We present a method for the silver-catalyzed oxacyclization of 3-alkynylpyrroles to create the pyrano[3,4-b]pyrrolone scaffold. This method exhibits high regioselectivity, enabling position-specific functionalization of the pyrrole core without the need for N-protection. It is also compatible with a broad range of substrates. Using this strategy, we synthesized a small library of novel triarylated pyranopyrroles, thereby enabling the creation of substitution patterns that were previously challenging to achieve. This methodology, therefore, provides a versatile approach to heteroaromatic architectures that are potentially relevant in drug discovery and chemical biology.
{"title":"Silver-Catalyzed Regioselective Oxacyclization of 3-Alkynyl Pyrroles: Straightforward Route to 2,3,5-Triarylated Pyrano[3,4-b]Pyrrolones","authors":"Fatma Cherif, , , Julien Petrignet, , , Pierre-Olivier Delaye, , , Moufida Romdhani-Younes, , and , Jérôme Thibonnet*, ","doi":"10.1021/acs.joc.5c02475","DOIUrl":"10.1021/acs.joc.5c02475","url":null,"abstract":"<p >We present a method for the silver-catalyzed oxacyclization of 3-alkynylpyrroles to create the pyrano[3,4-<i>b</i>]pyrrolone scaffold. This method exhibits high regioselectivity, enabling position-specific functionalization of the pyrrole core without the need for <i>N</i>-protection. It is also compatible with a broad range of substrates. Using this strategy, we synthesized a small library of novel triarylated pyranopyrroles, thereby enabling the creation of substitution patterns that were previously challenging to achieve. This methodology, therefore, provides a versatile approach to heteroaromatic architectures that are potentially relevant in drug discovery and chemical biology.</p>","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"91 5","pages":"2004–2017"},"PeriodicalIF":3.6,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056438","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}
Li Zhao, , , Wei Hu, , , Yong-Ke He*, , , Shaoyu Li*, , and , Yuming Yang*,
The photocatalytic carbofunctionalization of N-sulfinylamines offers an efficient route to diverse sulfinamides, yet the direct use of inexpensive boronic acids as radical precursors has been limited due to their high oxidation potentials. To address this, we developed a Lewis base-assisted strategy that generates a sp3-hybridized tetracoordinated boronate complex in situ with a markedly lowered redox potential. This approach enables a practical and atom-economical photocatalytic synthesis of sulfinamides directly from N-sulfinylamines and commercially available boronic acids.
n -亚亚胺的光催化碳官能化提供了一种有效的途径来制备各种亚亚胺,但由于其高氧化电位,直接使用廉价的硼酸作为自由基前体一直受到限制。为了解决这个问题,我们开发了一种Lewis碱辅助策略,在原位生成sp3杂交的四配位硼酸盐配合物,其氧化还原电位明显降低。该方法实现了一种实用且原子经济的光催化合成亚胺,直接从n -亚胺和市售硼酸中合成亚胺。
{"title":"Photocatalytic Sulfinamide Synthesis with Boronic Acids and N-Sulfinylamines","authors":"Li Zhao, , , Wei Hu, , , Yong-Ke He*, , , Shaoyu Li*, , and , Yuming Yang*, ","doi":"10.1021/acs.joc.5c02893","DOIUrl":"10.1021/acs.joc.5c02893","url":null,"abstract":"<p >The photocatalytic carbofunctionalization of <i>N</i>-sulfinylamines offers an efficient route to diverse sulfinamides, yet the direct use of inexpensive boronic acids as radical precursors has been limited due to their high oxidation potentials. To address this, we developed a Lewis base-assisted strategy that generates a sp<sup>3</sup>-hybridized tetracoordinated boronate complex in situ with a markedly lowered redox potential. This approach enables a practical and atom-economical photocatalytic synthesis of sulfinamides directly from <i>N</i>-sulfinylamines and commercially available boronic acids.</p>","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"91 5","pages":"2296–2301"},"PeriodicalIF":3.6,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056440","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}
Riju Moni Moran,Kangkana Chutia,Rajashree Bhuyan,Pranjal Gogoi
A Pd-catalyzed cascade process has been developed for the direct synthesis of hydroxylated fluorenes from o-bromophenyl-substituted p-quinone methides (p-QMs) and 3-hydroxy-substituted arylboronic acids. This cascade process comprises Suzuki coupling, followed by intramolecular ipso-Friedel–Crafts arylation, which affords the functionalized fluorenes in good yields. This protocol offers several advantages, including substrate versatility and high regioselectivity. Additionally, both symmetrical and unsymmetrical p-quinone methides participate smoothly in this cascade process.
