Pub Date : 2024-09-26DOI: 10.1038/s44160-024-00654-x
Zeng Gao, Lin Liu, Ji-Ren Liu, Wang Wang, Ning-Yuan Yang, Lizhi Tao, Zhong-Liang Li, Qiang-Shuai Gu, Xin-Yuan Liu
Transition-metal-catalysed enantioconvergent cross-coupling reactions of highly reactive alkyl radicals often suffer from reduced chemoselectivity, mainly due to side reactions with closed-shell reactants. A strategy to overcome this challenge has yet to be identified, posing substantial limitations on the synthetic utility of this method. Here we report a method for enantioconvergent radical carbon–carbon cross-coupling of highly reactive cyclopropyl radicals with terminal alkynes, using redox state-tuned copper catalysis, under mild conditions. Key to this method is the use of hard chiral N,N,N-ligands in combination with Cu(II) salts of hard ligands/counterions, which results in elevated concentrations of Cu(II) species and thus enhanced cross-coupling reactions. This protocol not only exhibits a broad substrate scope across a wide range of both racemic cyclopropyl halide and terminal alkyne coupling partners but also provides access to useful yet synthetically challenging enantioenriched cyclopropane building blocks. The synthetic use of highly reactive alkyl radicals typically results in low chemoselectivity due to competing side reactions. Now, a redox-state-tuned copper catalytic method is reported, which enables the enantioconvergent cross-coupling of cyclopropyl radicals and terminal alkynes with high chemo- and stereoselectivity.
{"title":"Copper-catalysed synthesis of chiral alkynyl cyclopropanes using enantioconvergent radical cross-coupling of cyclopropyl halides with terminal alkynes","authors":"Zeng Gao, Lin Liu, Ji-Ren Liu, Wang Wang, Ning-Yuan Yang, Lizhi Tao, Zhong-Liang Li, Qiang-Shuai Gu, Xin-Yuan Liu","doi":"10.1038/s44160-024-00654-x","DOIUrl":"10.1038/s44160-024-00654-x","url":null,"abstract":"Transition-metal-catalysed enantioconvergent cross-coupling reactions of highly reactive alkyl radicals often suffer from reduced chemoselectivity, mainly due to side reactions with closed-shell reactants. A strategy to overcome this challenge has yet to be identified, posing substantial limitations on the synthetic utility of this method. Here we report a method for enantioconvergent radical carbon–carbon cross-coupling of highly reactive cyclopropyl radicals with terminal alkynes, using redox state-tuned copper catalysis, under mild conditions. Key to this method is the use of hard chiral N,N,N-ligands in combination with Cu(II) salts of hard ligands/counterions, which results in elevated concentrations of Cu(II) species and thus enhanced cross-coupling reactions. This protocol not only exhibits a broad substrate scope across a wide range of both racemic cyclopropyl halide and terminal alkyne coupling partners but also provides access to useful yet synthetically challenging enantioenriched cyclopropane building blocks. The synthetic use of highly reactive alkyl radicals typically results in low chemoselectivity due to competing side reactions. Now, a redox-state-tuned copper catalytic method is reported, which enables the enantioconvergent cross-coupling of cyclopropyl radicals and terminal alkynes with high chemo- and stereoselectivity.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"4 1","pages":"84-96"},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995913","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}
Pub Date : 2024-09-26DOI: 10.1038/s44160-024-00658-7
Tong-De Tan, Kai Ze Tee, Xiaohua Luo, Peng-Cheng Qian, Xinglong Zhang, Ming Joo Koh
Stereodefined trisubstituted alkenes are key constituents of biologically active molecules and also serve as indispensable substrates for a wide range of stereospecific reactions affording sp3-hybridized skeletons. However, there is a persisting lack of methods that generate the thermodynamically less stable Z-isomers. Here we report an iron-catalysed multicomponent strategy that merges allenes, dialkylzinc compounds and haloalkanes to construct trisubstituted alkenes with excellent control of regioselectivity and Z-selectivity. Selective installation of diverse C(sp3) groups enables access to a broad library of functionalized unsaturated products. The synthetic utility of the method is highlighted through the synthesis of a glucosylceramide synthase inhibitor. Contrary to conventional mechanisms for metal-catalysed allene functionalization, our studies suggest a kinetically controlled pathway involving sequential radical-mediated alkylferration of the less hindered C=C bond and inner-sphere alkylation via reductive elimination. Mechanistic and computational investigations reveal the origins of the stereochemical outcome. Catalytic methods that generate Z-alkenes are rare due to the energetic favourability of the corresponding E-alkenes. Now, a bisphosphine–iron catalyst mediates the multicomponent dialkylation of allenes, using dialkylzinc reagents and alkyl halides, to selectively form functionalized trisubstituted Z-alkenes.
