Pub Date : 2024-12-03DOI: 10.1038/s41929-024-01258-6
Sharon Pinus, Jérôme Genzling, Mihai Burai-Patrascu, Nicolas Moitessier
Impressive progress in computational asymmetric catalysis has been made in the past twenty years owing to advancements in algorithm and method development for predicting catalyst enantioselectivity. These methods/algorithms describe reactions that can be categorized into two groups: reactions where the mechanism (or transition state for the enantioselective step) is known and used to determine catalyst stereoselectivity by modelling the diastereomeric transition states and reactions where knowledge of the mechanism is not required and leveraging experimental data to establish correlations between reaction descriptors and enantioselectivity is imperative. Although these methods have reached a suitable level of proficiency for the prediction of enantioselectivity, this field remains largely unexplored/underused by experimental chemists. In this Review we aim to shed light on the models, methods and applications used in asymmetric synthesis, with accessible language suitable for experimental chemists. Our hope is that these methods will ultimately be adopted by synthetic chemists for the design of new catalysts. The capability and importance of computational methods in organic chemistry is steadily increasing. This Review provides an overview of computational methods for the design of asymmetric catalysts, with the aim of avoiding specialist computational language to make the field more accessible to experimental chemists.
{"title":"Computational methods for asymmetric catalysis","authors":"Sharon Pinus, Jérôme Genzling, Mihai Burai-Patrascu, Nicolas Moitessier","doi":"10.1038/s41929-024-01258-6","DOIUrl":"10.1038/s41929-024-01258-6","url":null,"abstract":"Impressive progress in computational asymmetric catalysis has been made in the past twenty years owing to advancements in algorithm and method development for predicting catalyst enantioselectivity. These methods/algorithms describe reactions that can be categorized into two groups: reactions where the mechanism (or transition state for the enantioselective step) is known and used to determine catalyst stereoselectivity by modelling the diastereomeric transition states and reactions where knowledge of the mechanism is not required and leveraging experimental data to establish correlations between reaction descriptors and enantioselectivity is imperative. Although these methods have reached a suitable level of proficiency for the prediction of enantioselectivity, this field remains largely unexplored/underused by experimental chemists. In this Review we aim to shed light on the models, methods and applications used in asymmetric synthesis, with accessible language suitable for experimental chemists. Our hope is that these methods will ultimately be adopted by synthetic chemists for the design of new catalysts. The capability and importance of computational methods in organic chemistry is steadily increasing. This Review provides an overview of computational methods for the design of asymmetric catalysts, with the aim of avoiding specialist computational language to make the field more accessible to experimental chemists.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"7 12","pages":"1272-1287"},"PeriodicalIF":42.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760500","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 : 2024-11-25DOI: 10.1038/s41929-024-01253-x
Decai Ding, Lingfeng Yin, Andrew T. Poore, Yeu-Shiuan Ho, Yu-Ho Cheng, Chi-Tien Hsieh, Stephen C. Yachuw, Rachael M. Knieser, Jeanette A. Krause, Shiliang Tian, Mu-Jeng Cheng, Wei Liu
Stereochemically controlled hydrogen bond donors play essential roles in the pharmaceutical industry. Consequently, organic molecules that bear difluoromethyl (CF2H) groups at chiral centres are emerging as pivotal components in pharmaceuticals owing to their distinct hydrogen-bonding property. However, a general approach for introducing CF2H groups in an enantioselective manner has remained elusive. Here we show that enantioconvergent difluoromethylation of racemic alkyl electrophiles, through alkyl radical intermediates, represents a strategy for constructing CF2H-containing stereocentres. This strategy is enabled by using copper catalysts bound with a chiral diamine ligand bearing electron-deficient phenyl groups, and a nucleophilic CF2H-zinc reagent. This method allows the high-yield conversion of a diverse range of alkyl halides into their alkyl-CF2H analogues with excellent enantioselectivity. Mechanistic studies reveal a route involving asymmetric difluoromethylation of alkyl radicals and crucial non-covalent interactions in the enantiodetermining steps. This copper-catalysed difluoromethylation process opens an avenue for the efficient preparation of CF2H-containing pharmaceuticals. Despite the importance of difluoromethyl (CF2H)-bearing centres for pharmaceuticals, there is currently no general strategy for the stereoselective introduction of a CF2H group at chiral centres. Here the authors describe an enantioconvergent difluoromethylation method for racemic alkyl halides to construct such stereocentres.
