Radical–polar crossover (RPCO) has emerged as a powerful synthetic strategy, using the complementary properties of both radical and classical polar chemistry. Radical–polar crossover, especially its oxidative radical–polar crossover (ORPCO), facilitates efficient asymmetric synthesis by converting radical intermediates to carbocations, which allow the formation of enantioselective bonds. This ability to form CC, CO, and CN bonds underlines its significant potential for late–stage functionalization of complex molecules and for diversification of medicinal products. This review summarizes the recent developments in the asymmetric ORPCO domain, including catalytic strategies, transformation mechanisms, and current characteristics. Research into new catalytic strategies and asymmetric bonding paradigms is an important frontier of future research, with the potential to significantly increase the scale and usefulness of ORPCO reactions.
{"title":"Recent Progress in Asymmetric Oxidative Radical–Polar Crossover Reactions","authors":"Xiaochong Guo, Kangping Wu, Mianling Zhang","doi":"10.1002/adsc.70315","DOIUrl":"https://doi.org/10.1002/adsc.70315","url":null,"abstract":"Radical–polar crossover (RPCO) has emerged as a powerful synthetic strategy, using the complementary properties of both radical and classical polar chemistry. Radical–polar crossover, especially its oxidative radical–polar crossover (ORPCO), facilitates efficient asymmetric synthesis by converting radical intermediates to carbocations, which allow the formation of enantioselective bonds. This ability to form C<span></span>C, C<span></span>O, and C<span></span>N bonds underlines its significant potential for late–stage functionalization of complex molecules and for diversification of medicinal products. This review summarizes the recent developments in the asymmetric ORPCO domain, including catalytic strategies, transformation mechanisms, and current characteristics. Research into new catalytic strategies and asymmetric bonding paradigms is an important frontier of future research, with the potential to significantly increase the scale and usefulness of ORPCO reactions.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"44 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147360098","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}
Kamil Hanek, Barbara Kaczmarek, Dawid Frąckowiak, Patrycja Żak
The mechanochemical synthesis of 4,5-dihydro-1,3-thiazol-2-amines and 1,3-thiazolidine-2-imine hydrochlorides has been performed starting from chloroalkyl isothiocyanate and amines in the presence of potassium carbonate. The proposed procedure is efficient under transition metal- and solvent-free ball-milling conditions with the use of a mixer mill. The reactions are selective and show no significant decrease in yields across a broad scope of substrates bearing different functional groups. Moreover, the successful 1 g scale-up experiment demonstrates the practical applicability of the method.
{"title":"Mechanochemical Synthesis of N, N-Disubstituted 2-Amino-Thiazolines, and 1,3-Thiazolidine-2-Imine Hydrochlorides","authors":"Kamil Hanek, Barbara Kaczmarek, Dawid Frąckowiak, Patrycja Żak","doi":"10.1002/adsc.70340","DOIUrl":"https://doi.org/10.1002/adsc.70340","url":null,"abstract":"The mechanochemical synthesis of 4,5-dihydro-1,3-thiazol-2-amines and 1,3-thiazolidine-2-imine hydrochlorides has been performed starting from chloroalkyl isothiocyanate and amines in the presence of potassium carbonate. The proposed procedure is efficient under transition metal- and solvent-free ball-milling conditions with the use of a mixer mill. The reactions are selective and show no significant decrease in yields across a broad scope of substrates bearing different functional groups. Moreover, the successful 1 g scale-up experiment demonstrates the practical applicability of the method.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"6 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147361002","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}
Pub Date : 2026-03-03Epub Date: 2026-03-07DOI: 10.1002/adsc.70242
Kate Andersen , Nora Struchtrup , Adam Sylvain‐Stewart , Liliia Pestereva , Benjamin Godwin , Gino A. DiLabio , Jeremy E. Wulff
Trifluoromethyl aryl diazirines are ubiquitous in chemical biology applications, and are increasingly used in materials science. While the electron‐withdrawing α‐CF3 group is known to stabilize the carbene resulting from diazirine activation, no alternative electron‐withdrawing groups have been systematically studied. Here, we describe the synthesis of the first α‐ester aryl diazirines and show that they activate at lower temperatures than their trifluoromethyl‐containing analogs, while still permitting tunable activation and good efficiency in CH insertion reactions. We anticipate the use of α‐ester aryl diazirines in materials science applications (due to their high insertion yield with a nonfunctionalized aliphatic model substrate) and biological wound healing (due to their ability to be thermally activated at < 37°C).
