Stefan Bernhard, Nadine Kümmerer, Dagmar Urgast, Frederik Hack, Julia Ungelenk, Andrea Frank, Dieter Schollmeyer, Udo Nubbemeyer
A seven-step ex-chiral-pool synthesis of optically active 4-alkylidene-tetrahydroisoquinolines was developed. Starting from 6-bromopiperonal and (S)-serine esters N-benzylation via reductive amination gave enantiopure N-piperonyl serine esters. Subsequent NH and OH protection delivered defined (S)-serine building blocks. Best results to achieve the conversion into the corresponding serinal were obtained via a two-step sequence of NaBH4/LiCl reduction and subsequent TEMPO oxidation. Then, chain elongation using the Masamune-Roush variant of the Horner olefination afforded (E)-ethyl 4-(N-6-bromopiperonyl) substituted pentenoates with high yields. Intramolecular Heck cyclization employing the Herrmann-Beller catalyst enabled generation of enantiopure 4-(2-ethoxycarbonylmethylidene)-tetrahydroisoquinoline building blocks with high (Z) selectivity. Subsequent selected functional group transformations gave carbinols and lactones, which will be used as key intermediates in crinane alkaloid total syntheses.
{"title":"Ex-Chiral-pool Synthesis of Optically Active 4-Alkylidene-Tetrahydroisoquinolines – Key Intermediates for Crinane Alkaloid Total Syntheses","authors":"Stefan Bernhard, Nadine Kümmerer, Dagmar Urgast, Frederik Hack, Julia Ungelenk, Andrea Frank, Dieter Schollmeyer, Udo Nubbemeyer","doi":"10.1055/a-2328-2947","DOIUrl":"https://doi.org/10.1055/a-2328-2947","url":null,"abstract":"A seven-step ex-chiral-pool synthesis of optically active 4-alkylidene-tetrahydroisoquinolines was developed. Starting from 6-bromopiperonal and (S)-serine esters N-benzylation via reductive amination gave enantiopure N-piperonyl serine esters. Subsequent NH and OH protection delivered defined (S)-serine building blocks. Best results to achieve the conversion into the corresponding serinal were obtained via a two-step sequence of NaBH4/LiCl reduction and subsequent TEMPO oxidation. Then, chain elongation using the Masamune-Roush variant of the Horner olefination afforded (E)-ethyl 4-(N-6-bromopiperonyl) substituted pentenoates with high yields. Intramolecular Heck cyclization employing the Herrmann-Beller catalyst enabled generation of enantiopure 4-(2-ethoxycarbonylmethylidene)-tetrahydroisoquinoline building blocks with high (Z) selectivity. Subsequent selected functional group transformations gave carbinols and lactones, which will be used as key intermediates in crinane alkaloid total syntheses.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":"61 21","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140975134","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}
Caitlyn M. Matherne, Jordan E. Wroblewski, Heather S Drago, Gabriela T Marchan, Alexis R Young, Nkechi Kingsley, Craig P. Plaisance, J. Fotie
Palladium nanoparticles are dispersed and stabilized in organically modified silicate (Pd@MTES), and characterized by a number of spectroscopic techniques, including FTIR, TEM, SEM, and XPS. The catalytic effect of this material toward the hydrosilylation of aldehydes and ketones is explored, and the scope of the reaction investigated, with 26 examples provided. This reaction proceeds under neat conditions via heterogenous catalysis, and a mechanistic pathway supported by DFT calculations is proposed.
{"title":"Palladium nano-dispersed and stabilized in organically modified silicate as a heterogenous catalyst for the conversion of aldehydes into O-silyl ether derivatives under neat conditions.","authors":"Caitlyn M. Matherne, Jordan E. Wroblewski, Heather S Drago, Gabriela T Marchan, Alexis R Young, Nkechi Kingsley, Craig P. Plaisance, J. Fotie","doi":"10.1055/a-2326-6277","DOIUrl":"https://doi.org/10.1055/a-2326-6277","url":null,"abstract":"Palladium nanoparticles are dispersed and stabilized in organically modified silicate (Pd@MTES), and characterized by a number of spectroscopic techniques, including FTIR, TEM, SEM, and XPS. The catalytic effect of this material toward the hydrosilylation of aldehydes and ketones is explored, and the scope of the reaction investigated, with 26 examples provided. This reaction proceeds under neat conditions via heterogenous catalysis, and a mechanistic pathway supported by DFT calculations is proposed.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":"36 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140981228","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}
Thi Minh Thi Le, Mingbing Zhong, P. Jubault, T. Poisson
The reduction of nitro compounds into the highly valuable anilines was reported using a Cu-catalyst and B2Pin2. The reaction proceeded under very mild reaction conditions and showcased an excellent functional group tolerance. This method was applied to a large panel of nitro derivatives including biorelevant molecules and important synthetic intermediates toward the synthesis of API. This novel reaction manifold intends to provide a complementary approach to the existing portfolio of nitro-reduction methods.