{"title":"Kinetically controlled Z-alkene synthesis using iron-catalysed allene dialkylation","authors":"Tong-De Tan, Kai Ze Tee, Xiaohua Luo, Peng-Cheng Qian, Xinglong Zhang, Ming Joo Koh","doi":"10.1038/s44160-024-00658-7","DOIUrl":"10.1038/s44160-024-00658-7","url":null,"abstract":"Stereodefined trisubstituted alkenes are key constituents of biologically active molecules and also serve as indispensable substrates for a wide range of stereospecific reactions affording sp3-hybridized skeletons. However, there is a persisting lack of methods that generate the thermodynamically less stable Z-isomers. Here we report an iron-catalysed multicomponent strategy that merges allenes, dialkylzinc compounds and haloalkanes to construct trisubstituted alkenes with excellent control of regioselectivity and Z-selectivity. Selective installation of diverse C(sp3) groups enables access to a broad library of functionalized unsaturated products. The synthetic utility of the method is highlighted through the synthesis of a glucosylceramide synthase inhibitor. Contrary to conventional mechanisms for metal-catalysed allene functionalization, our studies suggest a kinetically controlled pathway involving sequential radical-mediated alkylferration of the less hindered C=C bond and inner-sphere alkylation via reductive elimination. Mechanistic and computational investigations reveal the origins of the stereochemical outcome. Catalytic methods that generate Z-alkenes are rare due to the energetic favourability of the corresponding E-alkenes. Now, a bisphosphine–iron catalyst mediates the multicomponent dialkylation of allenes, using dialkylzinc reagents and alkyl halides, to selectively form functionalized trisubstituted Z-alkenes.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"4 1","pages":"116-123"},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995894","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}
Pub Date : 2024-09-20DOI: 10.1038/s44160-024-00653-y
Singly bonded, low-valent group 13 compounds are rare, and their reactions are typically limited to oxidative additions. Now, a compound with a singly bonded gallium(i) centre has been prepared using a sterically hindered ligand. This compound exhibits varied reactivity, undergoing both oxidative addition and redox-invariant carbometallation reactions.
{"title":"A gallium(i) compound with variable reactivity","authors":"","doi":"10.1038/s44160-024-00653-y","DOIUrl":"10.1038/s44160-024-00653-y","url":null,"abstract":"Singly bonded, low-valent group 13 compounds are rare, and their reactions are typically limited to oxidative additions. Now, a compound with a singly bonded gallium(i) centre has been prepared using a sterically hindered ligand. This compound exhibits varied reactivity, undergoing both oxidative addition and redox-invariant carbometallation reactions.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"4 1","pages":"11-12"},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995914","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}
Pub Date : 2024-09-20DOI: 10.1038/s44160-024-00655-w
Josh Phipps, Shengqian Ma
Supramolecular peptide complexes with interlocking heterochiral linkers showcase a route for self-assembled nanostructures with exceptional mechanical stability.