{"title":"Alpha‐Ester Aryl Diazirines: Low‐Temperature Carbene Progenitors for Materials Applications","authors":"Kate Andersen , Nora Struchtrup , Adam Sylvain‐Stewart , Liliia Pestereva , Benjamin Godwin , Gino A. DiLabio , Jeremy E. Wulff","doi":"10.1002/adsc.70242","DOIUrl":"10.1002/adsc.70242","url":null,"abstract":"<div><div>Trifluoromethyl aryl diazirines are ubiquitous in chemical biology applications, and are increasingly used in materials science. While the electron‐withdrawing <em>α</em>‐CF<sub>3</sub> group is known to stabilize the carbene resulting from diazirine activation, no alternative electron‐withdrawing groups have been systematically studied. Here, we describe the synthesis of the first <em>α</em>‐ester aryl diazirines and show that they activate at lower temperatures than their trifluoromethyl‐containing analogs, while still permitting tunable activation and good efficiency in CH insertion reactions. We anticipate the use of <em>α</em>‐ester aryl diazirines in materials science applications (due to their high insertion yield with a nonfunctionalized aliphatic model substrate) and biological wound healing (due to their ability to be thermally activated at < 37°C).</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"368 5","pages":"Article e70242"},"PeriodicalIF":4.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260853","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}
Pub Date : 2026-03-03Epub Date: 2026-03-07DOI: 10.1002/adsc.70307
Wei Rao , Yifan Jiang , Qiong Liu , Junjun Zhang , Die He , Rong Chen
While high‐valent copper intermediates are pivotal for efficient peroxydisulfate (PDS) activation, their generation and role in heterogeneous catalysis remain unclear. Herein, we demonstrate that a nonstoichiometric Cu0.84Bi2.08O4 catalyst enables the dark activation of PDS via a novel pathway dominated by a surface‐bound Cu(III)‐peroxo intermediate (≡Cu(III)‐O−O−SO3). A suite of spectroscopic and chemical probes revealed that this Cu(III)‐peroxo species, along with superoxide radicals (•O2−), acts as the primary oxidant, enabling the highly selective and rapid degradation of bisphenol A (BPA) and other phenolic pollutants. Furthermore, H2O2 generated from PDS hydrolysis synergistically participates in the reaction, accounting for the exceptionally high PDS utilization efficiency of the system. The system exhibits remarkable robustness, maintaining high activity over a wide pH range (4–11) and demonstrating strong resistance to interference from ions. This study elucidates a distinct Cu(III)‐peroxo‐mediated mechanism and offers a new strategy for designing highly selective catalysts for environmental remediation.
