The (3 + 2) cycloaddition of arynes with allylic ylides remains a formidable challenge because both intermediates are highly reactive and prone to spontaneous quenching. Here, we report a (3 + 2) cycloaddition of pyrazolone MBH carbonates with arynes, enabling the efficient synthesis of diverse indene-fused spiropyrazolones. The key is employing a new bifunctional Lewis base catalyst to facilitate the cycloaddition of in situ generated allylic pyridinium ylides with arynes.
{"title":"Bifunctional Lewis Base-Catalyzed (3 + 2) Cycloadditions of Pyrazolone-Derived MBH Carbonates with Arynes","authors":"Laiping Yao, Yiqiao Gu, Yuling Wu, Cheng Peng, Bo Han, Gu Zhan","doi":"10.1021/acs.orglett.4c03410","DOIUrl":"https://doi.org/10.1021/acs.orglett.4c03410","url":null,"abstract":"The (3 + 2) cycloaddition of arynes with allylic ylides remains a formidable challenge because both intermediates are highly reactive and prone to spontaneous quenching. Here, we report a (3 + 2) cycloaddition of pyrazolone MBH carbonates with arynes, enabling the efficient synthesis of diverse indene-fused spiropyrazolones. The key is employing a new bifunctional Lewis base catalyst to facilitate the cycloaddition of <i>in situ</i> generated allylic pyridinium ylides with arynes.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440795","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}
We present the reductive homologation of nitroalkanes through the utilization of the denitrative aminoalkylation reaction. This transformation is accomplished by the radical–radical coupling of alkyl radicals derived from nitroalkanes and persistent aminoalkyl radicals. By capitalizing on the diverse α-functionalization of nitroalkanes, α,β-multifunctionalized amines can be readily accessed.
{"title":"Reductive Homologation of Nitroalkanes via Denitrative Aminoalkylation","authors":"Ayumi Osawa, Maanashaa Balasubramanian, Yoshiaki Nakao","doi":"10.1021/acs.orglett.4c03269","DOIUrl":"https://doi.org/10.1021/acs.orglett.4c03269","url":null,"abstract":"We present the reductive homologation of nitroalkanes through the utilization of the denitrative aminoalkylation reaction. This transformation is accomplished by the radical–radical coupling of alkyl radicals derived from nitroalkanes and persistent aminoalkyl radicals. By capitalizing on the diverse α-functionalization of nitroalkanes, α,β-multifunctionalized amines can be readily accessed.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440802","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 : 2024-10-16DOI: 10.1021/acs.orglett.4c03646
Jeonghyun Min, Keunju Park, Kyeongwon Moon, Hyung Sik Kim, Pargat Singh, In Su Kim
Sulfur-containing organic molecules are recognized as promising candidates for catalytic C–H functionalization and medicinal chemistry owing to the exceptional ability of the sulfur atom to bind to transition metals and target enzymes. In this study, we report the Rh(III)-catalyzed thione-directed C–H amidation of various thiochromone analogues derived from flavones, isoflavones, and xanthones. Post-transformations of C5-amidated thiochromone products were investigated, and a series of mechanistic studies were performed.
{"title":"Thione-Directed C–H Amidation of Chromone Analogues with Dioxazolones under Rh(III) Catalysis","authors":"Jeonghyun Min, Keunju Park, Kyeongwon Moon, Hyung Sik Kim, Pargat Singh, In Su Kim","doi":"10.1021/acs.orglett.4c03646","DOIUrl":"https://doi.org/10.1021/acs.orglett.4c03646","url":null,"abstract":"Sulfur-containing organic molecules are recognized as promising candidates for catalytic C–H functionalization and medicinal chemistry owing to the exceptional ability of the sulfur atom to bind to transition metals and target enzymes. In this study, we report the Rh(III)-catalyzed thione-directed C–H amidation of various thiochromone analogues derived from flavones, isoflavones, and xanthones. Post-transformations of C5-amidated thiochromone products were investigated, and a series of mechanistic studies were performed.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440804","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 : 2024-10-16DOI: 10.1021/acs.orglett.4c03760
Nicolas Marie, Kim Uyen Ly, Norio Shibata, Vincent Bizet, Dominique Cahard
SCF3-substituted internal alkynes undergo regio- and stereoselective hydrohalogenation to provide the corresponding β-halo-α-SCF3-alkenes. The regioselectivity is ensured by the strong polarization of the C≡C triple bond in SCF3-alkynes, while the stereoselectivity is governed by the strength of the proton donor and/or by the solvent polarity. The potential of β-iodo-α-SCF3-alkenes was illustrated in several cross-coupling, protodeiodination, and cyanation reactions.
