Metal–ligand cooperation (MLC) reaction revolutionizes the boundaries of homogeneous catalysis by permitting ligand‐centered reactivity beyond traditional metal‐orientated reactivity. Pyridine is key motif in many pharmaceuticals and agrochemical products, but it also shows promise in participating MLC reaction for further derivatization. However, such unique reaction integration into CO bond functionalization remains underexplored, largely due to poorly understood reactivity profiles. In this work, a mechanistic investigation into nickel‐catalyzed CO bond activation of pyridine‐based aryl ethers is reported to elucidate the electronic and structural features of the active species and MLC/metal–ligand role reversal (MLRR) pathway. With detailed mechanistic studies including density functional theory calculation, X‐ray absorption spectroscopy, electron spin resonance, and model catalyst, two distinct catalytic cycles are elucidated: 1) a two‐electron‐based CO arylation at nickel center and 2) a single‐electron‐driven pyridine homocoupling reaction via MLC and MLRR manifolds. These insights subsequently allow establishment of a synthetic methodology for switchable CO bond cleavage and homocoupling in substrate scope studies.
{"title":"Discovery of Switchable Metal‐ and Ligand‐Centered Reactivity via Mechanistic Studies on CO Activation of Pyridines","authors":"Ting‐Hsuan Wang, Jiun‐Shian Shen, Manman Zhu, Bamlaku Semagne Aweke, Sin‐Yu Chen, Yin‐Zhi Weng, Chih‐Wen Pao, Glenn P. A. Yap, Ping‐Yu Chen, Lili Zhao, Tiow‐Gan Ong, Chen‐Hsun Hung","doi":"10.1002/adsc.70184","DOIUrl":"https://doi.org/10.1002/adsc.70184","url":null,"abstract":"Metal–ligand cooperation (MLC) reaction revolutionizes the boundaries of homogeneous catalysis by permitting ligand‐centered reactivity beyond traditional metal‐orientated reactivity. Pyridine is key motif in many pharmaceuticals and agrochemical products, but it also shows promise in participating MLC reaction for further derivatization. However, such unique reaction integration into CO bond functionalization remains underexplored, largely due to poorly understood reactivity profiles. In this work, a mechanistic investigation into nickel‐catalyzed CO bond activation of pyridine‐based aryl ethers is reported to elucidate the electronic and structural features of the active species and MLC/metal–ligand role reversal (MLRR) pathway. With detailed mechanistic studies including density functional theory calculation, X‐ray absorption spectroscopy, electron spin resonance, and model catalyst, two distinct catalytic cycles are elucidated: 1) a two‐electron‐based CO arylation at nickel center and 2) a single‐electron‐driven pyridine homocoupling reaction via MLC and MLRR manifolds. These insights subsequently allow establishment of a synthetic methodology for switchable CO bond cleavage and homocoupling in substrate scope studies.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"1 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhuang Wang , Rongxin Yang , Yuxiu Liu , Hongjian Song , Qingmin Wang
An electro‐oxidative protocol for the alkoxylation‐thiolation of vinyl ethers is developed, employing nonvolatile diaryl disulfides as atom‐economical arylthio sources under oxidant‐free and metal‐free conditions. 4‐(Trifluoromethyl)pyridine is used as a base additive to suppress side reactions and improve the yield. A wide range of substrates with diverse structures and functional groups are compatible with this protocol. Mechanism experiments show that the reaction involves a mechanism in which an arylthio radical is generated at the anode as the key intermediate.
