The photochromic behaviors of spiropyrans that are fused with an aromatic ring adjacent to the spirocarbon have not been well studied. A series of benzofuranone-based spiropyrans containing a thiophene, benzothiophene, selenophene, or indole ring close to the spirocarbon center were synthesized through rhodium(III)-catalyzed annulation of hydroxyl 1,2-diarylethane-1,2-diones with internal alkynes. Their temperature-dependent photochromic properties were observed experimentally and explained by density functional theory (DFT) calculations.
{"title":"Benzofuranone-based spiropyrans: synthesis, temperature-dependent photochromic properties, and DFT calculations","authors":"Xincheng Zhou, Zhichao Chang, Yongchun Hu, Jianming Zhong, Jiaying Liao, Chunying Rong, Wang Zhou","doi":"10.1039/d4qo02123a","DOIUrl":"https://doi.org/10.1039/d4qo02123a","url":null,"abstract":"The photochromic behaviors of spiropyrans that are fused with an aromatic ring adjacent to the spirocarbon have not been well studied. A series of benzofuranone-based spiropyrans containing a thiophene, benzothiophene, selenophene, or indole ring close to the spirocarbon center were synthesized through rhodium(<small>III</small>)-catalyzed annulation of hydroxyl 1,2-diarylethane-1,2-diones with internal alkynes. Their temperature-dependent photochromic properties were observed experimentally and explained by density functional theory (DFT) calculations.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"13 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968530","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}
Dmitry L Lipilin, Mikhail O Zubkov, Mikhail Kosobokov, Alexander Dilman
Since the advent of photocatalysis, the radical addition to alkenes has become one of the most fruitful processes for building up the molecular complexity. Herein we describe a novel approach to photocatalyzed addition to alkenes, in which both new C–O and C–H bonds are formed by an ionic, rather than conventional radical mechanism. This occurs due to two consecutive radical-polar crossover events, providing the generation of both radical cation and carbanion species during the reaction. Such a transformation is demonstrated by the acridine-catalyzed addition of carboxylic acids to styrenes. Unique mechanism allows to carry out the reaction in the absence of additives, and also to reverse the regioselectivity of conventional ionic addition to alkenes.
{"title":"Photocatalyzed anti-Markovnikov addition of carboxylic acids to alkenes: ionic mechanism under radical conditions","authors":"Dmitry L Lipilin, Mikhail O Zubkov, Mikhail Kosobokov, Alexander Dilman","doi":"10.1039/d4qo02280g","DOIUrl":"https://doi.org/10.1039/d4qo02280g","url":null,"abstract":"Since the advent of photocatalysis, the radical addition to alkenes has become one of the most fruitful processes for building up the molecular complexity. Herein we describe a novel approach to photocatalyzed addition to alkenes, in which both new C–O and C–H bonds are formed by an ionic, rather than conventional radical mechanism. This occurs due to two consecutive radical-polar crossover events, providing the generation of both radical cation and carbanion species during the reaction. Such a transformation is demonstrated by the acridine-catalyzed addition of carboxylic acids to styrenes. Unique mechanism allows to carry out the reaction in the absence of additives, and also to reverse the regioselectivity of conventional ionic addition to alkenes.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"93 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142975561","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}
Hypericumonates A–F (1–6), six pairs of new α-pyrone meroterpenoid dimers, along with four possible precursors (7–10) were isolated from the leaves and twigs of Hypericum monogynum. Hypericumonates A–C, the first α-pyrone meroterpenoid dimers with two motifs (a 6/6/4-6/6 ring system) connected via C-8–C-9, were proposed via [2 + 2] cycloaddition of α-pyrone meroterpenoid. Their structures were determined by spectroscopic analysis, quantum chemical calculations, and single-crystal X-ray diffraction analysis. From biosynthesis analysis, five pairs of new α-pyrone meroterpenoid dimers (1–5) are derived from a new isopentenyl-α-pyrone (7). Compounds 2 is an unusual homodimer, whereas compounds 1 and 3–6 represent rare heterodimers. Inspired by the traditional anti-inflammatory usages of H. monogynum, all dimers except for 6 were discovered to show good NO inhibitory effect with IC50 values of 2.41 ± 0.31 μM to 14.25 ± 1.93 μM, better than the positive control, minocycline (IC50: 19.09 ± 1.34 μM). Further mechanistic study implied that (+)-1 could prohibit the expression of iNOS and COX-2 in BV-2 cells, and the molecular docking study implied the possible interaction between (+)-1/(−)-1 and these two proteins.
