A calcium triflate promoted reaction of Morita–Baylis–Hillman (MBH) ketones, derived by the oxidation of MBH adducts, with 2-aminobenzothiazoles resulted in the formation of a 4H-pyrimido[2,1-b]benzothiazole. Formally, the transformation represents a [3+3] annulation and presumably proceeds via an aza-Michael addition followed by an intramolecular condensation. The reaction is completely regioselective and tolerates a wide range of substrates to afford a variety of analogs of the fused heterocycle in good yields.
{"title":"A Formal [3+3] Annulation of Morita–Baylis–Hillman Ketones to Construct Pyrimidobenzothiazoles","authors":"Rajkiran Kumari, Suman Kumawat, Easwar Srinivasan","doi":"10.1055/a-2373-0255","DOIUrl":"https://doi.org/10.1055/a-2373-0255","url":null,"abstract":"A calcium triflate promoted reaction of Morita–Baylis–Hillman (MBH) ketones, derived by the oxidation of MBH adducts, with 2-aminobenzothiazoles resulted in the formation of a 4H-pyrimido[2,1-b]benzothiazole. Formally, the transformation represents a [3+3] annulation and presumably proceeds via an aza-Michael addition followed by an intramolecular condensation. The reaction is completely regioselective and tolerates a wide range of substrates to afford a variety of analogs of the fused heterocycle in good yields.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141802273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
1,3-Difluorinated compounds are characterized by their unique conformation, influenced by 1,3-dipolar minimization effects. However, their synthetic methods are relatively limited. Here, we describe a ring-opening 1,3-difluorination of benzylidenecyclopropanes (BCPs) using HF·Py, mediated by an electron-poor hypervalent iodine reagent, which is generated in-situ by the oxidation of o-nitroiodobenzene with mCPBA. The protocol features mild reaction conditions, good functional group tolerance, and moderate to good yields. Additionally, the synthetic utility of this method is showcased by further transformations of the olefin group and allylic fluoride motif.
{"title":"Hypervalent Iodine-Mediated Ring-Opening 1,3-Difluorination of Benzylidenecyclopropanes","authors":"Long-Ling Huang, Jia-Yi Li, Qigang Sun, Gui-Yang Zhao, Honggen Wang, Qingjiang Li","doi":"10.1055/a-2373-0304","DOIUrl":"https://doi.org/10.1055/a-2373-0304","url":null,"abstract":"1,3-Difluorinated compounds are characterized by their unique conformation, influenced by 1,3-dipolar minimization effects. However, their synthetic methods are relatively limited. Here, we describe a ring-opening 1,3-difluorination of benzylidenecyclopropanes (BCPs) using HF·Py, mediated by an electron-poor hypervalent iodine reagent, which is generated in-situ by the oxidation of o-nitroiodobenzene with mCPBA. The protocol features mild reaction conditions, good functional group tolerance, and moderate to good yields. Additionally, the synthetic utility of this method is showcased by further transformations of the olefin group and allylic fluoride motif.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":"51 42","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141805045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rafia Khatoon, Tanvi Jandial, Anish Gupta, Sujata Kundan, V. Sridharan
An efficient one-pot, two-step synthesis of structurally diverse 4-indolyl/pyrrolyl-chromanes was developed starting from O-propargylated salicylaldehydes, 2,6-dialkylphenols and indoles/pyrrole. This process begins with a sequential secondary amine-catalyzed formation of p-quinone methides followed by Brønsted acid-catalyzed 1,8-addition with indoles/pyrrole to access the functionalized chromanes in high yields (up to 91%). This sequential reaction generates three new C–C bonds, shows high step- and atom-economy with only one molecule of water as the side product and gives access to complex molecular frameworks without the need for the isolation of the intermediates.