{"title":"Electro‐Oxidative Alkoxylation‐Thiolation of Vinyl Ethers","authors":"Zhuang Wang , Rongxin Yang , Yuxiu Liu , Hongjian Song , Qingmin Wang","doi":"10.1002/adsc.70132","DOIUrl":"10.1002/adsc.70132","url":null,"abstract":"<div><div>An electro‐oxidative protocol for the alkoxylation‐thiolation of vinyl ethers is developed, employing nonvolatile diaryl disulfides as atom‐economical arylthio sources under oxidant‐free and metal‐free conditions. 4‐(Trifluoromethyl)pyridine is used as a base additive to suppress side reactions and improve the yield. A wide range of substrates with diverse structures and functional groups are compatible with this protocol. Mechanism experiments show that the reaction involves a mechanism in which an arylthio radical is generated at the anode as the key intermediate.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"367 22","pages":"Article e70132"},"PeriodicalIF":4.0,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Radical migration, especially 1,2‐radical migration (1,2‐RaM), has emerged as a powerful strategy in reaction discovery and synthetic development, enabling highly selective 1,3‐difunctionalization of alkenes and granting access to previously unexplored functional molecules and chemical space, with broad implications for complex molecule construction and medicinal chemistry. Herein, we report efficient and regioselective catalytic methods that, for the first time, combine 1,2‐radical migration (1,2‐RaM) with ruthenium‐catalyzed remote C–H activation to achieve difunctionalization at the meta ‐position of aromatic C(sp 2 )–H bonds and the C3 position of aliphatic C(sp 3 )–H bonds. This transformation demonstrates broad functional group tolerance and scalability to gram‐scale synthesis, offering a novel approach for the construction of complex molecules.
{"title":"1,3‐Difunctionalization of Allyl Carboxylates Enabled by 1,2‐Radical Migration (RaM) and Ruthenium‐Catalyzed Remote C–H Activation","authors":"Jin‐Ye Li, Yu‐Yong Luan, Xue‐Ya Gou, Zhe Zhang, Wei‐Yu Shi, Jia‐Jun Ma, Xue‐Yuan Liu, Yong‐Min Liang","doi":"10.1002/adsc.70229","DOIUrl":"https://doi.org/10.1002/adsc.70229","url":null,"abstract":"Radical migration, especially 1,2‐radical migration (1,2‐RaM), has emerged as a powerful strategy in reaction discovery and synthetic development, enabling highly selective 1,3‐difunctionalization of alkenes and granting access to previously unexplored functional molecules and chemical space, with broad implications for complex molecule construction and medicinal chemistry. Herein, we report efficient and regioselective catalytic methods that, for the first time, combine 1,2‐radical migration (1,2‐RaM) with ruthenium‐catalyzed remote C–H activation to achieve difunctionalization at the <jats:italic>meta</jats:italic> ‐position of aromatic C(sp <jats:sup>2</jats:sup> )–H bonds and the C3 position of aliphatic C(sp <jats:sup>3</jats:sup> )–H bonds. This transformation demonstrates broad functional group tolerance and scalability to gram‐scale synthesis, offering a novel approach for the construction of complex molecules.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"21 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
An aerobic oxidative dethioacetalization catalyzed by an iron octacarboxyphthalocyanine complex, which is designed by mimicking enzymatic oxidation, in an aqueous media is developed. The developed method can efficiently convert a broad range of dithioacetals, including those derived from aryl and aliphatic ketones and aldehydes, into the corresponding carbonyl compounds while tolerating various functional groups. This protocol is readily scalable to the gram scale. Mechanistic studies indicate that the iron phthalocyanine complex initiates the reaction by accepting a single electron from the sulfur atom of the dithioacetal, forming a radical cation intermediate. This is followed by unimolecular fragmentation and subsequent degradation of the resulting hemithioacetal to afford the corresponding carbonyl product, along with 1,2‐dithiolane and its oxides.
