Abstract A photoredox-catalyzed protocol for performing radical difunctionalization of alkenes using N-heterocyclic carbene (NHC) boranes and alkynyl bromines is described. The alkynylborylation difunctionalization reaction involves photoredox generation of boryl radical, with subsequent radical addition to the double bond followed by the capture of alkynyl bromide to form a C–C bond. This method features mild reaction conditions, remarkable chemoselectivity, broad substrate scope and good to excellent yields (up to 89%). The modification of coumarin derivatives indicates that this approach can provide a useful route for the synthesis of complex alkynylborylated products.
{"title":"Visible-Light-Enabled Radical Alkynylborylation of Activated Alkenes","authors":"Jin Xie, Congjun Zhu, Shunruo Yao","doi":"10.1055/s-0042-1751512","DOIUrl":"https://doi.org/10.1055/s-0042-1751512","url":null,"abstract":"Abstract A photoredox-catalyzed protocol for performing radical difunctionalization of alkenes using N-heterocyclic carbene (NHC) boranes and alkynyl bromines is described. The alkynylborylation difunctionalization reaction involves photoredox generation of boryl radical, with subsequent radical addition to the double bond followed by the capture of alkynyl bromide to form a C–C bond. This method features mild reaction conditions, remarkable chemoselectivity, broad substrate scope and good to excellent yields (up to 89%). The modification of coumarin derivatives indicates that this approach can provide a useful route for the synthesis of complex alkynylborylated products.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":"25 31","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135808791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A cascade, metal promoted transformations utilizing chloro allenylamide, primary amine and aryl iodide afforded piperizinones in good yields. Under the optimized conditions the cascade is performed as one-pot process allowing formation of three bonds. The synthetic route, controlled by the reaction rates of several processes involved, introduces two points of diversity and is well suited for combinatorial synthesis or related technologies.
{"title":"Synthesis of Piperazin-2-one Derivatives via Cascade Double Nucleophilic Substitution","authors":"Milos Petkovic, Dusica Kusljevic, Milos Jovanovic, Predrag Jovanovic, Gordana Tasic, Milena Simic, Vladimir Savic","doi":"10.1055/a-2201-9951","DOIUrl":"https://doi.org/10.1055/a-2201-9951","url":null,"abstract":"A cascade, metal promoted transformations utilizing chloro allenylamide, primary amine and aryl iodide afforded piperizinones in good yields. Under the optimized conditions the cascade is performed as one-pot process allowing formation of three bonds. The synthetic route, controlled by the reaction rates of several processes involved, introduces two points of diversity and is well suited for combinatorial synthesis or related technologies.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":"63 2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135809109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Borylation of haloarene is one of the most important methodologies to synthesize borylated arenes. Generally, borylation of haloarene occurs smoothly at sterically less-hindered para- or meta-position by using a transition metal, a photoredox catalyst, or basic conditions. This study reports on ortho-specific and chemoselective borylation of ortho-iodoarene possessing carboxamide under visible-light irradiation. When a haloarene containing both C–I and C–X bonds is employed as a substrate, another C–X bond (not ortho) remains intact during the reaction. Mechanistic studies revealed that the key to success of this reaction is to generate diboron-bridged five-membered ring as a transition state, in which the diboron-bridged five-membered ring and the benzene ring in the transition state are perpendicular to each other owing to steric repulsion by the iodine atom at the ortho-position. This chemoselectivity is suitable for the synthesis of borylated building blocks.
{"title":"Carboxamide-accelerated Chemoselective Borylation of Iodoarenes under Photoirradiation","authors":"Yusei Nakashima, Michinori Sumimoto, Takashi Nishikata","doi":"10.1055/a-2202-2263","DOIUrl":"https://doi.org/10.1055/a-2202-2263","url":null,"abstract":"Borylation of haloarene is one of the most important methodologies to synthesize borylated arenes. Generally, borylation of haloarene occurs smoothly at sterically less-hindered para- or meta-position by using a transition metal, a photoredox catalyst, or basic conditions. This study reports on ortho-specific and chemoselective borylation of ortho-iodoarene possessing carboxamide under visible-light irradiation. When a haloarene containing both C–I and C–X bonds is employed as a substrate, another C–X bond (not ortho) remains intact during the reaction. Mechanistic studies revealed that the key to success of this reaction is to generate diboron-bridged five-membered ring as a transition state, in which the diboron-bridged five-membered ring and the benzene ring in the transition state are perpendicular to each other owing to steric repulsion by the iodine atom at the ortho-position. This chemoselectivity is suitable for the synthesis of borylated building blocks.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":"53 14","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135869650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract 3-(2-{3-[(2,4-Diamino-6-ethylpyrimidin-5-yl)oxy]propoxy}phenyl)propanoic acid, known as P218, has demonstrated great potency and safety in preclinical and human studies. However, the previous synthetic methods for P218 gave low yields and required hazardous reagents and challenging procedures. In this study, we have successfully developed a decagram-scale synthetic route for P218 with practical and scalable methods for large-scale production. Furthermore, this is also a first report of a novel synthetic approach for P218-OH, a hydroxylated metabolite of P218, by modification of our discovery route. Our synthetic procedures for P218 and P218-OH are a significant advancement in drug development processes, including manufacturing processes and drug metabolism studies.