{"title":"Nonstoichiometric Copper Bismuth Oxide Catalyst Boosting Surface‐Bound Cu(III)‐Peroxo Intermediate for Selective Oxidation via Dark Peroxydisulfate Activation","authors":"Wei Rao , Yifan Jiang , Qiong Liu , Junjun Zhang , Die He , Rong Chen","doi":"10.1002/adsc.70307","DOIUrl":"10.1002/adsc.70307","url":null,"abstract":"<div><div>While high‐valent copper intermediates are pivotal for efficient peroxydisulfate (PDS) activation, their generation and role in heterogeneous catalysis remain unclear. Herein, we demonstrate that a nonstoichiometric Cu<sub>0.84</sub>Bi<sub>2.08</sub>O<sub>4</sub> catalyst enables the dark activation of PDS via a novel pathway dominated by a surface‐bound Cu(III)‐peroxo intermediate (<strong>≡</strong>Cu(III)‐O−O−SO<sub>3</sub>). A suite of spectroscopic and chemical probes revealed that this Cu(III)‐peroxo species, along with superoxide radicals (•O<sub>2</sub><sup>−</sup>), acts as the primary oxidant, enabling the highly selective and rapid degradation of bisphenol A (BPA) and other phenolic pollutants. Furthermore, H<sub>2</sub>O<sub>2</sub> generated from PDS hydrolysis synergistically participates in the reaction, accounting for the exceptionally high PDS utilization efficiency of the system. The system exhibits remarkable robustness, maintaining high activity over a wide pH range (4–11) and demonstrating strong resistance to interference from ions. This study elucidates a distinct Cu(III)‐peroxo‐mediated mechanism and offers a new strategy for designing highly selective catalysts for environmental remediation.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"368 5","pages":"Article e70307"},"PeriodicalIF":4.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147319850","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}
Pub Date : 2026-03-03Epub Date: 2026-03-07DOI: 10.1002/adsc.70348
Yuping Wu , Xinyu Du , Yaoguo Wang , Zixin Feng , YunRu Ma , Yingying Fan , Li Niu
Constructing polymer photocatalysts that can concurrently accomplish charge transfer and mass transport to catalytic sites remains a formidable task. In this study, by cross‐linking electron‐rich polyphenol and electron‐poor phenothiazine units, two hydrophilic and porous organic polymer photocatalysts characterized by densely packed donor–acceptor units are deliberately designed. The hydrophilic phenolic hydroxyl group in the donor moiety and the aperture channel neighboring the acceptor unit facilitate the capture of water and oxygen at the catalytic site. Meanwhile, the donor–acceptor columns serve as charge supply chains and numerous water oxidation and oxygen reduction centers. These photocatalysts are used for the photocatalytic synthesis of hydrogen peroxide from water and oxygen without the use of sacrificial reagents. Therein, the polymer containing tetramethyl groups shows high selectivity for the photogeneration of hydrogen peroxide, achieving a yield rate of 691.3 μmol g−1 h−1 (16.73 mM g−1) and an apparent quantum yield (AQY) of 11.9% under 630 nm irradiation. This organic polymer catalyst system exhibits considerable potential as a promising artificial photosynthesis system capable of realizing simultaneous charge transfer and mass transfer.
构建能够同时完成电荷转移和质量传递到催化位点的聚合物光催化剂仍然是一项艰巨的任务。在这项研究中，通过交联富电子多酚和贫电子吩噻嗪单元，故意设计了两种亲水性和多孔的有机聚合物光催化剂，其特征是密集排列的供体-受体单元。供体部分的亲水酚羟基和邻近受体单元的孔径通道有助于在催化位点捕获水和氧。同时，供体-受体柱作为电荷供应链和众多的水氧化和氧还原中心。这些光催化剂用于水和氧的光催化合成过氧化氢，而不使用牺牲试剂。其中，含四甲基的聚合物对过氧化氢的光生成表现出较高的选择性，在630 nm辐照下的产率为691.3 μmol g−1 h−1 (16.73 mM g−1)，表观量子产率（AQY）为11.9%。该有机聚合物催化剂体系作为一种有潜力的人工光合作用体系，能够同时实现电荷传递和质量传递。
{"title":"Organic Polymers Enabling Concurrent Charge and Mass Transfer for Photocatalytic Hydrogen Peroxide Synthesis","authors":"Yuping Wu , Xinyu Du , Yaoguo Wang , Zixin Feng , YunRu Ma , Yingying Fan , Li Niu","doi":"10.1002/adsc.70348","DOIUrl":"10.1002/adsc.70348","url":null,"abstract":"<div><div>Constructing polymer photocatalysts that can concurrently accomplish charge transfer and mass transport to catalytic sites remains a formidable task. In this study, by cross‐linking electron‐rich polyphenol and electron‐poor phenothiazine units, two hydrophilic and porous organic polymer photocatalysts characterized by densely packed donor–acceptor units are deliberately designed. The hydrophilic phenolic hydroxyl group in the donor moiety and the aperture channel neighboring the acceptor unit facilitate the capture of water and oxygen at the catalytic site. Meanwhile, the donor–acceptor columns serve as charge supply chains and numerous water oxidation and oxygen reduction centers. These photocatalysts are used for the photocatalytic synthesis of hydrogen peroxide from water and oxygen without the use of sacrificial reagents. Therein, the polymer containing tetramethyl groups shows high selectivity for the photogeneration of hydrogen peroxide, achieving a yield rate of 691.3 μmol g<sup>−1</sup> h<sup>−1</sup> (16.73 mM g<sup>−1</sup>) and an apparent quantum yield (AQY) of 11.9% under 630 nm irradiation. This organic polymer catalyst system exhibits considerable potential as a promising artificial photosynthesis system capable of realizing simultaneous charge transfer and mass transfer.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"368 5","pages":"Article e70348"},"PeriodicalIF":4.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147319851","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}
