{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T08:35:22Z","timestamp":1793003722053,"version":"4.5.0"},"reference-count":47,"publisher":"American Chemical Society (ACS)","license":[{"start":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:00:00Z","timestamp":1792800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001501","name":"University Grants Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001501","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001843","name":"Anusandhan National Research Foundation","doi-asserted-by":"publisher","award":["ANRF\/ARG\/2025\/001147"],"award-info":[{"award-number":["ANRF\/ARG\/2025\/001147"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["SR\/FST\/CSI-270\/2015"],"award-info":[{"award-number":["SR\/FST\/CSI-270\/2015"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006464","name":"Birla Institute of Technology and Science, Pilani","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006464","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Despite the electron-rich nature of pyrrole, the development of methods for its enantioselective C3-functionalization remains a significant synthetic challenge. In this work, a direct catalytic asymmetric synthesis of unblocked C3-nitroalkylated pyrroles has been established through a one-pot sequential process. This process involves an amine-catalyzed Michael addition of succinaldehyde to various nitroolefins, followed by an in situ Paal\u2013Knorr cyclization with primary amines, for the rapid synthesis of a broad range of C3-nitroalkylated N-alkyl, N-aryl, and NH-pyrroles in good yields and high enantioselectivity. Broad substrate scope and functional group tolerance enable efficient access to diverse chiral pyrroles, with gram-scale synthesis and late-stage functionalization highlighting the method's practicality.<\/jats:p>","DOI":"10.1021\/acs.joc.6c02177","type":"journal-article","created":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T06:02:12Z","timestamp":1792821732000},"source":"Crossref","is-referenced-by-count":0,"title":["Direct Enantioselective Construction of C3-Nitroalkylated Pyrroles by an Amine-Catalyzed Michael\/Paal\u2013Knorr Strategy"],"prefix":"10.1021","author":[{"given":"Imtiyaz Ahmad","family":"Shah","sequence":"first","affiliation":[{"name":"Birla Institute of Technology and Science Pilani , , Pilani Campus, Vidya Vihar , , ,","place":["Pilani, Rajasthan, India, 333031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mainika","family":"Verma","sequence":"additional","affiliation":[{"name":"Birla Institute of Technology and Science Pilani , , Pilani Campus, Vidya Vihar , , ,","place":["Pilani, Rajasthan, India, 333031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Jangir","sequence":"additional","affiliation":[{"name":"Birla Institute of Technology and Science Pilani , , Pilani Campus, Vidya Vihar , , ,","place":["Pilani, Rajasthan, India, 333031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Patel","sequence":"additional","affiliation":[{"name":"Birla Institute of Technology and Science Pilani , , Pilani Campus, Vidya Vihar , , ,","place":["Pilani, Rajasthan, India, 333031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0518-8431","authenticated-orcid":true,"given":"Krishnan","family":"Rangan","sequence":"additional","affiliation":[{"name":"Birla Institute of Technology and Science , , Hyderabad Campus , ,","place":["Hyderabad, Telangana, India, 500078"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eldhose","family":"Iype","sequence":"additional","affiliation":[{"name":"American University of the Middle East , , ,","place":["Egaila, Kuwait, 54200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4621-1236","authenticated-orcid":true,"given":"Indresh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Birla Institute of Technology and Science Pilani , , Pilani Campus, Vidya Vihar , , ,","place":["Pilani, Rajasthan, India, 333031"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,26]]},"reference":[{"key":"2026102402020279100_cit1a","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1039\/B926045E","article-title":"Chiral Molecules Containing the Pyrrole Framework","volume":"46","author":"Thirumalairajan","year":"2010","journal-title":"Chem. Commun."