Yihui Mao, Xiangquan Wang, Chengcheng Zhong, Jinkang Jin, Zhan Lu
A visible-light-induced photocatalytic oxytrifluoromethylation reaction of alkenes has been reported for the efficient synthesis of diverse five-membered cyclic carbonates and vicinal diols bearing trifluoroethyl substituted quaternary centers under mild conditions. This protocol features a broad substrate scope and the ability to be performed on a gram scale. In addition, the synthesis of CF3-containing lactone, acyclic carbamate derivatives, and anticonvulsant molecules demonstrated the practicality of this method. Mechanistic studies indicate that the reaction undergoes a process of oxidative radical-polar crossover, leading to the formation of a benzylic carbocation which then undergoes nucleophilic cyclization.
{"title":"Photoredox-Catalyzed Oxytrifluoromethylation of Alkenes toward CF3-Containing Five-Membered Cyclic Carbonates","authors":"Yihui Mao, Xiangquan Wang, Chengcheng Zhong, Jinkang Jin, Zhan Lu","doi":"10.1039/d4qo00824c","DOIUrl":"https://doi.org/10.1039/d4qo00824c","url":null,"abstract":"A visible-light-induced photocatalytic oxytrifluoromethylation reaction of alkenes has been reported for the efficient synthesis of diverse five-membered cyclic carbonates and vicinal diols bearing trifluoroethyl substituted quaternary centers under mild conditions. This protocol features a broad substrate scope and the ability to be performed on a gram scale. In addition, the synthesis of CF3-containing lactone, acyclic carbamate derivatives, and anticonvulsant molecules demonstrated the practicality of this method. Mechanistic studies indicate that the reaction undergoes a process of oxidative radical-polar crossover, leading to the formation of a benzylic carbocation which then undergoes nucleophilic cyclization.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430407","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}
Yueyue Xing, Tianyu Bo, Nan Zhang, Meiqi Wu, Jiawei Wang, Shigang Shen, Yafang Wang, Changying Song, Tiesheng Shi, Shuying Huo
Multi-cyclic peptides constrained by disulfide bonds (MDBs) or thioether bridges play a critical role on improving the biological and pharmaceutical activities of peptide drugs. The synthesis of correct MDBs and thioether-bridged bicyclic peptides still re-mains as a significant challenge task. In this work, benzeneseleninic acid (BA) used as an oxidant and deprotecting reagent for the synthesis of peptide MDBs and thioether-bridged bicyclic peptides has been investigated. Peptide disulfide bond can be formed by direct oxidation of two sulfhydryl groups by BA in neutral media or via two concerted steps, namely deprotecting two acetamidomethyl (Acm) groups and oxidation by BA in acidic media. As such, two disulfide bonds in a-conotoxin SI, apamin, a-conotoxin IMI and a peptide containing methionine residue were synthesized regioselectively by use of the BA oxidation and deprotection reactions (BA-ODr). Moreover, the relative positions of two Acm-protected cysteines and two free cysteines have no impact on the BA-ODr approach for the construction of two disulfide bonds in peptides. Utilization of the BA deprotection reaction, bicyclic peptides were synthesized based on the crosslinking of xylylene dibromide with sulfhydryl group giving satisfied yields. Furthermore, two disulfide bonds in a-conotoxin SI and three disulfide bonds in conotoxin mr3e, enterotoxin STp, μ-conotoxin KIIIA, linaclotide and ziconotide were also synthesized regioselectively with reasonable yields through oxidation of fully reduced peptides by BA. BA is readily accessible conferring efficient BA-ODr and oxidative folding strategies for preparation of MBDs and thioether bridges in peptides.