{"title":"Aerobic Oxidative Dethioacetalization Catalyzed by an Iron Phthalocyanine Complex","authors":"Hirofumi Ueda, Ryo Sato, Hayato Machii, Nagao Kobayashi, Hidetoshi Tokuyama","doi":"10.1002/adsc.70154","DOIUrl":"https://doi.org/10.1002/adsc.70154","url":null,"abstract":"An aerobic oxidative dethioacetalization catalyzed by an iron octacarboxyphthalocyanine complex, which is designed by mimicking enzymatic oxidation, in an aqueous media is developed. The developed method can efficiently convert a broad range of dithioacetals, including those derived from aryl and aliphatic ketones and aldehydes, into the corresponding carbonyl compounds while tolerating various functional groups. This protocol is readily scalable to the gram scale. Mechanistic studies indicate that the iron phthalocyanine complex initiates the reaction by accepting a single electron from the sulfur atom of the dithioacetal, forming a radical cation intermediate. This is followed by unimolecular fragmentation and subsequent degradation of the resulting hemithioacetal to afford the corresponding carbonyl product, along with 1,2‐dithiolane and its oxides.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"29 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nadir Rosenblat, Anna Vaisman, Yugang Bai, N. Gabriel Lemcoff
Latent catalysts represent a specialized class of precatalysts that remain dormant under ambient conditions until activated by external stimuli to initiate catalytic activity. This study investigates the initiation behavior of latent olefin metathesis precatalysts, focusing on two different types: sulfur‐chelated systems and phosphite‐ligated ruthenium complexes. The initiation process was first monitored in situ by tracking characteristic proton nuclear magnetic resonance ( 1 H‐NMR) signals in the presence of butyl vinyl ether under two activation modes: heating and light irradiation. The analysis for both activation stimuli enabled the determination of initiation rate constants and revealed details of the distinct mechanistic pathways. Moreover, comparing the initiation kinetics and catalytic performance in ring‐closing metathesis (RCM) and ring‐opening metathesis polymerization (ROMP) established structure–activity relationships. The ligand environment was found to significantly modulate precatalyst reactivity, with sulfur‐chelated complexes mostly showing enhanced thermal activity, while phosphite systems demonstrated superior photochemical responsiveness. These findings provide support for advancing the development of next‐generation latent metathesis catalysts with tailored activation profiles for precision polymer synthesis and spatiotemporal control of polymerization processes.
{"title":"Initiation Kinetics of Latent Olefin Metathesis Precatalysts","authors":"Nadir Rosenblat, Anna Vaisman, Yugang Bai, N. Gabriel Lemcoff","doi":"10.1002/adsc.70251","DOIUrl":"https://doi.org/10.1002/adsc.70251","url":null,"abstract":"Latent catalysts represent a specialized class of precatalysts that remain dormant under ambient conditions until activated by external stimuli to initiate catalytic activity. This study investigates the initiation behavior of latent olefin metathesis precatalysts, focusing on two different types: sulfur‐chelated systems and phosphite‐ligated ruthenium complexes. The initiation process was first monitored in situ by tracking characteristic proton nuclear magnetic resonance ( <jats:sup>1</jats:sup> H‐NMR) signals in the presence of butyl vinyl ether under two activation modes: heating and light irradiation. The analysis for both activation stimuli enabled the determination of initiation rate constants and revealed details of the distinct mechanistic pathways. Moreover, comparing the initiation kinetics and catalytic performance in ring‐closing metathesis (RCM) and ring‐opening metathesis polymerization (ROMP) established structure–activity relationships. The ligand environment was found to significantly modulate precatalyst reactivity, with sulfur‐chelated complexes mostly showing enhanced thermal activity, while phosphite systems demonstrated superior photochemical responsiveness. These findings provide support for advancing the development of next‐generation latent metathesis catalysts with tailored activation profiles for precision polymer synthesis and spatiotemporal control of polymerization processes.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"27 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yifan Jiang, Haichao Huang, Dechen Sun, Lei Gong, Wei Yuan, Yu‐Mei Lin
2 H ‐Indazole scaffolds represent privileged structural motifs prevalent in a wide range of bioactive compounds and pharmaceutical agents. Despite their significance, conventional synthetic approaches to 2 H ‐indazole derivatives often suffer from limitations such as harsh reaction conditions, the use of expensive or toxic catalysts, and multistep procedures. To address these challenges, we report a cost‐effective, environmentally benign, and one‐pot strategy for the synthesis of biologically and synthetically valuable 3‐arylamino‐2‐aryl‐2 H ‐indazoles. This method employs readily available o ‐nitrobenzyl alcohols as key building blocks and utilizes a Lewis acid iron salt as a catalyst under visible light irradiation, harnessing the excited‐state reactivity of the substrates. The transformation proceeds efficiently without the need for precious metal catalysts, external oxidants, or additives and operates under mild and sustainable conditions. The protocol enables the construction of structurally complex 2 H ‐indazoles, including those embedded in medium‐sized rings. Notably, the synthesized 3‐arylamino‐2‐aryl‐2 H ‐indazoles exhibit a selective fluorescence quenching response toward hypochlorite, highlighting their potential as an effective probe for ClO − detection.