{"title":"One-Pot, Two-Step Synthesis of Highly Functionalized 4-Indolyl/Pyrrolyl-Chromanes via para-Quinone Methide Formation-1,8-Addition Sequence","authors":"Rafia Khatoon, Tanvi Jandial, Anish Gupta, Sujata Kundan, V. Sridharan","doi":"10.1055/a-2371-3579","DOIUrl":"https://doi.org/10.1055/a-2371-3579","url":null,"abstract":"An efficient one-pot, two-step synthesis of structurally diverse 4-indolyl/pyrrolyl-chromanes was developed starting from O-propargylated salicylaldehydes, 2,6-dialkylphenols and indoles/pyrrole. This process begins with a sequential secondary amine-catalyzed formation of p-quinone methides followed by Brønsted acid-catalyzed 1,8-addition with indoles/pyrrole to access the functionalized chromanes in high yields (up to 91%). This sequential reaction generates three new C–C bonds, shows high step- and atom-economy with only one molecule of water as the side product and gives access to complex molecular frameworks without the need for the isolation of the intermediates.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":"89 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141812734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A highly convenient and straightforward strategy for the synthesis of difluoromethyl substituted tricyclic fused chromono[3,2-c]pyrazolines/pyrazoles is developed via [3+2]-cycloaddition of difluoroacetohydrazonoyl bromides with 3-electron-withdrawing-group substituted chromones. The reaction has the advantages of mild conditions, good tolerance of functional groups and simple operation.
{"title":"Synthesis of Difluoromethyl Chromono[3,2-c]pyrazolines/pyrazoles by [3+2] Cycloaddition Reaction of Difluoroacetohydrazonoyl Bromides with 3-EWG-Chromones","authors":"Ke‐Hu Wang, Xiuwen Liang, Wenjing Luo, Maizhuo Chen, Junjiao Wang, Danfeng Huang, Yulai Hu","doi":"10.1055/a-2368-8392","DOIUrl":"https://doi.org/10.1055/a-2368-8392","url":null,"abstract":"A highly convenient and straightforward strategy for the synthesis of difluoromethyl substituted tricyclic fused chromono[3,2-c]pyrazolines/pyrazoles is developed via [3+2]-cycloaddition of difluoroacetohydrazonoyl bromides with 3-electron-withdrawing-group substituted chromones. The reaction has the advantages of mild conditions, good tolerance of functional groups and simple operation.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":" 71","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141825203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Spirocyclic β-lactams are a family of natural and synthetic chemicals with different biological activity, including antibacterial properties and interaction with critical physiological targets such as T-type calcium channels and acetyl-CoA cholesterol acyltransferase. Their unique chemical structure, combining spiro ring system with β-lactam group, offers promising opportunities for targeted medication discovery in medicinal chemistry. Spirocyclic β-lactams have the potential to be adaptable frameworks for developing novel therapeutic medicines with particular three-dimensional pharmacophoric characteristics and increased biological efficacy. Numerous methods are employed in the synthesis of spirocyclic β-lactams, such as cyclization, functional group modifications, asymmetric synthesis utilizing chiral catalysts and biomimetic approaches. In this Short Review, two distinct approaches to recent synthesis of spirocyclic β-lactams are discussed: one is based on constructing the β-lactam ring, while the other entails transforming monocyclic β-lactams into spirocyclic structures (from 2021 to till date). These methods include detailed reaction processes and biological function descriptions of target spirocycles. The applications of spirocyclic β-lactams in medicinal chemistry highlight their role in synthesis of structurally diverse compounds with significant therapeutic potential, demonstrating creative chemical methods of building complex molecular structures. 1 Introduction 2 β-Lactam Ring Synthesis 3 Non-β-Lactam Ring Synthesis 4 Miscellaneous Examples 5 Conclusion and Outlook 6 References
{"title":"Chemical Methods for Construction of Spirocyclic β-Lactams and their Biological Importance","authors":"Pooja Yadav, Shiwani Berry, Aman Bhalla","doi":"10.1055/a-2368-8443","DOIUrl":"https://doi.org/10.1055/a-2368-8443","url":null,"abstract":"Spirocyclic β-lactams are a family of natural and synthetic chemicals with different biological activity, including antibacterial properties and interaction with critical physiological targets such as T-type calcium channels and acetyl-CoA cholesterol acyltransferase. Their unique chemical structure, combining spiro ring system with β-lactam group, offers promising opportunities for targeted medication discovery in medicinal chemistry. Spirocyclic β-lactams have the potential to be adaptable frameworks for developing novel therapeutic medicines with particular three-dimensional pharmacophoric characteristics and increased biological efficacy. Numerous methods are employed in the synthesis of spirocyclic β-lactams, such as cyclization, functional group modifications, asymmetric synthesis utilizing chiral catalysts and biomimetic approaches. In this Short Review, two