Lasso peptides and lanthipeptides are two major classes of ribosomally synthesized and post-translationally modified peptides (RiPPs), each defined by distinct post-translational modification (PTM) enzymes. We identify a hybrid biosynthetic gene cluster that integrates PTM enzymes from both pathways to produce a unique lasso peptide featuring a dehydroalanine residue and C-terminal Asp side-chain methylation. Elucidation of its biosynthesis uncovers unprecedented combinatorial RiPP maturation. This study establishes a paradigm for hybrid RiPP biosynthesis and enables discovery and engineering of novel RiPPs.
{"title":"Discovery and Biosynthesis of Dehydroalanine-Containing Lasso Peptide by a Hybrid Biosynthetic System.","authors":"Yu-Xia Ma,Jin-Ming Di,Jin-Long Lu,Weikang Zhai,Guang-Cheng Lou,Xin-Rong Li,Jiao-Jiao Cui,Jiang Xiong,Hongping Han,Kun Gao,Xinxiang Lei,Shangwen Luo,Shi-Hui Dong","doi":"10.1021/acs.orglett.5c04385","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04385","url":null,"abstract":"Lasso peptides and lanthipeptides are two major classes of ribosomally synthesized and post-translationally modified peptides (RiPPs), each defined by distinct post-translational modification (PTM) enzymes. We identify a hybrid biosynthetic gene cluster that integrates PTM enzymes from both pathways to produce a unique lasso peptide featuring a dehydroalanine residue and C-terminal Asp side-chain methylation. Elucidation of its biosynthesis uncovers unprecedented combinatorial RiPP maturation. This study establishes a paradigm for hybrid RiPP biosynthesis and enables discovery and engineering of novel RiPPs.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"26 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674361","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 : 2025-12-04DOI: 10.1021/acs.orglett.5c04757
Deeksha,Ritesh Singh
Herein, we present a highly efficient (one-pot) and unprecedented method for synthesizing 1,4-Benzoxazinones and 4,1-Benzoxazepinones under transition metal-free conditions through direct aryl C-H amination. For the first time, this work harnesses the 1,3-bis-electrophilic potential of α-bromohydroxamates, enabling direct O-alkylation of phenols and benzyl alcohols via an in situ-generated aza-oxyallyl cation, followed by aryl C-H amination via a nitrenium ion catalyzed by hypervalent iodine. When p-OMe-substituted phenols are used, the current system produces spiroxazolidinones, a class with limited, radical-based methods reported in the literature. Late-stage modifications of natural products and other valuable synthetic transformations underscore the synthetic utility of the method.
{"title":"A Modular Approach to Access 1,4-Benzoxazinones, Spirooxazolidinones, and 4,1-Benzoxazepinones via Oxidative Aryl C-N Bond Formation Using Catalytic Hypervalent Iodine.","authors":" Deeksha,Ritesh Singh","doi":"10.1021/acs.orglett.5c04757","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04757","url":null,"abstract":"Herein, we present a highly efficient (one-pot) and unprecedented method for synthesizing 1,4-Benzoxazinones and 4,1-Benzoxazepinones under transition metal-free conditions through direct aryl C-H amination. For the first time, this work harnesses the 1,3-bis-electrophilic potential of α-bromohydroxamates, enabling direct O-alkylation of phenols and benzyl alcohols via an in situ-generated aza-oxyallyl cation, followed by aryl C-H amination via a nitrenium ion catalyzed by hypervalent iodine. When p-OMe-substituted phenols are used, the current system produces spiroxazolidinones, a class with limited, radical-based methods reported in the literature. Late-stage modifications of natural products and other valuable synthetic transformations underscore the synthetic utility of the method.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"130 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674365","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 : 2025-12-04DOI: 10.1021/acs.orglett.5c04761
Renan de O Gonçalves,Jeimy A C Vélez,Natalí P Debia,Pedro H R Oliveira,Allya Larroza,Diego Alves,Márcio W Paixão
N-Monomethyl secondary amines are privileged structural motifs that frequently occur in pharmaceuticals and bioactive molecules. However, their synthesis often requires harsh conditions or suffers from poor selectivity. Here, we report a redox-neutral, iron-catalyzed strategy that enables the efficient formation of these motifs via a tandem alkylation-reduction of (Z)-N-methyl nitrones. The transformation proceeds through an Fe(III)-mediated ligand-to-metal charge transfer (LMCT) process that generates alkyl radicals from readily available carboxylic acids under visible light irradiation, followed by Fe(II)-promoted N-O bond cleavage of the resulting hydroxylamines. This dual catalytic reactivity provides a straightforward and sustainable route to N-monomethyl amines under mild conditions, without the need for exogenous reductants, ligands, or precious metals. The method exhibits a broad substrate scope, excellent functional group tolerance, and high selectivity, highlighting its potential as a practical platform for late-stage amine diversification.
