{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:17:51Z","timestamp":1787617071211,"version":"build-2736575974"},"reference-count":39,"publisher":"American Chemical Society (ACS)","issue":"31","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100008256","name":"Nanjing Tech University","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100008256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Postgraduate Research & Practice Innovation Program of Jiangsu Province","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The introduction of a privileged trifluoromethyl group into targeted molecules typically exerts a profound physicochemical impact. Efficient methods for the synthesis of trifluoromethylated 1,4-dihydropyrimidines remain challenging. Herein, a base-promoted formal [3 + 3]-cyclization of \u03b2-trifluoromethyl enones with readily available amidines for accessing structurally unique 1,4-dihydropyrimidines featuring a CF3-tetrasubstituted carbon center was developed. The mild reaction, integrating heterocycle assembly and precisely regioselective trifluoromethyl group installation in a one-pot, simple, and efficient manner, demonstrates advantages including broad substrate scope, excellent functional group compatibility, good scalability, and the modification of complex molecules.<\/jats:p>","DOI":"10.1021\/acs.joc.6c01384","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:10:17Z","timestamp":1785849017000},"page":"10753-10760","source":"Crossref","is-referenced-by-count":1,"title":["Formal [3 + 3]-Cyclization\nof \u03b2-Trifluoromethyl\nEnones and Amidines: Synthesis of 1,4-Dihydropyrimidines Featuring\na CF3-Tetrasubstituted Carbon Center"],"prefix":"10.1021","volume":"91","author":[{"given":"Xiao-Xiao","family":"Sun","sequence":"first","affiliation":[{"name":"Nanjing Tech University , , ,","place":["Nanjing, China, 211816"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Fei","family":"Hu","sequence":"additional","affiliation":[{"name":"Nanjing Tech University , , ,","place":["Nanjing, China, 211816"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Nanjing Tech University , , ,","place":["Nanjing, China, 211816"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0555-4307","authenticated-orcid":true,"given":"Danhua","family":"Ge","sequence":"additional","affiliation":[{"name":"Nanjing Tech University , , ,","place":["Nanjing, China, 211816"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9629-6464","authenticated-orcid":true,"given":"Mengtao","family":"Ma","sequence":"additional","affiliation":[{"name":"Nanjing Forestry University , , ,","place":["Nanjing, China, 210037"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Xu","sequence":"additional","affiliation":[{"name":"Nanjing Tech University , , ,","place":["Nanjing, China, 211816"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3365-9288","authenticated-orcid":true,"given":"Zhi-Liang","family":"Shen","sequence":"additional","affiliation":[{"name":"Nanjing Tech University , , ,","place":["Nanjing, China, 211816"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9173-1508","authenticated-orcid":true,"given":"Xue-Qiang","family":"Chu","sequence":"additional","affiliation":[{"name":"Nanjing Tech University , , ,","place":["Nanjing, China, 211816"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"2026080708075038800_cit1","doi-asserted-by":"publisher","first-page":"3552","DOI":"10.1021\/acs.jmedchem.6b01807","article-title":"The Necessary\nNitrogen Atom: a Versatile High-Impact\nDesign Element for Multiparameter Optimization","volume":"60","author":"Pennington","year":"2017","journal-title":"J. Med. Chem."},{"key":"2026080708075038800_cit2","unstructured":"https:\/\/www.fda.gov\/drugs\/development-approval-process-drugs\/drug-approvals-and-databases."},{"key":"2026080708075038800_cit3","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/S0223-5234(00)01189-2","article-title":"Biologically\nActive Dihydropyrimidones of the Biginelli-type\u2013a Literature\nSurvey","volume":"35","author":"Kappe","year":"2000","journal-title":"Eur. J. Med. Chem."