Pub Date : 2025-10-13Epub Date: 2025-10-02DOI: 10.1039/d5qo01211b
Bendu Pan , Yunru Wu , Liwei Zhao , Rihui Cao , Liqin Qiu
Herein, we report a novel metal-free cascade SNAr reaction/allylic amination strategy toward pyrimidinamine derivatives promoted by cost-effective triethylamine, enabling the efficient synthesis of a wide range of 2-chlorotetrahydropteridines in moderate to good yields under an air atmosphere. This operationally simple protocol demonstrates notable advantages including one-pot synthesis and utilization of environmentally benign solvents. The obtained 2-chlorotetrahydropteridines serve as versatile synthons for constructing diverse 2-substituted tetrahydropteridine derivatives through conventional palladium-catalyzed Suzuki-coupling and Buchwald–Hartwig amination reactions using as the N-heterocyclic carbene–palladium catalyst. Systematic mechanistic investigations, including successful isolation and monitoring of key intermediates, provide a deeper insight into the reaction pathway. The methodology's sustainability is further demonstrated through solvent-free optimization, feasibility for gram-scale production, and synthetic application of the resulting products. This green synthetic approach significantly reduces environmental impact by eliminating the need for an inert atmosphere, establishing a robust platform for the sustainable synthesis of tetrahydropteridines.
{"title":"Metal-free cascade SNAr reaction/allylic amination enabled by triethylamine: a green chemistry approach to access tetrahydropteridines","authors":"Bendu Pan , Yunru Wu , Liwei Zhao , Rihui Cao , Liqin Qiu","doi":"10.1039/d5qo01211b","DOIUrl":"10.1039/d5qo01211b","url":null,"abstract":"<div><div>Herein, we report a novel metal-free cascade S<sub>N</sub>Ar reaction/allylic amination strategy toward pyrimidinamine derivatives promoted by cost-effective triethylamine, enabling the efficient synthesis of a wide range of 2-chlorotetrahydropteridines in moderate to good yields under an air atmosphere. This operationally simple protocol demonstrates notable advantages including one-pot synthesis and utilization of environmentally benign solvents. The obtained 2-chlorotetrahydropteridines serve as versatile synthons for constructing diverse 2-substituted tetrahydropteridine derivatives through conventional palladium-catalyzed Suzuki-coupling and Buchwald–Hartwig amination reactions using as the N-heterocyclic carbene–palladium catalyst. Systematic mechanistic investigations, including successful isolation and monitoring of key intermediates, provide a deeper insight into the reaction pathway. The methodology's sustainability is further demonstrated through solvent-free optimization, feasibility for gram-scale production, and synthetic application of the resulting products. This green synthetic approach significantly reduces environmental impact by eliminating the need for an inert atmosphere, establishing a robust platform for the sustainable synthesis of tetrahydropteridines.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 7127-7135"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The integration of γ-keto sulfones, despite being medicinally relevant building blocks, with the bioactive diarylmethane motif remains elusive. On the other hand, the fixation of SO2 into organic molecules for accessing value-added products is gaining wide attention in organic synthesis. Herein, we disclose the 1,6-hydrosulfonylation of p-quinone methides via the strain-release driven ring-scission of strained 3°-cyclopropanols in the presence of a SO2-surrogate like K2S2O5 and a Brønsted acid under visible-light photoredox catalysis to access a library of γ-keto alkylsulfonylated diarylmethanes in moderate to good yields. Also, the 1,6-hydrosulfonylation of p-quinone methides has been developed via aromaticity-driven bond-scission in pro-aromatics like 4-alkyl-1,4-DHPs in the presence of K2S2O5 and a Brønsted acid under visible-light photoredox catalysis to access a library of alkylsulfonylated diarylmethanes. The efficiency of the developed reactions has been established through broad substrate-scope studies, and the mechanistic probing studies have been complemented with DFT calculations to support the proposed mechanisms. In addition, antiproliferative studies revealed oral cancer activity for some of the synthesized sulfonylated diarylmethane derivatives.
