Pub Date : 2026-02-02DOI: 10.1021/acs.orglett.5c04971
Joanna Urbańczyk, Aidan P McKay, David B Cordes, Tomas Lebl, Miles H Aukland, Allan J B Watson
Diversity-oriented synthesis (DOS) is an attractive approach for the design of functional molecules with (homo)allylic amines representing a particularly attractive DOS platform. Herein, we demonstrate the application of newly developed photocatalytic cross-nucleophilic coupling to provide rapid access to (homo)allylic amines, which can be smoothly converted to a range of heterocyclic scaffolds. Employing this approach, a variety of aza-heterocycles were accessed, including α-haloaziridines, pyrrolidines, and oxazinan-2-ones, with structural diversity examined by using uniform manifold approximation and projection (UMAP).
{"title":"A Polarity-Mismatched Photocatalytic Cross-Coupling Enables Diversity-Oriented Synthesis of aza-Heterocycles.","authors":"Joanna Urbańczyk, Aidan P McKay, David B Cordes, Tomas Lebl, Miles H Aukland, Allan J B Watson","doi":"10.1021/acs.orglett.5c04971","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04971","url":null,"abstract":"<p><p>Diversity-oriented synthesis (DOS) is an attractive approach for the design of functional molecules with (homo)allylic amines representing a particularly attractive DOS platform. Herein, we demonstrate the application of newly developed photocatalytic cross-nucleophilic coupling to provide rapid access to (homo)allylic amines, which can be smoothly converted to a range of heterocyclic scaffolds. Employing this approach, a variety of aza-heterocycles were accessed, including α-haloaziridines, pyrrolidines, and oxazinan-2-ones, with structural diversity examined by using uniform manifold approximation and projection (UMAP).</p>","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103131","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 : 2026-02-02DOI: 10.1021/acs.orglett.5c05448
Cheng Pan,Hamza Khan,Xiaoting Liu,Limin Wang,Jianwei Han
Using (vinyl tosyloxy)benziodolium salts, we divergently synthesized a series of conjugated diene derivatives with the Mizoroki–Heck reaction. Subsequent coupling reactions of these dienes provide access to polycyclic aromatic conjugated diene derivatives. Derivatization of ester-substituted conjugated dienes enabled the synthesis of ortho-iodoarylpyranones. Further oxidation of ortho-iodoarylpyranones furnishes cyclic arylidonium salts, which serve as versatile reagents for polycyclic aromatic hydrocarbons.
{"title":"(Vinyl tosyloxy)benziodolium Salts: Divergent Construction of Conjugated Diene Derivatives via Sequential Coupling Reactions","authors":"Cheng Pan,Hamza Khan,Xiaoting Liu,Limin Wang,Jianwei Han","doi":"10.1021/acs.orglett.5c05448","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05448","url":null,"abstract":"Using (vinyl tosyloxy)benziodolium salts, we divergently synthesized a series of conjugated diene derivatives with the Mizoroki–Heck reaction. Subsequent coupling reactions of these dienes provide access to polycyclic aromatic conjugated diene derivatives. Derivatization of ester-substituted conjugated dienes enabled the synthesis of ortho-iodoarylpyranones. Further oxidation of ortho-iodoarylpyranones furnishes cyclic arylidonium salts, which serve as versatile reagents for polycyclic aromatic hydrocarbons.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"8 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098071","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 : 2026-02-01DOI: 10.1021/acs.orglett.5c05238
Zhaozhan Wang,Yinghao Zhu,Bhalchandra M. Bhanage,Chen Li,Yong Yang
In this work, we report an efficient protocol for direct amine synthesis from alkenes catalyzed by a heterogeneous molecular catalyst Ru3/QDPOP, which features well-defined trinuclear Rh centers stabilized by a phosphine-functionalized porous organic polymer. The catalyst exhibited high activity and excellent regioselectivity toward the desired linear amines, significantly surpassing previously reported homo- and heterogeneous Ru-based catalysts. Various secondary and tertiary amines, including pharmaceutically relevant compounds, can be effectively synthesized from diverse amines and alkenes under mild conditions. Moreover, the catalyst is stable and recyclable, maintaining high performance over five cycles without appreciable loss in performance.