n -单甲基仲胺是一种特殊的结构基序，经常出现在药物和生物活性分子中。然而，它们的合成往往需要苛刻的条件或选择性差。在这里，我们报告了一种氧化还原中性的铁催化策略，通过(Z)- n-甲基硝基酮的串联烷基化还原，可以有效地形成这些基序。该转化过程通过铁（III）介导的配体到金属电荷转移（LMCT）过程进行，该过程在可见光照射下从现成的羧酸中产生烷基自由基，然后由铁（II）促进的N-O键裂解所产生的羟胺。这种双催化反应性在温和条件下为n -单甲基胺提供了一种直接和可持续的途径，而不需要外源还原剂、配体或贵金属。该方法具有广泛的底物范围，优异的官能团耐受性和高选择性，突出了其作为后期胺多样化实用平台的潜力。
{"title":"Iron-Catalyzed Alkylation-Reduction of N-Methyl Nitrones via LMCT Activation.","authors":"Renan de O Gonçalves,Jeimy A C Vélez,Natalí P Debia,Pedro H R Oliveira,Allya Larroza,Diego Alves,Márcio W Paixão","doi":"10.1021/acs.orglett.5c04761","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04761","url":null,"abstract":"N-Monomethyl secondary amines are privileged structural motifs that frequently occur in pharmaceuticals and bioactive molecules. However, their synthesis often requires harsh conditions or suffers from poor selectivity. Here, we report a redox-neutral, iron-catalyzed strategy that enables the efficient formation of these motifs via a tandem alkylation-reduction of (Z)-N-methyl nitrones. The transformation proceeds through an Fe(III)-mediated ligand-to-metal charge transfer (LMCT) process that generates alkyl radicals from readily available carboxylic acids under visible light irradiation, followed by Fe(II)-promoted N-O bond cleavage of the resulting hydroxylamines. This dual catalytic reactivity provides a straightforward and sustainable route to N-monomethyl amines under mild conditions, without the need for exogenous reductants, ligands, or precious metals. The method exhibits a broad substrate scope, excellent functional group tolerance, and high selectivity, highlighting its potential as a practical platform for late-stage amine diversification.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"115 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664362","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 Tf2O-mediated formal [3 + 2]-cycloaddition of phenylarsine oxide and internal alkynes has been developed. An initially formed arsenic dication undergoes disproportionation to form key arsenic cation species, which are then coupled with alkynes, finally delivering the corresponding 2,3-disubstituted benzarsole derivatives with concomitant unique phenyl group migration. This strategy is also applicable to the three-component coupling of phenylarsine oxide, arylboronic acids, and alkynes. Moreover, ring transformations of the obtained benzarsoles are described.