{"title":"Stereodivergent Hydrohalogenation of SCF3 Alkynes and Cross- Coupling Reactions","authors":"Nicolas Marie, Kim Uyen Ly, Norio Shibata, Vincent Bizet, Dominique Cahard","doi":"10.1021/acs.orglett.4c03760","DOIUrl":"https://doi.org/10.1021/acs.orglett.4c03760","url":null,"abstract":"SCF<sub>3</sub>-substituted internal alkynes undergo regio- and stereoselective hydrohalogenation to provide the corresponding β-halo-α-SCF<sub>3</sub>-alkenes. The regioselectivity is ensured by the strong polarization of the C≡C triple bond in SCF<sub>3</sub>-alkynes, while the stereoselectivity is governed by the strength of the proton donor and/or by the solvent polarity. The potential of β-iodo-α-SCF<sub>3</sub>-alkenes was illustrated in several cross-coupling, protodeiodination, and cyanation reactions.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440809","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}
Presented herein is a synthetic biological method using genome mining and heterologous expression systems that provides access to natural products with desirable structural features as building blocks. In this investigation, we synthesized polyketide–peptide hybrid macrocycles with DNA tags, which have the potential to access a DNA-encoded library containing over one million compounds. This study demonstrates that synthetic biology offers a tool for expanding the diversity of building blocks, facilitating the exploration of unexplored chemical space.
本文介绍的是一种利用基因组挖掘和异源表达系统的合成生物学方法，这种方法可以获得具有理想结构特征的天然产品作为构建模块。在这项研究中，我们合成了带有 DNA 标记的多酮肽杂交大环，这种方法有可能获得包含 100 多万种化合物的 DNA 编码库。这项研究表明，合成生物学为扩大构建模块的多样性提供了一种工具，有助于探索尚未开发的化学空间。
{"title":"Semi-synthesis of a DNA-Tagged Polyketide–Peptide Hybrid Macrocycle Using a Biosynthetically Prepared Fungal Macrolide as a Synthetic Component","authors":"Soya Koremura, Akihiro Sugawara, Yohei Morishita, Taro Ozaki, Teigo Asai","doi":"10.1021/acs.orglett.4c03588","DOIUrl":"https://doi.org/10.1021/acs.orglett.4c03588","url":null,"abstract":"Presented herein is a synthetic biological method using genome mining and heterologous expression systems that provides access to natural products with desirable structural features as building blocks. In this investigation, we synthesized polyketide–peptide hybrid macrocycles with DNA tags, which have the potential to access a DNA-encoded library containing over one million compounds. This study demonstrates that synthetic biology offers a tool for expanding the diversity of building blocks, facilitating the exploration of unexplored chemical space.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444476","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 : 2024-10-16DOI: 10.1021/acs.orglett.4c03495
Rongbiao Wei, Yao Huang, Oleg I. Afanasyev, Yuanming Li, Denis Chusov, Saihu Liao
Both fluorosulfonyl and cyano groups are important structural motifs in bioactive molecules. Herein, we report a new difunctionalization reaction of alkenes based on fluorosulfonyl radicals, which allows for the introduction of the fluorosulfonyl and cyano groups into unactivated alkenes in one step. This transformation is enabled by merging photoredox and copper catalysis, featuring visible light catalysis, mild conditions, and good functional group tolerance. Further transformation of products via SuFEx reactions is also demonstrated.