{"title":"Enantioconvergent copper-catalysed difluoromethylation of alkyl halides","authors":"Decai Ding, Lingfeng Yin, Andrew T. Poore, Yeu-Shiuan Ho, Yu-Ho Cheng, Chi-Tien Hsieh, Stephen C. Yachuw, Rachael M. Knieser, Jeanette A. Krause, Shiliang Tian, Mu-Jeng Cheng, Wei Liu","doi":"10.1038/s41929-024-01253-x","DOIUrl":"10.1038/s41929-024-01253-x","url":null,"abstract":"Stereochemically controlled hydrogen bond donors play essential roles in the pharmaceutical industry. Consequently, organic molecules that bear difluoromethyl (CF2H) groups at chiral centres are emerging as pivotal components in pharmaceuticals owing to their distinct hydrogen-bonding property. However, a general approach for introducing CF2H groups in an enantioselective manner has remained elusive. Here we show that enantioconvergent difluoromethylation of racemic alkyl electrophiles, through alkyl radical intermediates, represents a strategy for constructing CF2H-containing stereocentres. This strategy is enabled by using copper catalysts bound with a chiral diamine ligand bearing electron-deficient phenyl groups, and a nucleophilic CF2H-zinc reagent. This method allows the high-yield conversion of a diverse range of alkyl halides into their alkyl-CF2H analogues with excellent enantioselectivity. Mechanistic studies reveal a route involving asymmetric difluoromethylation of alkyl radicals and crucial non-covalent interactions in the enantiodetermining steps. This copper-catalysed difluoromethylation process opens an avenue for the efficient preparation of CF2H-containing pharmaceuticals. Despite the importance of difluoromethyl (CF2H)-bearing centres for pharmaceuticals, there is currently no general strategy for the stereoselective introduction of a CF2H group at chiral centres. Here the authors describe an enantioconvergent difluoromethylation method for racemic alkyl halides to construct such stereocentres.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"7 12","pages":"1372-1381"},"PeriodicalIF":42.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142697111","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 : 2024-11-21DOI: 10.1038/s41929-024-01242-0
Patricia Brizuela, M. Teresa Quirós
Metal-catalysed multicomponent cross-coupling reactions enable the efficient and diverse synthesis of complex molecules. Now, clever use of anionic ligands facilitates the coordination of native functional groups to the catalyst to control regioselectivity, avoiding the installation of directing groups and expanding the accessible chemical space.
{"title":"Seeking selectivity in alkene couplings","authors":"Patricia Brizuela, M. Teresa Quirós","doi":"10.1038/s41929-024-01242-0","DOIUrl":"10.1038/s41929-024-01242-0","url":null,"abstract":"Metal-catalysed multicomponent cross-coupling reactions enable the efficient and diverse synthesis of complex molecules. Now, clever use of anionic ligands facilitates the coordination of native functional groups to the catalyst to control regioselectivity, avoiding the installation of directing groups and expanding the accessible chemical space.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"7 11","pages":"1148-1150"},"PeriodicalIF":42.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142679045","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 : 2024-11-21DOI: 10.1038/s41929-024-01254-w
Ricardo J. Fernández-Terán
The synthesis of rigid C(sp3)-rich isosteric mimics of heteroaromatic rings has proved a significant challenge, but is of importance in drug discovery. Now, two studies report the synthesis of densely functionalized azetidines and bicycloalkanes, using a similar concept of breaking planarity.
