{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:28:03Z","timestamp":1788532083220,"version":"build-2803163510"},"reference-count":42,"publisher":"American Chemical Society (ACS)","issue":"35","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2023NSCQ-MSX0296"],"award-info":[{"award-number":["CSTB2023NSCQ-MSX0296"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Projects of Fuling","award":["2024AAN3074"],"award-info":[{"award-number":["2024AAN3074"]}]},{"name":"State Key Laboratory of Neurology and Oncology Drug Development","award":["SKLSIM-20250478"],"award-info":[{"award-number":["SKLSIM-20250478"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Herein we report a general catalytic asymmetric umpolung (n+1) (n = 4, 5) cyclization using bifunctional hydroxylamines as bis-electrophiles, affording five- and six-membered azaspirooxindoles in good yields with excellent enantioselectivities (up to 98% ee) under mild phase-transfer catalytic conditions. Mechanistic studies reveal cooperative halogen-bonding, together with ion-pairing interactions, between the catalyst and substrate as key to reactivity and stereocontrol. Such discovery will inspire the design of new bifunctional phase-transfer catalysts with halogen-bonding donors in the future.<\/jats:p>","DOI":"10.1021\/acs.orglett.6c02735","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T01:01:20Z","timestamp":1787187680000},"page":"10912-10917","source":"Crossref","is-referenced-by-count":0,"title":["Catalytic Asymmetric Umpolung (n+1) Cyclization of\nBifunctional Hydroxylamines: Entry to Chiral Spirooxindole-Fused Azacycles"],"prefix":"10.1021","volume":"28","author":[{"given":"Yukun","family":"Zhao","sequence":"first","affiliation":[{"name":"Chongqing University Fuling Hospital , No.2 Gaosuntang Road , Fuling District, ,","place":["Chongqing, China, 408000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenshuang","family":"Li","sequence":"additional","affiliation":[{"name":"Chongqing University , , ,","place":["Chongqing, China, 401331"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Chen","sequence":"additional","affiliation":[{"name":"Chongqing University , , ,","place":["Chongqing, China, 401331"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Li","sequence":"additional","affiliation":[{"name":"Chongqing University , , ,","place":["Chongqing, China, 401331"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Gan","sequence":"additional","affiliation":[{"name":"Chongqing University Fuling Hospital , No.2 Gaosuntang Road , Fuling District, ,","place":["Chongqing, China, 408000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8600-965X","authenticated-orcid":true,"given":"Lin","family":"Hu","sequence":"additional","affiliation":[{"name":"Chongqing University , , ,","place":["Chongqing, China, 401331"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"2026090409095093000_cit1a","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1038\/s41570-021-00266-5","article-title":"Bifunctional Reagents in Organic\nSynthesis","volume":"5","author":"Huang","year":"2021","journal-title":"Nat. Rev. Chem."},{"key":"2026090409095093000_cit1b","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1021\/acs.joc.5c02969","article-title":"Synthesis\nof Indole-Fused\nDioxonanes via Bro\u0337nsted Acid-Catalyzed (5 + 4) Cycloaddition","volume":"91","author":"Wang","year":"2026","journal-title":"J. Org. Chem."},{"key":"2026090409095093000_cit2a","doi-asserted-by":"publisher","first-page":"10257","DOI":"10.1021\/jm501100b","article-title":"Analysis\nof the Structural Diversity, Substitution Patterns, and Frequency\nof Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals","volume":"57","author":"Vitaku","year":"2014","journal-title":"J. Med. Chem."},{"key":"2026090409095093000_cit2b","doi-asserted-by":"publisher","first-page":"44247","DOI":"10.1039\/D0RA09198G","article-title":"Prescribed Drugs Containing Nitrogen Heterocycles:\nan Overview","volume":"10","author":"Heravi","year":"2020","journal-title":"RSC Adv."},{"key":"2026090409095093000_cit2c","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1021\/acs.orglett.5c05359","article-title":"Catalytic Asymmetric\nSynthesis of 1,2-Fused Tricyclic Indoles Containing an Eight-Membered\nBiaryl Bridge","volume":"28","author":"Feng","year":"2026","journal-title":"Org. Lett."