{"title":"Six pairs of α-pyrone meroterpenoid dimers from Hypericum monogynum with anti-neuroinflammatory activity","authors":"Jun Jin, Yan-Ling Li, Li-Hua Chen, Feng Zhang, Xin-Yu Zuo, Yan-Rong Zeng, Jue Yang, Xiao-Jiang Hao, Chun-Mao Yuan","doi":"10.1039/d4qo02179g","DOIUrl":"https://doi.org/10.1039/d4qo02179g","url":null,"abstract":"Hypericumonates A–F (<strong>1–6</strong>), six pairs of new α-pyrone meroterpenoid dimers, along with four possible precursors (<strong>7–10</strong>) were isolated from the leaves and twigs of <em>Hypericum monogynum</em>. Hypericumonates A–C, the first α-pyrone meroterpenoid dimers with two motifs (a 6/6/4-6/6 ring system) connected <em>via</em> C-8–C-9, were proposed <em>via</em> [2 + 2] cycloaddition of α-pyrone meroterpenoid. Their structures were determined by spectroscopic analysis, quantum chemical calculations, and single-crystal X-ray diffraction analysis. From biosynthesis analysis, five pairs of new α-pyrone meroterpenoid dimers (<strong>1–5</strong>) are derived from a new isopentenyl-α-pyrone (<strong>7</strong>). Compounds <strong>2</strong> is an unusual homodimer, whereas compounds <strong>1</strong> and <strong>3–6</strong> represent rare heterodimers. Inspired by the traditional anti-inflammatory usages of <em>H. monogynum</em>, all dimers except for <strong>6</strong> were discovered to show good NO inhibitory effect with IC<small><sub>50</sub></small> values of 2.41 ± 0.31 μM to 14.25 ± 1.93 μM, better than the positive control, minocycline (IC<small><sub>50</sub></small>: 19.09 ± 1.34 μM). Further mechanistic study implied that (+)-<strong>1</strong> could prohibit the expression of iNOS and COX-2 in BV-2 cells, and the molecular docking study implied the possible interaction between (+)-<strong>1</strong>/(−)-<strong>1</strong> and these two proteins.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"83 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968531","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}
Guodan Lu, Tao Zhang, Xionglve Cheng, Kehan Qian, Yong Wang, Xiaobing Wan
Anion relay chemistry (ARC) is a multi-component union strategy that has emerged as a powerful approach for synthesizing complex structures. However, previous studies have primarily concentrated on thermally controlled reaction modes. In this study, we report the development of an unprecedented visible-light-driven anion relay chemistry (ARC) strategy. Utilizing an energy-transfer process, we successfully transformed tosylhydrazones into anionic donors, facilitating the synthesis of fully substituted pyrazole derivatives under mild conditions. Furthermore, a combination of experimental mechanistic investigations and computational studies (DFT) not only corroborated the proposed mechanism of the reaction but also inspired additional avenues for future research.
{"title":"Visible-light-driven Anion Relay Chemistry (ARC): Construction of Fully Substituted Pyrazoles","authors":"Guodan Lu, Tao Zhang, Xionglve Cheng, Kehan Qian, Yong Wang, Xiaobing Wan","doi":"10.1039/d4qo02072c","DOIUrl":"https://doi.org/10.1039/d4qo02072c","url":null,"abstract":"Anion relay chemistry (ARC) is a multi-component union strategy that has emerged as a powerful approach for synthesizing complex structures. However, previous studies have primarily concentrated on thermally controlled reaction modes. In this study, we report the development of an unprecedented visible-light-driven anion relay chemistry (ARC) strategy. Utilizing an energy-transfer process, we successfully transformed tosylhydrazones into anionic donors, facilitating the synthesis of fully substituted pyrazole derivatives under mild conditions. Furthermore, a combination of experimental mechanistic investigations and computational studies (DFT) not only corroborated the proposed mechanism of the reaction but also inspired additional avenues for future research.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"23 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142975425","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}
Takafumi Yashima, Ryoga Hori, Taisei Maruyama, Kohta Nakashima, Hiroki Fujihara, Masaya Naito, Shinobu Miyagawa, Yuji Tokunaga
We present two methodologies for synthesizing cross–chain bridging cryptand 1 that incorporates tri- and tetra(ethylene glycol) linkers (methods B and C). Method B involves the synthesis through the intramolecular cross-linking of C2-symmetric crown ether 3. While this method does not substantially reduce the lengthy reaction steps compared to the previous approach, it improves the overall yield of cryptand 1a containing three tri(ethylene glycol) linkers and allows for the creation of a new form of a cross–chain bridging cryptand 1c with one distinct and two identical linkers. However, method C entails a synthesis accomplished through a triple-linking reaction in a single step. This method offered a streamlined synthesis of cryptand 1. The crucial triple linking reaction produced cross–chain bridging cryptand 1 as the major isomer and the corresponding linear regioisomer 6 as the minor isomer. Moreover, we observed the interconversion of enantiomers of cryptand 1c, which contains a 28-membered macrocycle, under chiral high-performance liquid chromatographic (HPLC) analytical conditions (with a half-life of 20.7 min at room temperature). Finally, X-ray crystallography confirmed the cross–chain bridging structure in the two chemically equivalent chains in the solid state of cryptand 1a.