distinct approaches to recent synthesis of spirocyclic β-lactams are discussed: one is based on constructing the β-lactam ring, while the other entails transforming monocyclic β-lactams into spirocyclic structures (from 2021 to till date). These methods include detailed reaction processes and biological function descriptions of target spirocycles. The applications of spirocyclic β-lactams in medicinal chemistry highlight their role in synthesis of structurally diverse compounds with significant therapeutic potential, demonstrating creative chemical methods of building complex molecular structures. \u00001 Introduction \u00002 β-Lactam Ring Synthesis \u00003 Non-β-Lactam Ring Synthesis \u00004 Miscellaneous Examples \u00005 Conclusion and Outlook \u00006 References","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":" 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141825998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marcus M. Sá, P. A. Moro, Theo V. C. Russo, Vinicius C Port, G. Caramori
A mild procedure for the diastereoselective preparation of functionalized 1,3-dienes and their synthetic versatility are described herein. The silver-catalyzed decomposition of α-diazo-γ,δ-unsaturated esters through β-hydride migration at room temperature resulted in the stereoselective formation of 12 conjugated (1E,3E)-dienes. Further synthetic post-modifications included intramolecular Heck reaction and hydrogenation, leading to a novel substituted indene and an aliphatic diester, respectively. To rationalize the observed reaction outcome, a computational investigation of the mechanisms was conducted, emphasizing the importance of factors such as metallocarbenoid stability, substituent effects, and microkinetics simulations to better understand the reaction intricacies.
{"title":"Mild and stereoselective synthesis of (1E,3E)-dienes through silver(I)-catalyzed β-hydride migration from allylic α-diazo esters","authors":"Marcus M. Sá, P. A. Moro, Theo V. C. Russo, Vinicius C Port, G. Caramori","doi":"10.1055/a-2369-3961","DOIUrl":"https://doi.org/10.1055/a-2369-3961","url":null,"abstract":"A mild procedure for the diastereoselective preparation of functionalized 1,3-dienes and their synthetic versatility are described herein. The silver-catalyzed decomposition of α-diazo-γ,δ-unsaturated esters through β-hydride migration at room temperature resulted in the stereoselective formation of 12 conjugated (1E,3E)-dienes. Further synthetic post-modifications included intramolecular Heck reaction and hydrogenation, leading to a novel substituted indene and an aliphatic diester, respectively. To rationalize the observed reaction outcome, a computational investigation of the mechanisms was conducted, emphasizing the importance of factors such as metallocarbenoid stability, substituent effects, and microkinetics simulations to better understand the reaction intricacies.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":" 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141824403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chiral 3-monosubstituted oxindoles are privileged structural motifs in a variety of natural products and synthetic pharmaceuticals. However, catalytic asymmetric synthesis of these structural motifs has remained a challenge mainly because of the ease of racemization of the tertiary stereocenter through enolization. In this short review, asymmetric synthetic methods for chiral 3-monosubstituted oxindoles are summarized from the perspective of four different strategies, including Michael addition, carbenoid-mediated C‒H insertion, decarboxylative protonation, and indole oxidation.
{"title":"Catalytic asymmetric synthesis of 3-monosubstituted oxindoles","authors":"Xigong Liu, Lei Liu","doi":"10.1055/a-2368-8554","DOIUrl":"https://doi.org/10.1055/a-2368-8554","url":null,"abstract":"Chiral 3-monosubstituted oxindoles are privileged structural motifs in a variety of natural products and synthetic pharmaceuticals. However, catalytic asymmetric synthesis of these structural motifs has remained a challenge mainly because of the ease of racemization of the tertiary stereocenter through enolization. In this short review, asymmetric synthetic methods for chiral 3-monosubstituted oxindoles are summarized from the perspective of four different strategies, including Michael addition, carbenoid-mediated C‒H insertion, decarboxylative protonation, and indole oxidation.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":" 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141827206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We report an efficient synthesis of 6-substituted imidazo[2,1-b]thiazoles through intramolecular cyclization of in situ generated thiazolium ylide from 2-aminothiazole and acetophenone. This one-pot cascade process efficiently forms two C-N bonds and is facilitated by Cu(OTf)2 and KI, both of which play key roles in the mechanism. The method utilizes commercially available starting materials and features mild reaction conditions, tolerance to different functional groups, and ease of operation. The synthetic applicability has further been demonstrated through post-modification of imidazo[2,1-b]thiazole analogues.
