A robust samarium diiodide-mediated radical thioetherification of alkyl bromides with thiols via ruthenium catalysis is reported. The synthesis of various alkyl-alkyl and alkyl-aryl thioethers could be achieved directly from alkyl bromides and thiols in only one step under the base-free and additive-free conditions. The efficiency of this protocol has been qualified by broad substrate scope and excellent functional group tolerance. Furthermore, the diversified synthesis of bioactive molecules could also be well tolerated.
{"title":"Samarium Diiodide-Mediated Radical Thioetherification of Alkyl Bromides with Thiols by Ruthenium Catalysis","authors":"Yongqi Liang, Kexin Li, Yongmei Cui, Chengwei Liu","doi":"10.1039/d5qo01523e","DOIUrl":"https://doi.org/10.1039/d5qo01523e","url":null,"abstract":"A robust samarium diiodide-mediated radical thioetherification of alkyl bromides with thiols via ruthenium catalysis is reported. The synthesis of various alkyl-alkyl and alkyl-aryl thioethers could be achieved directly from alkyl bromides and thiols in only one step under the base-free and additive-free conditions. The efficiency of this protocol has been qualified by broad substrate scope and excellent functional group tolerance. Furthermore, the diversified synthesis of bioactive molecules could also be well tolerated.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"44 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048738","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}
Júlia Viñas-Lóbez, Nicolas Sellet, Bibiana Fabri, Guillaume Levitre, Adiran De Aguirre, Amalia Isabel Poblador Bahamonde, Céline Besnard, Jerome Lacour
Polycyclic scaffolds are central to numerous natural products and pharmaceuticals, motivating concise, stereocontrolled routes to their construction. We report a photoredox-enabled synthesis of trans-fused [n.3.0] bicyclic ketones (n = 4, 5, 10) from malonate-derived enol ethers. α-Brominated intermediates, formed by acylation with 2-bromo-2-methylpropanoyl bromide, undergo radical cyclization under two complementary conditions: (i) acridinium orange (AOH+) with Hantzsch ester (HE) at 455 nm, or (ii) photoexcited HE alone at 365 nm. Both modes trigger 6-endo-trig Giese addition, C-O bond fragmentation, and hydrogen-atom transfer to α-branched cyclic ketones that ring-close under mild Brønsted or Lewis acid activation to trans-fused products with exclusive junction control. Mechanistic studies (Stern-Volmer, UV-Vis, electrochemistry) support two activation pathways -AOH+* quenching by HE or direct HE excitation -each generating the same radical intermediates in fine. DFT calculations validate mechanistic pathways and regioselectivity in favor of a philicity matching of the electrophilic radical and the polar electron-rich enol ether. The method accommodates ring-size diversity, accesses trans-hydrindanone architectures, and outcompetes 5-exo-trig spirocyclization.
{"title":"Densely-Functionalized Bicyclic Cyclopentanones by Combined Photoinduced 6-endo-trig Giese Additions and Mild Aldol Cyclizations","authors":"Júlia Viñas-Lóbez, Nicolas Sellet, Bibiana Fabri, Guillaume Levitre, Adiran De Aguirre, Amalia Isabel Poblador Bahamonde, Céline Besnard, Jerome Lacour","doi":"10.1039/d5qo01635e","DOIUrl":"https://doi.org/10.1039/d5qo01635e","url":null,"abstract":"Polycyclic scaffolds are central to numerous natural products and pharmaceuticals, motivating concise, stereocontrolled routes to their construction. We report a photoredox-enabled synthesis of trans-fused [n.3.0] bicyclic ketones (n = 4, 5, 10) from malonate-derived enol ethers. α-Brominated intermediates, formed by acylation with 2-bromo-2-methylpropanoyl bromide, undergo radical cyclization under two complementary conditions: (i) acridinium orange (<strong>AOH<small><sup>+</sup></small></strong>) with Hantzsch ester (<strong>HE</strong>) at 455 nm, or (ii) photoexcited <strong>HE </strong>alone at 365 nm. Both modes trigger 6-<em>endo-trig</em> Giese addition, C-O bond fragmentation, and hydrogen-atom transfer to α-branched cyclic ketones that ring-close under mild Brønsted or Lewis acid activation to trans-fused products with exclusive junction control. Mechanistic studies (Stern-Volmer, UV-Vis, electrochemistry) support two activation pathways -<strong>AOH<small><sup>+</sup></small>*</strong> quenching by <strong>HE </strong>or direct <strong>HE </strong>excitation -each generating the same radical intermediates in fine. DFT calculations validate mechanistic pathways and regioselectivity in favor of a philicity matching of the electrophilic radical and the polar electron-rich enol ether. The method accommodates ring-size diversity, accesses trans-hydrindanone architectures, and outcompetes 5-<em>exo-trig</em> spirocyclization.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"28 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048861","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}