},{"key":"2026090409095093000_cit2d","doi-asserted-by":"publisher","DOI":"10.70401\/cc.2026.0018","article-title":"Catalytic\nAtroposelective Synthesis of C\u2013N Axially Chiral 5-Pyrazolyl\nIndoles via Multicomponent Tandem Cycloaddition","volume":"2","author":"Chen","year":"2025","journal-title":"Chiral Chem."},{"key":"2026090409095093000_cit3a","doi-asserted-by":"publisher","first-page":"12398","DOI":"10.1021\/ja0753389","article-title":"Palladium-Catalyzed\nAsymmetric [3 + 2] Cycloaddition of Trimethylenemethane with Imines","volume":"129","author":"Trost","year":"2007","journal-title":"J. Am. Chem. Soc."},{"key":"2026090409095093000_cit3b","doi-asserted-by":"publisher","first-page":"8238","DOI":"10.1021\/ja102102d","article-title":"Enantioselective Construction of Highly Substituted\nPyrrolidines by Palladium-Catalyzed Asymmetric [3 + 2] Cycloaddition\nof Trimethylenemethane with Ketimines","volume":"132","author":"Trost","year":"2010","journal-title":"J. Am.\nChem. Soc."},{"key":"2026090409095093000_cit4","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202203212","article-title":"Phosphine-Catalyzed Enantioselective\n(3 + 2) Annulation of Vinylcyclopropanes with Imines for the Synthesis\nof Chiral Pyrrolidines","volume":"61","author":"Zhang","year":"2022","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090409095093000_cit5","doi-asserted-by":"publisher","first-page":"3934","DOI":"10.1021\/acscatal.7b00787","article-title":"Asymmetric [3 + 2] Cycloaddition\nof 2,2\u2032-Diester Aziridines\nto Synthesize Pyrrolidine Derivatives","volume":"7","author":"Liao","year":"2017","journal-title":"ACS Catal."},{"key":"2026090409095093000_cit6","doi-asserted-by":"publisher","first-page":"5364","DOI":"10.1021\/ja0709730","article-title":"Chiral Calcium\nComplexes as Bro\u0337nsted\nBase Catalysts for Asymmetric Addition of \u03b1-Amino Acid Derivatives\nto \u03b1,\u03b2-Unsaturated Carbonyl Compounds","volume":"129","author":"Saito","year":"2007","journal-title":"J. Am. Chem. Soc."},{"key":"2026090409095093000_cit7","doi-asserted-by":"publisher","first-page":"10248","DOI":"10.1021\/ja104480g","article-title":"Enantioselective (Formal) Aza-Diels\u2013Alder\nReactions with Non-Danishefsky-Type Dienes","volume":"132","author":"Tambar","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"2026090409095093000_cit8","doi-asserted-by":"publisher","first-page":"4445","DOI":"10.1021\/jacs.5b00033","article-title":"Zn-Catalyzed Enantio- and Diastereoselective\nFormal [4 + 2] Cycloaddition Involving Two Electron-Deficient Partners:\nAsymmetric Synthesis of Piperidines from 1-Azadienes and Nitro-Alkenes","volume":"137","author":"Chu","year":"2015","journal-title":"J. Am. Chem. Soc."},{"key":"2026090409095093000_cit9","doi-asserted-by":"publisher","first-page":"11088","DOI":"10.1002\/anie.201304969","article-title":"Highly Enantioselective Aza-Diels\u2013Alder Reaction\nof 1-Azadienes with Enecarbamates Catalyzed by Chiral Phosphoric Acids","volume":"52","author":"He","year":"2013","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090409095093000_cit10a","doi-asserted-by":"publisher","first-page":"5679","DOI":"10.1021\/acs.orglett.9b02012","article-title":"General [4 + 1] Cyclization\nApproach To Access 2,2-Disubstituted Tetrahydrofurans Enabled by Electrophilic\nBifunctional Peroxides","volume":"21","author":"Gao","year":"2019","journal-title":"Org. Lett."},{"key":"2026090409095093000_cit10b","doi-asserted-by":"publisher","first-page":"13189","DOI":"10.1039\/D0CC05565D","article-title":"Formal [5 + 1] Annulation Reactions of Dielectrophilic Peroxides:\nFacile Access to Functionalized Dihydropyrans","volume":"56","author":"Zhong","year":"2020","journal-title":"Chem. Commun."},{"key":"2026090409095093000_cit10c","doi-asserted-by":"publisher","first-page":"19813","DOI":"10.1002\/anie.202105282","article-title":"A Unified Catalytic Asymmetric (4 + 1) and (5 + 1)\nAnnulation Strategy to Access Chiral Spirooxindole-Fused Oxacycles","volume":"60","author":"Gao","year":"2021","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090409095093000_cit10d","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1039\/D1CC06207G","article-title":"Annulation\u2013retro-Claisen Cascade of Bifunctional Peroxides for the\nSynthesis of Lactone Natural Products","volume":"58","author":"Xu","year":"2021","journal-title":"Chem.\nCommun."