{"title":"Pd-Catalyzed Suzuki Coupling Followed by Intramolecular Ipso-Friedel–Crafts Arylation Process: Cascade Synthesis of Hydroxylated Fluorenes","authors":"Riju Moni Moran,Kangkana Chutia,Rajashree Bhuyan,Pranjal Gogoi","doi":"10.1021/acs.joc.5c02946","DOIUrl":"https://doi.org/10.1021/acs.joc.5c02946","url":null,"abstract":"A Pd-catalyzed cascade process has been developed for the direct synthesis of hydroxylated fluorenes from o-bromophenyl-substituted p-quinone methides (p-QMs) and 3-hydroxy-substituted arylboronic acids. This cascade process comprises Suzuki coupling, followed by intramolecular ipso-Friedel–Crafts arylation, which affords the functionalized fluorenes in good yields. This protocol offers several advantages, including substrate versatility and high regioselectivity. Additionally, both symmetrical and unsymmetrical p-quinone methides participate smoothly in this cascade process.","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"87 1","pages":""},"PeriodicalIF":4.354,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045031","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}
Pankaj K. Majhi, , , Catherine M. Fleming, , and , Andrew Sutherland*,
Aryl iodides are privileged intermediates in organic synthesis, underpinning cross-coupling chemistry, late-stage functionalization, and radiolabeling in medicinal chemistry. However, regioselective arene iodination remains a challenge, as traditional electrophilic iodination methods often require harsh conditions, exhibit poor selectivity, or suffer from limited functional group tolerance and substrate scope. We report a rapid and regioselective arene iodination enabled by Lewis acid activation of N-iodosaccharin. Iron(III) chloride and silver(I) triflimide were found to catalyze the efficient iodination of a broad range of electron-rich arenes at room temperature. The method displayed broad functional group tolerance and was applicable to complex substrates, including natural products and pharmaceuticals. Furthermore, the iodination was found to be compatible with cross-coupling reactions, allowing one-pot halogenation and arylation sequences for direct access to biaryl compounds.
{"title":"Regioselective Iodination of Arenes Using Iron- or Silver-Catalyzed Activation of N-Iodosaccharin","authors":"Pankaj K. Majhi, , , Catherine M. Fleming, , and , Andrew Sutherland*, ","doi":"10.1021/acs.joc.5c03183","DOIUrl":"10.1021/acs.joc.5c03183","url":null,"abstract":"<p >Aryl iodides are privileged intermediates in organic synthesis, underpinning cross-coupling chemistry, late-stage functionalization, and radiolabeling in medicinal chemistry. However, regioselective arene iodination remains a challenge, as traditional electrophilic iodination methods often require harsh conditions, exhibit poor selectivity, or suffer from limited functional group tolerance and substrate scope. We report a rapid and regioselective arene iodination enabled by Lewis acid activation of <i>N</i>-iodosaccharin. Iron(III) chloride and silver(I) triflimide were found to catalyze the efficient iodination of a broad range of electron-rich arenes at room temperature. The method displayed broad functional group tolerance and was applicable to complex substrates, including natural products and pharmaceuticals. Furthermore, the iodination was found to be compatible with cross-coupling reactions, allowing one-pot halogenation and arylation sequences for direct access to biaryl compounds.</p>","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"91 5","pages":"2257–2267"},"PeriodicalIF":3.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.joc.5c03183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A visible-light-driven cross-dehydrogenative coupling of azauracils with aldehydes is described by using dual acridinium photoredox and pyridine N-oxide hydrogen atom transfer catalysis. This oxidant-free method generates acyl radicals under mild conditions, tolerates diverse functional groups, proceeds under air, and is scalable to gram quantities. Mechanistic studies support the selective oxidation of pyridine N-oxide by the photoexcited catalyst, enabling aldehyde activation. This operationally simple protocol provides a sustainable platform for the late-stage functionalization of nitrogen-rich heterocycles.