具有互锁异手性连接体的超分子肽复合物展示了具有特殊机械稳定性的自组装纳米结构的途径。
{"title":"Heterochiral catenanes create robust nanostructures","authors":"Josh Phipps, Shengqian Ma","doi":"10.1038/s44160-024-00655-w","DOIUrl":"10.1038/s44160-024-00655-w","url":null,"abstract":"Supramolecular peptide complexes with interlocking heterochiral linkers showcase a route for self-assembled nanostructures with exceptional mechanical stability.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"4 1","pages":"7-8"},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995915","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}
Pub Date : 2024-09-19DOI: 10.1038/s44160-024-00644-z
Youxing Liu, Lu Li, Zhiyuan Sang, Hao Tan, Na Ye, Chenglong Sun, Zongqiang Sun, Mingchuan Luo, Shaojun Guo
Covalent organic frameworks (COFs) can be used as photocatalysts for the direct photosynthesis of hydrogen peroxide (H2O2) from oxygen, water and sunlight. However, their highly symmetric structure can lead to weak adsorption of O2 and, therefore, unsatisfactory photocatalytic performance. Here we explore the local asymmetric electron distribution induced by Pauli and electron–electron repulsion in COFs to construct localized bonding sites for O2 species, which promotes photocatalytic H2O2 production. Experimental results and theoretical calculations reveal that TAPT–FTPB COFs (where TAPT is 1,3,5-tris-(4-aminophenyl) triazine and FTPB is 5-(5-formylthiophen-2-yl)thiophene-2-carbaldehyde) with an asymmetric electron distribution show strong O2 adsorption interaction and a record-breaking solar-to-chemical conversion efficiency of 1.22% for direct photosynthesis of H2O2 from oxygen and water, which is higher than in the photosynthesis of plants (~0.1%). A flow-type photocatalytic microreactor integrated with TAPT–FTPB COFs exhibits 100% sterilization efficiency for killing bacteria and 97.8% conversion for photocatalytic 2-thiophene methylamine coupling. This work reports a strategy for manipulating the local electron distribution in COFs, opening the door for research on the rational design of high-performance photocatalysis with a local asymmetric electron distribution. Covalent organic frameworks (COFs) are promising photocatalysts for the direct photosynthesis of H2O2, but their symmetric structure can lead to weak O2 adsorption. Now thiophene sulfur atoms are introduced into COFs to induce local asymmetric electron distributions, which enhance the O2 adsorption capacity and interaction of the COFs, promoting direct photosynthesis of H2O2.
{"title":"Enhanced hydrogen peroxide photosynthesis in covalent organic frameworks through induced asymmetric electron distribution","authors":"Youxing Liu, Lu Li, Zhiyuan Sang, Hao Tan, Na Ye, Chenglong Sun, Zongqiang Sun, Mingchuan Luo, Shaojun Guo","doi":"10.1038/s44160-024-00644-z","DOIUrl":"10.1038/s44160-024-00644-z","url":null,"abstract":"Covalent organic frameworks (COFs) can be used as photocatalysts for the direct photosynthesis of hydrogen peroxide (H2O2) from oxygen, water and sunlight. However, their highly symmetric structure can lead to weak adsorption of O2 and, therefore, unsatisfactory photocatalytic performance. Here we explore the local asymmetric electron distribution induced by Pauli and electron–electron repulsion in COFs to construct localized bonding sites for O2 species, which promotes photocatalytic H2O2 production. Experimental results and theoretical calculations reveal that TAPT–FTPB COFs (where TAPT is 1,3,5-tris-(4-aminophenyl) triazine and FTPB is 5-(5-formylthiophen-2-yl)thiophene-2-carbaldehyde) with an asymmetric electron distribution show strong O2 adsorption interaction and a record-breaking solar-to-chemical conversion efficiency of 1.22% for direct photosynthesis of H2O2 from oxygen and water, which is higher than in the photosynthesis of plants (~0.1%). A flow-type photocatalytic microreactor integrated with TAPT–FTPB COFs exhibits 100% sterilization efficiency for killing bacteria and 97.8% conversion for photocatalytic 2-thiophene methylamine coupling. This work reports a strategy for manipulating the local electron distribution in COFs, opening the door for research on the rational design of high-performance photocatalysis with a local asymmetric electron distribution. Covalent organic frameworks (COFs) are promising photocatalysts for the direct photosynthesis of H2O2, but their symmetric structure can lead to weak O2 adsorption. Now thiophene sulfur atoms are introduced into COFs to induce local asymmetric electron distributions, which enhance the O2 adsorption capacity and interaction of the COFs, promoting direct photosynthesis of H2O2.