受二硫键（MDB）或硫醚桥约束的多环肽对提高肽类药物的生物和药物活性起着至关重要的作用。正确合成二硫键和硫醚桥双环肽仍然是一项重大挑战。本研究以苯硒酸 (BA) 作为氧化剂和脱保护试剂，对多肽二硫键和硫醚桥双环肽的合成进行了研究。肽二硫键可以通过 BA 在中性介质中直接氧化两个巯基形成，也可以通过两个协同步骤形成，即在酸性介质中去保护两个乙酰氨基甲基（Acm）基团和 BA 氧化。因此，利用 BA 氧化和脱保护反应（BA-ODr），可以选择性地合成 a-conotoxin SI、阿帕明、a-conotoxin IMI 和含有蛋氨酸残基的肽中的两个二硫键。此外，两个受 Acm 保护的半胱氨酸和两个游离半胱氨酸的相对位置对 BA-ODr 在肽中构建两个二硫键的方法没有影响。利用 BA 脱保护反应，在二溴二苯基与巯基交联的基础上合成了双环肽，并获得了满意的收率。此外，通过 BA 氧化完全还原的肽，还以合理的产率选择性地合成了 a-conotoxin SI 中的两个二硫键和 conotoxin mr3e、肠毒素 STp、μ-conotoxin KIIIA、linaclotide 和 ziconotide 中的三个二硫键。BA 易于获得，因此可以采用高效的 BA-ODr 和氧化折叠策略来制备肽中的 MBD 和硫醚桥。
{"title":"Benzeneseleninic acid used as an oxidizing and deprotecting reagent for the syn-thesis of multi-cyclic peptides constrained by multiple disulfide bonds and thioether bridges","authors":"Yueyue Xing, Tianyu Bo, Nan Zhang, Meiqi Wu, Jiawei Wang, Shigang Shen, Yafang Wang, Changying Song, Tiesheng Shi, Shuying Huo","doi":"10.1039/d4qo00589a","DOIUrl":"https://doi.org/10.1039/d4qo00589a","url":null,"abstract":"Multi-cyclic peptides constrained by disulfide bonds (MDBs) or thioether bridges play a critical role on improving the biological and pharmaceutical activities of peptide drugs. The synthesis of correct MDBs and thioether-bridged bicyclic peptides still re-mains as a significant challenge task. In this work, benzeneseleninic acid (BA) used as an oxidant and deprotecting reagent for the synthesis of peptide MDBs and thioether-bridged bicyclic peptides has been investigated. Peptide disulfide bond can be formed by direct oxidation of two sulfhydryl groups by BA in neutral media or via two concerted steps, namely deprotecting two acetamidomethyl (Acm) groups and oxidation by BA in acidic media. As such, two disulfide bonds in a-conotoxin SI, apamin, a-conotoxin IMI and a peptide containing methionine residue were synthesized regioselectively by use of the BA oxidation and deprotection reactions (BA-ODr). Moreover, the relative positions of two Acm-protected cysteines and two free cysteines have no impact on the BA-ODr approach for the construction of two disulfide bonds in peptides. Utilization of the BA deprotection reaction, bicyclic peptides were synthesized based on the crosslinking of xylylene dibromide with sulfhydryl group giving satisfied yields. Furthermore, two disulfide bonds in a-conotoxin SI and three disulfide bonds in conotoxin mr3e, enterotoxin STp, μ-conotoxin KIIIA, linaclotide and ziconotide were also synthesized regioselectively with reasonable yields through oxidation of fully reduced peptides by BA. BA is readily accessible conferring efficient BA-ODr and oxidative folding strategies for preparation of MBDs and thioether bridges in peptides.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334223","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 controlled pH-reversible conjugation of amine-functionalized molecules to nano-sized carrier systems is a promising achievement to enhance the efficacy of small molecular drugs at the target site. Various pH-responsive structures, such as ketals or hydrazones are accessible for drug delivery but suffer from high pH-gradients and elaborative modifications. The latter often further affects the specific activity of the released drugs. In this study, we establish the synthesis of a highly pH-sensitive bifunctional linker based on 2-propionic-3-methylmaleic anhydride. The underlying chemical structure enables the pH-reversible conjugation of different amines, although the attachment of primary amines competes with the formation of a pH-resistant imide structure. Remarkably, by analysis of the pH-reversible amidation profile in different solvents, the ring-opened amide structures are generated with primary aliphatic amines in diethyl ether. The formed conjugates rapidly phase separate from the reaction mixture and preserve the pH sensitivity of the linker system. Based on these findings, this manufacturing process is highly relevant in providing amine-conjugated 2-propionic-3-methylmaleic anhydride linkers and restoring their pH-responsiveness, particularly for primary amine-bearing drugs. This can pave their way for future applications, for instance, in nanomedicine.