Mohammad Saim Raza, K. M. Roshani, Rama Krishna Peddinti
Owing to the increased interest in the biological activity and reactivity of indole-fused heterocycles, in particular, 1,7-fused motifs (pyrroloquinolines), have received growing devotion over the last few decades. Alternatively, bicyclo[3.2.1]octanes (BCOs) have found extensive application in medicinal chemistry. However, the easy synthesis of 1,7-fused indole scaffolds from easily accessible precursors has remained a challenging goal. Herein, we developed base- and solvent-controlled diastereodivergent (4+2) annulation between enone-tethered indoles and alkylidene pyrazolones, enabling direct synthesis of spiro(pyrroloquinoline-pyrazolone) frameworks. This method enabled two distinct diastereomers having three contiguous chiral centres, including one chiral quaternary spiro centre (47 examples, up to 98%). Moreover, the use of indole acceptors allows the synthesis of hitherto unknown indole-fused oxa-azabicyclo[3.2.1]octanes to be accessed in high yields (17 examples, up to 93%). The current protocols feature operational simplicity, high atom economy, gram-scale synthesis, and post-synthetic modifications. Furthermore, this annulation could be applicable in the synthesis of drug-relevant molecules. Additionally, mechanistic studies on the reaction pathways of these annulations are included.
{"title":"Diastereodivergent Access of Spiro (Pyrroloquinoline-Pyrazolone) and Oxa-azabicyclo[3.2.1]octane Scaffolds via Cascade Approaches","authors":"Mohammad Saim Raza, K. M. Roshani, Rama Krishna Peddinti","doi":"10.1039/d5qo01604e","DOIUrl":"https://doi.org/10.1039/d5qo01604e","url":null,"abstract":"Owing to the increased interest in the biological activity and reactivity of indole-fused heterocycles, in particular, 1,7-fused motifs (pyrroloquinolines), have received growing devotion over the last few decades. Alternatively, bicyclo[3.2.1]octanes (BCOs) have found extensive application in medicinal chemistry. However, the easy synthesis of 1,7-fused indole scaffolds from easily accessible precursors has remained a challenging goal. Herein, we developed base- and solvent-controlled diastereodivergent (4+2) annulation between enone-tethered indoles and alkylidene pyrazolones, enabling direct synthesis of spiro(pyrroloquinoline-pyrazolone) frameworks. This method enabled two distinct diastereomers having three contiguous chiral centres, including one chiral quaternary spiro centre (47 examples, up to 98%). Moreover, the use of indole acceptors allows the synthesis of hitherto unknown indole-fused oxa-azabicyclo[3.2.1]octanes to be accessed in high yields (17 examples, up to 93%). The current protocols feature operational simplicity, high atom economy, gram-scale synthesis, and post-synthetic modifications. Furthermore, this annulation could be applicable in the synthesis of drug-relevant molecules. Additionally, mechanistic studies on the reaction pathways of these annulations are included.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"13 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043189","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}
Jingwen Jia, Hong-Yu Ma, Juan Fan, Xiao-Zuan Chen, Zhong-Wen Liu, Xian-Ying Shi
A rhodium-catalyzed regioselective C-H alkenylation of benzaldehydes has been developed employing acrylates as alkenyl surrogates, in which weakly coordinating aldehyde is rarely utilized as a traceless-directing group. This approach offers direct access to less common meta-alkenylated aromatic compounds starting from more accessible orthoor para-substituted benzaldehydes. The natural product 3aa was successfully synthesized in a single step using this protocol demonstrating its synthetic utility. Notably, the active catalyst is regenerated via two plausible pathways involving metal oxidation and hydrogen transfer with acrylates serving as efficient hydrogen scavengers.
