Under acidic conditions, propargylic alcohols undergo Meyer–Schuster or Rupe rearrangements to afford two isomeric α,β-unsaturated ketones. Herein, we disclose a mechanistically distinct base-mediated regioselective conversion of TMS ethers of propargylic alcohols to 1,3-enynes in high yields with broad functional-group compatibility. Alternatively, trapping of the in situ-generated lithium acetylide with electrophiles enables access to functionalized internal 1,3-enynes. Owing to the ready accessibility of propargylic alcohols, this method provides a practical and attractive entry to synthetically valuable 1,3-enynes.
{"title":"Base-Promoted Conversion of Propargylic Alcohols to 1,3-Enynes","authors":"Morgane Delattre,Milena Wiegand,Qian Wang,Jieping Zhu","doi":"10.1021/acs.orglett.6c00196","DOIUrl":"https://doi.org/10.1021/acs.orglett.6c00196","url":null,"abstract":"Under acidic conditions, propargylic alcohols undergo Meyer–Schuster or Rupe rearrangements to afford two isomeric α,β-unsaturated ketones. Herein, we disclose a mechanistically distinct base-mediated regioselective conversion of TMS ethers of propargylic alcohols to 1,3-enynes in high yields with broad functional-group compatibility. Alternatively, trapping of the in situ-generated lithium acetylide with electrophiles enables access to functionalized internal 1,3-enynes. Owing to the ready accessibility of propargylic alcohols, this method provides a practical and attractive entry to synthetically valuable 1,3-enynes.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"1 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111172","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}
Despite the broad utility of cyclic diaryl λ3-bromanes as aryne precursors for nucleophilic additions by heteroatom-based nucleophiles under mild basic conditions, their capacity to install arylchalcogen bonds in a regioselective manner is largely unexplored and challenging. The higher oxidative addition barrier of cyclic diaryl λ3-bromanes relative to their iodine analogues leads to transition-metal-catalyzed aryl–chalcogen bond formation requiring more forcing conditions, which decreases the regioselectivity. Moreover, the oxidizing character of hypervalent bromanes might be problematic. Herein, we disclose a photocatalytic strategy to achieve highly regioselective thiolation and selenylation of cyclic diaryl λ3-bromanes. This reaction proceeds under mild reaction conditions and exhibits a broad substrate scope with a good functional group tolerance and excellent regioselectivity.
{"title":"Regioselective Thiolation and Selenylation of Cyclic Diaryl λ3-Bromanes Enabled by Visible-Light Photocatalysis","authors":"Xue-Ying Yang,Qiang Wang,Si-Rui Jia,Shi-Yu Fu,Ming-Chuan Wang,Zhi-Yue Dong,Wan-Xuan Zhang,Bin-Jie Li,Wen-Jing Xiao","doi":"10.1021/acs.orglett.5c05455","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05455","url":null,"abstract":"Despite the broad utility of cyclic diaryl λ3-bromanes as aryne precursors for nucleophilic additions by heteroatom-based nucleophiles under mild basic conditions, their capacity to install arylchalcogen bonds in a regioselective manner is largely unexplored and challenging. The higher oxidative addition barrier of cyclic diaryl λ3-bromanes relative to their iodine analogues leads to transition-metal-catalyzed aryl–chalcogen bond formation requiring more forcing conditions, which decreases the regioselectivity. Moreover, the oxidizing character of hypervalent bromanes might be problematic. Herein, we disclose a photocatalytic strategy to achieve highly regioselective thiolation and selenylation of cyclic diaryl λ3-bromanes. This reaction proceeds under mild reaction conditions and exhibits a broad substrate scope with a good functional group tolerance and excellent regioselectivity.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"50 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111256","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}
Sulfur-containing compounds are essential motifs of natural molecules. We herein report a photoinduced iron-catalyzed strategy for efficient sulfoxide deoxygenation under mild conditions. The iron catalyst as the sole additive acts dually: it activates hydrocarbon reductants (also as a solvent) via a ligand-to-metal charge transfer pathway and serves as an “electron buffer” to regulate subsequent electron transfer. This unique mechanism enables a non-chromatography protocol with high efficiency (majority at >95%, up to 99%) and selectivity. The operationally simple method exhibits broad functional group tolerance and wide application in late-stage transformation of drug-derived sulfoxides into bioactive sulfides.