{"title":"Restoring the pH-Responsiveness for Amine-Conjugated 2-Propionic-3-Methylmaleic Anhydride Linkers","authors":"Lutz Nuhn, Alina Heck","doi":"10.1039/d4qo01077a","DOIUrl":"https://doi.org/10.1039/d4qo01077a","url":null,"abstract":"The controlled pH-reversible conjugation of amine-functionalized molecules to nano-sized carrier systems is a promising achievement to enhance the efficacy of small molecular drugs at the target site. Various pH-responsive structures, such as ketals or hydrazones are accessible for drug delivery but suffer from high pH-gradients and elaborative modifications. The latter often further affects the specific activity of the released drugs. In this study, we establish the synthesis of a highly pH-sensitive bifunctional linker based on 2-propionic-3-methylmaleic anhydride. The underlying chemical structure enables the pH-reversible conjugation of different amines, although the attachment of primary amines competes with the formation of a pH-resistant imide structure. Remarkably, by analysis of the pH-reversible amidation profile in different solvents, the ring-opened amide structures are generated with primary aliphatic amines in diethyl ether. The formed conjugates rapidly phase separate from the reaction mixture and preserve the pH sensitivity of the linker system. Based on these findings, this manufacturing process is highly relevant in providing amine-conjugated 2-propionic-3-methylmaleic anhydride linkers and restoring their pH-responsiveness, particularly for primary amine-bearing drugs. This can pave their way for future applications, for instance, in nanomedicine.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334379","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 reported an practical synthetic method for the efficient preparation of fluoroalkylated quinoline-2,4-diones using N-(2-cyanophenyl)-N-methylacrylamide as substrates, fluoroalkyl carboxylic acids as reactants, and Fe(OH)(OAc)2 as catalyst. This reaction started from photo-driven ligand-to-metal charge transfer (LMCT) process to decarboxylate and produced fluoroalkyl radicals, which then underwent radical cascade cyclization with the substrate. The target products were obtained in 55-91% yields. Gram scale experiment was also completed by using continuous-flow-photocatalytic-device.
{"title":"Photo-Induced Synthesis of Fluoroalkylated Quinolinones via Iron-Catalyzed LMCT Decarboxylation Process","authors":"Zhuoheng Song, Lin Guo, Chao Yang, Wujiong Xia","doi":"10.1039/d4qo00707g","DOIUrl":"https://doi.org/10.1039/d4qo00707g","url":null,"abstract":"Herein, we reported an practical synthetic method for the efficient preparation of fluoroalkylated quinoline-2,4-diones using N-(2-cyanophenyl)-N-methylacrylamide as substrates, fluoroalkyl carboxylic acids as reactants, and Fe(OH)(OAc)2 as catalyst. This reaction started from photo-driven ligand-to-metal charge transfer (LMCT) process to decarboxylate and produced fluoroalkyl radicals, which then underwent radical cascade cyclization with the substrate. The target products were obtained in 55-91% yields. Gram scale experiment was also completed by using continuous-flow-photocatalytic-device.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334301","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}
Anna Kubíčková, Svatava Voltrová, Adam Kleman, Blanka Klepetarova, Petr Beier
An efficient one-pot microwave-assisted potassium fluoride-mediated synthesis of 1-fluoroalkyl-3-fluoroisoquinolines and fused fluoroalkylpyridines from N-fluoroalkylated 1,2,3-triazoles was developed. The reaction is of wide scope and allows the preparation of structurally diverse 3-fluoroisoquinolines with fluoroalkyl group in position 1, substitution in position 4 and a substitution on the fused benzene (or heteroaromatic) ring. N-Fluoroalkylated ketenimines, which undergo stereoselective 1,3-fluorine shift to difluoroazadienes, were identified as intermediates in the reaction sequence. The presence of fluorine in position 3 and halogen in postion 4 of the resulting isoquinolines allowed for further modification by nucleophilic aromatic substitution and cross-coupling reactions, respectively. The developed methodologies were utillized for the synthesis of derivatives of drug candidates.