{"title":"Shining light to break planarity","authors":"Ricardo J. Fernández-Terán","doi":"10.1038/s41929-024-01254-w","DOIUrl":"10.1038/s41929-024-01254-w","url":null,"abstract":"The synthesis of rigid C(sp3)-rich isosteric mimics of heteroaromatic rings has proved a significant challenge, but is of importance in drug discovery. Now, two studies report the synthesis of densely functionalized azetidines and bicycloalkanes, using a similar concept of breaking planarity.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"7 11","pages":"1151-1153"},"PeriodicalIF":42.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142679046","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 : 2024-11-21DOI: 10.1038/s41929-024-01270-w
Francesco Zamberlan
{"title":"An enantioselective HAT for diols","authors":"Francesco Zamberlan","doi":"10.1038/s41929-024-01270-w","DOIUrl":"10.1038/s41929-024-01270-w","url":null,"abstract":"","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"7 11","pages":"1146-1146"},"PeriodicalIF":42.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142679043","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 : 2024-11-15DOI: 10.1038/s41929-024-01250-0
Wei Jie Teh, Eleonora Romeo, Shibo Xi, Ben Rowley, Francesc Illas, Federico Calle-Vallejo, Boon Siang Yeo
A crucial task towards creating a sustainable chemical industry is the electrification of chemical processes that produce value-added molecules. One such molecule is 1,3-butadiene (1,3-BD), the feedstock used for manufacturing synthetic rubber. 1,3-BD is traditionally derived, as a by-product, during the energy-intensive steam cracking of naphtha to ethylene. Here we introduce an alternative approach to selectively produce 1,3-BD from the electroreduction of acetylene (e-C2H2R). By using a potassium iodide electrolyte, we created Cuδ+–Cu0 sites on a Cu2O-nanocube-derived catalyst, which are efficacious for promoting e-C2H2R to 1,3-BD. 1,3-BD was formed with a Faradaic efficiency reaching 93% at −0.85 V versus standard hydrogen electrode (SHE) and a partial current density of −75 mA cm−2 at −1.0 V versus SHE. Density functional theory calculations show that I− preserves Cuδ+–Cu0 sites, which facilitate the favourable binding of acetylene, leading to 1,3-BD formation through the coupling of *C2H3 moieties. Electrifying energy-intensive processes is a promising approach for decarbonization. Now, 1,3-butadiene is electrochemically produced from acetylene on I−−induced Cuδ+–Cu0 sites with a Faradaic efficiency of over 90% at −0.85 VSHE and a partial current density of −75 mA cm−2 at −1.0 VSHE.
{"title":"Selective electroreduction of acetylene to 1,3-butadiene on iodide-induced Cuδ+–Cu0 sites","authors":"Wei Jie Teh, Eleonora Romeo, Shibo Xi, Ben Rowley, Francesc Illas, Federico Calle-Vallejo, Boon Siang Yeo","doi":"10.1038/s41929-024-01250-0","DOIUrl":"10.1038/s41929-024-01250-0","url":null,"abstract":"A crucial task towards creating a sustainable chemical industry is the electrification of chemical processes that produce value-added molecules. One such molecule is 1,3-butadiene (1,3-BD), the feedstock used for manufacturing synthetic rubber. 1,3-BD is traditionally derived, as a by-product, during the energy-intensive steam cracking of naphtha to ethylene. Here we introduce an alternative approach to selectively produce 1,3-BD from the electroreduction of acetylene (e-C2H2R). By using a potassium iodide electrolyte, we created Cuδ+–Cu0 sites on a Cu2O-nanocube-derived catalyst, which are efficacious for promoting e-C2H2R to 1,3-BD. 1,3-BD was formed with a Faradaic efficiency reaching 93% at −0.85 V versus standard hydrogen electrode (SHE) and a partial current density of −75 mA cm−2 at −1.0 V versus SHE. Density functional theory calculations show that I− preserves Cuδ+–Cu0 sites, which facilitate the favourable binding of acetylene, leading to 1,3-BD formation through the coupling of *C2H3 moieties. Electrifying energy-intensive processes is a promising approach for decarbonization. Now, 1,3-butadiene is electrochemically produced from acetylene on I−−induced Cuδ+–Cu0 sites with a Faradaic efficiency of over 90% at −0.85 VSHE and a partial current density of −75 mA cm−2 at −1.0 VSHE.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"7 12","pages":"1382-1393"},"PeriodicalIF":42.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41929-024-01250-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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