{"title":"Hydrocarbon-Involved Sulfoxide Deoxygenation via Bifunctional Iron-Enabled Electron Buffering and Ligand-to-Metal Charge Transfer","authors":"Lifang Wang, Bolin Qiao, Wenlong He, Ran Xu, Shuyang Liu, Hui Zi, Fangyi Qu, Ziyi Xu, Ruixiao Tian, Shi-Jun Li, Yu Lan, Yunhe Jin","doi":"10.1021/acs.orglett.6c00033","DOIUrl":"https://doi.org/10.1021/acs.orglett.6c00033","url":null,"abstract":"Sulfur-containing compounds are essential motifs of natural molecules. We herein report a photoinduced iron-catalyzed strategy for efficient sulfoxide deoxygenation under mild conditions. The iron catalyst as the sole additive acts dually: it activates hydrocarbon reductants (also as a solvent) via a ligand-to-metal charge transfer pathway and serves as an “electron buffer” to regulate subsequent electron transfer. This unique mechanism enables a non-chromatography protocol with high efficiency (majority at >95%, up to 99%) and selectivity. The operationally simple method exhibits broad functional group tolerance and wide application in late-stage transformation of drug-derived sulfoxides into bioactive sulfides.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"21 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146110704","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}
Pub Date : 2026-02-03DOI: 10.1021/acs.orglett.6c00097
Usha Yadav, Sanoop P. Chandrasekharan, Anamika Dhami, Kishor Mohanan
In this paper, we disclose the utility of trifluorodiazoethane in forging trifluoromethylated β-lactams through a streamlined, one-pot Cu-catalyzed reaction involving nitrosoarenes and alkynes. This process involves the in situ generation of trifluoromethylnitrones from trifluorodiazoethane and nitrosoarenes, followed by their reaction with arylacetylenes under Kinugasa conditions, leading to the formation of trifluoromethylated β-lactams. A broad scope of reaction partners, including the Seyferth–Gilbert reagent, various nitrosoarenes, and alkynes, was demonstrated, along with an illustration of the potential of this strategy through multiple synthetic modifications.
{"title":"Cu-Catalyzed One-Pot Synthesis of Trifluoromethylated β-Lactams by Reaction of Nitrosoarenes, Trifluorodiazoethane and Arylacetylenes","authors":"Usha Yadav, Sanoop P. Chandrasekharan, Anamika Dhami, Kishor Mohanan","doi":"10.1021/acs.orglett.6c00097","DOIUrl":"https://doi.org/10.1021/acs.orglett.6c00097","url":null,"abstract":"In this paper, we disclose the utility of trifluorodiazoethane in forging trifluoromethylated β-lactams through a streamlined, one-pot Cu-catalyzed reaction involving nitrosoarenes and alkynes. This process involves the in situ generation of trifluoromethylnitrones from trifluorodiazoethane and nitrosoarenes, followed by their reaction with arylacetylenes under Kinugasa conditions, leading to the formation of trifluoromethylated β-lactams. A broad scope of reaction partners, including the Seyferth–Gilbert reagent, various nitrosoarenes, and alkynes, was demonstrated, along with an illustration of the potential of this strategy through multiple synthetic modifications.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"30 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146110705","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}
Pub Date : 2026-02-03DOI: 10.1021/acs.orglett.5c04873
John Putziger, Elya Kandahari, Song Lin
The reactivity and synthetic utility of TEMPO-derived alkoxyamines as functional handles remains insufficiently explored. This report interrogates the factors governing the stereospecific substitution of electroactivated TEMPO-derived α-carbonyl alkoxyamines. Concurrent with direct electrolysis, electroanalytical studies and theoretical calculations provided a complementary platform by which one could predict the efficacy for substrates to undergo desired substitution using benzoic acid or N-sulfonyl carbamate nucleophiles.