{"title":"One-Pot Multistep Synthesis of 1-Fluoroalkylisoquinolines and Fused Fluoroalkylpyridines from N Fluoroalkyl-1,2,3-triazoles","authors":"Anna Kubíčková, Svatava Voltrová, Adam Kleman, Blanka Klepetarova, Petr Beier","doi":"10.1039/d4qo00713a","DOIUrl":"https://doi.org/10.1039/d4qo00713a","url":null,"abstract":"An efficient one-pot microwave-assisted potassium fluoride-mediated synthesis of 1-fluoroalkyl-3-fluoroisoquinolines and fused fluoroalkylpyridines from N-fluoroalkylated 1,2,3-triazoles was developed. The reaction is of wide scope and allows the preparation of structurally diverse 3-fluoroisoquinolines with fluoroalkyl group in position 1, substitution in position 4 and a substitution on the fused benzene (or heteroaromatic) ring. N-Fluoroalkylated ketenimines, which undergo stereoselective 1,3-fluorine shift to difluoroazadienes, were identified as intermediates in the reaction sequence. The presence of fluorine in position 3 and halogen in postion 4 of the resulting isoquinolines allowed for further modification by nucleophilic aromatic substitution and cross-coupling reactions, respectively. The developed methodologies were utillized for the synthesis of derivatives of drug candidates.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334359","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}
Regioselective borylation of (hetero)arenes under mild conditions is an appealing strategy for constructing boron-containing compounds, particularly considering their broad applications in organic synthesis, medicinal chemistry and material science. In this manuscript, we developed a Fe(OTf)3-promoted, DG (directing group)-controlled, regioselective electrophilic C–H borylation of 2-arylphenolic compounds with BBr3 at room temperature. C2′-borylation was dramatically accelerated by an LA-catalyst, affording DAOB (diaryloxaborin) with a broad substrate scope in moderate-to-excellent yields. The selective ortho-borylation was successfully achieved by introducing phenolic carbamate as a directing group to overcome the competing Fries rearrangement, giving desired 2-HAB ((2-hydroxyaryl)boronic acid) in good yields for most substrates.
{"title":"Directing group controlled regioselective C–H borylation of 2-arylphenolic compounds at room temperature","authors":"Jiao Kang, Jing Liu, Zhilong Chen","doi":"10.1039/d4qo00805g","DOIUrl":"https://doi.org/10.1039/d4qo00805g","url":null,"abstract":"Regioselective borylation of (hetero)arenes under mild conditions is an appealing strategy for constructing boron-containing compounds, particularly considering their broad applications in organic synthesis, medicinal chemistry and material science. In this manuscript, we developed a Fe(OTf)<small><sub>3</sub></small>-promoted, DG (directing group)-controlled, regioselective electrophilic C–H borylation of 2-arylphenolic compounds with BBr<small><sub>3</sub></small> at room temperature. C2′-borylation was dramatically accelerated by an LA-catalyst, affording DAOB (diaryloxaborin) with a broad substrate scope in moderate-to-excellent yields. The selective <em>ortho</em>-borylation was successfully achieved by introducing phenolic carbamate as a directing group to overcome the competing Fries rearrangement, giving desired 2-HAB ((2-hydroxyaryl)boronic acid) in good yields for most substrates.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334234","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}
Developing new chemical toolboxes for site-specific nucleic acid post-synthetic modification is of great challenge and urgently required for precisely expanding DNA functionality, which holds significant research implications in nucleic acid chemistry, biology, and beyond. Herein, we demonstrate the first site-specific DNA post-synthetic modification via fast photocatalytic allylation under visible light. Allyl sulfone groups were introduced into oligonucleotides, not only at the terminal sites via traditional amidation reactions but also at the internal and terminal sites via DNA solid-phase synthesis. This visible-light-induced photocatalytic decarboxylative allylation proceeds rapidly on the oligonucleotides bearing allyl sulfone groups under open-to-air conditions within minutes, exhibiting excellent chemoselectivity and compatibility with various functional groups while retaining the DNA integrity. Specifically, introducing allyl sulfone into oligonucleotides via DNA solid-phase synthesis enables site-specific DNA modification on chemically synthesized single-stranded DNA at internal and terminal positions, hybridized double-stranded DNA, and enzymatically amplified long-chain DNA under visible light. The versatile reactivity of allyl sulfone scaffolds further enables diverse on-DNA photocatalytic transformations, promising to advance chemical toolboxes for DNA post-synthetic modification through diverse photochemical methods.
