Pub Date : 2026-01-12DOI: 10.1038/s41557-025-02047-9
Yongquan Ning, Rongkai Wu, Yongyue Ning, Qingmin Song, Jiahua Deng, Qingchi Jiao, Paramasivam Sivaguru, Jacek Mlynarski, Graham de Ruiter, Xin Hong, Xihe Bi
The [2+2] cycloaddition reaction has been pivotal in advancing synthetic organic chemistry. However, thermal [2 + 2] cycloaddition reactions are symmetry-forbidden due to ground-state orbital symmetry constraints, making them challenging to achieve under non-photochemical conditions. Here we report a stepwise radical intramolecular thermal crossed [2 + 2] cycloaddition, enabled by the fluorine effect of in-situ-generated N-(homo)allyl gem-difluoroenamines and homoallyl gem-difluorovinyl ethers. Silver-catalysed gem-difluoroalkenylation of N-(homo)allylamines and homoallyl alcohols with trifluoromethyl triftosylhydrazones, respectively, followed by an intramolecular crossed [2 + 2] cycloaddition of the in-situ-generated gem-difluoroalkenes enables the synthesis of a range of medically relevant gem-difluoro heterobicyclo[n.1.1]alkanes, including azabicyclo[2.1.1]hexanes, azabicyclo[3.1.1]heptanes and oxabicyclo[3.1.1]heptanes. This methodology features readily available starting materials, high chemo-, regio- and stereoselectivity, excellent functional group compatibility and high yields. Notably, further conversion of the formed azabicyclo[2.1.1]hexanes into azabicyclic endoperoxides via oxygen incorporation highlights the properties of these gem-difluorinated bridged azabicyclic compounds. Combined experimental and computational studies support a stepwise radical mechanism for the thermal crossed [2+2] cycloaddition. Thermal [2+2] cycloaddition reactions are symmetry-forbidden due to ground-state orbital symmetry constraints, making them challenging to achieve under non-photochemical conditions. Now a stepwise radical intramolecular thermal crossed [2+2] cycloaddition of N-(homo)allyl gem-difluoroenamines and homoallyl gem-difluorovinyl ethers has been accomplished, through tandem gem-difluoroalkenylation of N-(homo)allylamines and homoallyl alcohols with trifluoromethyl triftosylhydrazones.
{"title":"Thermal [2+2] cycloaddition as a route to gem-difluoro heterobicyclo[n.1.1]alkanes","authors":"Yongquan Ning, Rongkai Wu, Yongyue Ning, Qingmin Song, Jiahua Deng, Qingchi Jiao, Paramasivam Sivaguru, Jacek Mlynarski, Graham de Ruiter, Xin Hong, Xihe Bi","doi":"10.1038/s41557-025-02047-9","DOIUrl":"10.1038/s41557-025-02047-9","url":null,"abstract":"The [2+2] cycloaddition reaction has been pivotal in advancing synthetic organic chemistry. However, thermal [2 + 2] cycloaddition reactions are symmetry-forbidden due to ground-state orbital symmetry constraints, making them challenging to achieve under non-photochemical conditions. Here we report a stepwise radical intramolecular thermal crossed [2 + 2] cycloaddition, enabled by the fluorine effect of in-situ-generated N-(homo)allyl gem-difluoroenamines and homoallyl gem-difluorovinyl ethers. Silver-catalysed gem-difluoroalkenylation of N-(homo)allylamines and homoallyl alcohols with trifluoromethyl triftosylhydrazones, respectively, followed by an intramolecular crossed [2 + 2] cycloaddition of the in-situ-generated gem-difluoroalkenes enables the synthesis of a range of medically relevant gem-difluoro heterobicyclo[n.1.1]alkanes, including azabicyclo[2.1.1]hexanes, azabicyclo[3.1.1]heptanes and oxabicyclo[3.1.1]heptanes. This methodology features readily available starting materials, high chemo-, regio- and stereoselectivity, excellent functional group compatibility and high yields. Notably, further conversion of the formed azabicyclo[2.1.1]hexanes into azabicyclic endoperoxides via oxygen incorporation highlights the properties of these gem-difluorinated bridged azabicyclic compounds. Combined experimental and computational studies support a stepwise radical mechanism for the thermal crossed [2+2] cycloaddition. Thermal [2+2] cycloaddition reactions are symmetry-forbidden due to ground-state orbital symmetry constraints, making them challenging to achieve under non-photochemical conditions. Now a stepwise radical intramolecular thermal crossed [2+2] cycloaddition of N-(homo)allyl gem-difluoroenamines and homoallyl gem-difluorovinyl ethers has been accomplished, through tandem gem-difluoroalkenylation of N-(homo)allylamines and homoallyl alcohols with trifluoromethyl triftosylhydrazones.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 2","pages":"283-293"},"PeriodicalIF":20.2,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959539","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 : 2026-01-07DOI: 10.1038/s41557-025-02021-5