},{"key":"2026102402020279100_cit1b","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1002\/tcr.202100010","article-title":"Recent Advances in Functionalization of Pyrroles and Their Translational Potential","volume":"21","author":"Hunjan","year":"2021","journal-title":"Chem. Rec."},{"key":"2026102402020279100_cit2a","doi-asserted-by":"publisher","first-page":"11385","DOI":"10.1039\/D4CC03601H","article-title":"Synthesis of Chiral Systems Featuring the Pyrrole Unit: A Review","volume":"60","author":"Campbell","year":"2024","journal-title":"Chem. Commun."},{"key":"2026102402020279100_cit2b","doi-asserted-by":"publisher","first-page":"2709","DOI":"10.1002\/ajoc.202100427","article-title":"Recent Advances in Metal- and Organocatalyzed Asymmetric Functionalization of Pyrroles","volume":"10","author":"Borah","year":"2021","journal-title":"Asian J. Org. Chem."},{"key":"2026102402020279100_cit3a","doi-asserted-by":"publisher","first-page":"3582","DOI":"10.1002\/anie.200300582","article-title":"Chemistry and Biology of Roseophilin and the Prodigiosin Alkaloids: A Survey of the Last 2500 Years","volume":"42","author":"F\u00fcrstner","year":"2003","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026102402020279100_cit3b","doi-asserted-by":"publisher","first-page":"9552","DOI":"10.1021\/ja046695b","article-title":"The Total Synthesis of (+)-Dragmacidin F","volume":"126","author":"Garg","year":"2004","journal-title":"J. Am. Chem. Soc."},{"key":"2026102402020279100_cit3c","doi-asserted-by":"publisher","first-page":"8475","DOI":"10.1002\/anie.201502259","article-title":"Enantioselective Synthesis of Pyrrole-Based Spiro- and Polycyclic Derivatives by Iridium-Catalyzed Asymmetric Allylic Dearomatization and Controllable Migration Reactions","volume":"54","author":"Zhuo","year":"2015","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026102402020279100_cit4a","doi-asserted-by":"publisher","first-page":"4370","DOI":"10.1021\/ja015717g","article-title":"New Strategies in Organic Catalysis: The First Enantioselective Organocatalytic Friedel\u2013Crafts Alkylation","volume":"123","author":"Paras","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"2026102402020279100_cit4b","doi-asserted-by":"publisher","first-page":"3439","DOI":"10.1002\/adsc.202100313","article-title":"Organocatalytic Enantioselective Friedel-Crafts Alkylation Reactions of Pyrroles","volume":"363","author":"Gavi\u00f1a","year":"2021","journal-title":"Adv. Synth. Catal"},{"key":"2026102402020279100_cit5a","doi-asserted-by":"publisher","first-page":"4064","DOI":"10.1002\/chem.201002248","article-title":"Selective Synthesis of \u03b2-Alkylpyrroles","volume":"17","author":"Tsuchimoto","year":"2011","journal-title":"Chem.\u2013Eur. J."},{"key":"2026102402020279100_cit5b","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1021\/jo9020776","article-title":"Efficient Construction of Five-Membered Aromatic and Nonaromatic Heterocycles from 1,6-Enynes by a Palladium-Catalyzed Domino Coupling\/Cycloisomerization Process","volume":"75","author":"Meng","year":"2010","journal-title":"J. Org. Chem."},{"key":"2026102402020279100_cit5c","doi-asserted-by":"publisher","first-page":"5157","DOI":"10.1039\/C0CC00500B","article-title":"Domino allylic amination\/Sonogashira\/heterocyclisation reactions: palladium-catalyzed three-component synthesis of pyrroles","volume":"46","author":"Lamand\u00e9-Langle","year":"2010","journal-title":"Chem. Commun."