Pub Date : 2026-03-03Epub Date: 2026-03-07DOI: 10.1002/adsc.70321
Zhenlei Zhang , Manqi Zhang , Wei Zhao , Jun Yu , Xiaozheng Li , Ruisong Shi , Jiajun Zheng
We present a method for the selective synthesis of thiochromanes and allyl sulfides that is both metal‐ and oxidant‐free. This method uses 2‐methylquinoline or acetophenone, paraformaldehyde, and thiols as substrates. Varying the thiol substrates allows for the controlled synthesis of either thiochromanes or allyl sulfides. This protocol uses HCl as a promoter, providing an easy, efficient way to produce these sulfur‐containing compounds. Mechanistic studies suggest that the transformation proceeds via a Mannich‐type reaction pathway.
{"title":"Substrate‐Guided Divergent Synthesis of Thiochromanes and Allyl Sulfides via a Mannich‐Type Reaction","authors":"Zhenlei Zhang , Manqi Zhang , Wei Zhao , Jun Yu , Xiaozheng Li , Ruisong Shi , Jiajun Zheng","doi":"10.1002/adsc.70321","DOIUrl":"10.1002/adsc.70321","url":null,"abstract":"<div><div>We present a method for the selective synthesis of thiochromanes and allyl sulfides that is both metal‐ and oxidant‐free. This method uses 2‐methylquinoline or acetophenone, paraformaldehyde, and thiols as substrates. Varying the thiol substrates allows for the controlled synthesis of either thiochromanes or allyl sulfides. This protocol uses HCl as a promoter, providing an easy, efficient way to produce these sulfur‐containing compounds. Mechanistic studies suggest that the transformation proceeds via a Mannich‐type reaction pathway.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"368 5","pages":"Article e70321"},"PeriodicalIF":4.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215814","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}
Pub Date : 2026-03-03Epub Date: 2026-03-07DOI: 10.1002/adsc.70317
Jinge Gui , Yingzi Wang , Xiaofei Xie , Zhibo Zhang , Siliang You , Yingguang Zhu , Kang Chen
A photoredox/Ti dual‐catalyzed deoxygenative coupling reaction between Morita–Baylis–Hillman acetates and unprotected cycloketone oximes has been developed. A broad range of cyano‐containing trisubstituted alkenes have been expediently synthesized in good chemo‐ and stereo‐selectivities under very mild conditions. Mechanistic experiments, scale‐up reaction, and functionalization of complex molecules were conducted, in order to showcase the mechanistic features and robustness of this protocol.
{"title":"Deoxygenative Coupling Between Morita–Baylis–Hillman Acetates and Unprotected Cycloketone Oximes Enabled by Photoredox/Ti Dual Catalysis","authors":"Jinge Gui , Yingzi Wang , Xiaofei Xie , Zhibo Zhang , Siliang You , Yingguang Zhu , Kang Chen","doi":"10.1002/adsc.70317","DOIUrl":"10.1002/adsc.70317","url":null,"abstract":"<div><div>A photoredox/Ti dual‐catalyzed deoxygenative coupling reaction between Morita–Baylis–Hillman acetates and unprotected cycloketone oximes has been developed. A broad range of cyano‐containing trisubstituted alkenes have been expediently synthesized in good chemo‐ and stereo‐selectivities under very mild conditions. Mechanistic experiments, scale‐up reaction, and functionalization of complex molecules were conducted, in order to showcase the mechanistic features and robustness of this protocol.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"368 5","pages":"Article e70317"},"PeriodicalIF":4.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260851","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}
Pub Date : 2026-03-03Epub Date: 2026-03-07DOI: 10.1002/adsc.70294
Jie Yang , Jing Xie , Daohong Yu , Wenjun Luo , Jinbin Zhu , Lipeng Long , Haiqing Luo , Wei Guo , Zhongxia Wang , Zhengwang Chen
A visible‐light‐driven, photocatalyst‐free 6π‐photocyclization of N‐substituted dieneamines has been developed. Various polysubstituted cyanodihydropyrroles and cyanopyrroles were constructed in good‐to‐excellent yields under nitrogen or air atmosphere. This novel strategy features formal hydroalkenylation, divergent synthesis, excellent regioselectivity, wide functional group tolerance, and operational convenience. Mechanistic studies suggest that both the 1,4‐H shift of the diradical intermediate and the deprotonation/protonation processes may be involved in the transformation.