{"title":"Visible-Light-Induced Acridinium and Pyridine N-Oxide Dual Catalysis for Direct Acylation of Azauracils with Aldehydes","authors":"Lusina Mantry, , , Sivakumar Sudharsan, , and , Parthasarathy Gandeepan*, ","doi":"10.1021/acs.joc.5c02718","DOIUrl":"10.1021/acs.joc.5c02718","url":null,"abstract":"<p >A visible-light-driven cross-dehydrogenative coupling of azauracils with aldehydes is described by using dual acridinium photoredox and pyridine <i>N</i>-oxide hydrogen atom transfer catalysis. This oxidant-free method generates acyl radicals under mild conditions, tolerates diverse functional groups, proceeds under air, and is scalable to gram quantities. Mechanistic studies support the selective oxidation of pyridine <i>N</i>-oxide by the photoexcited catalyst, enabling aldehyde activation. This operationally simple protocol provides a sustainable platform for the late-stage functionalization of nitrogen-rich heterocycles.</p>","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"91 5","pages":"2113–2120"},"PeriodicalIF":3.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045036","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}
Vasiliy M. Muzalevskiy, , , Zoia A. Sizova, , , Andrei A. Vasil’ev, , and , Valentine G. Nenajdenko*,
Reaction of β-halo-β-(trifluoromethyl)styrenes with arylboronic acids can be directed in a different way depending on strength of the applied base and order of the reactant mixing. The standard Suzuki cross-coupling (Pd(OAc)2/SPhos or Pd(PPh3)4) using K3PO4 or Na2CO3 as the bases afforded regio- and stereoselectively CF3-containing 1,2-diarylethenes (CF3-stilbenes) in up to 98% yield. However, pretreatment of these β-halo-β-(trifluoromethyl)styrenes with t-BuOK resulted in formation in situ of the corresponding CF3-acetylenes. Subsequent Pd-catalyzed syn-addition of arylboronic acids can be performed as one-pot protocol to open access to CF3-containing 1,1-diarylethenes having cis-arranged CF3 group and aryl moiety of starting styrene. These alkenes were isolated in up to 96% yield. Both types of alkenes can be efficiently reduced into the corresponding CF3-substituted ethanes using ammonium formate-Pd/C system.
{"title":"Regio- and Stereoselective Synthesis of CF3-Containing 1,2- and 1,1-Diarylethenes. Switchable Reaction of β-Halo-β-(trifluoromethyl)styrenes with Boronic Acids","authors":"Vasiliy M. Muzalevskiy, , , Zoia A. Sizova, , , Andrei A. Vasil’ev, , and , Valentine G. Nenajdenko*, ","doi":"10.1021/acs.joc.5c02697","DOIUrl":"10.1021/acs.joc.5c02697","url":null,"abstract":"<p >Reaction of β-halo-β-(trifluoromethyl)styrenes with arylboronic acids can be directed in a different way depending on strength of the applied base and order of the reactant mixing. The standard Suzuki cross-coupling (Pd(OAc)<sub>2</sub>/SPhos or Pd(PPh<sub>3</sub>)<sub>4</sub>) using K<sub>3</sub>PO<sub>4</sub> or Na<sub>2</sub>CO<sub>3</sub> as the bases afforded regio- and stereoselectively CF<sub>3</sub>-containing 1,2-diarylethenes (CF<sub>3</sub>-stilbenes) in up to 98% yield. However, pretreatment of these β-halo-β-(trifluoromethyl)styrenes with <i>t</i>-BuOK resulted in formation in situ of the corresponding CF<sub>3</sub>-acetylenes. Subsequent Pd-catalyzed <i>syn</i>-addition of arylboronic acids can be performed as one-pot protocol to open access to CF<sub>3</sub>-containing 1,1-diarylethenes having <i>cis</i>-arranged CF<sub>3</sub> group and aryl moiety of starting styrene. These alkenes were isolated in up to 96% yield. Both types of alkenes can be efficiently reduced into the corresponding CF<sub>3</sub>-substituted ethanes using ammonium formate-Pd/C system.</p>","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"91 5","pages":"2074–2087"},"PeriodicalIF":3.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044868","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}
Qingqing Dong, , , Lizhe He, , , Adam Czader, , and , Robert J. Comito*,
N-H imines are synthetically versatile but sensitive intermediates in organic synthesis. This work introduces a cascade synthesis of basic amines through N-H imine intermediates, featuring an efficient aza-Norrish Type II fragmentation, followed by photoalkylation. Our method selectively converts bench-stable phenacylamines to α-quaternary primary amines in one pot using mild and metal-free UV photocatalysis. Our work constitutes a rare use of amine photofragmentation in organic synthesis.