},{"key":"2026102402020279100_cit5d","doi-asserted-by":"publisher","first-page":"5178","DOI":"10.1021\/acs.joc.7b00446","article-title":"Indium-Catalyzed Regioselective \u03b2-Alkylation of Pyrroles with Carbonyl Compounds and Hydrosilanes and Its Application to Construction of a Quaternary Carbon Center with a \u03b2-Pyrrolyl Group","volume":"82","author":"Nomiyama","year":"2017","journal-title":"J. Org. Chem."},{"key":"2026102402020279100_cit5e","doi-asserted-by":"publisher","first-page":"21510","DOI":"10.1021\/acsomega.5c00371","article-title":"\u03b2-Selective Addition of Pyrroles to Electron-Deficient Alkenes in Both Catalytic and Stoichiometric Modes on B(C6F5)3","volume":"10","author":"Sekine","year":"2025","journal-title":"ACS Omega"},{"key":"2026102402020279100_cit6","doi-asserted-by":"publisher","first-page":"5944","DOI":"10.1021\/ol202244u","article-title":"Enantioselective Friedel-Crafts Reaction of Acylpyrroles with Glyoxylates Catalyzed by BINOL-Ti(IV) Complexes","volume":"13","author":"Majer","year":"2011","journal-title":"Org. Lett."},{"key":"2026102402020279100_cit7","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1021\/ol300632p","article-title":"Rh2(S-biTISP)2-Catalyzed Asymmetric Functionalization of Indoles and Pyrroles with Vinylcarbenoids","volume":"14","author":"Lian","year":"2012","journal-title":"Org. Lett."},{"key":"2026102402020279100_cit8","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.tetasy.2015.01.004","article-title":"Highly enantioselective catalytic Friedel-Crafts reactions of cyclic \u03b1-alkylidene \u03b2-oxo imides","volume":"26","author":"Oyama","year":"2015","journal-title":"Tetrahedron: Asymmetry"},{"key":"2026102402020279100_cit9","doi-asserted-by":"publisher","first-page":"8432","DOI":"10.1039\/C4CC10055G","article-title":"Reversal of enantioselective Friedel-Crafts C3-alkylation of pyrrole by slightly tuning the amide units of N, N\u2032-dioxide ligands","volume":"51","author":"Zhang","year":"2015","journal-title":"Chem. Commun."},{"key":"2026102402020279100_cit10","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1039\/C6QO00273K","article-title":"Enantioselective \u03b2-alkylation of pyrroles with the formation of an all-carbon quaternary stereocenter","volume":"3","author":"Ma","year":"2016","journal-title":"Org. Chem. Front."},{"key":"2026102402020279100_cit11","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1039\/C7QO00815E","article-title":"Enantioselective palladium-catalyzed C-H functionalization of pyrroles using an axially chiral 2,2\u2032-bipyridine ligand","volume":"5","author":"Shen","year":"2018","journal-title":"Org. Chem. Front."},{"key":"2026102402020279100_cit12a","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1002\/1099-0690(200206)2002:12&lt;1877::AID-EJOC1877&gt;3.0.CO;2-U","article-title":"Asymmetric Michael Additions to Nitroalkenes","author":"Berner","year":"2002","journal-title":"Eur. J. Org. Chem."},{"key":"2026102402020279100_cit12b","doi-asserted-by":"publisher","first-page":"5450","DOI":"10.1021\/jo200546a","article-title":"Catalytic Asymmetric Friedel\u2013Crafts\/Protonation of Nitroalkenes and N-Heteroaromatics","volume":"76","author":"Arai","year":"2011","journal-title":"J. Org. Chem."},{"key":"2026102402020279100_cit13a","doi-asserted-by":"publisher","first-page":"4533","DOI":"10.1039\/D0OB00956C","article-title":"Synthesis and Practical Applications of 2-(2-Nitroalkyl)Pyrroles","volume":"18","author":"Palmieri","year":"2020","journal-title":"Org. Biomol. Chem."},{"key":"2026102402020279100_cit13b","doi-asserted-by":"publisher","first-page":"6899","DOI":"10.1021\/jo9013029","article-title":"Chiral Br\u00f8nsted Acid-Catalyzed Asymmetric Friedel\u2013Crafts Alkylation of Pyrroles with Nitroolefins","volume":"74","author":"Sheng","year":"2009","journal-title":"J. Org. Chem."},{"key":"2026102402020279100_cit13c","doi-asserted-by":"publisher","first-page":"3285","DOI":"10.1039\/b904275j","article-title":"Asymmetric Friedel\u2013Crafts Reaction of N-Heterocycles and Nitroalkenes Catalyzed by Imidazoline\u2013Aminophenol\u2013Cu Complex","volume":"45","author":"Yokoyama","year":"2009","journal-title":"Chem. Commun."