{"title":"Copper Catalyzed Chemoselective Nitro Reduction","authors":"Thi Minh Thi Le, Mingbing Zhong, P. Jubault, T. Poisson","doi":"10.1055/a-2326-6363","DOIUrl":"https://doi.org/10.1055/a-2326-6363","url":null,"abstract":"The reduction of nitro compounds into the highly valuable anilines was reported using a Cu-catalyst and B2Pin2. The reaction proceeded under very mild reaction conditions and showcased an excellent functional group tolerance. This method was applied to a large panel of nitro derivatives including biorelevant molecules and important synthetic intermediates toward the synthesis of API. This novel reaction manifold intends to provide a complementary approach to the existing portfolio of nitro-reduction methods.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":"21 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140982250","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}
Diarylacetylenes undergo anti-dimagnesiation using magnesium bromide and Na dispersion to afford (E)-1,2-dimagnesioalkenes. This dimagnesiation utilizes simple MgBr2 as a reduction-resistant electrophile, contrasting with the previously reported dimagnesiation using tricky organomagnesium halides. The resulting vicinal double Grignard reagents react with various electrophiles to yield multi-substituted alkenes stereoselectively.
利用溴化镁和 Na 色散对二烷基乙炔进行反二镁反应，可得到 (E)-1,2-二镁烯烃。这种二镁反应利用简单的 MgBr2 作为抗还原亲电子体，与之前报道的利用棘手的有机卤化镁进行的二镁反应形成鲜明对比。生成的邻位双格氏试剂与各种亲电体反应，立体选择性地生成多取代烯。
{"title":"Sodium-mediated Reductive anti-Dimagnesiation of Diarylacetylenes with Magnesium Bromide","authors":"Haruka Yamaguchi, Fumiya Takahashi, Takashi Kurogi, Hideki Yorimitsu","doi":"10.1055/a-2326-6416","DOIUrl":"https://doi.org/10.1055/a-2326-6416","url":null,"abstract":"Diarylacetylenes undergo anti-dimagnesiation using magnesium bromide and Na dispersion to afford (E)-1,2-dimagnesioalkenes. This dimagnesiation utilizes simple MgBr2 as a reduction-resistant electrophile, contrasting with the previously reported dimagnesiation using tricky organomagnesium halides. The resulting vicinal double Grignard reagents react with various electrophiles to yield multi-substituted alkenes stereoselectively.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":"79 23","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140979013","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}
B. Gopal, Prasoon Raj Singh, Shubham Bhatt, Avijit Goswami
A BF3·OEt2 promoted facile synthesis of cyclic amidines has been developed via the (3+2)-cycloaddition of cyanamides with donor-acceptor cyclopropanes (DACs). In addition to this, the protocol has been successfully extended to construct dimerized amidine derivative and gram-scale synthesis with great efficiency.
{"title":"BF3·OEt2 Mediated (3+2) Cycloaddition Reactions of DACs with Cyanamides: Access to Cyclic Amidines","authors":"B. Gopal, Prasoon Raj Singh, Shubham Bhatt, Avijit Goswami","doi":"10.1055/a-2323-0721","DOIUrl":"https://doi.org/10.1055/a-2323-0721","url":null,"abstract":"A BF3·OEt2 promoted facile synthesis of cyclic amidines has been developed via the (3+2)-cycloaddition of cyanamides with donor-acceptor cyclopropanes (DACs). In addition to this, the protocol has been successfully extended to construct dimerized amidine derivative and gram-scale synthesis with great efficiency.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":"122 45","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140985334","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}
The highly efficient synthesis of all-carbon tetrasubstituted olefins has been concerned for decades, especially for multi-aryl substituted olefins which widely used in functional organic materials and pharmaceuticals. This work presents a carbonyl-directed palladium-catalyzed consecutive arylation of terminal alkenes with aryl iodides under mild conditions, a series of triarylated tetrasubstituted olefins were obtained in moderate yields. Because a weak chelation effect is generally difficult to support such a thorough tri-fold Heck arylation, and the β-trans-selective alkenyl C–H activation cannot be achieved via a twisted endo-metallacyclic intermediate, thus, the key to success is the compatibility between several mechanisms, including Heck, C–H activation and E,Z-isomerization. Here, the judicious selection of a flexible-alkyl-chain-tethered carbonyl group seems to be critical, it provides a proper chelation effect that not only assists a distal alkenyl functionalization or isomerization, but also avoids byproducts caused by other possible β-H elimination or migration. The strategy developed herein greatly streamlines the preparation of the target molecules, and the protocol covers a range of readily available terminal alkenes bearing native directing groups (e.g., aldehyde, ketone and ester), and aryl iodides.