{"title":"Development of a Practical Synthetic Method for Clinical Candidate 3-(2-{3-[(2,4-Diamino-6-ethylpyrimidin-5-yl)oxy]propoxy} phenyl)propanoic acid (P218) and Its Hydroxylated Metabolites","authors":"Nitipol Srimongkolpithak, Onanong Vorasin, Tanawat Phumjan, Siriporn Saepua, Daniel Iwaniuk, Sumalee Kamchonwongpaisan, Yongyuth Yuthavong, Chawanee Thongpanchang","doi":"10.1055/s-0042-1751502","DOIUrl":"https://doi.org/10.1055/s-0042-1751502","url":null,"abstract":"Abstract 3-(2-{3-[(2,4-Diamino-6-ethylpyrimidin-5-yl)oxy]propoxy}phenyl)propanoic acid, known as P218, has demonstrated great potency and safety in preclinical and human studies. However, the previous synthetic methods for P218 gave low yields and required hazardous reagents and challenging procedures. In this study, we have successfully developed a decagram-scale synthetic route for P218 with practical and scalable methods for large-scale production. Furthermore, this is also a first report of a novel synthetic approach for P218-OH, a hydroxylated metabolite of P218, by modification of our discovery route. Our synthetic procedures for P218 and P218-OH are a significant advancement in drug development processes, including manufacturing processes and drug metabolism studies.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":"326 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136019317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Linked PDF of Table of Contents","authors":"","doi":"10.1055/s-0040-1720097","DOIUrl":"https://doi.org/10.1055/s-0040-1720097","url":null,"abstract":"","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":"182 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136102384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
An efficient deprotection procedure for α,α,α-trihalogen (Cl, Br) methyl alcohols under mild reaction conditions to produce the high-performance liquid chromatography yield of series aldehydes and haloforms have been implemented. This can be applied to the de-protection of aromatic, aliphatic, and heterocyclic trihalomethyl alcohol compounds.
{"title":"Base-catalyzed Deprotection of Aldehyde: New Haloform Reaction","authors":"Gulizhabaier Abulipizi, Kadierya Abuduwaili, Shiying Tian, Mailikezhati Maihemuti, Abudu Rexit Abulikemu","doi":"10.1055/a-2201-3503","DOIUrl":"https://doi.org/10.1055/a-2201-3503","url":null,"abstract":"An efficient deprotection procedure for α,α,α-trihalogen (Cl, Br) methyl alcohols under mild reaction conditions to produce the high-performance liquid chromatography yield of series aldehydes and haloforms have been implemented. This can be applied to the de-protection of aromatic, aliphatic, and heterocyclic trihalomethyl alcohol compounds.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":"150 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136104285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cheng-Lin Ding, Jun-Song Zhong, Hong Yan, Keyin Ye
Electrochemical hydrocarboxylation and deuterocarboxylation of allenes and carbon dioxide were achieved with H2O and D2O, respectively. This reaction generally affords good to excellent regioselectivity in the formation of diverse carboxylic acids.
{"title":"Electrochemical hydro- and deuterocarboxylation of allenes","authors":"Cheng-Lin Ding, Jun-Song Zhong, Hong Yan, Keyin Ye","doi":"10.1055/a-2200-5332","DOIUrl":"https://doi.org/10.1055/a-2200-5332","url":null,"abstract":"Electrochemical hydrocarboxylation and deuterocarboxylation of allenes and carbon dioxide were achieved with H2O and D2O, respectively. This reaction generally affords good to excellent regioselectivity in the formation of diverse carboxylic acids.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":"112 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136316684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lukas Marek, Jiri Vana, Jan Svoboda, Marketa Svobodova, Jiri Hanusek
Novel synthetic strategy involving the Eschenmoser coupling reaction of 4-bromoisoquinoline-1,3(2H,4H)-diones with substituted thioformanilides, thioacetanilides and thiobenzanilides gave 18 (Z)-4-((subst. phenylamino)-methylidene)isoquinoline-1,3(2H,4H)-diones. The reaction occurs under mild conditions (DMF or MeCN, 25-60 °C) without any base or thiophile and in good yields (43-95 %). Furthermore, for the synthesis of starting thioformanilides carrying basic substituents, a new thioacylation protocol was developed that involves a thioacylating agent formed from CS2 and LiBEt3H.