{"title":"Cyano-Fluorosulfonylation of Unactivated Alkenes by Photoredox and Copper Dual Catalysis","authors":"Rongbiao Wei, Yao Huang, Oleg I. Afanasyev, Yuanming Li, Denis Chusov, Saihu Liao","doi":"10.1021/acs.orglett.4c03495","DOIUrl":"https://doi.org/10.1021/acs.orglett.4c03495","url":null,"abstract":"Both fluorosulfonyl and cyano groups are important structural motifs in bioactive molecules. Herein, we report a new difunctionalization reaction of alkenes based on fluorosulfonyl radicals, which allows for the introduction of the fluorosulfonyl and cyano groups into unactivated alkenes in one step. This transformation is enabled by merging photoredox and copper catalysis, featuring visible light catalysis, mild conditions, and good functional group tolerance. Further transformation of products via SuFEx reactions is also demonstrated.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440744","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 : 2024-10-16DOI: 10.1021/acs.orglett.4c03650
Phathutshedzo Masithi, Ashlyn D. Bhana, Gerhard A. Venter, Hong Su, Christopher D. Spicer, Wade F. Petersen, Roger Hunter
Herein, we describe a Cinchona-aminocatalyzed enantioselective α-hydrazination of an α-formyl amide for the production of protected quaternized serines as tertiary amides with ee’s of generally >98% and ≤99% yields. The proposed TS model supported by density functional theory calculations involves a quinuclidinium ion Brønsted acid-assisted delivery of DtBAD, which occurs from the Re face of an H-bonded enaminone when using a 9S-cinchonamine catalyst, resulting in a hydrazide with the R-configuration as determined by X-ray analysis.
在此，我们介绍了一种由 Cinchona-aminocatalyzed 对映体选择性 α-hydrazination 催化的 α-甲酰基酰胺化反应，用于生产作为叔酰胺的受保护季铵化丝氨酸，ee's 一般为 98%，收率≤99%。密度泛函理论计算支持的拟议 TS 模型涉及喹啉离子布氏酸辅助 DtBAD 的传递，当使用 9S- 腙胺催化剂时，DtBAD 从 H 键烯丙酮的 Re 面发生传递，从而产生一种通过 X 射线分析确定为 R 构型的酰肼。
{"title":"Cinchona Organocatalyzed Enantioselective Amination for Quaternized Serines as Tertiary Amides","authors":"Phathutshedzo Masithi, Ashlyn D. Bhana, Gerhard A. Venter, Hong Su, Christopher D. Spicer, Wade F. Petersen, Roger Hunter","doi":"10.1021/acs.orglett.4c03650","DOIUrl":"https://doi.org/10.1021/acs.orglett.4c03650","url":null,"abstract":"Herein, we describe a <i>Cinchona</i>-aminocatalyzed enantioselective α-hydrazination of an α-formyl amide for the production of protected quaternized serines as tertiary amides with <i>ee</i>’s of generally >98% and ≤99% yields. The proposed TS model supported by density functional theory calculations involves a quinuclidinium ion Brønsted acid-assisted delivery of D<sup><i>t</i></sup>BAD, which occurs from the <i>Re</i> face of an H-bonded enaminone when using a 9<i>S</i>-cinchonamine catalyst, resulting in a hydrazide with the <i>R</i>-configuration as determined by X-ray analysis.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440792","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}
Gem-borylsilylalkanes are versatile intermediates in organic synthesis, and the traditional synthesis methods have mainly focused on metal reagents, the insertion reactions of diazo compounds, and hydrosilylation/hydroborylation reactions of unsaturated bonds. Herein, a novel, efficient gem-borylsilylalkanes synthesis via a radical approach is reported. This method introduced a β-gem-borylsilyl NHPI ester as the precursor of the β-borylsilyl radical that, coupling with radical acceptors under photo conditions, and the corresponding gem-borylsilylalkanes bearing unsaturated bonds, facilitate subsequent transformations.