{"title":"Remote-Carbonyl-Directed Consecutive Arylation of Terminal Alkenes for the Synthesis of Tetrasubstituted Olefins","authors":"Kun Li, Runze Luan, Yu Du, Weiping Su","doi":"10.1055/a-2323-0633","DOIUrl":"https://doi.org/10.1055/a-2323-0633","url":null,"abstract":"The highly efficient synthesis of all-carbon tetrasubstituted olefins has been concerned for decades, especially for multi-aryl substituted olefins which widely used in functional organic materials and pharmaceuticals. This work presents a carbonyl-directed palladium-catalyzed consecutive arylation of terminal alkenes with aryl iodides under mild conditions, a series of triarylated tetrasubstituted olefins were obtained in moderate yields. Because a weak chelation effect is generally difficult to support such a thorough tri-fold Heck arylation, and the β-trans-selective alkenyl C–H activation cannot be achieved via a twisted endo-metallacyclic intermediate, thus, the key to success is the compatibility between several mechanisms, including Heck, C–H activation and E,Z-isomerization. Here, the judicious selection of a flexible-alkyl-chain-tethered carbonyl group seems to be critical, it provides a proper chelation effect that not only assists a distal alkenyl functionalization or isomerization, but also avoids byproducts caused by other possible β-H elimination or migration. The strategy developed herein greatly streamlines the preparation of the target molecules, and the protocol covers a range of readily available terminal alkenes bearing native directing groups (e.g., aldehyde, ketone and ester), and aryl iodides.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":" 27","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140992704","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. Shatsauskas, Sergey A. Kirnosov, Ekaterina S. Keyn, V. Shuvalov, A. Kostyuchenko, A. Fisyuk
Two approaches were proposed to the synthesis of dibenzo[b,h][1,5]naphthyridin-7(12H)-ones. The one-step method based on the Pictet–Spengler reaction of 3-amino-2-phenylquinolin-4(1H)-one with aromatic aldehydes requires heating in a strong acidic media, which leads to significant limitations on the possible products. The second approach is based on the conversion of 3-amino-2-phenylquinolin-4(1H)-one to 4-phenyl[1,3]oxazolo[4,5-c]quinolines followed by rearrangement under the action of AlCl3. A significant advantage of the two-step synthesis is the possibility of obtaining a wider range of dibenzo[b,h][1,5]naphthyridin-7(12H)-ones, including those not available using the Pictet–Spengler reaction.