{"title":"Photocatalyst‐Free, Visible Light‐Driven 6π‐Photocyclization: A Facile Access to Multisubstituted Cyanodihydropyrroles and Cyanopyrroles","authors":"Jie Yang , Jing Xie , Daohong Yu , Wenjun Luo , Jinbin Zhu , Lipeng Long , Haiqing Luo , Wei Guo , Zhongxia Wang , Zhengwang Chen","doi":"10.1002/adsc.70294","DOIUrl":"10.1002/adsc.70294","url":null,"abstract":"<div><div>A visible‐light‐driven, photocatalyst‐free 6π‐photocyclization of <em>N</em>‐substituted dieneamines has been developed. Various polysubstituted cyanodihydropyrroles and cyanopyrroles were constructed in good‐to‐excellent yields under nitrogen or air atmosphere. This novel strategy features formal hydroalkenylation, divergent synthesis, excellent regioselectivity, wide functional group tolerance, and operational convenience. Mechanistic studies suggest that both the 1,4‐H shift of the diradical intermediate and the deprotonation/protonation processes may be involved in the transformation.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"368 5","pages":"Article e70294"},"PeriodicalIF":4.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147287332","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}
Pub Date : 2026-03-03Epub Date: 2025-12-23DOI: 10.1002/adsc.70212
Li Zhang , Xiang Li , Jin Zhou , Yulin Luo , Qiwen Pang , Wei Huang , Bo Han , Xiang‐Hong He
The development of oxygen‐containing three‐dimensional bicyclic scaffolds as bioisosteres of aromatic rings is of increasing importance for improving physicochemical and pharmacokinetic profiles in modern pharmaceutical development. Herein, we report a catalyst‐ and additive‐free strategy to access a series of multifunctional oxa‐bicyclo[2.1.1]hexane derivatives in a single operation from readily accessible α‐diazoketones and bicyclo[1.1.0]butanes. The process involves a visible‐light‐mediated sequential Wolff rearrangement/[2π + 2σ] cycloaddition. Generally, this reaction proceeds under mild conditions and features broad substrate scope, good functional group tolerance, and high regiospecificity. The synthetic utility of this method is demonstrated through diverse synthetic transformations of the resulting products. Furthermore, control experiments and mechanistic studies were conducted, and a plausible mechanism is proposed to rationalize the observed efficiency.