{"title":"Weakly Coordinating Aldehyde as a Traceless Directing Group for Rhodium-Catalyzed Regioselective C-H Alkenylation of Benzaldehydes","authors":"Jingwen Jia, Hong-Yu Ma, Juan Fan, Xiao-Zuan Chen, Zhong-Wen Liu, Xian-Ying Shi","doi":"10.1039/d5qo01713k","DOIUrl":"https://doi.org/10.1039/d5qo01713k","url":null,"abstract":"A rhodium-catalyzed regioselective C-H alkenylation of benzaldehydes has been developed employing acrylates as alkenyl surrogates, in which weakly coordinating aldehyde is rarely utilized as a traceless-directing group. This approach offers direct access to less common meta-alkenylated aromatic compounds starting from more accessible orthoor para-substituted benzaldehydes. The natural product 3aa was successfully synthesized in a single step using this protocol demonstrating its synthetic utility. Notably, the active catalyst is regenerated via two plausible pathways involving metal oxidation and hydrogen transfer with acrylates serving as efficient hydrogen scavengers.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"7 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044867","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}
Shaojuan Chen, Yaojie Liu, Kun Liu, Mo Xian, Zhiyi Xu, Long Jiang, Weizhi Sun, Zongjiang Yu, Chao Xu
This study develops a new efficient synthesis method for 5-bromo-1,3-difluoro-2-nitrobenzene. Using 4-bromo-2,6-difluoroaniline as a raw material, the process employs a novel imidazole-modified iron porphyrin catalyst, tert-butylhydrogen peroxide as an oxidant, and dichloromethane as a solvent, yielding approximately 70% product after 24 hours at room temperature. The catalyst design was inspired by the imidazole group of a bifunctional small molecule (DFSM) in promoting the formation of the P450 enzyme's FeIV+˙O intermediate. This insight led to the creation of imidazole-modified iron porphyrin catalysts with varying side-chain carbon chain lengths. Theoretical calculations demonstrated that a 2-carbon chain length catalyst effectively extracts hydrogen atoms from the oxidant, enhancing FeIV+˙O formation and boosting catalytic efficiency. Consequently, two types of side-chain imidazole-modified catalysts, FeCnIPP (–CH3, n = 2–6) and FeTAC2IPP (–NH2), were synthesized by modifying tetra-p-methylphenylporphyrin iron (FeTMPP) and tetra-p-aminophenyl porphyrin iron (FeTAPP) structures. Experimental results showed that FeC2IPP and FeTAC2IPP achieved product yields 3.31-fold and 1.58-fold higher than those of the unmodified catalysts. To enhance the stability of the iron porphyrins, a graphene-oxide-immobilized catalyst (GO-FeTAC2IPP) was developed. This catalyst is recyclable up to five times while maintaining over 90% of its initial yield. This study provides a novel method for the efficient synthesis of nitro compounds, enabling the conversion of various amino substrates into nitro compounds. The findings offer a new technical pathway for related fields with promising applications.