},{"key":"2026090409095093000_cit10e","doi-asserted-by":"publisher","first-page":"8387","DOI":"10.1021\/acs.orglett.2c03440","article-title":"Tunable Reaction Mode\nof Bifunctional Peroxides with Ketones to Access \u03b1-Oxacyclic Ketones and Enals","volume":"24","author":"Wen","year":"2022","journal-title":"Org. Lett."},{"key":"2026090409095093000_cit10f","doi-asserted-by":"publisher","first-page":"2215","DOI":"10.1039\/D4QO00215F","article-title":"A Formal (3 + 2) Annulation\u2013Cannizzaro Cascade of Bifunctional\nPeroxides for the Synthesis of Dihydrofurans","volume":"11","author":"Chen","year":"2024","journal-title":"Org. Chem. Front."},{"key":"2026090409095093000_cit10g","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1039\/D4QO01940G","article-title":"A New Tandem Reaction\nof Bifunctional Peroxides Enables the Expedient Synthesis of Functionalized\nDihydrofurans","volume":"12","author":"He","year":"2025","journal-title":"Org. Chem. Front."},{"key":"2026090409095093000_cit11","doi-asserted-by":"publisher","first-page":"2481","DOI":"10.1002\/chem.201601607","article-title":"Transition-Metal-Catalyzed Electrophilic\nAmination: Application of O-Benzoylhydroxylamines\nin the Construction of the C\u2013N Bond","volume":"23","author":"Dong","year":"2017","journal-title":"Chem. Eur. J."},{"key":"2026090409095093000_cit12","doi-asserted-by":"publisher","first-page":"13495","DOI":"10.1039\/D1CC05282A","article-title":"O-Protected\nNH-free Hydroxylamines: Emerging Electrophilic Aminating Reagents\nfor Organic Synthesis","volume":"57","author":"Jinan","year":"2021","journal-title":"Chem. Commun."},{"key":"2026090409095093000_cit13a","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.chempr.2016.10.012","article-title":"A Modular Strategy for the Direct Catalytic Asymmetric \u03b1-Amination of Carbonyl Compounds","volume":"1","author":"Ohmatsu","year":"2016","journal-title":"Chem."},{"key":"2026090409095093000_cit13b","doi-asserted-by":"publisher","first-page":"14531","DOI":"10.1002\/anie.201708176","article-title":"A Simple and Broadly Applicable C\u2013N Bond Forming\nDearomatization Protocol Enabled by Bifunctional Amino Reagents","volume":"56","author":"Ma","year":"2017","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090409095093000_cit14","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202512867","article-title":"Mannich Cyclization of Bifunctional Hydroxylamines by Aza-Kornblum\u2013DeLaMare\nRearrangement to Form Cyclopentyl \u03b2-Amino Esters","volume":"64","author":"Zhao","year":"2025","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090409095093000_cit15a","doi-asserted-by":"publisher","first-page":"8758","DOI":"10.1021\/ja903520c","article-title":"Thiourea-Catalyzed Highly Enantio- and Diastereoselective\nAdditions of Oxindoles to Nitroolefins: Application to the Formal\nSynthesis of (+)-Physostigmine","volume":"131","author":"Bui","year":"2009","journal-title":"J. Am. Chem.\nSoc."},{"key":"2026090409095093000_cit15b","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1021\/ja1102844","article-title":"Chiral 1,2,3-Triazoliums\nas New Cationic Organic Catalysts with Anion-Recognition Ability:\nApplication to Asymmetric Alkylation of Oxindoles","volume":"133","author":"Ohmatsu","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"2026090409095093000_cit15c","doi-asserted-by":"publisher","first-page":"5922","DOI":"10.1021\/acs.orglett.5b03082","article-title":"Unified Approach to\nthe Spiro(pyrrolidinyl-oxindole) and Hexahydropyrrolo[2,3-b]indole\nAlkaloids: Total Syntheses of Pseudophrynamines 270 and 272A","volume":"17","author":"De","year":"2015","journal-title":"Org. Lett."},{"key":"2026090409095093000_cit15d","doi-asserted-by":"publisher","first-page":"6327","DOI":"10.1021\/acs.orglett.8b02327","article-title":"Thiourea-Catalyzed\nEnantioselective Malonate Addition onto 3-Sulfonyl-3\u2032-indolyl-2-oxindoles:\nFormal Total Syntheses of (\u2212)-Chimonanthine, (\u2212)-Folicanthine,\nand (+)-Calycanthine","volume":"20","author":"Babu","year":"2018","journal-title":"Org. Lett."},{"key":"2026090409095093000_cit15e","doi-asserted-by":"publisher","first-page":"3929","DOI":"10.1039\/D2CC01008A","article-title":"Concise Total Syntheses of Bis(cyclotryptamine) Alkaloids via Thiourea\nCatalyzed One-Pot Sequential Michael Addition","volume":"58","author":"Khatua","year":"2022","journal-title":"Chem. Commun."