},{"key":"2026080708075038800_cit4","doi-asserted-by":"publisher","first-page":"784","DOI":"10.3390\/molecules28020784","article-title":"Synthesis\nof Dihydropyrimidines: Isosteres of Nifedipine and Evaluation of Their\nCalcium Channel Blocking Efficiency","volume":"28","author":"Zohny","year":"2023","journal-title":"Molecules"},{"key":"2026080708075038800_cit5","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1021\/jo00110a021","article-title":"Novel Alkaloids\nfrom the Sponge Batzella sp.: Inhibitors of HIVgp 120-Human CD4 Binding","volume":"60","author":"Patil","year":"1995","journal-title":"J. Org. Chem."},{"key":"2026080708075038800_cit6","volume-title":"Dictionary of Marine\nNatural Products with CD-ROM","author":"Blunt","year":"2008"},{"key":"2026080708075038800_cit7","doi-asserted-by":"publisher","first-page":"4533","DOI":"10.1016\/j.bmc.2015.06.008","article-title":"Structure\nBased Library Design (SBLD) for New 1,4-Dihydropyrimidine Scaffold\nas Simultaneous COX-1\/COX-2 and 5-LOX Inhibitors","volume":"23","author":"Lokwani","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"2026080708075038800_cit8","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.bmcl.2014.11.061","article-title":"Structure\nActivity Relationships of Human Galactokinase Inhibitors","volume":"25","author":"Liu","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026080708075038800_cit9","doi-asserted-by":"publisher","first-page":"4359","DOI":"10.1021\/jm800219f","article-title":"The Many\nRoles for Fluorine in Medicinal Chemistry","volume":"51","author":"Hagmann","year":"2008","journal-title":"J.\nMed. Chem."},{"key":"2026080708075038800_cit10","unstructured":"Vandyck, K.; Hache\u0301, G. Y. P.; Rombouts, G.; Verschueren, W. G.; Raboisson, P. J.-M. B.\n          4,4-Disubstituted-1,4-Dihydropyrimidines\nand the Use Thereof as Medicaments for the Treatment of Hepatitis\nB. WO2013\/102655A1, July 11, 2013."},{"key":"2026080708075038800_cit11","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1021\/acs.jmedchem.6b01706","article-title":"Discovery of a Novel\nSeries of Orally Bioavailable\nand CNS Penetrant Glucagon-like Peptide-1 Receptor (GLP-1R) Noncompetitive\nAntagonists Based on a 1,3-Disubstituted-7-aryl-5,5-bis(trifluoromethyl)-5,8-dihydropyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione\nCore","volume":"60","author":"Nance","year":"2017","journal-title":"J. Med. Chem."},{"key":"2026080708075038800_cit12","unstructured":"Mita, T.; Kudo, Y.; Mizukoshi, T.; Hotta, H.; Maeda, K.; Takii, S.\n          Preparation of Cycloalkyl- or Heterocyclylbenzanilide\nCompounds as Pesticides. JP2005272452A, 2005."},{"key":"2026080708075038800_cit13","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1002\/anie.201711316","article-title":"Borazine-CF3-Adducts for\nRapid, Room Temperature, and Broad Scope Trifluoromethylation","volume":"57","author":"Geri","year":"2018","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026080708075038800_cit14","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1134\/S1070363212090307","article-title":"(2,6-Dioxacyclohexyl)-2,2,2-Trifluoro-1-Trifluoromethylethylamides\nin Cyclocondensation with Primary Amines","volume":"82","author":"Sokolov","year":"2012","journal-title":"Russ.\nJ. Gen. Chem."},{"key":"2026080708075038800_cit15","doi-asserted-by":"publisher","first-page":"3245","DOI":"10.1002\/adsc.201800704","article-title":"Copper-Catalyzed [4\n+ 2] Cycloaddition Using N-(2-Pyridyl)ketimines and\nTerminal Alkynes","volume":"360","author":"Tatsumi","year":"2018","journal-title":"Adv. Synth. Catal."},{"key":"2026080708075038800_cit16","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1021\/acs.orglett.5c00381","article-title":"Perfluoroalkyl Editing\nof Fluoroalkynes:\nChemo-, Regio-, and Stereoselective Synthesis of (E)-(2-Amino-fluoroalkenyl)pyrimidines","volume":"27","author":"Li","year":"2025","journal-title":"Org.\nLett."},{"key":"2026080708075038800_cit17","doi-asserted-by":"publisher","first-page":"6816","DOI":"10.1039\/D2GC02045A","article-title":"Four-Component Defluorination Reaction\nof Allylic Fluorides, Amidines, and Cs2CO3 under\nTransition-Metal-Free Conditions","volume":"24","author":"Chen","year":"2022","journal-title":"Green Chem."