},{"key":"2026102402020279100_cit13d","doi-asserted-by":"publisher","first-page":"7491","DOI":"10.1021\/acs.joc.8b01141","article-title":"Enantioselective Michael Addition of Pyrroles with Nitroalkenes in Aqueous Media Catalyzed by a Water-Soluble Catalyst","volume":"83","author":"Gui","year":"2018","journal-title":"J. Org. Chem."},{"key":"2026102402020279100_cit14a","doi-asserted-by":"publisher","first-page":"8104","DOI":"10.1021\/acs.jmedchem.1c00040","article-title":"Discovery of a Biased Allosteric Modulator for Cannabinoid 1 Receptor: Preclinical Anti-Glaucoma Efficacy","volume":"64","author":"Garai","year":"2021","journal-title":"J. Med. Chem."},{"key":"2026102402020279100_cit14b","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1021\/acsbiomedchemau.5c00169","article-title":"Allosteric Modulation of Cannabinoid Type 1 Receptor by ZCZ011: Integration of In Vitro Pharmacology and Molecular Dynamics Simulation","volume":"5","author":"Yadav","year":"2025","journal-title":"ACS Bio Med Chem Au"},{"key":"2026102402020279100_cit15a","doi-asserted-by":"publisher","first-page":"5853","DOI":"10.1016\/S0040-4039(00)00983-7","article-title":"Synthesis of a rhazinilam analogue acting as an inhibitor of tubulin assembly","volume":"41","author":"Dupont","year":"2000","journal-title":"Tetrahedron Lett."},{"key":"2026102402020279100_cit15b","doi-asserted-by":"publisher","first-page":"5289","DOI":"10.1016\/j.bmcl.2009.07.148","article-title":"Pyrrole[2,3-d]azepino compounds as agonists of the farnesoid X receptor (FXR)","volume":"19","author":"Mehlmann","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026102402020279100_cit15c","unstructured":"(c)\n          \n            \n              Clark\n              B. P.\n            ; TimmsG. H.; Tupper, D. E.\n          Pyrroloazepine compounds useful as dopaminergic agents. U.S. Patent 5258378, Nov 2, 1993."},{"key":"2026102402020279100_cit16a","doi-asserted-by":"publisher","first-page":"10545","DOI":"10.1002\/anie.201705068","article-title":"Iridium-Catalyzed Enantioselective Synthesis of Pyrrole-Annulated Medium-Sized-Ring Compounds","volume":"56","author":"Huang","year":"2017","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026102402020279100_cit16b","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1021\/ol800256j","article-title":"Regio- and Enantioselective Catalytic Cyclization of Pyrroles onto N-Acyliminium Ions","volume":"10","author":"Raheem","year":"2008","journal-title":"Org. Lett."},{"key":"2026102402020279100_cit17a","doi-asserted-by":"publisher","DOI":"10.1016\/j.tgchem.2024.100060","article-title":"ANO-catalyzed multicomponent synthesis of 3-nitroalkyl-N-substituted pyrroles","volume":"5","author":"Dapper","year":"2025","journal-title":"Tetrahedron Green Chem."},{"key":"2026102402020279100_cit17b","doi-asserted-by":"publisher","first-page":"2339","DOI":"10.1039\/C9QO00224C","article-title":"A hexameric resorcinarene capsule as a hydrogen bonding catalyst in the conjugate addition of pyrroles and indoles to nitroalkenes","volume":"6","author":"Gambaro","year":"2019","journal-title":"Org. Chem. Front."},{"key":"2026102402020279100_cit18a","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1002\/anie.200603129","article-title":"Asymmetric Organocatalytic Domino Reactions","volume":"46","author":"Enders","year":"2007","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026102402020279100_cit18b","doi-asserted-by":"publisher","first-page":"4126","DOI":"10.1039\/D5QO00347D","article-title":"Recent Advances in Organocatalytic Asymmetric Multicomponent Reactions","volume":"12","author":"Jiang","year":"2025","journal-title":"Org. Chem. Front."