{"title":"Electrochemical Activation of α-Carbonyl Alkoxyamines for Direct Nucleophilic Substitution","authors":"John Putziger, Elya Kandahari, Song Lin","doi":"10.1021/acs.orglett.5c04873","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04873","url":null,"abstract":"The reactivity and synthetic utility of TEMPO-derived alkoxyamines as functional handles remains insufficiently explored. This report interrogates the factors governing the stereospecific substitution of electroactivated TEMPO-derived α-carbonyl alkoxyamines. Concurrent with direct electrolysis, electroanalytical studies and theoretical calculations provided a complementary platform by which one could predict the efficacy for substrates to undergo desired substitution using benzoic acid or <i>N</i>-sulfonyl carbamate nucleophiles.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"41 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146110703","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}
Pub Date : 2026-02-03DOI: 10.1021/acs.orglett.5c05386
Yi-Kao Xu,Yuan-Qing Dong,Jun Jiang,Cui-Ting Li,Wei-Min He,Gongde Wu,Bo Zhou,Long-Wu Ye
Dearomative cyclopropanation of benzofurans is a powerful strategy for the assembly of valuable O-heterocycles. However, transition metal-catalyzed cyclopropanation of benzofurans is generally limited to diazo compounds. Herein, a copper-catalyzed dearomative cyclopropanation of benzofurans with diynes via vinyl cations is described, enabling the atom-economical and practical synthesis of various cyclopropa[b]benzofurans in generally moderate to excellent yields. Furthermore, preliminary studies on asymmetric catalysis reveal that the desired chiral cyclopropa[b]benzofurans could be synthesized with good to excellent ee’s.
{"title":"Copper-Catalyzed Dearomative Cyclopropanation of Benzofurans with Diynes via Vinyl Cations","authors":"Yi-Kao Xu,Yuan-Qing Dong,Jun Jiang,Cui-Ting Li,Wei-Min He,Gongde Wu,Bo Zhou,Long-Wu Ye","doi":"10.1021/acs.orglett.5c05386","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05386","url":null,"abstract":"Dearomative cyclopropanation of benzofurans is a powerful strategy for the assembly of valuable O-heterocycles. However, transition metal-catalyzed cyclopropanation of benzofurans is generally limited to diazo compounds. Herein, a copper-catalyzed dearomative cyclopropanation of benzofurans with diynes via vinyl cations is described, enabling the atom-economical and practical synthesis of various cyclopropa[b]benzofurans in generally moderate to excellent yields. Furthermore, preliminary studies on asymmetric catalysis reveal that the desired chiral cyclopropa[b]benzofurans could be synthesized with good to excellent ee’s.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"1 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111193","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}
Pub Date : 2026-02-03DOI: 10.1021/acs.orglett.6c00100
Mohammed M. A. Ahmed, Jordan Nafie, Jeffrey D. Rudolf
Myxobacterial terpenoids are rare and only a few myxobacterial terpene synthases are known. A terpene synthase, IbdS, from Polyangium aurulentum sp. SDU3-1 was found to produce the Δ9,10 isomer (1) of the spirocyclic 6/7/5-tricyclic bonnadiene, along with several 6/10-eunicellanes and cembrenoids as minor products. Sequence comparison and site-directed mutagenesis of IbdS and the actinobacterial bonnadiene synthase revealed a single residue switch at position 57 controlling isomer selectivity.
{"title":"A Single Residue Switch Controls Isomer Selectivity in the Myxobacterial Isobonnadiene Synthase","authors":"Mohammed M. A. Ahmed, Jordan Nafie, Jeffrey D. Rudolf","doi":"10.1021/acs.orglett.6c00100","DOIUrl":"https://doi.org/10.1021/acs.orglett.6c00100","url":null,"abstract":"Myxobacterial terpenoids are rare and only a few myxobacterial terpene synthases are known. A terpene synthase, IbdS, from <i>Polyangium aurulentum</i> sp. SDU3-1 was found to produce the Δ<sup>9,10</sup> isomer (<b>1</b>) of the spirocyclic 6/7/5-tricyclic bonnadiene, along with several 6/10-eunicellanes and cembrenoids as minor products. Sequence comparison and site-directed mutagenesis of IbdS and the actinobacterial bonnadiene synthase revealed a single residue switch at position 57 controlling isomer selectivity.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"176 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146110706","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}
The utilization of hydrazones as carbon or nitrogen sources in transition-metal-catalyzed synthetic chemistry has been well developed; however, their application as electrophilic sulfur cation surrogates remains uncharted territory. Herein, we report the unexpected discovery that sulfonyl hydrazones serve as programmable sulfur transfer in nickel-catalyzed C–S coupling with a broad range of organic halides. This method forges the nickel catalytic cycle toward selective C–S cross-coupling while effectively suppressing the competing formation of conventional C–C coupling products. Mechanistic studies indicate that the success of this strategy stems from the favorable reduction potential imparted by the electron-withdrawing SO2R group, which enables manganese to reduce the hydrazones in situ, generating key electrophilic sulfur species to engage in a distinctive nickel catalytic cycle that favors C–S over C–C bond formation.