{"title":"1,6-Hydrosulfonylation of p-quinone methides enabled via strain-release-/aromaticity-driven alkyl radical generation and SO2-capture: synthesis and antiproliferative studies of sulfonylated diarylmethanes","authors":"Dipun Kumar Penthi , Tonish Kumar Sahu , Rahimuddin Khan , Shanti Gopal Patra , Tabrez Khan","doi":"10.1039/d5qo00981b","DOIUrl":"10.1039/d5qo00981b","url":null,"abstract":"<div><div>The integration of γ-keto sulfones, despite being medicinally relevant building blocks, with the bioactive diarylmethane motif remains elusive. On the other hand, the fixation of SO<sub>2</sub> into organic molecules for accessing value-added products is gaining wide attention in organic synthesis. Herein, we disclose the 1,6-hydrosulfonylation of <em>p</em>-quinone methides <em>via</em> the strain-release driven ring-scission of strained 3°-cyclopropanols in the presence of a SO<sub>2</sub>-surrogate like K<sub>2</sub>S<sub>2</sub>O<sub>5</sub> and a Brønsted acid under visible-light photoredox catalysis to access a library of γ-keto alkylsulfonylated diarylmethanes in moderate to good yields. Also, the 1,6-hydrosulfonylation of <em>p</em>-quinone methides has been developed <em>via</em> aromaticity-driven bond-scission in pro-aromatics like 4-alkyl-1,4-DHPs in the presence of K<sub>2</sub>S<sub>2</sub>O<sub>5</sub> and a Brønsted acid under visible-light photoredox catalysis to access a library of alkylsulfonylated diarylmethanes. The efficiency of the developed reactions has been established through broad substrate-scope studies, and the mechanistic probing studies have been complemented with DFT calculations to support the proposed mechanisms. In addition, antiproliferative studies revealed oral cancer activity for some of the synthesized sulfonylated diarylmethane derivatives.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 6922-6935"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13Epub Date: 2025-09-24DOI: 10.1039/d5qo00862j
Chengfei Fu , Xing Chen , Junjie Zhao , Linglong Wan , Zhaoyu Sun , Xinhua Liu , Yazhou Lou
The breaking of the endocyclic S-aryl bond of strainless thioxanthene derivatives by transition metal-catalyzed ring-opening reactions is still underdeveloped. Herein, we present the synthesis of asymmetric triarylmethanes through desymmetric ring-opening reactions of strainless thioxanthene sulfonium salts with palladium catalysis. The reaction exhibited a broad substrate scope, high efficiency, and excellent chemoselectivity. Gram-scale experiments and an asymmetric attempt for enantioselective and endocyclic bond-breaking reactions of the six-membered diarylthiolium salts were also investigated. Meanwhile, compound showed comparatively good inhibition activities on NO generation in RAW264.7 cells through anti-inflammatory examination.
{"title":"Palladium-catalyzed endocyclic bond cleavage of thioxanthene-derived sulfonium salts","authors":"Chengfei Fu , Xing Chen , Junjie Zhao , Linglong Wan , Zhaoyu Sun , Xinhua Liu , Yazhou Lou","doi":"10.1039/d5qo00862j","DOIUrl":"10.1039/d5qo00862j","url":null,"abstract":"<div><div>The breaking of the endocyclic S-aryl bond of strainless thioxanthene derivatives by transition metal-catalyzed ring-opening reactions is still underdeveloped. Herein, we present the synthesis of asymmetric triarylmethanes through desymmetric ring-opening reactions of strainless thioxanthene sulfonium salts with palladium catalysis. The reaction exhibited a broad substrate scope, high efficiency, and excellent chemoselectivity. Gram-scale experiments and an asymmetric attempt for enantioselective and endocyclic bond-breaking reactions of the six-membered diarylthiolium salts were also investigated. Meanwhile, compound showed comparatively good inhibition activities on NO generation in RAW264.7 cells through anti-inflammatory examination.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 7136-7142"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13Epub Date: 2025-09-24DOI: 10.1039/d5qo01137j
Peng Ye , Ya-Ling Zhang , Le-Nan Xiong , Yang-Jie Mao , Yu-Qi Cui , Yong Luo , Dan-Qian Xu , Shao-Jie Lou
The selective C–H arylation of N-containing aromatics with sterically demanding 2,6-disubstituted arylating reagents represents a straightforward way for the modular synthesis of ortho-tetrasubstituted heterobiaryls, yet has remained scarcely explored due to significant steric constraints and challenging selectivity control. Herein, we report a novel synergistic Pd–Ag catalysis system, which enables the regioselective C–H arylation of different types of N-heterocyclic N-oxides with diverse ortho-disubstituted aryl iodides for the first time. This protocol offers a step-economic route for the synthesis of ortho-tetrasubstituted heterobiaryl N-oxides, featuring a novel catalytic mode, high regioselectivity, high yields, and broad substrate scope (45 examples, >19 : 1 r.r. in most cases). The mechanistic details have been clarified by deuterium-labeling experiments, isolation and transformation of key intermediates, and DFT calculations, demonstrating the critical roles of Ag additive and DPEphos ligand for achieving high levels of reactivity and regioselectivity.
