Cyclic peptides are highly valued in drug discovery due to their enhanced biological properties. Despite there potential, the construction of S-alkynyl moiety in a cyclic peptides remains challenging due to limited synthetic strategies. Herein, we describe a copper-catalyzed alkynylation of thiosulfonate-based peptides, enabling efficient and selective synthesis of S-alkynylated cysteines and peptides. The adjustment of the amount of base could significantly increase the efficiency. This method features a broad substrate scope, operational simplicity and compatibility with complex peptide structures.
{"title":"Cu-Catalyzed Alkynylation of Thiosulfonate-Based Peptide: An Efficient Approach to S-Alkynyl-Containing Cyclic Peptides","authors":"Zhou Zhang, Junjie Ying, Qingqing Lu, Qinshuo Zhang, Chunfa Xu","doi":"10.1039/d5qo00152h","DOIUrl":"https://doi.org/10.1039/d5qo00152h","url":null,"abstract":"Cyclic peptides are highly valued in drug discovery due to their enhanced biological properties. Despite there potential, the construction of S-alkynyl moiety in a cyclic peptides remains challenging due to limited synthetic strategies. Herein, we describe a copper-catalyzed alkynylation of thiosulfonate-based peptides, enabling efficient and selective synthesis of S-alkynylated cysteines and peptides. The adjustment of the amount of base could significantly increase the efficiency. This method features a broad substrate scope, operational simplicity and compatibility with complex peptide structures.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"29 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486509","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}
Wei-Jing Yang, Jun-Hao Zhang, Ning Li, Ming-Sheng Xie, Hai-Ming Guo
A highly catalytic asymmetric α-amination of α-azaaryl-α-fluoro esters with azodicarboxylates as the electrophilic aminating agents was reported. With C1-symmetric imidazolidine-pyrroloimidazolone pyridine as the tridentate ligand and Ni(BF4)2‧6H2O as the Lewis acid, diverse chiral α-hydrazino-α-fluorinated ester derivatives were obtained in high yields (up to 97% yield) and excellent enantioselectivities (up to 98% ee).
{"title":"Ni(II)-Catalyzed Enantioselective α-Hydrazination of α-Fluoroesters: Access to Chiral Quaternary α-Fluorinated α-Amino Acid Derivatives","authors":"Wei-Jing Yang, Jun-Hao Zhang, Ning Li, Ming-Sheng Xie, Hai-Ming Guo","doi":"10.1039/d4qo02418d","DOIUrl":"https://doi.org/10.1039/d4qo02418d","url":null,"abstract":"A highly catalytic asymmetric α-amination of α-azaaryl-α-fluoro esters with azodicarboxylates as the electrophilic aminating agents was reported. With C1-symmetric imidazolidine-pyrroloimidazolone pyridine as the tridentate ligand and Ni(BF4)2‧6H2O as the Lewis acid, diverse chiral α-hydrazino-α-fluorinated ester derivatives were obtained in high yields (up to 97% yield) and excellent enantioselectivities (up to 98% ee).","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"26 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486512","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}
Herein, we disclose a novel carbonylative Suzuki-Miyaura reaction for the synthesis of diaryl ketones via palladium-catalyzed difluorocarbene transfer. BrCF2CO2Et was employed as a safe and effective carbonyl surrogate. The CO was readily in situ generated from the reaction of H2O with intermediate PdII=CF2. The current protocol offers a pragmatic and efficient approach for the synthesis of a series of diaryl ketones with the yield up to 97%. The broad substrate scope and further synthetic application in drugs and functional compounds represent that this carbonylative reaction is a highly appealing strategy.