{"title":"Synthesis of a cross-chain bridging cryptand","authors":"Takafumi Yashima, Ryoga Hori, Taisei Maruyama, Kohta Nakashima, Hiroki Fujihara, Masaya Naito, Shinobu Miyagawa, Yuji Tokunaga","doi":"10.1039/d4qo02330g","DOIUrl":"https://doi.org/10.1039/d4qo02330g","url":null,"abstract":"We present two methodologies for synthesizing cross–chain bridging cryptand 1 that incorporates tri- and tetra(ethylene glycol) linkers (methods B and C). Method B involves the synthesis through the intramolecular cross-linking of C2-symmetric crown ether 3. While this method does not substantially reduce the lengthy reaction steps compared to the previous approach, it improves the overall yield of cryptand 1a containing three tri(ethylene glycol) linkers and allows for the creation of a new form of a cross–chain bridging cryptand 1c with one distinct and two identical linkers. However, method C entails a synthesis accomplished through a triple-linking reaction in a single step. This method offered a streamlined synthesis of cryptand 1. The crucial triple linking reaction produced cross–chain bridging cryptand 1 as the major isomer and the corresponding linear regioisomer 6 as the minor isomer. Moreover, we observed the interconversion of enantiomers of cryptand 1c, which contains a 28-membered macrocycle, under chiral high-performance liquid chromatographic (HPLC) analytical conditions (with a half-life of 20.7 min at room temperature). Finally, X-ray crystallography confirmed the cross–chain bridging structure in the two chemically equivalent chains in the solid state of cryptand 1a.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"75 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939653","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}
Molecules bearing the difluoroalkyl groups were very important in pharmaceuticals, argrochemicals and materials. In recent years, more and more attentions were paid to develop novel synthetic method for constructing compounds including CF2R groups. In particular, the construction of difluoralkyl stereogenic center is thriving. This review focused on catalytic asymmetric difluoroalkylation to construction of difluoralkyl stereogenic center which summarized the synthetic methods, the active intermediate involved and asymmetric strategies applied. The product diversity, selectivity and proposed mechanism were highlighted and at the same time, the outlook and existing challenges were provided.
{"title":"Progress in Catalytic Enantioselective Construction of Difluoroalkylated Stereogenic Center","authors":"Li-Juan Tang, Yongshun Wen, Hong-Xian Jin, Wenjun Luo, Lipeng Long, Jiayi Shen, Haiqing Luo, Daohong Yu","doi":"10.1039/d4qo02309a","DOIUrl":"https://doi.org/10.1039/d4qo02309a","url":null,"abstract":"Molecules bearing the difluoroalkyl groups were very important in pharmaceuticals, argrochemicals and materials. In recent years, more and more attentions were paid to develop novel synthetic method for constructing compounds including CF2R groups. In particular, the construction of difluoralkyl stereogenic center is thriving. This review focused on catalytic asymmetric difluoroalkylation to construction of difluoralkyl stereogenic center which summarized the synthetic methods, the active intermediate involved and asymmetric strategies applied. The product diversity, selectivity and proposed mechanism were highlighted and at the same time, the outlook and existing challenges were provided.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"118 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961290","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}
Anil Rangnath Pawar, Sabina Yashmin, Abu Taleb Khan
A novel metal-free synthetic method is presented for the 2-arylchromeno[2,3,4,5-lmna]phenanthridines from the one-pot reaction of aryl amine, aromatic aldehyde and cyclic ketone in the presence of 30 mol% (±)-CSA. This protocol efficiently exploits DMSO as a solvent as well as a source of -O- for the installation of regioselective keto functionality in the key reaction intermediate 5-aryl-3,4-dihydrobenzo[a]phenanthridin-1(2H)-one (H) through multicomponent reaction. Due to its rigid structure, H facilitates further domino reactions such as 6πe electrocyclization and aromatization, which have not been studied before. The sophisticated aspect of this approach lies in its ability to create two C=C, one C=N, and two C-O bonds simultaneously in a single step without requiring a base or an activator for the oxygenation process.