Elisabeth Hennes, Belén Lucas, Natalie S. Scholes, Xiu-Fen Cheng, Daniel C. Scott, Matthias Bischoff, Katharina Reich, Raphael Gasper, María Lucas, Teng Teng Xu, Sofia Rossini, Lisa-Marie Pulvermacher, Lara Dötsch, Hana Imrichova, Alexandra Brause, Siska Führer, Kesava Reddy Naredla, Sonja Sievers, Kamal Kumar, Petra Janning, Ciriana Orabona, Malte Gersch, Peter J. Murray, Brenda A. Schulman, Georg E. Winter, Slava Ziegler, Herbert Waldmann
Targeted protein degradation modulates protein function beyond the inhibition of enzyme activity or protein–protein interactions. Most degrader drugs function by directly mediating the proximity between a neosubstrate and a hijacked E3 ligase. Here we identify pseudo-natural products derived from (−)-myrtanol, termed iDegs, that inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs boost IDO1 ubiquitination and degradation by the cullin-RING E3 ligase CRL2KLHDC3, which we identified to natively mediate ubiquitin-mediated degradation of IDO1. Therefore, iDegs increase IDO1 turnover using the native proteolytic pathway. In contrast to clinically explored IDO1 inhibitors, iDegs reduce the formation of kynurenine by both inhibition and induced degradation of the enzyme and thus also modulate the non-enzymatic functions of IDO1. This unique mechanism of action may open up alternative therapeutic opportunities for the treatment of cancer beyond classical inhibition of IDO1. In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.
{"title":"Monovalent pseudo-natural products supercharge degradation of IDO1 by its native E3 KLHDC3","authors":"Elisabeth Hennes, Belén Lucas, Natalie S. Scholes, Xiu-Fen Cheng, Daniel C. Scott, Matthias Bischoff, Katharina Reich, Raphael Gasper, María Lucas, Teng Teng Xu, Sofia Rossini, Lisa-Marie Pulvermacher, Lara Dötsch, Hana Imrichova, Alexandra Brause, Siska Führer, Kesava Reddy Naredla, Sonja Sievers, Kamal Kumar, Petra Janning, Ciriana Orabona, Malte Gersch, Peter J. Murray, Brenda A. Schulman, Georg E. Winter, Slava Ziegler, Herbert Waldmann","doi":"10.1038/s41557-025-02021-5","DOIUrl":"10.1038/s41557-025-02021-5","url":null,"abstract":"Targeted protein degradation modulates protein function beyond the inhibition of enzyme activity or protein–protein interactions. Most degrader drugs function by directly mediating the proximity between a neosubstrate and a hijacked E3 ligase. Here we identify pseudo-natural products derived from (−)-myrtanol, termed iDegs, that inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs boost IDO1 ubiquitination and degradation by the cullin-RING E3 ligase CRL2KLHDC3, which we identified to natively mediate ubiquitin-mediated degradation of IDO1. Therefore, iDegs increase IDO1 turnover using the native proteolytic pathway. In contrast to clinically explored IDO1 inhibitors, iDegs reduce the formation of kynurenine by both inhibition and induced degradation of the enzyme and thus also modulate the non-enzymatic functions of IDO1. This unique mechanism of action may open up alternative therapeutic opportunities for the treatment of cancer beyond classical inhibition of IDO1. In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 3","pages":"585-596"},"PeriodicalIF":20.2,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41557-025-02021-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918018","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}
Pub Date : 2026-01-07DOI: 10.1038/s41557-025-02037-x
Morgan Kim, So Yeon Ahn, Seongmin Kim, Junhwan Won, Dongwook Kim, Seung Youn Hong