{"title":"Synthesis of Benzarsoles by Arsenic Cation-Mediated Formal [3 + 2]-Cycloaddition with Alkynes.","authors":"Hiroki Iwamoto,Kazutoshi Nishimura,Kosuke Yasui,Koji Hirano","doi":"10.1021/acs.orglett.5c04431","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04431","url":null,"abstract":"A Tf2O-mediated formal [3 + 2]-cycloaddition of phenylarsine oxide and internal alkynes has been developed. An initially formed arsenic dication undergoes disproportionation to form key arsenic cation species, which are then coupled with alkynes, finally delivering the corresponding 2,3-disubstituted benzarsole derivatives with concomitant unique phenyl group migration. This strategy is also applicable to the three-component coupling of phenylarsine oxide, arylboronic acids, and alkynes. Moreover, ring transformations of the obtained benzarsoles are described.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"8 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674362","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}
cis,trans-Cycloocta-1,3-dienes (TCODs) are highly strained and elusive due to rapid 4π-electrocyclization. Here, we report the first stable isolation of cis,trans-cycloocta-1,3-dienes as Pt(II) complexes. X-ray crystallography revealed marked elongation of the trans C═C bond and dihedral distortion relative to trans-cyclooctenes (TCOs). The Pt-TCOD complexes underwent ligand exchange, desilylation to π-allyl species, and enantioselective decomplexation. These findings establish TCOD-metal complexes as isolable surrogates for elusive strained alkenes, providing a foundation for new developments in organometallic and strained-ring chemistry.
{"title":"Synthesis and Properties of Medium-Sized cis,trans-Cycloocta-1,3-diene-Pt(II) Complexes.","authors":"Hayate Kinouchi,Tomohiro Ito,Aki Kohyama,Yusuke Kuroda,Hiroshi Takikawa,Kiyosei Takasu","doi":"10.1021/acs.orglett.5c04468","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04468","url":null,"abstract":"cis,trans-Cycloocta-1,3-dienes (TCODs) are highly strained and elusive due to rapid 4π-electrocyclization. Here, we report the first stable isolation of cis,trans-cycloocta-1,3-dienes as Pt(II) complexes. X-ray crystallography revealed marked elongation of the trans C═C bond and dihedral distortion relative to trans-cyclooctenes (TCOs). The Pt-TCOD complexes underwent ligand exchange, desilylation to π-allyl species, and enantioselective decomplexation. These findings establish TCOD-metal complexes as isolable surrogates for elusive strained alkenes, providing a foundation for new developments in organometallic and strained-ring chemistry.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"34 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674368","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 : 2025-12-04DOI: 10.1021/acs.orglett.5c04428
Jie Wang,Yi Gao,Xin-Zhe Niu,Xue-Qing Song,Ya-Li Song,Longfei Li,Zhi-Hao You
Employing a sequential gold and organocatalytic system, we have achieved a one-pot double annulation of versatile 1,3-dicarbonyl compounds bearing a 3-butynoic acid moiety. This process proceeds through a gold-catalyzed 5-endo-dig cyclization, followed by a thiourea-catalyzed intramolecular vinylogous aldol reaction. By strategically employing desymmetrization and dynamic kinetic resolution, respectively, this methodology enables the efficient and asymmetric construction of a series of spiro-butenolide architectures incorporating contiguous tetrasubstituted carbon stereocenters.
{"title":"Sequential Gold and Organocatalyzed Bicyclization for Asymmetric Construction of Contiguous Tetrasubstituted Carbon Stereocenters.","authors":"Jie Wang,Yi Gao,Xin-Zhe Niu,Xue-Qing Song,Ya-Li Song,Longfei Li,Zhi-Hao You","doi":"10.1021/acs.orglett.5c04428","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04428","url":null,"abstract":"Employing a sequential gold and organocatalytic system, we have achieved a one-pot double annulation of versatile 1,3-dicarbonyl compounds bearing a 3-butynoic acid moiety. This process proceeds through a gold-catalyzed 5-endo-dig cyclization, followed by a thiourea-catalyzed intramolecular vinylogous aldol reaction. By strategically employing desymmetrization and dynamic kinetic resolution, respectively, this methodology enables the efficient and asymmetric construction of a series of spiro-butenolide architectures incorporating contiguous tetrasubstituted carbon stereocenters.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"15 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674366","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 : 2025-12-04DOI: 10.1021/acs.orglett.5c04649
Wei Hu,Li Zhao,Yahan Zhang,Yong-Ke He,Yuming Yang,Jie Wu,Shaoyu Li
The alkylation of N-sulfinylamines has emerged as a straightforward and promising platform for the construction of sulfinamides. Nevertheless, extant strategies─whether through two-electron nucleophilic addition or single-electron radical pathways─remain confined to two-component reactions, exhibiting intrinsic constraints in terms of carbon nucleophile diversity, synthetic efficiency, and structural variety of the products. Herein, we have successfully developed a photocatalytic radical-polar crossover process that addresses these challenges by enabling a three-component coupling reaction of Tr-NSO, alkenes and alkyl/aryl trifluoroborate salts. Despite the difficulty in controlling chemoselectivity among competing pathways, this strategy affords highly functionalized sulfinamides that are otherwise inaccessible through conventional means. Furthermore, mechanistic investigations, involving the trapping of radical and carbanionic intermediates along with fluorescence quenching studies, offer compelling support for the proposed reaction pathway.