开发新的化学工具箱用于位点特异性核酸合成后修饰是一项巨大的挑战，也是精确扩展 DNA 功能的迫切需要，对核酸化学、生物学及其他领域具有重要的研究意义。在此，我们首次展示了在可见光下通过快速光催化烯丙基化作用对 DNA 进行位点特异性合成后修饰的方法。烯丙基砜基团不仅通过传统的酰胺化反应被引入寡核苷酸的末端位点，还通过 DNA 固相合成被引入内部和末端位点。这种可见光诱导的光催化脱羧烯丙基化反应在露天条件下几分钟内就能在带有烯丙基砜基团的寡核苷酸上迅速进行，在保留 DNA 完整性的同时，还表现出极佳的化学选择性和与各种官能团的兼容性。具体来说，通过 DNA 固相合成将烯丙基砜引入寡核苷酸，可在可见光下对化学合成的单链 DNA 的内部和末端位置、杂交的双链 DNA 以及酶扩增的长链 DNA 进行特定位点的 DNA 修饰。烯丙基砜支架的多功能反应性进一步实现了多种 DNA 上的光催化转化，有望通过多种光化学方法推进 DNA 后合成修饰的化学工具箱。
{"title":"Site-Specific DNA Post-Synthetic Modification via Fast Photocatalytic Allylation","authors":"Ying Huang, Yixin Zhang, Chenchen Hu, Yiyun Chen","doi":"10.1039/d4qo00752b","DOIUrl":"https://doi.org/10.1039/d4qo00752b","url":null,"abstract":"Developing new chemical toolboxes for site-specific nucleic acid post-synthetic modification is of great challenge and urgently required for precisely expanding DNA functionality, which holds significant research implications in nucleic acid chemistry, biology, and beyond. Herein, we demonstrate the first site-specific DNA post-synthetic modification via fast photocatalytic allylation under visible light. Allyl sulfone groups were introduced into oligonucleotides, not only at the terminal sites via traditional amidation reactions but also at the internal and terminal sites via DNA solid-phase synthesis. This visible-light-induced photocatalytic decarboxylative allylation proceeds rapidly on the oligonucleotides bearing allyl sulfone groups under open-to-air conditions within minutes, exhibiting excellent chemoselectivity and compatibility with various functional groups while retaining the DNA integrity. Specifically, introducing allyl sulfone into oligonucleotides via DNA solid-phase synthesis enables site-specific DNA modification on chemically synthesized single-stranded DNA at internal and terminal positions, hybridized double-stranded DNA, and enzymatically amplified long-chain DNA under visible light. The versatile reactivity of allyl sulfone scaffolds further enables diverse on-DNA photocatalytic transformations, promising to advance chemical toolboxes for DNA post-synthetic modification through diverse photochemical methods.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334375","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 lactam and sulfoximine motifs are common in natural and biologically active molecules, and alkenes are important building blocks in synthetic chemistry. Through photoredox-mediated formation cation intermediates, we have developed a highly versatile method for the preparation of various sulfoximidoyl lactams via C-N bond formation between C=C and amide motifs. The mild reaction conditions, broad functional group tolerance and excellent trans-selectivity would make it a general and efficient approach towards such novel analogues containing both valuable sulfoximine and lactam motifs for possible therapeutic use.