Systematic evaluation of homologous series plays a pivotal role in synthetic and medicinal chemistry. Despite their structural resemblance, the preparation of homologues often requires individual synthetic planning tailored to distinct precursors and reactions. Here we introduce a strategy that integrates single-carbon insertion into established methods, specifically redirecting alkene vicinal difunctionalization towards direct routes for 1,3-difunctionalized products. This transformation is enabled by a designer methylene dication reagent, iodomethylthianthrenium salt, which facilitates the photocatalytic conversion of alkenes into linchpin 1,3-dielectrophilic intermediates, allowing seamless incorporation of nucleophiles at distal positions. Mechanistic studies suggest that the reaction proceeds via an α-thianthrenium methyl radical with unusual ambiphilic reactivity governed by multiple stereoelectronic effects. This approach shows high compatibility in pharmaceutical and late-stage settings, providing broad access to diverse 1,3-difunctionalized products, including azetidines, 1,3-diazides and 1,3-dihalides. This work establishes 'homologative alkene difunctionalization' as a powerful platform for repurposing ubiquitous alkenes as meritorious synthetic intermediates to unveil heretofore unknown 1,3-substitution patterns.
{"title":"Homologative alkene difunctionalization.","authors":"Morgan Kim, So Yeon Ahn, Seongmin Kim, Junhwan Won, Dongwook Kim, Seung Youn Hong","doi":"10.1038/s41557-025-02037-x","DOIUrl":"https://doi.org/10.1038/s41557-025-02037-x","url":null,"abstract":"<p><p>Systematic evaluation of homologous series plays a pivotal role in synthetic and medicinal chemistry. Despite their structural resemblance, the preparation of homologues often requires individual synthetic planning tailored to distinct precursors and reactions. Here we introduce a strategy that integrates single-carbon insertion into established methods, specifically redirecting alkene vicinal difunctionalization towards direct routes for 1,3-difunctionalized products. This transformation is enabled by a designer methylene dication reagent, iodomethylthianthrenium salt, which facilitates the photocatalytic conversion of alkenes into linchpin 1,3-dielectrophilic intermediates, allowing seamless incorporation of nucleophiles at distal positions. Mechanistic studies suggest that the reaction proceeds via an α-thianthrenium methyl radical with unusual ambiphilic reactivity governed by multiple stereoelectronic effects. This approach shows high compatibility in pharmaceutical and late-stage settings, providing broad access to diverse 1,3-difunctionalized products, including azetidines, 1,3-diazides and 1,3-dihalides. This work establishes 'homologative alkene difunctionalization' as a powerful platform for repurposing ubiquitous alkenes as meritorious synthetic intermediates to unveil heretofore unknown 1,3-substitution patterns.</p>","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":" ","pages":""},"PeriodicalIF":20.2,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917968","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 : 2026-01-07DOI: 10.1038/s41557-025-02017-1
Xiaping Fu, Weibing Liu, Yana Demyanenko, Wael Kamel, Ravi Teja Ravi, Vincenzo Ruscica, Marko Noerenberg, Xuejian Yin, Yi Jiang, Chi-Hang Fan, Katarzyna M. Kowalczyk, Eduardo Kitano, James Morgan, Simon Aldridge, Maud Dumoux, Alfredo Castello, Shabaz Mohammed, Benjamin G. Davis
Metal-mediated chemistries now find increasing application in in vitro biomolecule modification. However, the perceived and potential toxicity of some metals has limited the application of organometallic reagents in more complex biological settings such as inside living cells. Ligands play a crucial role in modulating both the reactivity and availability of transition metals. Here we reveal that organonickel-mediated S-arylation tolerates flexible chelation with biocompatible ligands without destroying the chemical reactivity of corresponding aryl-nickel reagents, enabling the creation of safe, site-selective C–S-bond-forming arylation manifolds. These balanced systems prove sufficiently benign for use on diverse protein substrates in vitro and in living prokaryotic and eukaryotic cells. This, in turn, enables deep chemical surveys of reactive cysteines in human cells with sensitivity sufficient to detect covalently targetable proteins from emerging intracellular viral and bacterial pathogens. Biocompatible ligand balancing thus offers a path to the broader use of transition metals in living systems. The perceived toxicity of organometallic reagents has limited their use in living systems. Now it has been shown that balancing flexible chelation with biocompatible ligands without precluding chemical reactivity enables organonickel-mediated S-arylation inside cells. This reaction enables deep chemical surveys of reactive proteins and covalent tracking of intracellular viral and bacterial pathogens.