{"title":"Highly Regioselective Hydroaminomethylation for Amine Synthesis Enabled by a Heterogeneous Molecular Catalyst Ru3/QDPOP","authors":"Zhaozhan Wang,Yinghao Zhu,Bhalchandra M. Bhanage,Chen Li,Yong Yang","doi":"10.1021/acs.orglett.5c05238","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05238","url":null,"abstract":"In this work, we report an efficient protocol for direct amine synthesis from alkenes catalyzed by a heterogeneous molecular catalyst Ru3/QDPOP, which features well-defined trinuclear Rh centers stabilized by a phosphine-functionalized porous organic polymer. The catalyst exhibited high activity and excellent regioselectivity toward the desired linear amines, significantly surpassing previously reported homo- and heterogeneous Ru-based catalysts. Various secondary and tertiary amines, including pharmaceutically relevant compounds, can be effectively synthesized from diverse amines and alkenes under mild conditions. Moreover, the catalyst is stable and recyclable, maintaining high performance over five cycles without appreciable loss in performance.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"79 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097892","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 : 2026-02-01DOI: 10.1021/acs.orglett.5c05228
Suparna Mondal,Debu Ghorai,Saleha Khatun,Santanu Panda
Azetidines are valuable motifs in drug discovery, yet access to densely substituted N-α-bisaryl-C3-quaternary azetidines remains limited. We report a strain-release multicomponent Petasis borono–Mannich reaction that enables the modular synthesis of N-α-bisaryl-C3-quaternary azetidines from readily available azabicyclo[1.1.0]butane (ABB)-carbinols, arylboronic acids, and aldehydes. This mild, operationally simple process tolerates diverse bisaryl combinations and overcomes the multistep constraints of existing methods. Importantly, an asymmetric variant was achieved using a BINOL-derived catalyst, providing the first access to chiral N-α-bisaryl-C3-quaternary azetidines in high enantiomeric purity.
{"title":"Strain-Release Asymmetric Multicomponent Reaction to Access Diverse N-α-Bisaryl-C3-quaternary Azetidines","authors":"Suparna Mondal,Debu Ghorai,Saleha Khatun,Santanu Panda","doi":"10.1021/acs.orglett.5c05228","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05228","url":null,"abstract":"Azetidines are valuable motifs in drug discovery, yet access to densely substituted N-α-bisaryl-C3-quaternary azetidines remains limited. We report a strain-release multicomponent Petasis borono–Mannich reaction that enables the modular synthesis of N-α-bisaryl-C3-quaternary azetidines from readily available azabicyclo[1.1.0]butane (ABB)-carbinols, arylboronic acids, and aldehydes. This mild, operationally simple process tolerates diverse bisaryl combinations and overcomes the multistep constraints of existing methods. Importantly, an asymmetric variant was achieved using a BINOL-derived catalyst, providing the first access to chiral N-α-bisaryl-C3-quaternary azetidines in high enantiomeric purity.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"23 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097894","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 : 2026-02-01DOI: 10.1021/acs.orglett.5c05387
Long Liang,Sen Yang,Xiao-Guo Zhang,Jian-Ping Wu,Zhen-Yu Wang,Lan-Jun Cheng,Xiang Wu
A DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone)-mediated oxidative [5+2] cycloaddition of isochroman-4-ones with alkynes has been described. This strategy provides an alternative method for the generation of the key benzopyrylium ylides as dipoles and affords structurally diverse benzo-fused 8-oxabicyclo[3.2.1]octanes in moderate to good yields. Mechanistic studies disclosed that the generation of benzopyrylium ylides is a radical-based process.
{"title":"DDQ-Mediated Oxidative [5+2] Cycloaddition Reactions of Isochroman-4-ones with Alkynes","authors":"Long Liang,Sen Yang,Xiao-Guo Zhang,Jian-Ping Wu,Zhen-Yu Wang,Lan-Jun Cheng,Xiang Wu","doi":"10.1021/acs.orglett.5c05387","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05387","url":null,"abstract":"A DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone)-mediated oxidative [5+2] cycloaddition of isochroman-4-ones with alkynes has been described. This strategy provides an alternative method for the generation of the key benzopyrylium ylides as dipoles and affords structurally diverse benzo-fused 8-oxabicyclo[3.2.1]octanes in moderate to good yields. Mechanistic studies disclosed that the generation of benzopyrylium ylides is a radical-based process.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"11 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097891","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 : 2026-02-01DOI: 10.1021/acs.orglett.6c00153
Laurianne Verret,Pascal Paquin,Martin Le Roy,Maxim Boucher,Éric Biron,Guillaume Bélanger-Chabot,Jean-François Morin,Jean-François Paquin
The pentafluorosulfanyl (SF5) group is a valuable fluorinated motif, but aliphatic SF5 synthesis remains challenging. We report a metal-free organophotoredox strategy to access aliphatic SF5 compounds via alkylation of vinylsulfur pentafluoride, prepared from an SF5-triflate precursor. This operationally simple transformation proceeds under mild conditions, tolerates a broad range of functional groups, and affords diverse SF5-substituted alkanes in moderate to good yields. The reaction is amenable to continuous-flow processing.