{"title":"Redox-Active Sulfonyl Hydrazones as Programmable Sulfur Transfer for Nickel-Catalyzed C–S Coupling with Organic Halides","authors":"Binglian Yang,Liguang Ji,Hui Wang,Fangcan Liang,Mengfan Zheng,Ji-Quan Liu,Chao-Jun Li,Dianhu Zhu","doi":"10.1021/acs.orglett.5c05399","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05399","url":null,"abstract":"The utilization of hydrazones as carbon or nitrogen sources in transition-metal-catalyzed synthetic chemistry has been well developed; however, their application as electrophilic sulfur cation surrogates remains uncharted territory. Herein, we report the unexpected discovery that sulfonyl hydrazones serve as programmable sulfur transfer in nickel-catalyzed C–S coupling with a broad range of organic halides. This method forges the nickel catalytic cycle toward selective C–S cross-coupling while effectively suppressing the competing formation of conventional C–C coupling products. Mechanistic studies indicate that the success of this strategy stems from the favorable reduction potential imparted by the electron-withdrawing SO2R group, which enables manganese to reduce the hydrazones in situ, generating key electrophilic sulfur species to engage in a distinctive nickel catalytic cycle that favors C–S over C–C bond formation.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"215 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111284","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}
Spiro-cyclobutanes are sp3-rich molecules with applications in synthetic chemistry and drug discovery. The existing literature focuses mainly on their synthesis via the metal-catalyzed functionalization of substrates, such as spiro-cyclobutenes. In this letter, we disclose a H-bond-directed photochemical synthesis of densely substituted spiro-cyclobutanes. Moreover, a strain-release- and H-bond-directed three-component reaction of alkenes, p-quinone methide, and NH4SCN is also discussed. The reaction outcome is explained through control experiments and DFT calculations.
{"title":"H-Bond- and Strain-Release-Guided Photoreaction of Alkenes, p-Quinone Methides, and Ammonium Thiocyanate","authors":"Jobsy Jose,Arun Yadav,Saumya Singh,Sathish Kumar Mudedla,Chandra Bhushan Tripathi","doi":"10.1021/acs.orglett.5c05458","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05458","url":null,"abstract":"Spiro-cyclobutanes are sp3-rich molecules with applications in synthetic chemistry and drug discovery. The existing literature focuses mainly on their synthesis via the metal-catalyzed functionalization of substrates, such as spiro-cyclobutenes. In this letter, we disclose a H-bond-directed photochemical synthesis of densely substituted spiro-cyclobutanes. Moreover, a strain-release- and H-bond-directed three-component reaction of alkenes, p-quinone methide, and NH4SCN is also discussed. The reaction outcome is explained through control experiments and DFT calculations.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"292 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098070","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}
Pub Date : 2026-02-02DOI: 10.1021/acs.orglett.6c00073
Max Schönenbroicher, Maximilian Seul, Simon Morgenschweis, Florian Heppner, Dirk Menche
The synthesis of the western fragment of vancoresmycin was accomplished in a highly modular and stereoselective manner. Central to this strategy was a modified Cu-catalyzed β-boration protocol for α,β-unsaturated enones, which enabled convergent construction of complex, densely functionalized polyketide architectures with high stereocontrol. Application to a structurally demanding fragment highlighted its potential as a general tool for 1,3-diol construction. In addition, NMR comparison confirmed the stereochemical assignment of the western part of vancoresmycin.
{"title":"Stereoselective Synthesis of the Western Fragment of Vancoresmycin.","authors":"Max Schönenbroicher, Maximilian Seul, Simon Morgenschweis, Florian Heppner, Dirk Menche","doi":"10.1021/acs.orglett.6c00073","DOIUrl":"https://doi.org/10.1021/acs.orglett.6c00073","url":null,"abstract":"<p><p>The synthesis of the western fragment of vancoresmycin was accomplished in a highly modular and stereoselective manner. Central to this strategy was a modified Cu-catalyzed β-boration protocol for α,β-unsaturated enones, which enabled convergent construction of complex, densely functionalized polyketide architectures with high stereocontrol. Application to a structurally demanding fragment highlighted its potential as a general tool for 1,3-diol construction. In addition, NMR comparison confirmed the stereochemical assignment of the western part of vancoresmycin.</p>","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103146","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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