{"title":"Palladium-Catalyzed Difluorocarbene Transfer Synthesis of Diaryl Ketones from Iodoarene and Arylboronic Acid","authors":"Zhiyong Tan, Tingting Chen, Jiayi Shen, Jinbin Zhu, Weihong Zhong, Wei Guo","doi":"10.1039/d4qo02405b","DOIUrl":"https://doi.org/10.1039/d4qo02405b","url":null,"abstract":"Herein, we disclose a novel carbonylative Suzuki-Miyaura reaction for the synthesis of diaryl ketones via palladium-catalyzed difluorocarbene transfer. BrCF2CO2Et was employed as a safe and effective carbonyl surrogate. The CO was readily in situ generated from the reaction of H2O with intermediate PdII=CF2. The current protocol offers a pragmatic and efficient approach for the synthesis of a series of diaryl ketones with the yield up to 97%. The broad substrate scope and further synthetic application in drugs and functional compounds represent that this carbonylative reaction is a highly appealing strategy.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"30 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477412","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}
Yu-Zhao Wang, Di-Di Tang, Han-Yue Zhang, Xiao-Yue Ma, De-Hua Xing, Chenjiang Liu, Yu Xia, Yan Li
Visible-light mediated 1,2- dicarbofunctionalization of alkenes provided a powerful tool for the synthesis of structurally complicated and diverse molecules from simple precursors in one step. In this paper, a photo-catalyzed three-component 1,2-alkylation of alkenes with alkylboronic pinacol esters (APEs) and aldehydes have been accomplished. This transition-metal-free protocol provided a clean and efficient manner to access secondary alcohols with wide substrate scope compatibility and good functional group tolerance, and allowed a variety of alkenes, APEs and aldehydes to be transformed to the desired products in moderate to good yields under metal free conditions. Mechanism studies disclosed that this transformation may be involved a radical addition and radical-radical cross coupling process.
{"title":"Visible-light induced three component radical cascade 1,2-dialkylation of alkenes to access alcohols","authors":"Yu-Zhao Wang, Di-Di Tang, Han-Yue Zhang, Xiao-Yue Ma, De-Hua Xing, Chenjiang Liu, Yu Xia, Yan Li","doi":"10.1039/d5qo00080g","DOIUrl":"https://doi.org/10.1039/d5qo00080g","url":null,"abstract":"Visible-light mediated 1,2- dicarbofunctionalization of alkenes provided a powerful tool for the synthesis of structurally complicated and diverse molecules from simple precursors in one step. In this paper, a photo-catalyzed three-component 1,2-alkylation of alkenes with alkylboronic pinacol esters (APEs) and aldehydes have been accomplished. This transition-metal-free protocol provided a clean and efficient manner to access secondary alcohols with wide substrate scope compatibility and good functional group tolerance, and allowed a variety of alkenes, APEs and aldehydes to be transformed to the desired products in moderate to good yields under metal free conditions. Mechanism studies disclosed that this transformation may be involved a radical addition and radical-radical cross coupling process.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"30 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470685","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}
Herein, a new one-pot transition-metal-free catalytic method for the synthesis of C3, 5-disubstituted oxindoles has been developed. The protocol features good functional group tolerance, mild reaction conditions and atom economy. In addition, this protocol provides a platform for the synthesis of novel and complex oxindole derivatives with the potential for biological activity.
{"title":"Transition-metal-free synthesis of C3,5-difunctionalized oxindole derivatives","authors":"Yifeng Liu, Pengyan Zhang, Liangjie Feng, Zhuan Zhang, Taoyuan Liang","doi":"10.1039/d4qo02428a","DOIUrl":"https://doi.org/10.1039/d4qo02428a","url":null,"abstract":"Herein, a new one-pot transition-metal-free catalytic method for the synthesis of C3, 5-disubstituted oxindoles has been developed. The protocol features good functional group tolerance, mild reaction conditions and atom economy. In addition, this protocol provides a platform for the synthesis of novel and complex oxindole derivatives with the potential for biological activity.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"25 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470687","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}
Shan Wang, Ting-Ting Yuan, Jun-Ting Liang, Xiao-Xia Liang, Xuan Deng, Zichen Xu, Ya-Jian Hu, Yu-Tao He
A visible light-mediated synthesis protocol for the three-component pyridylsilylation of olefins to access β-pyridyl silicons has been developed. The reaction cascade is initiated by an in situ generated methoxy radical enabled by EDA complexes formed between the electron-deficient N-methoxypyridinium salts and a base. The reaction using hydrosilane as the silicon source to access silyl radical proceeds well via hydrogen atom transfer process between a silane Si–H bond and the methoxy radical. This protocol features exogenous photocatalyst-free conditions and high atom economy, thereby providing a powerful synthon for preparing silyl- and pyridyl-containing compounds with excellent functional group compatibility. Therefore, it is expected that this method will find applications in synthetic chemistry and drug discovery.