{"title":"Cascade Photofragmentation/Photoalkylation for the Synthesis of α-Tertiary Alkyl Primary Amines","authors":"Qingqing Dong, , , Lizhe He, , , Adam Czader, , and , Robert J. Comito*, ","doi":"10.1021/acs.joc.5c03147","DOIUrl":"10.1021/acs.joc.5c03147","url":null,"abstract":"<p ><i>N</i>-H imines are synthetically versatile but sensitive intermediates in organic synthesis. This work introduces a cascade synthesis of basic amines through <i>N</i>-H imine intermediates, featuring an efficient <i>aza</i>-Norrish Type II fragmentation, followed by photoalkylation. Our method selectively converts bench-stable phenacylamines to α-quaternary primary amines in one pot using mild and metal-free UV photocatalysis. Our work constitutes a rare use of amine photofragmentation in organic synthesis.</p>","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"91 5","pages":"2315–2319"},"PeriodicalIF":3.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045032","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}
Pauline E. Iwerks, , , Eva R. McKinney, , , Sarah F. Oppenheim, , , Tashani M. Williams, , , Elizabeth A. Scholer, , and , Anna C. Brezny*,
Oxygen atom transfer (OAT) is a useful reaction in chemical synthesis, but because of the low reactivity of O2 with organic substrates, harsh oxidants are often required. In contrast, metalloenzymes such as Cytochrome P450 catalyze a wide range of OAT reactions under mild conditions with O2 as the source of the O atoms. In this work, we use a synthetic manganese porphyrin catalyst to mimic this reactivity. Our method enables electrochemical epoxidation of styrenes using O2 through the generation of a Mn-superoxo intermediate. We report the reactivity of 12 styrene derivatives, with yields impacted by the position and electronic properties of the substituents. Spectroelectrochemical analyses indicate the generation of high-valent intermediates that enable epoxidation under these mild conditions.
{"title":"Electrochemical Aerobic Epoxidation of Styrenes Catalyzed by Manganese Tetraphenylporphyrin","authors":"Pauline E. Iwerks, , , Eva R. McKinney, , , Sarah F. Oppenheim, , , Tashani M. Williams, , , Elizabeth A. Scholer, , and , Anna C. Brezny*, ","doi":"10.1021/acs.joc.5c02884","DOIUrl":"10.1021/acs.joc.5c02884","url":null,"abstract":"<p >Oxygen atom transfer (OAT) is a useful reaction in chemical synthesis, but because of the low reactivity of O<sub>2</sub> with organic substrates, harsh oxidants are often required. In contrast, metalloenzymes such as Cytochrome P450 catalyze a wide range of OAT reactions under mild conditions with O<sub>2</sub> as the source of the O atoms. In this work, we use a synthetic manganese porphyrin catalyst to mimic this reactivity. Our method enables electrochemical epoxidation of styrenes using O<sub>2</sub> through the generation of a Mn-superoxo intermediate. We report the reactivity of 12 styrene derivatives, with yields impacted by the position and electronic properties of the substituents. Spectroelectrochemical analyses indicate the generation of high-valent intermediates that enable epoxidation under these mild conditions.</p>","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"91 5","pages":"2187–2192"},"PeriodicalIF":3.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
An oxone-promoted radical annulation of 2-cyanoaryl acrylamides involving carbon–carbon double bond cleavage has been developed for the construction of 3-hydroxyquinoline-2,4(1H,3H)-diones. Such transformation exhibits good functional group tolerance and scalability. The reaction proceeds through an initial radical cyclization to form a 4-aminoquinolinone intermediate followed by hydroxylation to afford the final product.