本研究开发了一种新的合成5-溴-1,3-二氟-2-硝基苯的高效方法。该工艺以4-溴-2,6-二氟苯胺为原料，采用新型咪唑修饰的卟啉铁催化剂，叔丁基过氧化氢为氧化剂，二氯甲烷为溶剂，室温下24小时产率约为70%。该催化剂的设计灵感来自于双功能小分子（DFSM）的咪唑基团促进P450酶的FeIV+˙O中间体的形成。这一见解导致了咪唑修饰的铁卟啉催化剂具有不同的侧链碳链长度。理论计算表明，2碳链长的催化剂能有效地从氧化剂中提取氢原子，促进FeIV+˙O的形成，提高催化效率。因此，通过对四对甲基苯基卟啉铁（FeTMPP）和四对氨基苯基卟啉铁（FeTAPP）结构进行修饰，合成了两种侧链咪唑修饰催化剂FeCnIPP （-CH3, n = 2-6）和FeTAC2IPP （-NH2）。实验结果表明，FeC2IPP和FeTAC2IPP的产物收率分别比未改性的催化剂高3.31倍和1.58倍。为了提高铁卟啉的稳定性，研制了氧化石墨烯固定化催化剂（GO-FeTAC2IPP）。这种催化剂可循环使用五次，同时保持其初始产量的90%以上。本研究为硝基化合物的高效合成提供了一种新方法，使各种氨基底物转化为硝基化合物成为可能。研究结果为相关领域提供了新的技术途径，具有广阔的应用前景。
{"title":"Theoretical guidance and feedback on the design, preparation, and efficient catalytic oxidation of novel imidazole-modified iron porphyrin catalysts","authors":"Shaojuan Chen, Yaojie Liu, Kun Liu, Mo Xian, Zhiyi Xu, Long Jiang, Weizhi Sun, Zongjiang Yu, Chao Xu","doi":"10.1039/d5qo01420d","DOIUrl":"https://doi.org/10.1039/d5qo01420d","url":null,"abstract":"This study develops a new efficient synthesis method for 5-bromo-1,3-difluoro-2-nitrobenzene. Using 4-bromo-2,6-difluoroaniline as a raw material, the process employs a novel imidazole-modified iron porphyrin catalyst, <em>tert</em>-butylhydrogen peroxide as an oxidant, and dichloromethane as a solvent, yielding approximately 70% product after 24 hours at room temperature. The catalyst design was inspired by the imidazole group of a bifunctional small molecule (DFSM) in promoting the formation of the P450 enzyme's Fe<small><sup>IV+</sup></small>˙<img alt=\"[double bond, length as m-dash]\" border=\"0\" src=\"https://www.rsc.org/images/entities/char_e001.gif\"/>O intermediate. This insight led to the creation of imidazole-modified iron porphyrin catalysts with varying side-chain carbon chain lengths. Theoretical calculations demonstrated that a 2-carbon chain length catalyst effectively extracts hydrogen atoms from the oxidant, enhancing Fe<small><sup>IV+</sup></small>˙<img alt=\"[double bond, length as m-dash]\" border=\"0\" src=\"https://www.rsc.org/images/entities/char_e001.gif\"/>O formation and boosting catalytic efficiency. Consequently, two types of side-chain imidazole-modified catalysts, FeC<small><sub><em>n</em></sub></small>IPP (–CH<small><sub>3</sub></small>, <em>n</em> = 2–6) and FeTAC<small><sub>2</sub></small>IPP (–NH<small><sub>2</sub></small>), were synthesized by modifying tetra-<em>p</em>-methylphenylporphyrin iron (FeTMPP) and tetra-<em>p</em>-aminophenyl porphyrin iron (FeTAPP) structures. Experimental results showed that FeC<small><sub>2</sub></small>IPP and FeTAC<small><sub>2</sub></small>IPP achieved product yields 3.31-fold and 1.58-fold higher than those of the unmodified catalysts. To enhance the stability of the iron porphyrins, a graphene-oxide-immobilized catalyst (GO-FeTAC<small><sub>2</sub></small>IPP) was developed. This catalyst is recyclable up to five times while maintaining over 90% of its initial yield. This study provides a novel method for the efficient synthesis of nitro compounds, enabling the conversion of various amino substrates into nitro compounds. The findings offer a new technical pathway for related fields with promising applications.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"101 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022041","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}
Nonulosonic acids (NulOs) represents an important class of monosaccharides, which has received increasing interest due to their biological roles and potential in vaccine development. As they are only sparsely found in nature, their chemical synthesis is key to exploit their full potential. In this work we describe a building block approach starting from the abundant natural products glucose and threonine. With a few simple modifications these can serve as coupling partners in a SmI2 mediated reductive coupling, where two new stereocenters are constructed together with the C9 backbone. The approach is easily modified to access the desired diastereomer and we demonstrate, by the synthesis of 7 NuIOs, how both natural occurring as well as unknown NuIOs can be synthesized in a few steps from the available building blocks. The stereochemistry of the newly established stereocenters are carefully studied by transforming the NuIOs derivatives into their pyranoses followed by NMR studies. The assignment of stereochemistry is furthermore supported by a crystal structure and a model for the coupling reaction allowing us to propose rules for the stereochemical outcome making this approach predictable.