{"title":"Visible light-mediated pyridylsilylation of olefins through hydrogen atom transfer","authors":"Shan Wang, Ting-Ting Yuan, Jun-Ting Liang, Xiao-Xia Liang, Xuan Deng, Zichen Xu, Ya-Jian Hu, Yu-Tao He","doi":"10.1039/d5qo00085h","DOIUrl":"https://doi.org/10.1039/d5qo00085h","url":null,"abstract":"A visible light-mediated synthesis protocol for the three-component pyridylsilylation of olefins to access β-pyridyl silicons has been developed. The reaction cascade is initiated by an in situ generated methoxy radical enabled by EDA complexes formed between the electron-deficient N-methoxypyridinium salts and a base. The reaction using hydrosilane as the silicon source to access silyl radical proceeds well via hydrogen atom transfer process between a silane Si–H bond and the methoxy radical. This protocol features exogenous photocatalyst-free conditions and high atom economy, thereby providing a powerful synthon for preparing silyl- and pyridyl-containing compounds with excellent functional group compatibility. Therefore, it is expected that this method will find applications in synthetic chemistry and drug discovery.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"28 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470686","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}
Liuzhou Gao, Linghui Meng, Yan Wen, Jingyi Hu, Yuxin Sun, Shenglong Wang, Guoqiang Wang, Yidong Wang
An operationally simple base-mediated silylacarboxylation of arylalkenes is developed to synthesize valuable β-silyl functionalized phenylacetic acid derivatives utilizing carbon dioxide and silanion reagents. The protocol is applicable to diversified sets of vinyl substrates including mono-, di-, and trisubstituted alkenes under mild conditions. Control experiments combined with DFT calculations reveal that the reaction starts with the nucleophilic addition of silanion species toward the alkenes; and then the in situ formed benzylic carbanion directly trapped with CO2, forming the silacarboxylation products. Based on the mechanistic insight, the scope of silyl nucleophiles for this transformation can be extended to the disilane (Si-Si) or silyl lithium (Si-Li) reagents. The relevance of this method to the synthesis of drug-relevant compounds further demonstrates its potential applications.
{"title":"t BuOK-Mediated Selective 1,2-Silacarboxylation of Arylalkenes with Si-B/Si-Si/Si-Li Reagents and CO2","authors":"Liuzhou Gao, Linghui Meng, Yan Wen, Jingyi Hu, Yuxin Sun, Shenglong Wang, Guoqiang Wang, Yidong Wang","doi":"10.1039/d4qo02261k","DOIUrl":"https://doi.org/10.1039/d4qo02261k","url":null,"abstract":"An operationally simple base-mediated silylacarboxylation of arylalkenes is developed to synthesize valuable β-silyl functionalized phenylacetic acid derivatives utilizing carbon dioxide and silanion reagents. The protocol is applicable to diversified sets of vinyl substrates including mono-, di-, and trisubstituted alkenes under mild conditions. Control experiments combined with DFT calculations reveal that the reaction starts with the nucleophilic addition of silanion species toward the alkenes; and then the in situ formed benzylic carbanion directly trapped with CO<small><sub>2</sub></small>, forming the silacarboxylation products. Based on the mechanistic insight, the scope of silyl nucleophiles for this transformation can be extended to the disilane (Si-Si) or silyl lithium (Si-Li) reagents. The relevance of this method to the synthesis of drug-relevant compounds further demonstrates its potential applications.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"23 2 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470689","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}
Si-Jing Jiang, Zhao-Zhao Li, Li-Na Yang, Ming Bian, Xiao-Han Qiu, Yu-Ning Gao, Hui-Yu Chen, Zhen-Jiang Liu
A metal-free protocol to synthesize 2-alkyl-3‑fluoroalkanesulfonyl benzofurans and indoles from o‑hydroxyphenyl/o‑aminophenyl propargyl alcohols or 2-propynolphenols/2-propynolanilines and fluoroalkanesulfinyl chlorides (RFSOCl) was disclosed. The mechanism is proposed to involve a sequential [1,2]/[2,3]-sigmatropic rearrangement/intramolecular oxy-addition/1,3-H migration cascade of the propargyl triflinates generated in situ via O-fluoroalkanesulfinylation of propargyl alcohols. The procedure utilizes readily available propargyl alcohols and RFSOCl as starting materials and offers a broad substrate scope with excellent performance (55 examples, up to 98% yield).