{"title":"Biocompatible ligand balancing in transition metal coordination enables benign in-cell protein arylation","authors":"Xiaping Fu, Weibing Liu, Yana Demyanenko, Wael Kamel, Ravi Teja Ravi, Vincenzo Ruscica, Marko Noerenberg, Xuejian Yin, Yi Jiang, Chi-Hang Fan, Katarzyna M. Kowalczyk, Eduardo Kitano, James Morgan, Simon Aldridge, Maud Dumoux, Alfredo Castello, Shabaz Mohammed, Benjamin G. Davis","doi":"10.1038/s41557-025-02017-1","DOIUrl":"10.1038/s41557-025-02017-1","url":null,"abstract":"Metal-mediated chemistries now find increasing application in in vitro biomolecule modification. However, the perceived and potential toxicity of some metals has limited the application of organometallic reagents in more complex biological settings such as inside living cells. Ligands play a crucial role in modulating both the reactivity and availability of transition metals. Here we reveal that organonickel-mediated S-arylation tolerates flexible chelation with biocompatible ligands without destroying the chemical reactivity of corresponding aryl-nickel reagents, enabling the creation of safe, site-selective C–S-bond-forming arylation manifolds. These balanced systems prove sufficiently benign for use on diverse protein substrates in vitro and in living prokaryotic and eukaryotic cells. This, in turn, enables deep chemical surveys of reactive cysteines in human cells with sensitivity sufficient to detect covalently targetable proteins from emerging intracellular viral and bacterial pathogens. Biocompatible ligand balancing thus offers a path to the broader use of transition metals in living systems. The perceived toxicity of organometallic reagents has limited their use in living systems. Now it has been shown that balancing flexible chelation with biocompatible ligands without precluding chemical reactivity enables organonickel-mediated S-arylation inside cells. This reaction enables deep chemical surveys of reactive proteins and covalent tracking of intracellular viral and bacterial pathogens.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 3","pages":"457-472"},"PeriodicalIF":20.2,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41557-025-02017-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918037","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}
Pub Date : 2026-01-06DOI: 10.1038/s41557-025-02028-y
Michelle Francl
It is 100 years since the initial development of quantum mechanics, and not only did it bring with it a greater understanding of the world around us, it also introduced a new lexicon. Now, Michelle Francl wonders how the language of quantum mechanics has been flipped to the dark side and appropriated by pseudoscience.
{"title":"Quantum quacks","authors":"Michelle Francl","doi":"10.1038/s41557-025-02028-y","DOIUrl":"10.1038/s41557-025-02028-y","url":null,"abstract":"It is 100 years since the initial development of quantum mechanics, and not only did it bring with it a greater understanding of the world around us, it also introduced a new lexicon. Now, Michelle Francl wonders how the language of quantum mechanics has been flipped to the dark side and appropriated by pseudoscience.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 1","pages":"4-5"},"PeriodicalIF":20.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905275","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 : 2026-01-06DOI: 10.1038/s41557-025-02023-3
Tao Gao, Yunan Qin
Lithium nucleation at the metal anode surface dictates the morphologies of lithium deposits, which impact battery stability and performances. Now, a physics-based framework decouples substrate- and solid-electrolyte interphase-controlled nucleation pathways by examining the interplay of short-range transport and reaction.