{"title":"Convergent and Stereoselective Synthesis of Nonulosonic Acids (NuIOs) Scaffolds via Imine/Aldehyde Reductive Coupling","authors":"Arminas Jurys, Christian Marcus Pedersen","doi":"10.1039/d5qo01524c","DOIUrl":"https://doi.org/10.1039/d5qo01524c","url":null,"abstract":"Nonulosonic acids (NulOs) represents an important class of monosaccharides, which has received increasing interest due to their biological roles and potential in vaccine development. As they are only sparsely found in nature, their chemical synthesis is key to exploit their full potential. In this work we describe a building block approach starting from the abundant natural products glucose and threonine. With a few simple modifications these can serve as coupling partners in a SmI2 mediated reductive coupling, where two new stereocenters are constructed together with the C9 backbone. The approach is easily modified to access the desired diastereomer and we demonstrate, by the synthesis of 7 NuIOs, how both natural occurring as well as unknown NuIOs can be synthesized in a few steps from the available building blocks. The stereochemistry of the newly established stereocenters are carefully studied by transforming the NuIOs derivatives into their pyranoses followed by NMR studies. The assignment of stereochemistry is furthermore supported by a crystal structure and a model for the coupling reaction allowing us to propose rules for the stereochemical outcome making this approach predictable.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"119 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022042","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}
A regioselective (3+2) cycloaddition between terminal alkynes and di-tert butyl azodicarboxylate under catalytic conditions is reported for the synthesis of novel N-aminooxazol-2-one scaffolds. The reaction employs an in situ-generated copper catalyst derived from inexpensive CuCl2 and TMEDA, with a catalytic amount of DABCO serving as a base. The (3+2) annulation features broad functional group tolerance and a straightforward protocol. Mechanistic studies revealed that under these mild and practical conditions, the non-isolated ynehydrazide intermediate-formed via the catalytic addition of terminal alkynes to azodicarboxylate-undergoes a subsequent copper-catalysed 5-endo-dig cyclization in situ, yielding the oxazol-2-one product. This transformation involves two consecutive steps within a single catalytic system, demonstrating high atom economy and step economy.
{"title":"Copper-catalyzed azodicarboxylate-alkyne (3+2) cycloaddition","authors":"Jian Lei, Jiayu Zhao, Jiangbin Guo, Xiaoyun Guo, Zhiwei Zeng, Xiaolan Xie, Fengjiao Lv","doi":"10.1039/d5qo01596k","DOIUrl":"https://doi.org/10.1039/d5qo01596k","url":null,"abstract":"A regioselective (3+2) cycloaddition between terminal alkynes and di-tert butyl azodicarboxylate under catalytic conditions is reported for the synthesis of novel N-aminooxazol-2-one scaffolds. The reaction employs an in situ-generated copper catalyst derived from inexpensive CuCl2 and TMEDA, with a catalytic amount of DABCO serving as a base. The (3+2) annulation features broad functional group tolerance and a straightforward protocol. Mechanistic studies revealed that under these mild and practical conditions, the non-isolated ynehydrazide intermediate-formed via the catalytic addition of terminal alkynes to azodicarboxylate-undergoes a subsequent copper-catalysed 5-endo-dig cyclization in situ, yielding the oxazol-2-one product. This transformation involves two consecutive steps within a single catalytic system, demonstrating high atom economy and step economy.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"48 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005785","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}
Sebastian Barata-Vallejo, Damian Emilio E. Yerien, Javier Alberto Ramírez, Al Postigo
The incorporation of fluorinated substituents into steroidal frameworks represents a valuable strategy for tuning biological and physicochemical properties. This review discusses recent progress in the fluoroalkylation of steroid derivatives, emphasizing synthetic methodologies for the introduction of trifluoromethyl, difluoromethyl, perfluoroalkyl, and partially fluorinated alkyl groups. Advances in nucleophilic, electrophilic, radical, and photoredox-mediated processes have broadened the scope of accessible fluorinated steroids, improving lipophilicity, metabolic stability, and receptor affinity. Representative examples of site-selective functionalization at key positions of the steroid nucleus are discussed, along with mechanistic and methodological insights. Particular attention is given to latestage transformations enabling efficient access to biologically relevant, structurally complex molecules. Collectively, this work provides a comprehensive overview of current synthetic strategies and highlights the potential of fluoroalkylation chemistry in the design of pharmacologically active steroids. Conceptual summarizing Tables 1 and 2, at the end of the manuscript, outline the salient features of this continuously adapting field of fluoroalkylation of the steroid scaffold.