{"title":"Metal-free sigmatropic rearrangement/cyclization/aromatization cascade reaction of hydroxy/aminophenyl propargyl alcohols with fluoroalkanesulfinyl chlorides: Synthesis of 3‑fluoroalkanesulfonyl benzofurans and indoles","authors":"Si-Jing Jiang, Zhao-Zhao Li, Li-Na Yang, Ming Bian, Xiao-Han Qiu, Yu-Ning Gao, Hui-Yu Chen, Zhen-Jiang Liu","doi":"10.1039/d5qo00107b","DOIUrl":"https://doi.org/10.1039/d5qo00107b","url":null,"abstract":"A metal-free protocol to synthesize 2-alkyl-3‑fluoroalkanesulfonyl benzofurans and indoles from <em>o</em>‑hydroxyphenyl/<em>o</em>‑aminophenyl propargyl alcohols or 2-propynolphenols/2-propynolanilines and fluoroalkanesulfinyl chlorides (R<small><sub>F</sub></small>SOCl) was disclosed. The mechanism is proposed to involve a sequential [1,2]/[2,3]-sigmatropic rearrangement/intramolecular oxy-addition/1,3-H migration cascade of the propargyl triflinates generated in situ via <em>O</em>-fluoroalkanesulfinylation of propargyl alcohols. The procedure utilizes readily available propargyl alcohols and R<small><sub>F</sub></small>SOCl as starting materials and offers a broad substrate scope with excellent performance (55 examples, up to 98% yield).","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"209 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470684","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}
Jin Zhang, Yang He, Xinhao Zhu, Yan Guo, Xiaogang Wang, Ruihong Wang, Michal Szostak
A new method for chemoselective transition-metal-free acylation of thioamides with ketones by N–C(S) bond cleavage is reported. The approach exploits acyclic twisted thioamides to accomplish selective thio-Claisen condensation by ground state-destabilization of the thioamide bond. The valuable 3-hydroxy-1-thioxoketone products are obtained from bench-stable thioamide precursors under mild transition-metal-free, room temperature conditions. Various ground-state-destabilized thio-amides are amenable to this selective thio-acylation protocol. The method advances the reactivity of twisted thioamides to C–C bond forming reactions under transition-metal-free conditions.
{"title":"Chemoselective Transition-Metal-Free Acylation of Thioamides by N–C(S) Bond Cleavage using Acyclic Twisted Thioamides","authors":"Jin Zhang, Yang He, Xinhao Zhu, Yan Guo, Xiaogang Wang, Ruihong Wang, Michal Szostak","doi":"10.1039/d4qo02417f","DOIUrl":"https://doi.org/10.1039/d4qo02417f","url":null,"abstract":"A new method for chemoselective transition-metal-free acylation of thioamides with ketones by N–C(S) bond cleavage is reported. The approach exploits acyclic twisted thioamides to accomplish selective thio-Claisen condensation by ground state-destabilization of the thioamide bond. The valuable 3-hydroxy-1-thioxoketone products are obtained from bench-stable thioamide precursors under mild transition-metal-free, room temperature conditions. Various ground-state-destabilized thio-amides are amenable to this selective thio-acylation protocol. The method advances the reactivity of twisted thioamides to C–C bond forming reactions under transition-metal-free conditions.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"52 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470683","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}
Chiral γ-hydroxy-γ-lactams were versatile building blocks for the synthesis of many important bioactive compounds. Herein, we disclosed a regio- and enantioselective direct α-selective allylation of amide moiety of maleimides with potassium allyltrifluoroborates via dual-functional InIII/N,N'-dioxide complex. This protocol provides a straightforward route to optically active γ-hydroxy-γ-lactams. Additionally, alkenyloxindoles were tolerated as well, affording enantioenriched 2-allylindolin-2-ols in high yields. The gram-scale synthesis and further transformations of the products demonstrate the potential utility of this method. Based on the experimental studies and DFT calculations, a possible catalytic cycle and transition states were provided to elucidate the regio- and enantioselectivity.
{"title":"Asymmetric α-selective allylation of amide unit of maleimides and alkenyloxindoles by dual-functional InIII/N,N'-dioxide complex","authors":"Wang-Yuren Li, Longqing Yang, Xiaoxue Tang, Wenjun Yan, Zhao Wu, Fei Wang, Shunxi Dong, Xiaoming Feng","doi":"10.1039/d4qo02320j","DOIUrl":"https://doi.org/10.1039/d4qo02320j","url":null,"abstract":"Chiral γ-hydroxy-γ-lactams were versatile building blocks for the synthesis of many important bioactive compounds. Herein, we disclosed a regio- and enantioselective direct α-selective allylation of amide moiety of maleimides with potassium allyltrifluoroborates via dual-functional InIII/N,N'-dioxide complex. This protocol provides a straightforward route to optically active γ-hydroxy-γ-lactams. Additionally, alkenyloxindoles were tolerated as well, affording enantioenriched 2-allylindolin-2-ols in high yields. The gram-scale synthesis and further transformations of the products demonstrate the potential utility of this method. Based on the experimental studies and DFT calculations, a possible catalytic cycle and transition states were provided to elucidate the regio- and enantioselectivity.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"34 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470690","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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