n -亚砜胺的烷基化反应已成为构建亚砜胺的一个简单而有前途的平台。然而，现有的策略──无论是通过双电子亲核加成还是单电子自由基途径──仍然局限于双组分反应，在碳亲核试剂的多样性、合成效率和产物的结构多样性方面表现出内在的限制。在这里，我们已经成功地开发了一种光催化自由基-极性交叉过程，通过实现Tr-NSO，烯烃和烷基/芳基三氟硼酸盐的三组分偶联反应来解决这些挑战。尽管在控制竞争途径之间的化学选择性方面存在困难，但该策略提供了通过常规手段无法获得的高度功能化亚胺。此外，机理研究，包括自由基和碳离子中间体的捕获以及荧光猝灭研究，为所提出的反应途径提供了强有力的支持。
{"title":"Radical-Polar Crossover Enabled Photoredox 1,2-Carbosulfinylation of Alkenes with N-Sulfinyltritylamine.","authors":"Wei Hu,Li Zhao,Yahan Zhang,Yong-Ke He,Yuming Yang,Jie Wu,Shaoyu Li","doi":"10.1021/acs.orglett.5c04649","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04649","url":null,"abstract":"The alkylation of N-sulfinylamines has emerged as a straightforward and promising platform for the construction of sulfinamides. Nevertheless, extant strategies─whether through two-electron nucleophilic addition or single-electron radical pathways─remain confined to two-component reactions, exhibiting intrinsic constraints in terms of carbon nucleophile diversity, synthetic efficiency, and structural variety of the products. Herein, we have successfully developed a photocatalytic radical-polar crossover process that addresses these challenges by enabling a three-component coupling reaction of Tr-NSO, alkenes and alkyl/aryl trifluoroborate salts. Despite the difficulty in controlling chemoselectivity among competing pathways, this strategy affords highly functionalized sulfinamides that are otherwise inaccessible through conventional means. Furthermore, mechanistic investigations, involving the trapping of radical and carbanionic intermediates along with fluorescence quenching studies, offer compelling support for the proposed reaction pathway.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"372 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674367","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 radical reaction of aryl-substituted vinyl cyclohexafluoropropane-1,3-bis(sulfonyl)amides (c-HFSI) followed by hydrolysis affords novel fluoroalkyl compounds. The key process in this reaction is the radical addition of c-HFSI to vinyl triflate, which is followed by β-cleavage (ring-opening reaction) and subsequent sulfur dioxide elimination to form fluoroalkyl radicals. By replacement of the hydrolysis with a reduction reaction, a robust polymer was obtained.