},{"key":"2026102402020279100_cit18c","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1039\/C5SC02913A","article-title":"Pot economy and one-pot synthesis","volume":"7","author":"Hayashi","year":"2016","journal-title":"Chem. Sci."},{"key":"2026102402020279100_cit19a","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1039\/C4OB01805B","article-title":"Linear dialdehydes as promising substrates for aminocatalyzed transformations","volume":"13","author":"Kumar","year":"2015","journal-title":"Org. Biomol. Chem."},{"key":"2026102402020279100_cit19b","doi-asserted-by":"publisher","first-page":"4320","DOI":"10.1002\/ejoc.201500623","article-title":"Asymmetric Formal [3+2] Cycloaddition Reaction of Succinaldehyde and Nitroalkene Catalyzed by Diphenylprolinol Silyl Ether","author":"Umemiya","year":"2015","journal-title":"Eur. J. Org. Chem."},{"key":"2026102402020279100_cit20a","doi-asserted-by":"publisher","first-page":"5747","DOI":"10.1039\/D2OB00961G","article-title":"Catalyst-Free Direct Regiospecific Multicomponent Synthesis of C3-Functionalized Pyrroles","volume":"20","author":"Pawar","year":"2022","journal-title":"Org. Biomol. Chem."},{"key":"2026102402020279100_cit20b","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1039\/D0CC06357F","article-title":"Direct catalytic synthesis of \u03b2-(C3)-substituted pyrroles: a complementary addition to the Paal\u2013Knorr reaction","volume":"57","author":"Pawar","year":"2021","journal-title":"Chem. Commun."},{"key":"2026102402020279100_cit21a","doi-asserted-by":"publisher","first-page":"7549","DOI":"10.1021\/acs.orglett.2c02922","article-title":"Enantioselective Direct Synthesis of C3-Hydroxyalkylated Pyrrole via an Amine-Catalyzed Aldol\/Paal-Knorr Reaction Sequence","volume":"24","author":"Pawar","year":"2022","journal-title":"Org. Lett."},{"key":"2026102402020279100_cit21b","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1039\/D4OB01729C","article-title":"Enantioselective Synthesis of \u03b1-(3-Pyrrolyl)methanamines with an Aza-Tetrasubstituted Center under Metal-Free Conditions","volume":"23","author":"Dolas","year":"2025","journal-title":"Org. Biomol. Chem."},{"key":"2026102402020279100_cit22","unstructured":"The X-ray crystallographic structures for 23 (CCDC 2590027) and 52 (2590024) have been deposited at the Cambridge Crystallographic Data Center (CCDC) (for more details, see the ESI\u2020)."},{"key":"2026102402020279100_cit23a","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202403580","article-title":"Switch of Five Contiguous Chiral Centers in the Synthesis of Both Enantiomers of Hajos\u2013Parrish Ketone Analogs via Diphenylprolinol Silyl Ether-Mediated Domino Reaction","volume":"31","author":"Hayashi","year":"2025","journal-title":"Chem. Eur. J."},{"key":"2026102402020279100_cit23b","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1021\/acs.joc.5c02124","article-title":"Enantiodivergent Reactions in Central and Axial Chirality: Concepts, Classifications, and Catalytic Strategies","volume":"91","author":"Hayashi","year":"2026","journal-title":"J. Org. Chem."}],"container-title":["The Journal of Organic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.joc.6c02177","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/joceah\/article-pdf\/doi\/10.1021\/acs.joc.6c02177\/68971266\/jo-2026-02177m.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/joceah\/article-pdf\/doi\/10.1021\/acs.joc.6c02177\/68971266\/jo-2026-02177m.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T08:04:56Z","timestamp":1793001896000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/joceah\/article\/doi\/10.1021\/acs.joc.6c02177\/5457706\/Direct-Enantioselective-Construction-of-C3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,26]]},"references-count":47,"URL":"https:\/\/doi.org\/10.1021\/acs.joc.6c02177","relation":{},"ISSN":["0022-3263","1520-6904"],"issn-type":[{"value":"0022-3263","type":"print"},{"value":"1520-6904","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,26]]}}}