{"title":"A synthesis of dibenzo[b,h][1,5]naphthyridin-7(12H)-ones: the Pictet–Spengler reaction vs a rearrangement of 4-phenyl[1,3]oxazolo[4,5-c]quinolines","authors":"A. Shatsauskas, Sergey A. Kirnosov, Ekaterina S. Keyn, V. Shuvalov, A. Kostyuchenko, A. Fisyuk","doi":"10.1055/a-2323-0770","DOIUrl":"https://doi.org/10.1055/a-2323-0770","url":null,"abstract":"Two approaches were proposed to the synthesis of dibenzo[b,h][1,5]naphthyridin-7(12H)-ones. The one-step method based on the Pictet–Spengler reaction of 3-amino-2-phenylquinolin-4(1H)-one with aromatic aldehydes requires heating in a strong acidic media, which leads to significant limitations on the possible products. The second approach is based on the conversion of 3-amino-2-phenylquinolin-4(1H)-one to 4-phenyl[1,3]oxazolo[4,5-c]quinolines followed by rearrangement under the action of AlCl3. A significant advantage of the two-step synthesis is the possibility of obtaining a wider range of dibenzo[b,h][1,5]naphthyridin-7(12H)-ones, including those not available using the Pictet–Spengler reaction.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":" 32","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140993553","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}
Kamal Kant, Chandresh K. Patel, Reetu Reetu, Yaqoob A. Teli, Priyadarshini Naik, Sanjukta Some, C. Hazra, N. Aljaar, Ananta K. Atta, C. Malakar
The process of crafting 1,3-enyne compounds holds widespread appeal in organic synthesis due to the compound's proven adaptability as an intermediate in many methods for creating compounds of significant biological and material interest. A variety of methods have been designed to formulate 1,3-enynes from diverse initial materials, such as alkynes, 1,3-conjugated diynes, cyclopropane substitutes, and propargyl alcohols. This review encapsulates a thorough synthesis of 1,3-enynes by utilizing distinct procedures: homo- and cross-coupling of alkynes, metal/acid-induced cyclopropane ring opening through a nucleophile assault, propargyl alcohols' rearrangement/dehydration sequence. In both the alkyne and 1,3-diyne procedures, managing the regio-, stereo-, and, where fitting, chemoselectivity is a key concern. In contrast, with the cyclopropyl ring opening procedure, the selection of enynes relies on nucleophile orientation. In this context, we underscore select efficient methods for the broad and selective synthesis of these pivotal compounds. Additionally, we provided specific examples to demonstrate the efficacy of these processes.
{"title":"Comprehensive Strategies on the Synthesis of Ene-Yne Derivatives","authors":"Kamal Kant, Chandresh K. Patel, Reetu Reetu, Yaqoob A. Teli, Priyadarshini Naik, Sanjukta Some, C. Hazra, N. Aljaar, Ananta K. Atta, C. Malakar","doi":"10.1055/a-2317-7262","DOIUrl":"https://doi.org/10.1055/a-2317-7262","url":null,"abstract":"The process of crafting 1,3-enyne compounds holds widespread appeal in organic synthesis due to the compound's proven adaptability as an intermediate in many methods for creating compounds of significant biological and material interest. A variety of methods have been designed to formulate 1,3-enynes from diverse initial materials, such as alkynes, 1,3-conjugated diynes, cyclopropane substitutes, and propargyl alcohols. This review encapsulates a thorough synthesis of 1,3-enynes by utilizing distinct procedures: homo- and cross-coupling of alkynes, metal/acid-induced cyclopropane ring opening through a nucleophile assault, propargyl alcohols' rearrangement/dehydration sequence. In both the alkyne and 1,3-diyne procedures, managing the regio-, stereo-, and, where fitting, chemoselectivity is a key concern. In contrast, with the cyclopropyl ring opening procedure, the selection of enynes relies on nucleophile orientation. In this context, we underscore select efficient methods for the broad and selective synthesis of these pivotal compounds. Additionally, we provided specific examples to demonstrate the efficacy of these processes.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":"73 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141052699","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 relay catalytic system has been developed for the asymmetric hydrogenative coupling of indoles with α,β-unsaturated ketones, affording enantioenriched chiral γ-indole alcohols with broad substrate scope and excellent enantioselectivities (32 examples, up to >99% ee). Mechanistic studies suggest that the relay catalytic system consists of a copper-catalyzed alkylation and ruthenium-catalyzed asymmetric hydrogenation.
{"title":"Asymmetric Hydrogenative Coupling of Indoles with Unsaturated Ketones Enabled by Copper/Ruthenium Relay Catalysis","authors":"Jian Zhang, Chen Guo, Weijun Tang, Dong Xue, Huaming Sun, Jianliang Xiao, Chao Wang","doi":"10.1055/a-2295-5417","DOIUrl":"https://doi.org/10.1055/a-2295-5417","url":null,"abstract":"A relay catalytic system has been developed for the asymmetric hydrogenative coupling of indoles with α,β-unsaturated ketones, affording enantioenriched chiral γ-indole alcohols with broad substrate scope and excellent enantioselectivities (32 examples, up to >99% ee). Mechanistic studies suggest that the relay catalytic system consists of a copper-catalyzed alkylation and ruthenium-catalyzed asymmetric hydrogenation.","PeriodicalId":510101,"journal":{"name":"Synthesis","volume":"114 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140380236","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：