OH system and it is active for aryl chlorides as arylating partners. Mechanistic experiments support the operation of a bimetallic pathway via two connected catalytic cycles: a Pd/PCy<small><sub>3</sub></small> system responsible for the oxidative addition and reductive elimination steps and a Pd/bipy-6-OH system that enables the C–H activation. Both cycles are connected by a transmetalation step. The phosphine ligand is not directly involved in the C–H activation but, hea compared to the monoligand system, the occurrence of the bimetallic route changes the nature of the key intermediate species in the C–H activation favoring this turnover limiting step and the overall reaction rate.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"35 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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