{"title":"FLUOROALKYLATION OF STEROID DERIVATIVES: SYNTHETIC STRATEGIES, MECHANISTIC TRENDS, AND PHARMACOLOGICAL PERSPECTIVES","authors":"Sebastian Barata-Vallejo, Damian Emilio E. Yerien, Javier Alberto Ramírez, Al Postigo","doi":"10.1039/d5qo01669j","DOIUrl":"https://doi.org/10.1039/d5qo01669j","url":null,"abstract":"The incorporation of fluorinated substituents into steroidal frameworks represents a valuable strategy for tuning biological and physicochemical properties. This review discusses recent progress in the fluoroalkylation of steroid derivatives, emphasizing synthetic methodologies for the introduction of trifluoromethyl, difluoromethyl, perfluoroalkyl, and partially fluorinated alkyl groups. Advances in nucleophilic, electrophilic, radical, and photoredox-mediated processes have broadened the scope of accessible fluorinated steroids, improving lipophilicity, metabolic stability, and receptor affinity. Representative examples of site-selective functionalization at key positions of the steroid nucleus are discussed, along with mechanistic and methodological insights. Particular attention is given to latestage transformations enabling efficient access to biologically relevant, structurally complex molecules. Collectively, this work provides a comprehensive overview of current synthetic strategies and highlights the potential of fluoroalkylation chemistry in the design of pharmacologically active steroids. Conceptual summarizing Tables 1 and 2, at the end of the manuscript, outline the salient features of this continuously adapting field of fluoroalkylation of the steroid scaffold.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"45 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005789","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}
Liang Wang Chen, Yong-Liang Pan, Sheng Fang, Huan Yuan, Pengju Feng, Bing Shu
In this study, a metal-free and efficient method for the synthesis of sulflimines and sulfoximines via difluorocarbene enabled selective Csp3–N bond cleavage/S=N bond formation between tertiary amines and sulfenamide/sulfinamides has been developed. In those reactions, difluoromethylammonium ylides in situ generated by difluorocarbene were necessary for subsequent functionalization. This method featured mild reaction conditions, general substrate scopes, good tolerance of functional groups. In addition, scale-up synthesis, related applications, and preliminary mechanistic studies were also accomplished.
{"title":"Difluorocarbene enabled selective Csp3–N bond cleavage in aliphatic tertiary amines to access sulflimines and sulfoximines","authors":"Liang Wang Chen, Yong-Liang Pan, Sheng Fang, Huan Yuan, Pengju Feng, Bing Shu","doi":"10.1039/d5qo01551k","DOIUrl":"https://doi.org/10.1039/d5qo01551k","url":null,"abstract":"In this study, a metal-free and efficient method for the synthesis of sulflimines and sulfoximines via difluorocarbene enabled selective Csp3–N bond cleavage/S=N bond formation between tertiary amines and sulfenamide/sulfinamides has been developed. In those reactions, difluoromethylammonium ylides in situ generated by difluorocarbene were necessary for subsequent functionalization. This method featured mild reaction conditions, general substrate scopes, good tolerance of functional groups. In addition, scale-up synthesis, related applications, and preliminary mechanistic studies were also accomplished.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"393 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005784","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}
Georg Berger, Jan Borstelmann, Frank - Rominger, Milan Kivala
Helically chiral π-expanded diindenoperylenes were synthesized and their chiroptical properties characterized. The enantiopure synthesis of the perylene framework was achieved by two-fold Yamamoto coupling of π-expanded dibromofluoranthenes, each comprising one dithia[7]helicene unit. Oxidation of the thiophene units to the corresponding sulfones allowed late-stage modification of the chiroptical and electrochemical properties.
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![[double bond, length as m-dash]](https://www.rsc.org/images/entities/char_e001.gif)
O intermediate. This insight led to the creation of imidazole-modified iron porphyrin catalysts with varying side-chain carbon chain lengths. Theoretical calculations demonstrated that a 2-carbon chain length catalyst effectively extracts hydrogen atoms from the oxidant, enhancing FeIV+˙
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