{"title":"Organophotoredox-Catalyzed Alkylation of Vinylsulfur Pentafluoride: Expanding Access to SF5-Containing Aliphatic Molecules","authors":"Laurianne Verret,Pascal Paquin,Martin Le Roy,Maxim Boucher,Éric Biron,Guillaume Bélanger-Chabot,Jean-François Morin,Jean-François Paquin","doi":"10.1021/acs.orglett.6c00153","DOIUrl":"https://doi.org/10.1021/acs.orglett.6c00153","url":null,"abstract":"The pentafluorosulfanyl (SF5) group is a valuable fluorinated motif, but aliphatic SF5 synthesis remains challenging. We report a metal-free organophotoredox strategy to access aliphatic SF5 compounds via alkylation of vinylsulfur pentafluoride, prepared from an SF5-triflate precursor. This operationally simple transformation proceeds under mild conditions, tolerates a broad range of functional groups, and affords diverse SF5-substituted alkanes in moderate to good yields. The reaction is amenable to continuous-flow processing.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"16 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097890","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}
The enantioselective first total synthesis of (−)-citrifelin A is described herein. We found that the oxa-Pictet–Spengler reaction and acid-promoted dihydropyran formation were effective for the stereocontrolled construction of the tetracyclic framework of 1. Starting from known materials, (−)-citrifelin A was synthesized in an eight-step longest linear sequence (LLS) with an overall yield of 17%.
{"title":"Enantioselective Total Synthesis of Citrifelin A via the Oxa-Pictet–Spengler Reaction and Acid-Promoted Dihydropyran Formation","authors":"Kazuki Hori,Miyu Saito,Karen Shigeta,Shogo Kamo,Kazuyuki Sugita","doi":"10.1021/acs.orglett.5c05264","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05264","url":null,"abstract":"The enantioselective first total synthesis of (−)-citrifelin A is described herein. We found that the oxa-Pictet–Spengler reaction and acid-promoted dihydropyran formation were effective for the stereocontrolled construction of the tetracyclic framework of 1. Starting from known materials, (−)-citrifelin A was synthesized in an eight-step longest linear sequence (LLS) with an overall yield of 17%.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"6 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098109","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 : 2026-02-01DOI: 10.1021/acs.orglett.6c00038
Xiaoyu Fang,Yu Jiang,Yuhan Xiao,Chenqi Wang,Ai-Jun Ma,Junyang Liu,Jia-Lei Yan
The first total synthesis of chrysosporazines B and C was accomplished in a concise and highly stereoselective manner with overall yields of 9.2% and 8.0%, respectively. Highlights of the synthesis include a Suzuki–Miyaura coupling of E-enol tosylate followed by Rh-catalyzed asymmetric hydrogenation to establish the nonsymmetric β,β-diaryl amino acid motif, a piperazinedione condensation and reduction to construct the piperazine framework, and a late-stage Pd-catalyzed carbonylation to furnish the hexahydro-6H-pyrazino[1,2-b]isoquinolin-6-one scaffold.