{"title":"Overcoming steric constraints in C–H arylation via Pd/Ag dual catalysis: a shortcut to ortho-tetrasubstituted heterobiaryl N-oxides","authors":"Peng Ye , Ya-Ling Zhang , Le-Nan Xiong , Yang-Jie Mao , Yu-Qi Cui , Yong Luo , Dan-Qian Xu , Shao-Jie Lou","doi":"10.1039/d5qo01137j","DOIUrl":"10.1039/d5qo01137j","url":null,"abstract":"<div><div>The selective C–H arylation of <em>N</em>-containing aromatics with sterically demanding 2,6-disubstituted arylating reagents represents a straightforward way for the modular synthesis of <em>ortho</em>-tetrasubstituted heterobiaryls, yet has remained scarcely explored due to significant steric constraints and challenging selectivity control. Herein, we report a novel synergistic Pd–Ag catalysis system, which enables the regioselective C–H arylation of different types of N-heterocyclic <em>N</em>-oxides with diverse <em>ortho</em>-disubstituted aryl iodides for the first time. This protocol offers a step-economic route for the synthesis of <em>ortho</em>-tetrasubstituted heterobiaryl <em>N</em>-oxides, featuring a novel catalytic mode, high regioselectivity, high yields, and broad substrate scope (45 examples, >19 : 1 r.r. in most cases). The mechanistic details have been clarified by deuterium-labeling experiments, isolation and transformation of key intermediates, and DFT calculations, demonstrating the critical roles of Ag additive and DPEphos ligand for achieving high levels of reactivity and regioselectivity.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 7107-7117"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13Epub Date: 2025-10-01DOI: 10.1039/d5qo01230a
Yunhe Li , Rui Jin , Ke Chu , Jinmei Qian , Ruiyu Liu
The cooperative catalysis between gold complexes and chiral phosphoric acids (CPA) enables asymmetric oxidative cyclization/Mannich reactions of homopropargyl amides, providing efficient access to chiral spiroindolenines with high enantioselectivity. However, the mechanistic details, particularly the origin of stereocontrol governed by the interplay of steric and dispersion effects, remain elusive. Herein, we present a comprehensive density functional theory (DFT) study to unravel the reaction mechanism and the decisive factors controlling enantioselectivity. Our computations reveal that the catalytic cycle proceeds through gold–carbene formation, regioselective N–H insertion, enolization, and the stereodetermining Mannich addition. The enantioselectivity is primarily dictated by the Mannich step, wherein the favored transition state (TS-SR) is stabilized by a synergistic network of noncovalent interactions, including hydrogen bonding and dispersion forces between the sulfonamide group and the CPA catalyst. Quantitative distortion–interaction analysis demonstrates that dispersion interactions contribute significantly (∼3.0 kcal mol−1) to the energy difference between diastereomeric transition states. This study not only clarifies the stereochemical model but also provides a rational basis for future catalyst design in gold/CPA cooperative catalysis.