2 H -吲哚唑支架代表了广泛存在于生物活性化合物和药物制剂中的特殊结构基序。尽管具有重要意义，但传统的2 H -吲哚唑衍生物的合成方法经常受到诸如苛刻的反应条件，使用昂贵或有毒的催化剂以及多步骤程序等限制。为了应对这些挑战，我们报告了一种具有成本效益，环境友好，一锅合成具有生物学和合成价值的3 -芳基- 2 -芳基- 2 H -吲哚的策略。该方法采用易于获得的邻硝基苯基醇作为关键构建单元，并利用刘易斯酸铁盐作为可见光照射下的催化剂，利用底物的激发态反应活性。在不需要贵金属催化剂、外部氧化剂或添加剂的情况下有效地进行转化，并在温和和可持续的条件下进行。该方案能够构建结构复杂的2 H -吲哚，包括那些嵌入在中等大小的环。值得注意的是，合成的3 -芳基氨基- 2 -芳基- 2 H -茚唑对次氯酸盐表现出选择性荧光猝灭反应，突出了它们作为ClO -检测有效探针的潜力。
{"title":"Harnessing the Excited‐State Reactivity of o ‐Nitrobenzyl Alcohols for the Rapid Synthesis of N ‐Substituted 2 H ‐Indazoles","authors":"Yifan Jiang, Haichao Huang, Dechen Sun, Lei Gong, Wei Yuan, Yu‐Mei Lin","doi":"10.1002/adsc.70247","DOIUrl":"https://doi.org/10.1002/adsc.70247","url":null,"abstract":"2 <jats:italic>H</jats:italic> ‐Indazole scaffolds represent privileged structural motifs prevalent in a wide range of bioactive compounds and pharmaceutical agents. Despite their significance, conventional synthetic approaches to 2 <jats:italic>H</jats:italic> ‐indazole derivatives often suffer from limitations such as harsh reaction conditions, the use of expensive or toxic catalysts, and multistep procedures. To address these challenges, we report a cost‐effective, environmentally benign, and one‐pot strategy for the synthesis of biologically and synthetically valuable 3‐arylamino‐2‐aryl‐2 <jats:italic>H</jats:italic> ‐indazoles. This method employs readily available <jats:italic>o</jats:italic> ‐nitrobenzyl alcohols as key building blocks and utilizes a Lewis acid iron salt as a catalyst under visible light irradiation, harnessing the excited‐state reactivity of the substrates. The transformation proceeds efficiently without the need for precious metal catalysts, external oxidants, or additives and operates under mild and sustainable conditions. The protocol enables the construction of structurally complex 2 <jats:italic>H</jats:italic> ‐indazoles, including those embedded in medium‐sized rings. Notably, the synthesized 3‐arylamino‐2‐aryl‐2 <jats:italic>H</jats:italic> ‐indazoles exhibit a selective fluorescence quenching response toward hypochlorite, highlighting their potential as an effective probe for ClO <jats:sup>−</jats:sup> detection.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"18 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juan M. Coto‐Cid, Patricia Rodríguez‐Salamanca, Christian M. Heckmann, Caroline E. Paul, Joaquín López‐Serrano, Rosario Fernández, José M. Lassaletta, Valentín Hornillos, Gonzalo de Gonzalo
Atropisomeric heterobiaryl primary amines are of significant interest in both organic and pharmaceutical chemistry. A series of transaminases have been employed to synthesize these valuable compounds with high yields (up to 98% conversion) and excellent enantioselectivities (up to ≥99% ee ) via dynamic kinetic resolution of the corresponding heterobiaryl aldehydes. This process features a Lewis acid–base interaction strategy to facilitate labilization of the stereogenic axis.