{"title":"Photocatalyzed Sulfoximination/Amidation of (Het)Arylethenes Tethered N-Tosyl Amide: A Versatile Entry to Sulfoximidoyl β- and γ-Lactams","authors":"Weilong Lin, Chengtan Li, Yuming Yang, Xiaolan Zheng, Cairong Zhang, Hui Cai","doi":"10.1039/d4qo00631c","DOIUrl":"https://doi.org/10.1039/d4qo00631c","url":null,"abstract":"The lactam and sulfoximine motifs are common in natural and biologically active molecules, and alkenes are important building blocks in synthetic chemistry. Through photoredox-mediated formation cation intermediates, we have developed a highly versatile method for the preparation of various sulfoximidoyl lactams via C-N bond formation between C=C and amide motifs. The mild reaction conditions, broad functional group tolerance and excellent trans-selectivity would make it a general and efficient approach towards such novel analogues containing both valuable sulfoximine and lactam motifs for possible therapeutic use.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334361","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}
A green and sustainable visible light-mediated deoxygenative amidation protocol to generate acyl radicals from commercially available carboxylic acids was described. The cheap, commercially available and user friendly organic photoredox catalyst, rhodamine B, could be employed in the dipeptide and amide coupling reactions under metal-free conditions by visible light irradiation. This method showed excellent functional selectivity for the formation of peptide bond or amide bond without affecting other functional groups such as alcohols, amides, halogens and heterocycles. This reaction was applicable to challenging amide coupling reactions of hindered carboxylic acids with low nucleophilic amines. The operationally straightforward method enriches the efficient synthesis of various dipeptides and amides in moderate to good yields (55-89%).
{"title":"Visible Light-Induced Deoxygenative Amidation Protocol for Synthesis of Dipeptide and Amide","authors":"Ji-Wei Ren, Cheng-Shuai Han, Huai-Xin Zhang, Qing-Hao Zhang, Xian-Ting Song, Jing-Hui Sun","doi":"10.1039/d4qo00793j","DOIUrl":"https://doi.org/10.1039/d4qo00793j","url":null,"abstract":"A green and sustainable visible light-mediated deoxygenative amidation protocol to generate acyl radicals from commercially available carboxylic acids was described. The cheap, commercially available and user friendly organic photoredox catalyst, rhodamine B, could be employed in the dipeptide and amide coupling reactions under metal-free conditions by visible light irradiation. This method showed excellent functional selectivity for the formation of peptide bond or amide bond without affecting other functional groups such as alcohols, amides, halogens and heterocycles. This reaction was applicable to challenging amide coupling reactions of hindered carboxylic acids with low nucleophilic amines. The operationally straightforward method enriches the efficient synthesis of various dipeptides and amides in moderate to good yields (55-89%).","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334238","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}
Single-atom editing, which involves precise modifications to a ring system through the selective insertion, deletion or substitution of atoms, represents a crucial advancement in the manipulation of chemically active molecules. This review focuses primarily on the editing of nitrogen atoms, including the insertion of N, the substitution of C with N and 14N with 15N for the construction of N-heterocycles. The emphasis on the nitrogen source facilitates a deeper understanding of the reactions involved. We anticipate that this review will not only underscore the innovative and enabling capabilities of current nitrogen single-atom editing techniques but also highlight the significant opportunities and untapped possibilities within this emerging and valuable field.
单原子编辑涉及通过选择性地插入、删除或替换原子对环状系统进行精确修改，是化学活性分子操作方面的一项重要进展。本综述主要侧重于氮原子的编辑，包括插入 N、用 N 替换 C 和用 15N 替换 14N 以构建 N 杂环。对氮源的强调有助于加深对相关反应的理解。我们预计，这篇综述不仅将强调当前氮单原子编辑技术的创新和赋能能力，还将突出这一新兴和有价值领域的重大机遇和尚未开发的可能性。
{"title":"Precision single-atom editing: new frontiers in nitrogen insertion and substitution for the generation of N-heterocycles","authors":"Xue Li, Jia Xu, Zhi-Gang Xu","doi":"10.1039/d4qo00812j","DOIUrl":"https://doi.org/10.1039/d4qo00812j","url":null,"abstract":"Single-atom editing, which involves precise modifications to a ring system through the selective insertion, deletion or substitution of atoms, represents a crucial advancement in the manipulation of chemically active molecules. This review focuses primarily on the editing of nitrogen atoms, including the insertion of N, the substitution of C with N and <small><sup>14</sup></small>N with <small><sup>15</sup></small>N for the construction of N-heterocycles. The emphasis on the nitrogen source facilitates a deeper understanding of the reactions involved. We anticipate that this review will not only underscore the innovative and enabling capabilities of current nitrogen single-atom editing techniques but also highlight the significant opportunities and untapped possibilities within this emerging and valuable field.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334302","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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