{"title":"Two roads to lithium nucleation","authors":"Tao Gao, Yunan Qin","doi":"10.1038/s41557-025-02023-3","DOIUrl":"10.1038/s41557-025-02023-3","url":null,"abstract":"Lithium nucleation at the metal anode surface dictates the morphologies of lithium deposits, which impact battery stability and performances. Now, a physics-based framework decouples substrate- and solid-electrolyte interphase-controlled nucleation pathways by examining the interplay of short-range transport and reaction.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 1","pages":"8-9"},"PeriodicalIF":20.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905277","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 : 2026-01-06DOI: 10.1038/s41557-025-02026-0
Xiao-Yu Li, Christof Sparr
Diamond’s elementary chiral constituent—skew-tetramantane—features extreme rigidity, stability and a precisely defined geometry, epitomizing the parent structure of a σ-helicene. While skew-tetramantane is naturally occurring in trace fractions in fossil fuels, efforts over several decades towards its selective synthesis remained unfruitful. With the recent advances in photocatalysis and transition metal catalysis to tame radical and carbene species, we have now devised a targeted total synthesis of skew-tetramantane by means of a stereoselective adamantalogous cage extension. A first cap attachment was effected by a photocatalytic Giese reaction, while remarkable regio-, diastereo- and enantiocontrol were achieved by an intramolecular C(sp3)−H insertion using Davies’ chiral rhodium catalysts. After a Buchner–Curtius–Schlotterbeck ring expansion and a stereoselective Mukaiyama hydration, the fusion to the adamantine skew-tetramantane structure was completed by an intramolecular C(sp3)−H insertion of a non-stabilized carbenoid. Here we show that this approach provides access to synthetic skew-tetramantane in isomerically pure form with σ-helicity defined by the catalyst, marking a selective pathway to higher diamondoids. skew-Tetramantane—diamond’s chiral core—previously only accessible from fossil fuels after elaborate separations, was selectively synthesized by a combination of visible-light photocatalytic reactions to modulate radical chemistry and catalyst-controlled C–H insertions. Operating under kinetic control, this stereoselective adamantalogous cage-extension strategy provides access to synthetic diamondoids beyond adamantane, diamantane and triamantane.
{"title":"Stereoselective total synthesis of skew-tetramantane","authors":"Xiao-Yu Li, Christof Sparr","doi":"10.1038/s41557-025-02026-0","DOIUrl":"10.1038/s41557-025-02026-0","url":null,"abstract":"Diamond’s elementary chiral constituent—skew-tetramantane—features extreme rigidity, stability and a precisely defined geometry, epitomizing the parent structure of a σ-helicene. While skew-tetramantane is naturally occurring in trace fractions in fossil fuels, efforts over several decades towards its selective synthesis remained unfruitful. With the recent advances in photocatalysis and transition metal catalysis to tame radical and carbene species, we have now devised a targeted total synthesis of skew-tetramantane by means of a stereoselective adamantalogous cage extension. A first cap attachment was effected by a photocatalytic Giese reaction, while remarkable regio-, diastereo- and enantiocontrol were achieved by an intramolecular C(sp3)−H insertion using Davies’ chiral rhodium catalysts. After a Buchner–Curtius–Schlotterbeck ring expansion and a stereoselective Mukaiyama hydration, the fusion to the adamantine skew-tetramantane structure was completed by an intramolecular C(sp3)−H insertion of a non-stabilized carbenoid. Here we show that this approach provides access to synthetic skew-tetramantane in isomerically pure form with σ-helicity defined by the catalyst, marking a selective pathway to higher diamondoids. skew-Tetramantane—diamond’s chiral core—previously only accessible from fossil fuels after elaborate separations, was selectively synthesized by a combination of visible-light photocatalytic reactions to modulate radical chemistry and catalyst-controlled C–H insertions. Operating under kinetic control, this stereoselective adamantalogous cage-extension strategy provides access to synthetic diamondoids beyond adamantane, diamantane and triamantane.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 3","pages":"597-602"},"PeriodicalIF":20.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41557-025-02026-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903264","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}