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"4 1","pages":"134-141"},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251972","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}
Pub Date : 2024-09-19DOI: 10.1038/s44160-024-00639-w
Simon H. F. Schreiner, Tobias Rüffer, Robert Kretschmer
Singly bonded metallylenes (R–M:) of the group 13 elements feature a non-bonding pair of electrons together with two vacant orbitals, which makes them highly reactive ambiphiles that readily activate small molecules by oxidative addition. As a consequence of their pronounced reactivity, examples of organometallics with singly bonded aluminium(I) and gallium(I) centres remain rare. Here we report the one-step synthesis of a monomeric gallium(I) compound that readily undergoes oxidative addition reactions and, more remarkably, carbometalation reactions with alkynes by retention of the low +I oxidation state and the singly bonded nature of gallium. This observation contrasts with common reports on the reactivity of low-valent main-group compounds, which are regularly oxidized to compounds in a more stable higher oxidation state. This approach provides access to low-valent main-group compounds and paves the way for the development of bond-functionalization strategies that may enable the discovery of catalytic processes in the future. A singly bonded gallanediyl undergoes carbometalation reactions with alkynes by retaining the low +I oxidation state and the singly bonded nature of gallium. The insertion into the gallium(I)–carbon bond proceeds regioselectively and gives exclusively the syn-addition products.
{"title":"A singly bonded gallanediyl with redox-active and redox-inert reactivity","authors":"Simon H. F. Schreiner, Tobias Rüffer, Robert Kretschmer","doi":"10.1038/s44160-024-00639-w","DOIUrl":"10.1038/s44160-024-00639-w","url":null,"abstract":"Singly bonded metallylenes (R–M:) of the group 13 elements feature a non-bonding pair of electrons together with two vacant orbitals, which makes them highly reactive ambiphiles that readily activate small molecules by oxidative addition. As a consequence of their pronounced reactivity, examples of organometallics with singly bonded aluminium(I) and gallium(I) centres remain rare. Here we report the one-step synthesis of a monomeric gallium(I) compound that readily undergoes oxidative addition reactions and, more remarkably, carbometalation reactions with alkynes by retention of the low +I oxidation state and the singly bonded nature of gallium. This observation contrasts with common reports on the reactivity of low-valent main-group compounds, which are regularly oxidized to compounds in a more stable higher oxidation state. This approach provides access to low-valent main-group compounds and paves the way for the development of bond-functionalization strategies that may enable the discovery of catalytic processes in the future. A singly bonded gallanediyl undergoes carbometalation reactions with alkynes by retaining the low +I oxidation state and the singly bonded nature of gallium. The insertion into the gallium(I)–carbon bond proceeds regioselectively and gives exclusively the syn-addition products.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"4 1","pages":"67-74"},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251973","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}
Pub Date : 2024-09-16DOI: 10.1038/s44160-024-00647-w
Matthew J. Harrington
Anisotropic gels made from supramolecular nanofibres are formed from mechanical or magnetic forces applied with orchestrated enzymatically-triggered pH changes.