{"title":"Synthesis of 2-arylchromeno[2,3,4,5-lmna]phenanthridines through a sequential multicomponent assembly, oxygenation and 6πe electrocyclization reactions","authors":"Anil Rangnath Pawar, Sabina Yashmin, Abu Taleb Khan","doi":"10.1039/d4qo02067g","DOIUrl":"https://doi.org/10.1039/d4qo02067g","url":null,"abstract":"A novel metal-free synthetic method is presented for the 2-arylchromeno[2,3,4,5-lmna]phenanthridines from the one-pot reaction of aryl amine, aromatic aldehyde and cyclic ketone in the presence of 30 mol% (±)-CSA. This protocol efficiently exploits DMSO as a solvent as well as a source of -O- for the installation of regioselective keto functionality in the key reaction intermediate 5-aryl-3,4-dihydrobenzo[a]phenanthridin-1(2H)-one (H) through multicomponent reaction. Due to its rigid structure, H facilitates further domino reactions such as 6πe electrocyclization and aromatization, which have not been studied before. The sophisticated aspect of this approach lies in its ability to create two C=C, one C=N, and two C-O bonds simultaneously in a single step without requiring a base or an activator for the oxygenation process.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"31 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937402","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}
Rapid and sensitive chiroptical sensing is of great significance for practical applications. Here, a novel rapid supramolecular chiroptical sensing strategy was developed to eliminate possible background interferences and enhance the chiroptical signal by non-chiral AIE-active thiol click reaction with chiral substrates. These AIE-thiols irreversibly bind amino acids, polypeptides, amines and amino alcohols based on a click-like reaction, and their sensing products further self-assemble resulting in higher chiroptical signal output. In particular, the AIE thiol generated from octyloxy-functionalized α-cyanostilbene can form supramolecular helix π-π stacking in the aggregated state, which can greatly contribute to the chiroptical sensing of the target substrate. The self-assemblies obtained from different AIE thiol sensing reactions exhibit different CD and CPL behaviors due to their different self-assembly modes, which are caused by the subtle differences in the non-covalent C-H…π, [π···π] and hydrogen bonding interactions of the chiroptical sensing reaction product. Their high reactivity and robust self-assembly sensing mechanism eliminates the interference of chiral substrates and their impurities, improving sensor sensitivity and selectivity. This strategy provides a simple and promising means of detecting chiral molecules, especially those without UV optical activity.
{"title":"Supramolecular Chiroptical Sensing by Achiral AIE-active Thiols","authors":"Xueyan Zhang, Yang Li, Li Wang, Hongcheng Liu","doi":"10.1039/d4qo02412e","DOIUrl":"https://doi.org/10.1039/d4qo02412e","url":null,"abstract":"Rapid and sensitive chiroptical sensing is of great significance for practical applications. Here, a novel rapid supramolecular chiroptical sensing strategy was developed to eliminate possible background interferences and enhance the chiroptical signal by non-chiral AIE-active thiol click reaction with chiral substrates. These AIE-thiols irreversibly bind amino acids, polypeptides, amines and amino alcohols based on a click-like reaction, and their sensing products further self-assemble resulting in higher chiroptical signal output. In particular, the AIE thiol generated from octyloxy-functionalized α-cyanostilbene can form supramolecular helix π-π stacking in the aggregated state, which can greatly contribute to the chiroptical sensing of the target substrate. The self-assemblies obtained from different AIE thiol sensing reactions exhibit different CD and CPL behaviors due to their different self-assembly modes, which are caused by the subtle differences in the non-covalent C-H…π, [π···π] and hydrogen bonding interactions of the chiroptical sensing reaction product. Their high reactivity and robust self-assembly sensing mechanism eliminates the interference of chiral substrates and their impurities, improving sensor sensitivity and selectivity. This strategy provides a simple and promising means of detecting chiral molecules, especially those without UV optical activity.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"19 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937398","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}
Changhee Park, Seyun Gi, Seongkyeong Yoon, Seong Jung Kwon, Sunggi Lee
Amine carboxyborane enabled an efficient halogen atom transfer (XAT) with 1o, 2o, and 3o alkyl bromides, resulting in Giese addition products with various electron-deficient double bonds. Moreover, direct addition of several boryl radicals was also possible using several ligated carboxyboranes.