{"title":"Asymmetric Synthesis of Atropisomeric Amines via Transaminase‐Catalyzed Dynamic Kinetic Resolution","authors":"Juan M. Coto‐Cid, Patricia Rodríguez‐Salamanca, Christian M. Heckmann, Caroline E. Paul, Joaquín López‐Serrano, Rosario Fernández, José M. Lassaletta, Valentín Hornillos, Gonzalo de Gonzalo","doi":"10.1002/adsc.70254","DOIUrl":"https://doi.org/10.1002/adsc.70254","url":null,"abstract":"Atropisomeric heterobiaryl primary amines are of significant interest in both organic and pharmaceutical chemistry. A series of transaminases have been employed to synthesize these valuable compounds with high yields (up to 98% conversion) and excellent enantioselectivities (up to ≥99% <jats:italic>ee</jats:italic> ) via dynamic kinetic resolution of the corresponding heterobiaryl aldehydes. This process features a Lewis acid–base interaction strategy to facilitate labilization of the stereogenic axis.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"72 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The rational design of efficient thermal‐photo CO 2 reduction catalysts necessitates synergistic integration of structural modulation and reactant activation strategies. Herein, a Mg‐doped Bi nanosphere catalyst is reported, engineered for efficient CO 2 reduction under H 2 O‐H 2 co‐feeding conditions. Mg doping not only optimizes the nanostructure by reducing the particle size but also modifies the surface charge distribution and enhances water adsorption, thereby promoting CO 2 activation and catalytic performance. Crucially, under H 2 OH 2 co‐feeding, H 2 O interacts with Bi to generate hydroxylated BiOH sites that promote CO 2 chemisorption, while H 2 supplies hydrogen species (*H) for CO 2 reduction. In situ diffuse reflectance infrared Fourier transform spectroscopy reveals a cooperative mechanism: CO 2 adsorbs on BiOH to form *CO 32− intermediates, which undergo sequential reduction facilitated by H 2 activation. This synergy achieves a CO production rate of 55.32 μmol·g −1 ·h −1 under 420 nm illumination with 100% selectivity, which is 2.4 times higher than that under a pure H 2 atmosphere. The work highlights the critical role of dopant‐driven active site engineering and reactant synergies (H 2 OH 2 ) in CO 2 valorization, providing a scalable strategy for catalytic performance enhancement.
{"title":"Enhancing Thermal‐Photocatalytic Reduction of CO 2 via H 2 O‐H 2 Co‐Feeding in Mg‐Doped Bismuth Catalysts","authors":"Haonan Li, Weimin Ma, Pei Kang, Yingxuan Li","doi":"10.1002/adsc.70239","DOIUrl":"https://doi.org/10.1002/adsc.70239","url":null,"abstract":"The rational design of efficient thermal‐photo CO <jats:sub>2</jats:sub> reduction catalysts necessitates synergistic integration of structural modulation and reactant activation strategies. Herein, a Mg‐doped Bi nanosphere catalyst is reported, engineered for efficient CO <jats:sub>2</jats:sub> reduction under H <jats:sub>2</jats:sub> O‐H <jats:sub>2</jats:sub> co‐feeding conditions. Mg doping not only optimizes the nanostructure by reducing the particle size but also modifies the surface charge distribution and enhances water adsorption, thereby promoting CO <jats:sub>2</jats:sub> activation and catalytic performance. Crucially, under H <jats:sub>2</jats:sub> OH <jats:sub>2</jats:sub> co‐feeding, H <jats:sub>2</jats:sub> O interacts with Bi to generate hydroxylated BiOH sites that promote CO <jats:sub>2</jats:sub> chemisorption, while H <jats:sub>2</jats:sub> supplies hydrogen species (*H) for CO <jats:sub>2</jats:sub> reduction. In situ diffuse reflectance infrared Fourier transform spectroscopy reveals a cooperative mechanism: CO <jats:sub>2</jats:sub> adsorbs on BiOH to form *CO <jats:sub>3</jats:sub> <jats:sup>2−</jats:sup> intermediates, which undergo sequential reduction facilitated by H <jats:sub>2</jats:sub> activation. This synergy achieves a CO production rate of 55.32 μmol·g <jats:sup>−1</jats:sup> ·h <jats:sup>−1</jats:sup> under 420 nm illumination with 100% selectivity, which is 2.4 times higher than that under a pure H <jats:sub>2</jats:sub> atmosphere. The work highlights the critical role of dopant‐driven active site engineering and reactant synergies (H <jats:sub>2</jats:sub> OH <jats:sub>2</jats:sub> ) in CO <jats:sub>2</jats:sub> valorization, providing a scalable strategy for catalytic performance enhancement.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"41 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natalia Kulbacka, Wangyu Shi, Sophie M. Guillaume, Jean‐François Carpentier, Jordi Benet‐Buchholz, Arjan W. Kleij
We report a method for the base‐mediated transformation of ether‐tethered acrylic ester‐based cyclic carbonates into functionalized cyclic acetals. The protocol builds on the use of hydroxyalkyl‐substituted cyclic carbonates that undergo an oxa ‐Michael addition reaction in the presence of alkyl propiolates thereby forging ( E )‐configured acrylic ether intermediates. The scope of the reaction involves the use of both five‐ and six‐membered cyclic carbonates, and correspondingly, both five‐ and six‐membered cyclic acetals can be prepared. The amount of reagents, the purification method, and the type of ester substrate all contribute to the efficiency of the transformation. Mechanistic control reactions point at the intermediacy of an alkoxide that induces an intramolecular Michael addition onto the acrylic double bond following alkoxide‐mediated formation of both an alcohol and ester in the final product. These functional groups, among others, further enable easy diversification of acetal‐based synthons.