{"title":"Photogeneration of β-Borylsilyl Radical via Decarboxylation of N-Hydroxyphthalimide Esters","authors":"Guotao Lin, Yu Guo, Mengjie Zhang, Qingqing Xuan, Jian Xu, Qiuling Song","doi":"10.1021/acs.orglett.4c03393","DOIUrl":"https://doi.org/10.1021/acs.orglett.4c03393","url":null,"abstract":"<i>Gem</i>-borylsilylalkanes are versatile intermediates in organic synthesis, and the traditional synthesis methods have mainly focused on metal reagents, the insertion reactions of diazo compounds, and hydrosilylation/hydroborylation reactions of unsaturated bonds. Herein, a novel, efficient <i>gem</i>-borylsilylalkanes synthesis via a radical approach is reported. This method introduced a β-<i>gem</i>-borylsilyl NHPI ester as the precursor of the β-borylsilyl radical that, coupling with radical acceptors under photo conditions, and the corresponding <i>gem</i>-borylsilylalkanes bearing unsaturated bonds, facilitate subsequent transformations.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440803","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 : 2024-10-16DOI: 10.1021/acs.orglett.4c03386
Qian-Hui Yu, Qing-Yu Luo, Yu-Hang Ye, Yang-Fan Wu, Xie-Ping Wu, En-Rui Zhang, Xi-Yuan Zhuo, Fei Du, Bin Pan, Wu Liang
A novel and efficient modular synthesis of gem-difluorotetrahydrocarbazolone scaffolds via copper-catalyzed radical cascade cyclization of bromodifluoroacetyl indoles and olefins has been reported. This operationally simple protocol provides straightforward and practical access to a series of privileged gem-difluorotetrahydrocarbazolone scaffolds from readily available starting materials, with the feature of broad functional group tolerance and mild reaction conditions. Moreover, the method could be used for the late-stage functionalization of bioactive molecules, which opens up the possibility for practical applications.
{"title":"Modular Synthesis of gem-Difluorotetrahydrocarbazolone Scaffolds via Copper-Catalyzed Cascade Reaction of Bromodifluoroacetyl Indoles and Olefins","authors":"Qian-Hui Yu, Qing-Yu Luo, Yu-Hang Ye, Yang-Fan Wu, Xie-Ping Wu, En-Rui Zhang, Xi-Yuan Zhuo, Fei Du, Bin Pan, Wu Liang","doi":"10.1021/acs.orglett.4c03386","DOIUrl":"https://doi.org/10.1021/acs.orglett.4c03386","url":null,"abstract":"A novel and efficient modular synthesis of <i>gem</i>-difluorotetrahydrocarbazolone scaffolds via copper-catalyzed radical cascade cyclization of bromodifluoroacetyl indoles and olefins has been reported. This operationally simple protocol provides straightforward and practical access to a series of privileged <i>gem</i>-difluorotetrahydrocarbazolone scaffolds from readily available starting materials, with the feature of broad functional group tolerance and mild reaction conditions. Moreover, the method could be used for the late-stage functionalization of bioactive molecules, which opens up the possibility for practical applications.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440745","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 : 2024-10-15DOI: 10.1021/acs.orglett.4c03346
Shao-Jie Wang, Li-Rong Jiang, He Wang, Tian-Yi Hu, Ling Zhou, Jie Chen
We report a novel halogen-bond-assisted NHC-catalyzed (dynamic) kinetic resolution strategy for the synthesis of axially chiral heterobiaryls. A class of axially chiral quinolines are prepared efficiently in excellent enantioselectivities (≤98% ee) employing 3–5 mol % NHC catalyst. Mechanistic studies reveal the indispensability of 5-bromo-2-iodobenzaldehyde in this reaction, in which a pivotal halogen bonding interaction plays a crucial role in the process.
{"title":"Halogen-Bond-Assisted NHC-Catalyzed (Dynamic) Kinetic Resolution for the Atroposelective Synthesis of Heterobiaryls","authors":"Shao-Jie Wang, Li-Rong Jiang, He Wang, Tian-Yi Hu, Ling Zhou, Jie Chen","doi":"10.1021/acs.orglett.4c03346","DOIUrl":"https://doi.org/10.1021/acs.orglett.4c03346","url":null,"abstract":"We report a novel halogen-bond-assisted NHC-catalyzed (dynamic) kinetic resolution strategy for the synthesis of axially chiral heterobiaryls. A class of axially chiral quinolines are prepared efficiently in excellent enantioselectivities (≤98% ee) employing 3–5 mol % NHC catalyst. Mechanistic studies reveal the indispensability of 5-bromo-2-iodobenzaldehyde in this reaction, in which a pivotal halogen bonding interaction plays a crucial role in the process.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436519","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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