{"title":"C═C Double Bond Cleavage of 2-Cyanoaryl Acrylamides for the Construction of 3-Hydroxyquinoline-2,4(1H,3H)-diones","authors":"Jia Hu, , , Tai-Gang Fan, , , Mei Wang, , , Zhe Yang, , , Junpeng Li, , , Jianqiang Wang*, , and , Ya-Min Li*, ","doi":"10.1021/acs.joc.5c02856","DOIUrl":"10.1021/acs.joc.5c02856","url":null,"abstract":"<p >An oxone-promoted radical annulation of 2-cyanoaryl acrylamides involving carbon–carbon double bond cleavage has been developed for the construction of 3-hydroxyquinoline-2,4(1<i>H</i>,3<i>H</i>)-diones. Such transformation exhibits good functional group tolerance and scalability. The reaction proceeds through an initial radical cyclization to form a 4-aminoquinolinone intermediate followed by hydroxylation to afford the final product.</p>","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"91 5","pages":"2152–2160"},"PeriodicalIF":3.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045034","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}
Red algae of the genus Laurencia are prolific sources of halogenated C15-acetogenins, many of which contain a tetrahydrofuran (THF) ring and a bromoallene terminus. Among them, Itomanallene B-type metabolites have presented a stereochemical paradox, as Laurencia intricata and Laurencia nangii yield epimeric structures despite sharing the same planar connectivity. In this study, we demonstrate that the chemical shift of the diagnostic C-4 proton provides a rapid and reliable indicator of the relative orientation (α,α′-syn vs α,α′-anti) of the THF side chains. Comparative analysis of reported NMR data reveals that anti configurations exhibit systematically more deshielded C-4 proton resonances than their syn counterparts. Applying this “chemical-shift litmus test” shows that Itomanallene B 1 from L. intricata possesses an α,α′-anti arrangement, whereas the metabolite previously reported as Itomanallene B 3 from L. nangii is instead the α,α′-syn epimer, 4-epi-Itomanallene B. This reassignment was unambiguously confirmed through the total asymmetric synthesis of the (aS,4S,6R,7R) stereoisomer of (+)-Itomanallene B, whose NMR data matched those of the natural product. The simplicity and diagnostic power of the C-4 proton chemical-shift approach provide an efficient tool for the stereochemical assignment of THF-containing C15-acetogenins, addressing a recurrent source of structural misinterpretation within the Laurencia genus.
{"title":"The Laurencia Stereochemical Paradox: Chemical Shift Litmus Test, Asymmetric Total Synthesis, and Structural Reassignment of (+)-Itomanallene B","authors":"Ervis Saraci, , , Federico Barbieri, , , Federica Plavi, , , Alessio Porta, , , Emanuele Casali*, , and , Giuseppe Zanoni*, ","doi":"10.1021/acs.joc.5c03161","DOIUrl":"10.1021/acs.joc.5c03161","url":null,"abstract":"<p >Red algae of the genus Laurencia are prolific sources of halogenated C<sub>15</sub>-acetogenins, many of which contain a tetrahydrofuran (THF) ring and a bromoallene terminus. Among them, Itomanallene B-type metabolites have presented a stereochemical paradox, as <i>Laurencia intricata</i> and <i>Laurencia nangii</i> yield epimeric structures despite sharing the same planar connectivity. In this study, we demonstrate that the chemical shift of the diagnostic C-4 proton provides a rapid and reliable indicator of the relative orientation (α,α′-<i>syn</i> vs α,α′-<i>anti</i>) of the THF side chains. Comparative analysis of reported NMR data reveals that <i>anti</i> configurations exhibit systematically more deshielded C-4 proton resonances than their <i>syn</i> counterparts. Applying this “chemical-shift litmus test” shows that Itomanallene B <b>1</b> from <i>L. intricata</i> possesses an α,α′-<i>anti</i> arrangement, whereas the metabolite previously reported as Itomanallene B <b>3</b> from <i>L. nangii</i> is instead the α,α′-<i>syn</i> epimer, 4-epi-Itomanallene B. This reassignment was unambiguously confirmed through the total asymmetric synthesis of the (a<i>S</i>,4<i>S</i>,6<i>R</i>,7<i>R</i>) stereoisomer of (+)-Itomanallene B, whose NMR data matched those of the natural product. The simplicity and diagnostic power of the C-4 proton chemical-shift approach provide an efficient tool for the stereochemical assignment of THF-containing C<sub>15</sub>-acetogenins, addressing a recurrent source of structural misinterpretation within the <i>Laurencia genus</i>.</p>","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"91 5","pages":"2239–2247"},"PeriodicalIF":3.6,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044657","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}