{"title":"Efficient synthesis of (Z)-4-((subst.phenylamino)methylidene)-isoquinoline-1,3(2H,4H)-diones using Eschenmoser coupling reaction","authors":"Lukas Marek, Jiri Vana, Jan Svoboda, Marketa Svobodova, Jiri Hanusek","doi":"10.1055/a-2198-1589","DOIUrl":"https://doi.org/10.1055/a-2198-1589","url":null,"abstract":"Novel synthetic strategy involving the Eschenmoser coupling reaction of 4-bromoisoquinoline-1,3(2H,4H)-diones with substituted thioformanilides, thioacetanilides and thiobenzanilides gave 18 (Z)-4-((subst. phenylamino)-methylidene)isoquinoline-1,3(2H,4H)-diones. The reaction occurs under mild conditions (DMF or MeCN, 25-60 °C) without any base or thiophile and in good yields (43-95 %). Furthermore, for the synthesis of starting thioformanilides carrying basic substituents, a new thioacylation protocol was developed that involves a thioacylating agent formed from CS2 and LiBEt3H.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":"43 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135218356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this article we have focused on the use of selenium in catalysis along with the proposed reaction mechanisms. With the increasing interest in selenium chemistry, we have attempted to highlight the most significant features on this subject, mainly in the last years. Selenium-containing catalysts have a key role in many transformations; for example, those oxidation reactions that should be performed under very mild and controlled conditions. In addition, the weak selenium-oxygen bonding interaction proved to be very useful as a catalytic approach for specific transformations. The catalytic cycles of each appropriate transformation are fully reviewed.
{"title":"Organoselenium Compounds in Catalysis","authors":"Carola Gallo-Rodriguez, Juan Bautista Rodriguez","doi":"10.1055/a-2197-7356","DOIUrl":"https://doi.org/10.1055/a-2197-7356","url":null,"abstract":"In this article we have focused on the use of selenium in catalysis along with the proposed reaction mechanisms. With the increasing interest in selenium chemistry, we have attempted to highlight the most significant features on this subject, mainly in the last years. Selenium-containing catalysts have a key role in many transformations; for example, those oxidation reactions that should be performed under very mild and controlled conditions. In addition, the weak selenium-oxygen bonding interaction proved to be very useful as a catalytic approach for specific transformations. The catalytic cycles of each appropriate transformation are fully reviewed.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":"55 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135266667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonas Donges, Andrea Frank, Dieter Schollmeyer, Udo Nubbemeyer
The 2-(1’-hydroxyalkyl) paraconyl alcohols (-)-VB-A and (-)-SCB-5 are known as highly active signaling molecules within antibiotics production in Streptomyces sp. These γ-butyrolactone type compounds are epimeric at the 1’-OH-group. A direct synthesis of (-)-VB-A from (-)-SCB-5 that uses a late-stage inversion of the 1’-hydroxy group is not favored because of side reactions of the carbinol in β-position to the lactone C=O function. Therefore, an orthogonally protected 1,4-diol incorporating the central syn/anti 1’,2,3-stereotriad as described within the (-)-SCB-5 synthesis was used as an advanced intermediate to generate (-)-VB-A, too. A combination of protecting group operations and a 1’-OH group inversion via oxidation and diastereoselective reduction delivered the anti/anti 1’,2,3-stereotriad. Final transformations related to that as described for (-)-SCB-5 enabled completion of the (-)-VB-A-synthesis.
{"title":"Synthesis of (-)-Virginiae Butanolide A (VB-A)","authors":"Jonas Donges, Andrea Frank, Dieter Schollmeyer, Udo Nubbemeyer","doi":"10.1055/a-2195-7907","DOIUrl":"https://doi.org/10.1055/a-2195-7907","url":null,"abstract":"The 2-(1’-hydroxyalkyl) paraconyl alcohols (-)-VB-A and (-)-SCB-5 are known as highly active signaling molecules within antibiotics production in Streptomyces sp. These γ-butyrolactone type compounds are epimeric at the 1’-OH-group. A direct synthesis of (-)-VB-A from (-)-SCB-5 that uses a late-stage inversion of the 1’-hydroxy group is not favored because of side reactions of the carbinol in β-position to the lactone C=O function. Therefore, an orthogonally protected 1,4-diol incorporating the central syn/anti 1’,2,3-stereotriad as described within the (-)-SCB-5 synthesis was used as an advanced intermediate to generate (-)-VB-A, too. A combination of protecting group operations and a 1’-OH group inversion via oxidation and diastereoselective reduction delivered the anti/anti 1’,2,3-stereotriad. Final transformations related to that as described for (-)-SCB-5 enabled completion of the (-)-VB-A-synthesis.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":"2 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135568175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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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