{"title":"Visible Light‐Driven Wolff Rearrangement/Formal (3+2) Cyclization of α‐Diazoketones with Bicyclo[1.1.0]butanes: Efficient and Highly Regioselective Access Oxabicyclo‐[2.1.1]hexane Scaffolds","authors":"Li Zhang , Xiang Li , Jin Zhou , Yulin Luo , Qiwen Pang , Wei Huang , Bo Han , Xiang‐Hong He","doi":"10.1002/adsc.70212","DOIUrl":"10.1002/adsc.70212","url":null,"abstract":"<div><div>The development of oxygen‐containing three‐dimensional bicyclic scaffolds as bioisosteres of aromatic rings is of increasing importance for improving physicochemical and pharmacokinetic profiles in modern pharmaceutical development. Herein, we report a catalyst‐ and additive‐free strategy to access a series of multifunctional oxa‐bicyclo[2.1.1]hexane derivatives in a single operation from readily accessible α‐diazoketones and bicyclo[1.1.0]butanes. The process involves a visible‐light‐mediated sequential Wolff rearrangement/[2<em>π</em> + 2<em>σ</em>] cycloaddition. Generally, this reaction proceeds under mild conditions and features broad substrate scope, good functional group tolerance, and high regiospecificity. The synthetic utility of this method is demonstrated through diverse synthetic transformations of the resulting products. Furthermore, control experiments and mechanistic studies were conducted, and a plausible mechanism is proposed to rationalize the observed efficiency.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"368 5","pages":"Article e70212"},"PeriodicalIF":4.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801133","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}
Regioselective, metal‐free, CH chlorination of phenols is challenging. These reactions generally proceed via electrophilic aromatic substitution, resulting in pure 2‐ or 4‐chlorinated products or a mixture of 2‐ and 4‐substituted isomers. However, 3‐substitution is electronically forbidden in these cases. Electrophilic aromatic chlorination involves toxic reagents, low tolerance for functional groups, and the generation of waste products from the chlorinating agent. Improvizations involving classical preformed chlorinating agents, oxidative chlorination, and transition metal catalysis, among others, require harsh conditions, high temperatures, directing groups, and low atom economy, despite achieving high selectivity. Few reports have also utilized the activation of arenes to facilitate regioselective nucleophilic chlorination. In a unique progression in phenol chemistry, we report a regioselective, indirect, catalyst‐ and metal‐free synthesis of 2‐chlorophenols via the chlorination of quinone monoacetals (QMA), derived from the oxidative dearomatization of phenol, using dimethyl chlorohydrosilane as a chloride source. Further, Brønsted acid‐catalyzed chlorination of QMA–MBH adducts afforded regioselective, metal‐free, solvent‐switchable 3‐ or 2‐chlorophenols via a one‐pot cascade reaction. C‐2‐chlorination proceeds via Michael addition of Cl− ion to the intermediate phenoxonium ion, while C‐3 chlorination occurs via Cl− addition to a silane‐activated quinone intermediate. This approach is well‐suited for late‐stage functionalization in pharmaceuticals, natural products, and complex molecules.
{"title":"Solvent‐Switchable Regiodivergent Chlorination of Quinone Monoacetals: A Practical Route to 2‐ and 3‐Chlorophenols","authors":"Pragya Sharma , Sharda Pasricha , Sunny Singh , Mainak Dey , Chinmoy Kumar Hazra","doi":"10.1002/adsc.70234","DOIUrl":"10.1002/adsc.70234","url":null,"abstract":"<div><div>Regioselective, metal‐free, CH chlorination of phenols is challenging. These reactions generally proceed via electrophilic aromatic substitution, resulting in pure 2‐ or 4‐chlorinated products or a mixture of 2‐ and 4‐substituted isomers. However, 3‐substitution is electronically forbidden in these cases. Electrophilic aromatic chlorination involves toxic reagents, low tolerance for functional groups, and the generation of waste products from the chlorinating agent. Improvizations involving classical preformed chlorinating agents, oxidative chlorination, and transition metal catalysis, among others, require harsh conditions, high temperatures, directing groups, and low atom economy, despite achieving high selectivity. Few reports have also utilized the activation of arenes to facilitate regioselective nucleophilic chlorination. In a unique progression in phenol chemistry, we report a regioselective, indirect, catalyst‐ and metal‐free synthesis of 2‐chlorophenols via the chlorination of quinone monoacetals (QMA), derived from the oxidative dearomatization of phenol, using dimethyl chlorohydrosilane as a chloride source. Further, Brønsted acid‐catalyzed chlorination of QMA–MBH adducts afforded regioselective, metal‐free, solvent‐switchable 3‐ or 2‐chlorophenols via a one‐pot cascade reaction. C‐2‐chlorination proceeds via Michael addition of Cl<sup>−</sup> ion to the intermediate phenoxonium ion, while C‐3 chlorination occurs via Cl<sup>−</sup> addition to a silane‐activated quinone intermediate. This approach is well‐suited for late‐stage functionalization in pharmaceuticals, natural products, and complex molecules.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"368 5","pages":"Article e70234"},"PeriodicalIF":4.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147320088","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}
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