},{"key":"2026080708075038800_cit18","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1039\/D1QO01439K","article-title":"Transition-Metal-Free Hydroamination\/Defluorination\/Cyclization\nof Perfluoroalkyl Alkynes with Amidines","volume":"9","author":"Sun","year":"2021","journal-title":"Org.\nChem. Front."},{"key":"2026080708075038800_cit19","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s00706-024-03180-w","article-title":"Recent Progress in\nthe Application\nof Amidines for the Synthesis of N-heterocyclic Compounds","volume":"155","author":"Doraghi","year":"2024","journal-title":"Monatsh. Chem."},{"issue":"part\nvi","key":"2026080708075038800_cit20","doi-asserted-by":"publisher","first-page":"85","DOI":"10.24820\/ark.5550190.p010.607","article-title":"Amidines: Their\nSynthesis, Reactivity,\nand Applications in Heterocyclic Synthesis","volume":"2018","author":"Aly","year":"2019","journal-title":"Arkivoc"},{"key":"2026080708075038800_cit21","doi-asserted-by":"publisher","first-page":"3133","DOI":"10.1002\/jhet.2927","article-title":"Synthesis and Antimicrobial Evaluation\nof Some Functionalized\nHeterocycles Derived from Novel Quinolinyl Chalcone","volume":"54","author":"Hassan","year":"2017","journal-title":"J. Heterocycl. Chem."},{"key":"2026080708075038800_cit22","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1002\/jhet.2734","article-title":"Regioselective Synthesis of 3-(Imidazol-4-yl) Indolin-2-Ones\nunder Microwave Heating","volume":"54","author":"Chen","year":"2017","journal-title":"J. Heterocycl. Chem."},{"key":"2026080708075038800_cit23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2019.115126","article-title":"Design,\nSynthesis, and Bioactivity of Dihydropyrimidine Derivatives as Kinesin\nSpindle Protein Inhibitors","volume":"27","author":"Tawfik","year":"2019","journal-title":"Bioorg. Med. Chem."},{"key":"2026080708075038800_cit24","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/S0022-1139(97)00027-4","article-title":"A Convenient Synthesis\nof 3-Polyfluoroalkyl Pyrazoles\nand 6-Polyfluoroalkyl Pyrimidines from \u03b2-Polyfluoroalkyl Enaminones","volume":"84","author":"Yu","year":"1997","journal-title":"J. Fluorine Chem."},{"key":"2026080708075038800_cit25","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1002\/cjoc.202400929","article-title":"1,2-Dichloroethane-Assisted Defluorination:\nRing-Opening Reaction of DABCO and Polyfluoroalkyl Peroxides: Synthesis\nof Fluorinated N-Ethyl Piperazines","volume":"43","author":"Ren","year":"2025","journal-title":"Chin. J. Chem."},{"key":"2026080708075038800_cit26","doi-asserted-by":"publisher","first-page":"2749","DOI":"10.1021\/acs.orglett.8b00963","article-title":"Combining\nFluoroalkylation and Defluorination to Enable Formal [3 + 2 + 1] Heteroannulation\nby Using Visible-Light Photoredox Organocatalysis","volume":"20","author":"Chu","year":"2018","journal-title":"Org. Lett."},{"key":"2026080708075038800_cit27","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.jfluchem.2006.11.003","article-title":"One-Pot\nSynthesis of Novel \u03b1,\u03b2-Dichloro-\u03b2-trifluoromethylated\nEnones and Their Application to the Synthesis of Trifluoromethylated\nHeterocycles","volume":"128","author":"Jeon","year":"2007","journal-title":"J. Fluorine Chem."},{"key":"2026080708075038800_cit28","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.70556","article-title":"Recent\nDevelopments in Defluorination Functionalization\nof \u03b2-Trifluoromethyl Enones","volume":"368","author":"Ge","year":"2026","journal-title":"Adv. Synth.\nCatal."},{"key":"2026080708075038800_cit29","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.70188","article-title":"Primary Amination of Enones Using Inorganic Ammonium\nSalts and Nitrogen Isotope Incorporation","volume":"368","author":"Gao","year":"2026","journal-title":"Adv.\nSynth. Catal."},{"key":"2026080708075038800_cit30","doi-asserted-by":"publisher","first-page":"16749","DOI":"10.1021\/acs.joc.5c01993","article-title":"Defluorination:\nHydrophosphorylation of Trifluoromethylated Enones: Insight into the\nRoles of H-Phosphine Oxide","volume":"90","author":"Ren","year":"2025","journal-title":"J. Org. Chem."