由超分子纳米纤维制成的各向异性凝胶是在机械力或磁力作用下，或在酶触发的 pH 值变化作用下形成的。
{"title":"External forces align supramolecular materials","authors":"Matthew J. Harrington","doi":"10.1038/s44160-024-00647-w","DOIUrl":"10.1038/s44160-024-00647-w","url":null,"abstract":"Anisotropic gels made from supramolecular nanofibres are formed from mechanical or magnetic forces applied with orchestrated enzymatically-triggered pH changes.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"3 12","pages":"1446-1447"},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251974","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}
Pub Date : 2024-09-12DOI: 10.1038/s44160-024-00648-9
Bingxing Zhang, Peng Zhou, Zhengwei Ye, Ishtiaque Ahmed Navid, Yuyang Pan, Yixin Xiao, Kai Sun, Zetian Mi
The photoelectrochemical synthesis of valuable multicarbon products from carbon dioxide, sunlight and water is a promising pathway for clean energy generation and carbon neutrality. However, it is challenging to create and stabilize efficient C–C coupling sites to achieve multicarbon products with high selectivity, yield and stability. Here we designed a low-coordinated copper-cluster catalyst interfacially coupled in situ with a GaN nanowire photocathode, achieving a high ethylene Faradaic efficiency of ∼61% and a partial current density of 14.2 mA cm−2, with a robust stability of ∼116 h. The in situ self-optimized Ga–N–O interface was confirmed to facilitate and stabilize the interfacially oxidized copper species of copper clusters, which function as efficient C–C coupling sites for ethylene production. Furthermore, the hydrogen-feeding effect of GaN for promoting CO hydrogenation also guides the facile CHO-involved C–C coupling pathway. This work sheds light on the interface design and understanding of efficient and stable (photo)electrosynthesis of highly valuable fuels from CO2. An interfacially coupled Cu-cluster/GaN photocathode is designed to overcome the efficiency and stability bottlenecks in photoelectrochemical CO2 reduction to multicarbon products. The self-optimized Ga–N–O interface facilitates and stabilizes interfacially oxidized copper species of copper clusters, which function as efficient C–C coupling sites for ethylene production.
利用二氧化碳、太阳光和水进行光电化学合成有价值的多碳产品，是实现清洁能源生产和碳中和的一条大有可为的途径。然而，如何创造并稳定高效的 C-C 偶联位点，以获得高选择性、高产率和高稳定性的多碳产物，是一项挑战。在此，我们设计了一种低配位铜簇催化剂，与氮化镓纳米线光电阴极原位界面耦合，实现了高达 61% 的乙烯法拉第效率和 14.2 mA cm-2 的部分电流密度，且稳定性高达 116 h。此外，GaN 在促进 CO 加氢方面的馈氢效应也引导了由 CHO 参与的 C-C 偶联途径。这项工作为从二氧化碳高效、稳定地（光）电合成高价值燃料的界面设计和理解提供了启示。
{"title":"Interfacially coupled Cu-cluster/GaN photocathode for efficient CO2 to ethylene conversion","authors":"Bingxing Zhang, Peng Zhou, Zhengwei Ye, Ishtiaque Ahmed Navid, Yuyang Pan, Yixin Xiao, Kai Sun, Zetian Mi","doi":"10.1038/s44160-024-00648-9","DOIUrl":"10.1038/s44160-024-00648-9","url":null,"abstract":"The photoelectrochemical synthesis of valuable multicarbon products from carbon dioxide, sunlight and water is a promising pathway for clean energy generation and carbon neutrality. However, it is challenging to create and stabilize efficient C–C coupling sites to achieve multicarbon products with high selectivity, yield and stability. Here we designed a low-coordinated copper-cluster catalyst interfacially coupled in situ with a GaN nanowire photocathode, achieving a high ethylene Faradaic efficiency of ∼61% and a partial current density of 14.2 mA cm−2, with a robust stability of ∼116 h. The in situ self-optimized Ga–N–O interface was confirmed to facilitate and stabilize the interfacially oxidized copper species of copper clusters, which function as efficient C–C coupling sites for ethylene production. Furthermore, the hydrogen-feeding effect of GaN for promoting CO hydrogenation also guides the facile CHO-involved C–C coupling pathway. This work sheds light on the interface design and understanding of efficient and stable (photo)electrosynthesis of highly valuable fuels from CO2. An interfacially coupled Cu-cluster/GaN photocathode is designed to overcome the efficiency and stability bottlenecks in photoelectrochemical CO2 reduction to multicarbon products. The self-optimized Ga–N–O interface facilitates and stabilizes interfacially oxidized copper species of copper clusters, which function as efficient C–C coupling sites for ethylene production.