{"title":"Synthesis of Keto Hexafluoro Alkyl Sulfonyl Amides Via Radical Ring-Opening Polymerization of Aryl-Substituted Vinyl Cyclohexafluoropropane-1,3-bis(sulfonyl)amides Followed by Hydrolysis","authors":"Takuji Kawamoto, Moeri Terauchi, Tetsushi Yamasaki, Takahiro Kawabata, Kenshin Muramatsu, Akio Kamimura","doi":"10.1021/acs.orglett.5c04505","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04505","url":null,"abstract":"The radical reaction of aryl-substituted vinyl cyclohexafluoropropane-1,3-bis(sulfonyl)amides (c-HFSI) followed by hydrolysis affords novel fluoroalkyl compounds. The key process in this reaction is the radical addition of c-HFSI to vinyl triflate, which is followed by β-cleavage (ring-opening reaction) and subsequent sulfur dioxide elimination to form fluoroalkyl radicals. By replacement of the hydrolysis with a reduction reaction, a robust polymer was obtained.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"223 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665162","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 : 2025-12-04DOI: 10.1021/acs.orglett.5c04485
Sumin Lee,Sekwang Baek,Yongho Kim,Eun Jeong Yoo
In this study, umpolung palladium catalysis was developed for achieving 1,2-dearomative allylation followed by intramolecular cyclization. The dearomatization involves activated N-arenes and the in situ generated nucleophilic η1-allyl-palladium species from a bis-allyl precursor, efficiently affording eight-membered heterocycles with potential bioactivity─structures that are otherwise difficult to access. The synthetic utility of this methodology was further demonstrated through versatile transformations of the heterocyclic products, enabling the construction of complex molecular architectures. Mechanistic studies revealed a regioselective dearomatization pathway involving η1-allyl-palladium, which was kinetically favored over alternative dearomatizations. These findings could expand the practical scope of umpolung palladium catalysis in organic synthesis.
{"title":"An Umpolung Strategy for Palladium-Catalyzed Dearomative Allylation toward Eight-Membered N-Heterocycles.","authors":"Sumin Lee,Sekwang Baek,Yongho Kim,Eun Jeong Yoo","doi":"10.1021/acs.orglett.5c04485","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04485","url":null,"abstract":"In this study, umpolung palladium catalysis was developed for achieving 1,2-dearomative allylation followed by intramolecular cyclization. The dearomatization involves activated N-arenes and the in situ generated nucleophilic η1-allyl-palladium species from a bis-allyl precursor, efficiently affording eight-membered heterocycles with potential bioactivity─structures that are otherwise difficult to access. The synthetic utility of this methodology was further demonstrated through versatile transformations of the heterocyclic products, enabling the construction of complex molecular architectures. Mechanistic studies revealed a regioselective dearomatization pathway involving η1-allyl-palladium, which was kinetically favored over alternative dearomatizations. These findings could expand the practical scope of umpolung palladium catalysis in organic synthesis.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"186 15 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664359","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}
Catalytic enantioselective benzoin condensation conditions that are potentially useful for the total synthesis of cycloimidamicins and structure–activity relationship studies of these natural products were developed. A triazole-based NHC catalyst promoted the transformation to afford the cyclization products. To make the reactions applicable to substrates with complex structural features, a Lewis acidic additive, B(OMe)Et2, was used, but fine-tuning of the base and solvent conditions was required to attain a good chemical yield and excellent enantioselectivity. These conditions showed a broad substrate scope and were not limited to substrates useful for the synthesis of cycloimidamicins and their related compounds. This study also clearly demonstrates the utility of N-heterocyclic carbene organocatalysts that have not been reported to exhibit perfect enantioselectivity in intramolecular benzoin condensation.
{"title":"Catalytic Asymmetric Benzoin Condensation for the Synthesis of Natural Products and Their Analogs","authors":"Hikaru Abe, Kazushige Sasaki, Chiharu Sakashita, Shunsuke Watanabe, Hidetoshi Noda, Takumi Watanabe, Masakatsu Shibasaki","doi":"10.1021/acs.orglett.5c04053","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04053","url":null,"abstract":"Catalytic enantioselective benzoin condensation conditions that are potentially useful for the total synthesis of cycloimidamicins and structure–activity relationship studies of these natural products were developed. A triazole-based NHC catalyst promoted the transformation to afford the cyclization products. To make the reactions applicable to substrates with complex structural features, a Lewis acidic additive, B(OMe)Et<sub>2</sub>, was used, but fine-tuning of the base and solvent conditions was required to attain a good chemical yield and excellent enantioselectivity. These conditions showed a broad substrate scope and were not limited to substrates useful for the synthesis of cycloimidamicins and their related compounds. This study also clearly demonstrates the utility of N-heterocyclic carbene organocatalysts that have not been reported to exhibit perfect enantioselectivity in intramolecular benzoin condensation.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"29 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665159","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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