},{"key":"2026080708075038800_cit31","doi-asserted-by":"publisher","DOI":"10.1002\/ajoc.202500468","article-title":"\u201cOn-Water\u201d\nBisphosphorylation of \u03b2-Trifluoromethyl\nEnones via Successive C(sp3)-F Bonds Functionalization:\nSynthesis of Multisubstituted Furans","volume":"14","author":"Zhang","year":"2025","journal-title":"Asian\nJ. Org. Chem."},{"key":"2026080708075038800_cit32","doi-asserted-by":"publisher","first-page":"3373","DOI":"10.1021\/acs.joc.4c03056","article-title":"Three-Component\nSulfonylation and Heteroannulation: Enabled by 3-Fold Defluorofunctionalization\nof Trifluoromethyl Enones","volume":"90","author":"Gao","year":"2025","journal-title":"J. Org. Chem."},{"key":"2026080708075038800_cit33","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202404324","article-title":"Defluorination: Diazolation-Cyclization:\nRely for Synthesis of Furan-Bridged Triheterocycles and Colorimetric\nSensor Application","volume":"31","author":"Feng","year":"2025","journal-title":"Chem. - Eur. J."},{"key":"2026080708075038800_cit34","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1021\/acs.orglett.4c04488","article-title":"Modular Synthesis of Furans with\nFour Nonidentical\nSubstituents by Aqueous Defluorination Reaction of Trifluoromethyl\nEnones with Two Nucleophiles","volume":"27","author":"Huang","year":"2025","journal-title":"Org. Lett."},{"key":"2026080708075038800_cit35","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.202400274","article-title":"Transition-Metal-Free\nCarbonyl Reduction\nand Hydrodefluorination of \u03b2-Trifluoromethyl Enones with Hydrosilanes:\nSynthesis of gem-Difluorovinyl Alcohols","volume":"27","author":"Zhang","year":"2024","journal-title":"Eur. J. Org. Chem."},{"key":"2026080708075038800_cit36","doi-asserted-by":"publisher","first-page":"6368","DOI":"10.1021\/acs.orglett.3c02357","article-title":"Combining Hydrodefluorination and\nDefluorophosphorylation for Chemo- and Stereoselective Synthesis of gem-Fluorophosphine Alkenes","volume":"25","author":"Hu","year":"2023","journal-title":"Org.\nLett."},{"key":"2026080708075038800_cit37","doi-asserted-by":"publisher","first-page":"3546","DOI":"10.1002\/adsc.202300741","article-title":"On-Water\u201d Synthesis of Sterically\nCongested \u03b3-Ketophosphine Oxides Featuring \u03b1 CF3- and P(O)-Tetrasubstituted Carbon Center","volume":"365","author":"Feng","year":"2023","journal-title":"Adv. Synth. Catal."},{"key":"2026080708075038800_cit38","doi-asserted-by":"publisher","first-page":"3745","DOI":"10.1021\/acs.orglett.3c01215","article-title":"Selective and Controllable Defluorophosphination\nand Defluorophosphorylation of Trifluoromethylated Enones: An Auxiliary\nFunction of Carbonyl Group","volume":"25","author":"Sun","year":"2023","journal-title":"Org. Lett."},{"key":"2026080708075038800_cit39","doi-asserted-by":"publisher","first-page":"6489","DOI":"10.1039\/D3GC01565C","article-title":"On-Water\u201d\nDefluorophosphorylation of Trifluoromethylated\nEnones with Phosphine Oxides","volume":"25","author":"Chu","year":"2023","journal-title":"Green Chem."}],"container-title":["The Journal of Organic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.joc.6c01384","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/joceah\/article-pdf\/91\/31\/10753\/66287475\/acs.joc.6c01384.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/joceah\/article-pdf\/91\/31\/10753\/66287475\/acs.joc.6c01384.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T12:22:43Z","timestamp":1786105363000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/joceah\/article\/91\/31\/10753\/5234391\/Formal-3-3-Cyclization-of-Trifluoromethyl-Enones"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":39,"journal-issue":{"issue":"31","published-online":{"date-parts":[[2026,7,27]]},"published-print":{"date-parts":[[2026,8,7]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.joc.6c01384","relation":{},"ISSN":["0022-3263","1520-6904"],"issn-type":[{"value":"0022-3263","type":"print"},{"value":"1520-6904","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]}}}