{"title":"Unraveling steric and dispersion effects in gold catalysis: a DFT study of asymmetric cyclization/Mannich reactions","authors":"Yunhe Li , Rui Jin , Ke Chu , Jinmei Qian , Ruiyu Liu","doi":"10.1039/d5qo01230a","DOIUrl":"10.1039/d5qo01230a","url":null,"abstract":"<div><div>The cooperative catalysis between gold complexes and chiral phosphoric acids (CPA) enables asymmetric oxidative cyclization/Mannich reactions of homopropargyl amides, providing efficient access to chiral spiroindolenines with high enantioselectivity. However, the mechanistic details, particularly the origin of stereocontrol governed by the interplay of steric and dispersion effects, remain elusive. Herein, we present a comprehensive density functional theory (DFT) study to unravel the reaction mechanism and the decisive factors controlling enantioselectivity. Our computations reveal that the catalytic cycle proceeds through gold–carbene formation, regioselective N–H insertion, enolization, and the stereodetermining Mannich addition. The enantioselectivity is primarily dictated by the Mannich step, wherein the favored transition state (TS-SR) is stabilized by a synergistic network of noncovalent interactions, including hydrogen bonding and dispersion forces between the sulfonamide group and the CPA catalyst. Quantitative distortion–interaction analysis demonstrates that dispersion interactions contribute significantly (∼3.0 kcal mol<sup>−1</sup>) to the energy difference between diastereomeric transition states. This study not only clarifies the stereochemical model but also provides a rational basis for future catalyst design in gold/CPA cooperative catalysis.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 7143-7150"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Herein, we report a Lewis and Brønsted acid-mediated cyclization/amidation reaction of o-alkynylbenzaldehydes with nitriles, constructing a series of amide-substituted benzo[a]fluorene derivatives. The transformation initiated via the acid-mediated 6-endo-dig cyclization of o-alkynylbenzaldehyde generates an isochromenylium intermediate that undergoes [4 + 2] benzannulation with a second substrate's alkyne group, eliminating additional unsaturated hydrocarbons. Nitrile, as a readily available amide source, facilitates direct C–N bond formation. This unified process forges multiple C–C bonds and a C–N bond in a single operation under mild conditions, achieving excellent step economy and chemoselectivity.
{"title":"Synergistic Lewis and Brønsted acid-mediated annulation of o-alkynylbenzaldehydes with nitriles for amide-substituted benzo[a]fluorenes","authors":"Zan Chen , Rong Xiong , Wenting Huang , Huanfeng Jiang , Wanqing Wu","doi":"10.1039/d5qo01170a","DOIUrl":"10.1039/d5qo01170a","url":null,"abstract":"<div><div>Herein, we report a Lewis and Brønsted acid-mediated cyclization/amidation reaction of <em>o</em>-alkynylbenzaldehydes with nitriles, constructing a series of amide-substituted benzo[<em>a</em>]fluorene derivatives. The transformation initiated <em>via</em> the acid-mediated 6-<em>endo-dig</em> cyclization of <em>o</em>-alkynylbenzaldehyde generates an isochromenylium intermediate that undergoes [4 + 2] benzannulation with a second substrate's alkyne group, eliminating additional unsaturated hydrocarbons. Nitrile, as a readily available amide source, facilitates direct C–N bond formation. This unified process forges multiple C–C bonds and a C–N bond in a single operation under mild conditions, achieving excellent step economy and chemoselectivity.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 7168-7173"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13Epub Date: 2025-09-24DOI: 10.1039/d5qo01162k
Qicai Ma , Yuanyuan Li , Zhiping Liu , Chengming Wang , Wei Zhou
This study presents an efficient method for synthesizing spiro-isoxazolines through a tandem palladium-catalyzed carboetherification approach. Utilizing cycloalkenyl-tethered oximes and aryl/alkenyl bromides, this protocol enables the construction of a wide range of novel spiro-isoxazoline compounds bearing diverse functional groups. Furthermore, we also investigated the asymmetric version of this tandem reaction, where the use of a chiral tert-butanesulfinamide monophosphine ligand achieved good chemical yield and excellent enantioselectivity.