{"title":"Domino Synthesis of Functionalized Cyclic Acetals From Organic Carbonates","authors":"Natalia Kulbacka, Wangyu Shi, Sophie M. Guillaume, Jean‐François Carpentier, Jordi Benet‐Buchholz, Arjan W. Kleij","doi":"10.1002/adsc.70248","DOIUrl":"https://doi.org/10.1002/adsc.70248","url":null,"abstract":"We report a method for the base‐mediated transformation of ether‐tethered acrylic ester‐based cyclic carbonates into functionalized cyclic acetals. The protocol builds on the use of hydroxyalkyl‐substituted cyclic carbonates that undergo an <jats:italic>oxa</jats:italic> ‐Michael addition reaction in the presence of alkyl propiolates thereby forging ( <jats:italic>E</jats:italic> )‐configured acrylic ether intermediates. The scope of the reaction involves the use of both five‐ and six‐membered cyclic carbonates, and correspondingly, both five‐ and six‐membered cyclic acetals can be prepared. The amount of reagents, the purification method, and the type of ester substrate all contribute to the efficiency of the transformation. Mechanistic control reactions point at the intermediacy of an alkoxide that induces an intramolecular Michael addition onto the acrylic double bond following alkoxide‐mediated formation of both an alcohol and ester in the final product. These functional groups, among others, further enable easy diversification of acetal‐based synthons.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"20 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145593780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elisabeth Söderberg, Marianne R. Molenaar, Katarzyna Zaczyk, Magnus Johansson, Martin A. Hayes, Per‐Olof Syrén
Amide bond formation is a basal transformation in synthetic chemistry and the pharmaceutical industry that is traditionally performed under harsh conditions, using excess amounts of amine and relying on coupling agents. Biocatalysis shows great potential in contributing to milder and more sustainable amide bond formation in water, in particular using the emerging family of amide bond synthetase (ABS) enzymes. Here, we use molecular dynamics, biocatalysis, and enzyme engineering to study amide bond formation in extant and ancestral ABS from Marinactinospora thermotolerans (McbA). Our results show that while being more thermostable, the C‐terminal domain that delivers the amine substrate to the adenylated acid intermediate is more flexible in ancestral McbA, presumably leading to an extended amine scope as observed experimentally from a small panel of aliphatic and aromatic substrates. An engineered ancestor of McbA harboring a single mutation that presumptively represent a catalytic shift residue when going from ancestral to modern biocatalyst, show two to ten‐fold improved conversions over its ancestral template while maintaining high thermostability, highlighting ancestral sequence reconstruction as a potent method in protein engineering. Kinetic experiments showed that the engineered ancestral enzyme had 2‐fold higher apparent kcat values in amide formation compared to extant enzyme, concomitant with relaxed substrate inhibition and loss‐of‐dependency on magnesium. Finally, we optimize ATP recycling utilizing a single polyphosphate kinase to showcase how engineered ancestral McbA together with reaction optimization is amenable for pharmacophore synthesis at a preparative scale.
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