{"title":"Total Synthesis of Chrysosporazines B and C","authors":"Xiaoyu Fang,Yu Jiang,Yuhan Xiao,Chenqi Wang,Ai-Jun Ma,Junyang Liu,Jia-Lei Yan","doi":"10.1021/acs.orglett.6c00038","DOIUrl":"https://doi.org/10.1021/acs.orglett.6c00038","url":null,"abstract":"The first total synthesis of chrysosporazines B and C was accomplished in a concise and highly stereoselective manner with overall yields of 9.2% and 8.0%, respectively. Highlights of the synthesis include a Suzuki–Miyaura coupling of E-enol tosylate followed by Rh-catalyzed asymmetric hydrogenation to establish the nonsymmetric β,β-diaryl amino acid motif, a piperazinedione condensation and reduction to construct the piperazine framework, and a late-stage Pd-catalyzed carbonylation to furnish the hexahydro-6H-pyrazino[1,2-b]isoquinolin-6-one scaffold.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"8 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098110","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}
Herein, we present a divergent synthesis of tacaman alkaloids featuring a pivotal pentacyclic intermediate bearing an exocyclic trisubstituted olefin, accessed via a base-promoted intramolecular cyclopropanation/cyclopropane ring-opening/oxa-Michael cascade and a subsequent electrophilic halomethylation–retro-aza-Michael sequence. This versatile common intermediate enabled the regio- and diastereoselective functionalization of the trisubstituted olefin, affording the total syntheses of tacamonine, tabercamine K, and 19S-hydroxyapotacamine in good yields with excellent stereocontrol. Notably, the Mukaiyama-type hydration reaction was applied to achieve tunable stereochemistry at the C19 and C20 hydroxyl positions.
{"title":"Divergent Total Synthesis of Tacaman Alkaloids: A Skeleton Reorganization Strategy","authors":"Xiao-Feng Guo,Ya-Kui Sun,Jin-Bao Qiao,Hui Shao,Yu-Ming Zhao","doi":"10.1021/acs.orglett.6c00063","DOIUrl":"https://doi.org/10.1021/acs.orglett.6c00063","url":null,"abstract":"Herein, we present a divergent synthesis of tacaman alkaloids featuring a pivotal pentacyclic intermediate bearing an exocyclic trisubstituted olefin, accessed via a base-promoted intramolecular cyclopropanation/cyclopropane ring-opening/oxa-Michael cascade and a subsequent electrophilic halomethylation–retro-aza-Michael sequence. This versatile common intermediate enabled the regio- and diastereoselective functionalization of the trisubstituted olefin, affording the total syntheses of tacamonine, tabercamine K, and 19S-hydroxyapotacamine in good yields with excellent stereocontrol. Notably, the Mukaiyama-type hydration reaction was applied to achieve tunable stereochemistry at the C19 and C20 hydroxyl positions.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"8 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098108","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 : 2026-01-30DOI: 10.1021/acs.orglett.5c05211
Jin-Tao Wang,Yi-Hui Li,Hua-Feng Cao,Yuan-Qing Xu,Zhong-Yan Cao,Peng-Fei Zhang,Shengnan Jin
The hydroalkynylation of unactivated olefins presents a significant challenge, primarily due to difficulties in controlling the regioselectivity and competing reaction pathways. Herein, we report a practical NiH-catalyzed γ-selective hydroalkynylation of unactivated alkenes tethered to nitrogen heterocycles performed under external ligand-free conditions. This method provides structurally diverse alkynes in good to excellent yields with high regioselectivity and broad functional group tolerance. The synthetic utility of this approach is demonstrated through facile transformations of the products into other valuable scaffolds. Additionally, regioselectivity can be switched to the β position by employing DPPB/(TolSO3)2Ni·6H2O as a catalyst. Preliminary mechanistic studies offer insight into the reaction pathway.
{"title":"Nickel-Catalyzed Regioselective Hydroalkynylation of Nitrogen Heterocycle-Tethered Unactivated Alkenes.","authors":"Jin-Tao Wang,Yi-Hui Li,Hua-Feng Cao,Yuan-Qing Xu,Zhong-Yan Cao,Peng-Fei Zhang,Shengnan Jin","doi":"10.1021/acs.orglett.5c05211","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05211","url":null,"abstract":"The hydroalkynylation of unactivated olefins presents a significant challenge, primarily due to difficulties in controlling the regioselectivity and competing reaction pathways. Herein, we report a practical NiH-catalyzed γ-selective hydroalkynylation of unactivated alkenes tethered to nitrogen heterocycles performed under external ligand-free conditions. This method provides structurally diverse alkynes in good to excellent yields with high regioselectivity and broad functional group tolerance. The synthetic utility of this approach is demonstrated through facile transformations of the products into other valuable scaffolds. Additionally, regioselectivity can be switched to the β position by employing DPPB/(TolSO3)2Ni·6H2O as a catalyst. Preliminary mechanistic studies offer insight into the reaction pathway.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"93 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089184","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号