{"title":"Access to spiro-isoxazolines via a palladium-catalyzed carboetherification of cycloalkenyl-tethered oximes","authors":"Qicai Ma , Yuanyuan Li , Zhiping Liu , Chengming Wang , Wei Zhou","doi":"10.1039/d5qo01162k","DOIUrl":"10.1039/d5qo01162k","url":null,"abstract":"<div><div>This study presents an efficient method for synthesizing spiro-isoxazolines through a tandem palladium-catalyzed carboetherification approach. Utilizing cycloalkenyl-tethered oximes and aryl/alkenyl bromides, this protocol enables the construction of a wide range of novel spiro-isoxazoline compounds bearing diverse functional groups. Furthermore, we also investigated the asymmetric version of this tandem reaction, where the use of a chiral <em>tert</em>-butanesulfinamide monophosphine ligand achieved good chemical yield and excellent enantioselectivity.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 7043-7048"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13Epub Date: 2025-09-29DOI: 10.1039/d5qo01266j
Vitaly V. Shorokhov , Beauty K. Chabuka , Albina A. Nikolaeva , Sergey S. Zhokhov , Ivan A. Andreev , Nina K. Ratmanova , Igor V. Trushkov , Olga A. Ivanova , Igor V. Alabugin
Ylides are versatile reagents known for their dual electrophilic and nucleophilic reactivity, mimicking carbenes in many reactions. In this study, we uncover a previously unreported reactivity pathway for ylides: a methylene insertion into C–C bonds. We show that sulfur ylides can achieve homologation of alkenes and aldehydes before proceeding through the classical Corey–Chaykovsky reaction. This process allows for the dual transfer of CH2 groups to both substrates, yielding benzylcyclopropanes and benzyloxiranes, valuable intermediates in organic synthesis. Remarkably, the same sulfur ylide reagent participates in two distinct carbene-like transformations within this cascade. Mechanistic studies reveal the role of a tightly coordinated stereoelectronic network playing a crucial role in facilitating anionic 1,2-aryl shifts.
{"title":"New mode of sulfur ylides reactivity: stereoelectronic control provides C–C bond insertion before cyclopropanation/epoxidation directly affording homologated three-membered rings","authors":"Vitaly V. Shorokhov , Beauty K. Chabuka , Albina A. Nikolaeva , Sergey S. Zhokhov , Ivan A. Andreev , Nina K. Ratmanova , Igor V. Trushkov , Olga A. Ivanova , Igor V. Alabugin","doi":"10.1039/d5qo01266j","DOIUrl":"10.1039/d5qo01266j","url":null,"abstract":"<div><div>Ylides are versatile reagents known for their dual electrophilic and nucleophilic reactivity, mimicking carbenes in many reactions. In this study, we uncover a previously unreported reactivity pathway for ylides: a methylene insertion into C–C bonds. We show that sulfur ylides can achieve homologation of alkenes and aldehydes before proceeding through the classical Corey–Chaykovsky reaction. This process allows for the dual transfer of CH<sub>2</sub> groups to both substrates, yielding benzylcyclopropanes and benzyloxiranes, valuable intermediates in organic synthesis. Remarkably, the same sulfur ylide reagent participates in two distinct carbene-like transformations within this cascade. Mechanistic studies reveal the role of a tightly coordinated stereoelectronic network playing a crucial role in facilitating anionic 1,2-aryl shifts.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 6852-6863"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13Epub Date: 2025-09-18DOI: 10.1039/d5qo01197c
Xu Xu , Yilian Song , Wenhao Xu , Xiaoping Wang , Haitao Chen , Yingsheng Zhao
Although ring-opening cross-coupling of gem-difluorocyclopropanes using transition metal catalysts is a well-explored strategy, the development of cost-effective metal catalysts for this transformation is still uncommon. This study presents a copper-catalyzed para-selective fluoroallylation of unprotected phenols achieved through a ring-opening cross-coupling approach. This straightforward method employs an inexpensive and easily accessible catalyst, offers a wide substrate scope, and supports late-stage functionalization of biologically active compounds. Mechanistic investigations suggest that an allyl–Cu(iii) intermediate is generated through C–C bond oxidative addition to Cu(i), followed by C–F bond elimination. The para-selectivity is primarily attributed to hydrogen bonding between hexafluoroisopropanol and the phenol.