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"3 12","pages":"1567-1576"},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195611","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 development of the sulfur(VI)–fluoride exchange (SuFEx) and modular diazotransfer (MoDAT) reactions represent important milestones in the evolution of click chemistry. However, their reactivity profiles, chemoselectivity origins and underlying mechanisms remain unclear. Here we report a computational study of the MoDAT and SuFEx pathways, focusing on the reaction between the diazotransfer reagent fluorosulfuryl azide and primary amines. Our calculations reveal that the MoDAT reaction possesses a small kinetic barrier and a strong driving force, making it kinetically and thermodynamically more favourable than the SuFEx reaction. Through mechanistic scrutiny and structure–activity relationship studies, we have formulated predictive models for the reactivity and selectivity of the MoDAT reaction. Leveraging these insights, an easy-to-prepare and easily handled diazotransfer reagent with excellent reactivity has been developed, which holds broad promise for applications in chemistry and biology. Computational analysis of competing sulfur(VI)–fluoride exchange and modular diazotransfer pathways in the reaction between primary amines and fluorosulfuryl azide reveals that diazotransfer is more kinetically and thermodynamically favoured. Predictive models are formulated by combining mechanistic analysis and structure–activity relationship studies, enabling the development of an easy-to-prepare and highly reactive diazotransfer reagent.
{"title":"Computational analysis of modular diazotransfer reactions for the development of predictive reactivity models and diazotransfer reagents","authors":"Meng-Meng Zheng, Liu Cai, Tiancheng Ma, Hao-Dong Tan, Xiaoyu Lai, Jiajia Dong, Xiao-Song Xue","doi":"10.1038/s44160-024-00633-2","DOIUrl":"10.1038/s44160-024-00633-2","url":null,"abstract":"The development of the sulfur(VI)–fluoride exchange (SuFEx) and modular diazotransfer (MoDAT) reactions represent important milestones in the evolution of click chemistry. However, their reactivity profiles, chemoselectivity origins and underlying mechanisms remain unclear. Here we report a computational study of the MoDAT and SuFEx pathways, focusing on the reaction between the diazotransfer reagent fluorosulfuryl azide and primary amines. Our calculations reveal that the MoDAT reaction possesses a small kinetic barrier and a strong driving force, making it kinetically and thermodynamically more favourable than the SuFEx reaction. Through mechanistic scrutiny and structure–activity relationship studies, we have formulated predictive models for the reactivity and selectivity of the MoDAT reaction. Leveraging these insights, an easy-to-prepare and easily handled diazotransfer reagent with excellent reactivity has been developed, which holds broad promise for applications in chemistry and biology. Computational analysis of competing sulfur(VI)–fluoride exchange and modular diazotransfer pathways in the reaction between primary amines and fluorosulfuryl azide reveals that diazotransfer is more kinetically and thermodynamically favoured. Predictive models are formulated by combining mechanistic analysis and structure–activity relationship studies, enabling the development of an easy-to-prepare and highly reactive diazotransfer reagent.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"3 12","pages":"1507-1517"},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195626","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}
Pub Date : 2024-09-10DOI: 10.1038/s44160-024-00634-1
Sulfur(vi) fluoride exchange and modular diazotransfer reactions have advanced click chemistry, but their mechanisms and reactivity profiles are not well understood. Now, a computational study of these reactions provides mechanistic insights and predictive reactivity models for modular diazotransfer, facilitating the development of an easy-to-prepare and -handle diazotransfer reagent with excellent reactivity.
{"title":"Computationally guided design of a diazotransfer reagent with high reactivity","authors":"","doi":"10.1038/s44160-024-00634-1","DOIUrl":"10.1038/s44160-024-00634-1","url":null,"abstract":"Sulfur(vi) fluoride exchange and modular diazotransfer reactions have advanced click chemistry, but their mechanisms and reactivity profiles are not well understood. Now, a computational study of these reactions provides mechanistic insights and predictive reactivity models for modular diazotransfer, facilitating the development of an easy-to-prepare and -handle diazotransfer reagent with excellent reactivity.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"3 12","pages":"1455-1456"},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195613","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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