},{"key":"2026090409095093000_cit16a","doi-asserted-by":"publisher","first-page":"5656","DOI":"10.1021\/cr068368n","article-title":"Recent Development\nand Application of Chiral Phase-Transfer Catalysts","volume":"107","author":"Hashimoto","year":"2007","journal-title":"Chem. Rev."},{"key":"2026090409095093000_cit16b","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1002\/cjoc.201900276","article-title":"Bifunctional Ion Pair Catalysts from\nChiral \u03b1-Amino Acids","volume":"37","author":"Wang","year":"2019","journal-title":"Chin. J. Chem."},{"key":"2026090409095093000_cit16c","doi-asserted-by":"publisher","first-page":"2088","DOI":"10.1021\/acs.accounts.5c00257","article-title":"Bioinspired\nChiral Peptide\u2013Phosphonium Salt Catalysis: From Enzymes to\nCationic Small-Molecule Enzyme Mimics","volume":"58","author":"Fang","year":"2025","journal-title":"Acc.\nChem. Res."},{"key":"2026090409095093000_cit17","doi-asserted-by":"publisher","first-page":"17371","DOI":"10.1021\/acs.joc.1c01678","article-title":"Spiro Scaffold Chiral Organocatalyst\nof 3,2\u2032-Pyrrolidinyl Spiro-oxindole Amine and Its Catalytic\nEvaluation in the Enantioselective Aldol Condensation between 3-(3-Hydroxy-1H-pyrazol-1-yl)-Oxindole\nand Paraformaldehyde","volume":"86","author":"Zou","year":"2021","journal-title":"J. Org. Chem."},{"key":"2026090409095093000_cit18a","doi-asserted-by":"publisher","first-page":"3483","DOI":"10.1002\/anie.201800261","article-title":"Halogen Bond Catalyzed\nBromocarbocyclization","volume":"57","author":"Chan","year":"2018","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090409095093000_cit18b","doi-asserted-by":"publisher","first-page":"3847","DOI":"10.1039\/C8CC00865E","article-title":"A Chiral Organic\nBase Catalyst with Halogen-Bonding-Donor Functionality: Asymmetric\nMannich Reactions of Malononitrile with N-Boc Aldimines\nand Ketimines","volume":"54","author":"Kuwano","year":"2018","journal-title":"Chem. Commun."},{"key":"2026090409095093000_cit18c","doi-asserted-by":"publisher","first-page":"6806","DOI":"10.1002\/anie.201915931","article-title":"Bidentate\nChiral Bis(imidazolium)-Based Halogen-Bond Donors: Synthesis and Applications\nin Enantioselective Recognition and Catalysis","volume":"59","author":"Sutar","year":"2020","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090409095093000_cit18d","doi-asserted-by":"publisher","first-page":"7051","DOI":"10.1039\/D1OB01092A","article-title":"In Silico Characterization\nand Prediction of Thiourea-Like Neutral Bidentate Halogen Bond Catalysts","volume":"19","author":"Yang","year":"2021","journal-title":"Org. Biomol. Chem."},{"key":"2026090409095093000_cit18e","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202301190","article-title":"Direct \u03c0-Activation vs. O-Activation in Halogen-Bonding Catalysis","volume":"62","author":"Robidas","year":"2023","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090409095093000_cit19a","doi-asserted-by":"publisher","first-page":"6690","DOI":"10.1039\/D2CP00075J","article-title":"The Mechanism and Impact of Mono\/Bis(iodoimidazolium) Halogen Bond\nDonor Catalysts on Michael Addition of Indole with trans-Crotonophenone: DFT Calculations","volume":"24","author":"Sun","year":"2022","journal-title":"Phys. Chem.\nChem. Phys."},{"key":"2026090409095093000_cit19b","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202506476","article-title":"Highly\nEnantioselective Organocatalysis with Bidentate Halogen Bond Donors","volume":"64","author":"Wolf","year":"2025","journal-title":"Angew. Chem., Int. Ed."}],"container-title":["Organic Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.orglett.6c02735","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/orlef7\/article-pdf\/28\/35\/10912\/66886923\/acs.orglett.6c02735.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/orlef7\/article-pdf\/28\/35\/10912\/66886923\/acs.orglett.6c02735.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:04:42Z","timestamp":1788530682000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/orlef7\/article\/28\/35\/10912\/5277218\/Catalytic-Asymmetric-Umpolung-n-1-Cyclization-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":42,"journal-issue":{"issue":"35","published-online":{"date-parts":[[2026,8,19]]},"published-print":{"date-parts":[[2026,9,4]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.orglett.6c02735","relation":{},"ISSN":["1523-7060","1523-7052"],"issn-type":[{"value":"1523-7060","type":"print"},{"value":"1523-7052","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]}}}