{"title":"Giese Reaction of Alkyl Bromides using Amine Carboxyboranes","authors":"Changhee Park, Seyun Gi, Seongkyeong Yoon, Seong Jung Kwon, Sunggi Lee","doi":"10.1039/d4qo02325k","DOIUrl":"https://doi.org/10.1039/d4qo02325k","url":null,"abstract":"Amine carboxyborane enabled an efficient halogen atom transfer (XAT) with 1<small><sup>o</sup></small>, 2<small><sup>o</sup></small>, and 3<small><sup>o</sup></small> alkyl bromides, resulting in Giese addition products with various electron-deficient double bonds. Moreover, direct addition of several boryl radicals was also possible using several ligated carboxyboranes.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"39 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937399","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}
Kang Lv, Yihang Zhou, Zitong Meng, Jing Zhang, Tao Liu
Density functional theory (DFT) calculations were performed to study Pd-catalyzed ipso,meta-dimethylation reaction of ortho-substituted iodoarenes. In the presence of K2CO3, aryl−I oxidative addition on Pd(0) catalysts can generate arylpalladium(II) intermediate, which undergoes two sequent processes of C−H activation, CH3−I oxidative addition (Ar−C reductive elimination/CH3−I oxidative addition/Ar−C oxidative addition), and Ar−C reductive elimination to generate dimethylated intermediate. Then hydrogen transfer, C−hydride reductive elimination, and ligand exchange can take place to generate 2,6-dimethylanisole 3b. With KOAc as the base, 2,3-dihydrobenzofuran 4b can be obtained via aryl−I oxidative addition, two sequent processes of C−H activation/Ar−C reductive elimination/CH3−I oxidative addition/Ar−C oxidative addition/Ar−C reductive elimination, the third C−H activation, reductive elimination, and ligand exchange, respectively. The competition between the third C−H activation and the hydrogen transfer from dimethylated intermediate determines the selectivity of the reaction. The hydrogen transfer is generally superior to the third C−H activation due to the stronger reactivity of methyl group in methanol than normal methyl group. When K2CO3 is used, such electronic effect is dominant. However, when KOAc is employed, different structure and properties with K2CO3 cause the ligand exchange step highly endergonic, thereby rendering subsequent hydrogen transfer not favorable and leading to 2,3-dihydrobenzofuran 4b to be the final product.
{"title":"Computational Study on Pd-Catalyzed ipso,meta-Dimethylation of ortho-Substituted Iodoarene: Mechanisms and the Role of Base","authors":"Kang Lv, Yihang Zhou, Zitong Meng, Jing Zhang, Tao Liu","doi":"10.1039/d4qo02168a","DOIUrl":"https://doi.org/10.1039/d4qo02168a","url":null,"abstract":"Density functional theory (DFT) calculations were performed to study Pd-catalyzed ipso,meta-dimethylation reaction of ortho-substituted iodoarenes. In the presence of K2CO3, aryl−I oxidative addition on Pd(0) catalysts can generate arylpalladium(II) intermediate, which undergoes two sequent processes of C−H activation, CH3−I oxidative addition (Ar−C reductive elimination/CH3−I oxidative addition/Ar−C oxidative addition), and Ar−C reductive elimination to generate dimethylated intermediate. Then hydrogen transfer, C−hydride reductive elimination, and ligand exchange can take place to generate 2,6-dimethylanisole 3b. With KOAc as the base, 2,3-dihydrobenzofuran 4b can be obtained via aryl−I oxidative addition, two sequent processes of C−H activation/Ar−C reductive elimination/CH3−I oxidative addition/Ar−C oxidative addition/Ar−C reductive elimination, the third C−H activation, reductive elimination, and ligand exchange, respectively. The competition between the third C−H activation and the hydrogen transfer from dimethylated intermediate determines the selectivity of the reaction. The hydrogen transfer is generally superior to the third C−H activation due to the stronger reactivity of methyl group in methanol than normal methyl group. When K2CO3 is used, such electronic effect is dominant. However, when KOAc is employed, different structure and properties with K2CO3 cause the ligand exchange step highly endergonic, thereby rendering subsequent hydrogen transfer not favorable and leading to 2,3-dihydrobenzofuran 4b to be the final product.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"15 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937397","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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