Pub Date : 2026-01-06DOI: 10.1038/s41557-025-02022-4
Tengfei Kang, Justin O’Yang, Kevin Kasten, Samuel S. Allsop, Toby Lewis-Atwell, Elliot H. E. Farrar, Martin Juhl, David B. Cordes, Aidan P. McKay, Matthew N. Grayson, Andrew D. Smith
The catalytic enantioselective [1,2]-Wittig rearrangement of allylic ethers constitutes a recognized synthetic challenge as it is traditionally considered to arise from a non-concerted reaction pathway via formation and recombination of radical pairs. Here we show a catalytic enantioselective solution to this challenge, demonstrating that [1,2]-Wittig products are generated via an alternative reaction cascade to traditional dogma. The developed process employs a chiral bifunctional iminophosphorane catalyst to promote an initial enantioselective [2,3]-sigmatropic rearrangement. A subsequent base-promoted, stereoconvergent, fragmentation–recombination process that proceeds with high enantiospecificity and retention of configuration, formally equivalent to a Woodward–Hoffmann forbidden thermal [1,3]-sigmatropic rearrangement, generates [1,2]-Wittig products in up to 97:3 enantiomeric ratio. Supported by extensive quantum chemistry calculations, this chirality transfer process will have broad implications for fundamental stereocontrol in organic transformations.
{"title":"The catalytic enantioselective [1,2]-Wittig rearrangement cascade of allylic ethers","authors":"Tengfei Kang, Justin O’Yang, Kevin Kasten, Samuel S. Allsop, Toby Lewis-Atwell, Elliot H. E. Farrar, Martin Juhl, David B. Cordes, Aidan P. McKay, Matthew N. Grayson, Andrew D. Smith","doi":"10.1038/s41557-025-02022-4","DOIUrl":"https://doi.org/10.1038/s41557-025-02022-4","url":null,"abstract":"The catalytic enantioselective [1,2]-Wittig rearrangement of allylic ethers constitutes a recognized synthetic challenge as it is traditionally considered to arise from a non-concerted reaction pathway via formation and recombination of radical pairs. Here we show a catalytic enantioselective solution to this challenge, demonstrating that [1,2]-Wittig products are generated via an alternative reaction cascade to traditional dogma. The developed process employs a chiral bifunctional iminophosphorane catalyst to promote an initial enantioselective [2,3]-sigmatropic rearrangement. A subsequent base-promoted, stereoconvergent, fragmentation–recombination process that proceeds with high enantiospecificity and retention of configuration, formally equivalent to a Woodward–Hoffmann forbidden thermal [1,3]-sigmatropic rearrangement, generates [1,2]-Wittig products in up to 97:3 enantiomeric ratio. Supported by extensive quantum chemistry calculations, this chirality transfer process will have broad implications for fundamental stereocontrol in organic transformations.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"177 1","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903259","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 : 2026-01-06DOI: 10.1038/s41557-025-02033-1
Sophie R. Beeren
Sophie Beeren discusses the development of cyclodextrins, moving from laboratory curiosities to common ingredients in daily products, active pharmaceutical ingredients and building blocks for supramolecular chemistry.
Sophie Beeren讨论了环糊精的发展，从实验室的好奇心到日常用品中的常见成分，活性药物成分和超分子化学的构建模块。
{"title":"Sweet molecular containers","authors":"Sophie R. Beeren","doi":"10.1038/s41557-025-02033-1","DOIUrl":"10.1038/s41557-025-02033-1","url":null,"abstract":"Sophie Beeren discusses the development of cyclodextrins, moving from laboratory curiosities to common ingredients in daily products, active pharmaceutical ingredients and building blocks for supramolecular chemistry.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 1","pages":"212-212"},"PeriodicalIF":20.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905273","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}
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