{"title":"Copper-catalyzed HFIP-promoted para-selective allylation of phenols via C–C bond activation of gem-difluorinated cyclopropanes","authors":"Xu Xu , Yilian Song , Wenhao Xu , Xiaoping Wang , Haitao Chen , Yingsheng Zhao","doi":"10.1039/d5qo01197c","DOIUrl":"10.1039/d5qo01197c","url":null,"abstract":"<div><div>Although ring-opening cross-coupling of <em>gem</em>-difluorocyclopropanes using transition metal catalysts is a well-explored strategy, the development of cost-effective metal catalysts for this transformation is still uncommon. This study presents a copper-catalyzed <em>para</em>-selective fluoroallylation of unprotected phenols achieved through a ring-opening cross-coupling approach. This straightforward method employs an inexpensive and easily accessible catalyst, offers a wide substrate scope, and supports late-stage functionalization of biologically active compounds. Mechanistic investigations suggest that an allyl–Cu(<span>iii</span>) intermediate is generated through C–C bond oxidative addition to Cu(<span>i</span>), followed by C–F bond elimination. The <em>para</em>-selectivity is primarily attributed to hydrogen bonding between hexafluoroisopropanol and the phenol.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 6915-6921"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13Epub Date: 2025-09-18DOI: 10.1039/d5qo01104c
Gaojie Zhu , Zimei Ma , Che Yang , Feng Sha , Glib Baryshnikov , Bin Zhu , Mingbo Zhou , Chengjie Li , Hans Ågren , Jianxin Song , Shijun Li , Qizhao Li , Yongshu Xie
Oxidative ring-closure of N-confused hexapyrrane and thiahexapyrrane followed by oxidative opening of the pyrrole and thiophene rings has been shown to be effective in synthesizing novel porphyrinoids. In this work, a furan unit is incorporated with the purpose of generating a CO double bond by oxidative furan ring-opening to disrupt the conjugation, resulting in structural distortion and chirality. Thus, a nonaromatic N-confused oxahexaphyrin () has been synthesized by the oxidative cyclization of N-confused oxahexapyrrane () with terminal confused pyrrole and furan units. Subsequent heating of in MeOH triggered furan-opening and fusion reactions to give globally nonaromatic porphyrinoids and , which both contain a carbonyl group and a multiply fused fragment. Thus, possesses a [6.5.6.5]-tetracyclic fragment involving an sp3-C. In contrast, one tetrafluorophenyl unit is generated in by fusion of one of the meso-C6F5 groups with a furan-generated carbon through removing one HF unit, leading to the formation of a fused [5.6.5.7.6]-pentacyclic fragment. As expected, the CO double bond present in the frameworks of and results in disrupted conjugation and structural distortion, and the fused rings are favorable for enhancing the stability of the distorted conformations, which enables chiral separation of enantiomers of with central chirality and with planar chirality via chiral high-performance liquid chromatography, with the maximum absorption dissymmetry factor (|gabs|) of 0.0021 observed for . This work provides insight into developing chiral porphyrinoids by post-synthetic methods based on the combination of a highly reactive N-confused pyrrole unit with a terminal furan ring.
n -杂化六吡喃和硫己吡喃的氧化闭环以及吡咯和噻吩环的氧化开环已被证明是合成新型卟啉类化合物的有效方法。在这项工作中，加入一个呋喃单元，目的是通过氧化呋喃开环破坏共轭，产生C=O双键，从而导致结构畸变和手性。因此，将n -杂化的n -杂化的oxahexyrane （N-O-P5）与末端杂化的吡咯和呋喃进行氧化环化，合成了一个非芳香族n -杂化的oxahexyranin(1)。随后在MeOH中加热1引发呋喃打开和融合反应，得到全局非芳香卟啉2和3，它们都含有羰基和多重融合片段。因此，2具有一个涉及sp3-C的[6.5.6.5]-四环片段。相反，在3中，通过去除一个HF单元，一个中位c6f5基团与呋喃生成的碳融合生成一个四氟苯基单元，从而形成一个融合的[5.6.5.7.6]-五环片段。正如预期的那样，2和3的框架中存在的C=O双键导致了偶联断裂和结构畸变，而融合环有利于增强畸变构象的稳定性，从而使2的中心手性对映体和3的平面手性对映体通过手性高效液相色谱进行了手性分离，2的最大吸收不对称因子（|gabs|）为0.0021。这项工作为基于高活性n混淆吡咯单元与末端呋喃环结合的后合成方法开发手性卟啉类化合物提供了见解。
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