我们报告了一种高效合成 6-取代咪唑并[2,1-b]噻唑的方法，该方法是通过 2-aminothiazole 和苯乙酮原位生成的噻唑鎓的分子内环化来实现的。这种一锅级联过程能有效地形成两个 C-N 键，Cu(OTf)2 和 KI 起到了促进作用。该方法利用市场上可买到的起始材料，反应条件温和，对不同官能团具有耐受性，操作简便。通过对咪唑并[2,1-b]噻唑类似物进行后修饰，进一步证明了该合成方法的适用性。
{"title":"Transition-Metal Catalyzed Rapid Synthesis of Imidiazo[2,1-b]thiazoles: Access to Aza-Fused Heterocycles via Aerobic Oxidative Coupling of 2-Aminothiazoles and Acetophenones","authors":"Soumyadipta Basak, Pratap Paul, J. Dash","doi":"10.1055/a-2369-3893","DOIUrl":"https://doi.org/10.1055/a-2369-3893","url":null,"abstract":"We report an efficient synthesis of 6-substituted imidazo[2,1-b]thiazoles through intramolecular cyclization of in situ generated thiazolium ylide from 2-aminothiazole and acetophenone. This one-pot cascade process efficiently forms two C-N bonds and is facilitated by Cu(OTf)2 and KI, both of which play key roles in the mechanism. The method utilizes commercially available starting materials and features mild reaction conditions, tolerance to different functional groups, and ease of operation. The synthetic applicability has further been demonstrated through post-modification of imidazo[2,1-b]thiazole analogues.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":" 36","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141827838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
An efficient methodology for the synthesis of highly diverse 4-aminoquinoline derivatives from activated alkynes and 2-aminobenzonitriles mediated by Lewis acid is described. The reaction proceeds via sequential aza-Michael addition/intramolecular annulation to afford highly substituted 4-aminoquinolines in good yields. The reaction is operationally simple and has high atom-economy with broad substrate scope. The post synthetic application of the reaction provides 4H-benzo[de][1,6]naphthyridines.
{"title":"Lewis acid mediated synthesis of 4-aminoquinoline derivatives from 2-aminobenzonitriles and activated alkynes via aza-Michael and annulation reaction","authors":"A. Saikia, Bikoshita Porashar","doi":"10.1055/a-2368-8500","DOIUrl":"https://doi.org/10.1055/a-2368-8500","url":null,"abstract":"An efficient methodology for the synthesis of highly diverse 4-aminoquinoline derivatives from activated alkynes and 2-aminobenzonitriles mediated by Lewis acid is described. The reaction proceeds via sequential aza-Michael addition/intramolecular annulation to afford highly substituted 4-aminoquinolines in good yields. The reaction is operationally simple and has high atom-economy with broad substrate scope. The post synthetic application of the reaction provides 4H-benzo[de][1,6]naphthyridines.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":" 36","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141824593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Homoallylic alcohol is a significantly useful intermediate in organic synthesis. Here we establish a three-component NHK-type reaction of 1,3-butadiene, aldehydes and aliphatic C–H partners by merging decatungstate and chromium catalysis, enabling a modular, redox-neutral and atom-economic strategy to access a diverse range of homoallylic alcohols.
均烯丙基醇是有机合成中一种非常有用的中间体。在这里，我们通过蜕钨酸盐和铬催化，建立了一个由 1,3-丁二烯、醛和脂肪族 C-H 合伙人组成的三组分 NHK 型反应，从而实现了一种模块化、氧化还原中性和原子经济的策略，以获得各种均烯丙基醇。
{"title":"Redox-Neutral 1,2-Dicarbonfunctionlization of 1,3-Butadiene by Merging Decatungstate and Chromium Catalysis","authors":"D. Ding, Pu-Sheng Wang","doi":"10.1055/a-2328-3037","DOIUrl":"https://doi.org/10.1055/a-2328-3037","url":null,"abstract":"Homoallylic alcohol is a significantly useful intermediate in organic synthesis. Here we establish a three-component NHK-type reaction of 1,3-butadiene, aldehydes and aliphatic C–H partners by merging decatungstate and chromium catalysis, enabling a modular, redox-neutral and atom-economic strategy to access a diverse range of homoallylic alcohols.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":"136 27","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140976887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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