{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:31:31Z","timestamp":1793345491058,"version":"4.5.0"},"reference-count":66,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T00:00:00Z","timestamp":1793232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T00:00:00Z","timestamp":1793232000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22525104"],"award-info":[{"award-number":["22525104"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22461160280"],"award-info":[{"award-number":["22461160280"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22371141"],"award-info":[{"award-number":["22371141"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22221002"],"award-info":[{"award-number":["22221002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    C\u2500H monofluoroalkylation of pyridines is a highly desirable transformation in medicinal chemistry because the monofluoroalkyl group is known to impart favorable properties to drug candidates, and pyridine rings are prevalent in drug molecules. However, only a few methods have been reported, and they are limited to\n                    <jats:italic>ortho<\/jats:italic>\n                    \u2010selective reactions. Herein, we report an unprecedented method for\n                    <jats:italic>meta<\/jats:italic>\n                    \u2010selective C\u2500H monofluoroalkylation of pyridines via reactions between difluoroalkyl radicals and dihydropyridines generated in situ. During the reactions, a defluorination\/olefin isomerization cascade converts initially formed difluoroalkylated dihydropyridines to monofluoroalkylated pyridines. The method accommodates a broad range of pyridine substrates, as well as other\n                    <jats:italic>N<\/jats:italic>\n                    \u2010heteroarenes and fluoroalkylating reagents, and shows promise for late\u2010stage functionalization of pyridine\u2010containing drugs.\n                  <\/jats:p>","DOI":"10.1002\/anie.1059611","type":"journal-article","created":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T06:44:37Z","timestamp":1793342677000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Meta<\/i>\n                    \u2010Selective C\u2500H Monofluoroalkylation of Pyridines With Difluoroalkyl Radicals"],"prefix":"10.1002","author":[{"given":"Ming","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Haihe Laboratory of Sustainable Chemical Transformations Frontiers Science Center for New Organic Matter Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Haihe Laboratory of Sustainable Chemical Transformations Frontiers Science Center for New Organic Matter Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Chang","sequence":"additional","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Haihe Laboratory of Sustainable Chemical Transformations Frontiers Science Center for New Organic Matter Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng\u2010Shi","family":"Hao","sequence":"additional","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Haihe Laboratory of Sustainable Chemical Transformations Frontiers Science Center for New Organic Matter Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2463-8030","authenticated-orcid":false,"given":"Zhu\u2010Jun","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Haihe Laboratory of Sustainable Chemical Transformations Frontiers Science Center for New Organic Matter Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3907-2530","authenticated-orcid":false,"given":"Jian\u2010Hua","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Haihe Laboratory of Sustainable Chemical Transformations Frontiers Science Center for New Organic Matter Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5863-0804","authenticated-orcid":false,"given":"Xiao\u2010Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Haihe Laboratory of Sustainable Chemical Transformations Frontiers Science Center for New Organic Matter Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1131943"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/c0cs00221f"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1021\/cr4002879","article-title":"Fluorine in Pharmaceutical Industry: Fluorine\u2010Containing Drugs Introduced to the Market in the Last Decade (2001\u22122011)","volume":"114","author":"Wang J.","year":"2014","journal-title":"Chemical Reviews"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.5b00392"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2020.101467","article-title":"Current Contributions of Organofluorine Compounds to the Agrochemical Industry","volume":"23","author":"Ogawa Y.","year":"2020","journal-title":"iScience"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3390\/molecules31030419","article-title":"The Pharmaceutical Industry in 2025: An Analysis of FDA Drug Approvals From the Perspective of Molecules","volume":"31","author":"Torre B. G.","year":"2026","journal-title":"Molecules"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202112251"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/B610213C"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1002\/chem.202003135","article-title":"The Role of Fluorine in Glycomimetic Drug Design","volume":"27","author":"Hevey R.","year":"2021","journal-title":"Chemistry \u2013 A European Journal"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202518500"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43586\u2010021\u201000042\u20101"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202009995"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c00190"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c01824"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar700149s"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cjoc.202400672"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.5c00177"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201412026"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201502882"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202102481"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102399\u20101"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202507632"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm501100b"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01786"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S329547"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c01122"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol3029737"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b09580"},{"key":"e_1_2_8_30_1","doi-asserted-by":"crossref","first-page":"2886","DOI":"10.1055\/s-0036-1588516","article-title":"Copper\u2010Mediated Synthesis of Monofluoro Aryl Acetates via Decarboxylative Cross\u2010Coupling","volume":"28","author":"Fahandej\u2010Sadi A.","year":"2017","journal-title":"Synlett"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9CC03737C"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.0c00789"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11680"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CC06466E"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfluchem.2020.109695"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202302941"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.2c00881"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c00962"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c06776"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202216894"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c13428"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade6029"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201048383\u20101"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c11759"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202423512"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c16051"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.31635\/ccschem.025.202506064"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6c02798"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.add8980"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007474\u20101"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c03091"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja076498n"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja209510q"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja412563e"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b03138"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c01631"},{"key":"e_1_2_8_57_1","doi-asserted-by":"crossref","first-page":"11016","DOI":"10.1002\/chem.201301158","article-title":"Tuning the Lewis Acidity of Boranes in Frustrated Lewis Pair Chemistry: Implications for the Hydrogenation of Electron\u2010Poor Alkenes","volume":"19","author":"Nicasio J. A.","year":"2013","journal-title":"Chemistry \u2013 A European Journal"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00238a031"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja8038823"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1039\/P19770001365"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr500465n"},{"key":"e_1_2_8_62_1","doi-asserted-by":"crossref","first-page":"10076","DOI":"10.1002\/anie.201305028","article-title":"Catalytic 1,4\u2010Selective Hydrosilylation of Pyridines and Benzannulated Congeners","volume":"52","author":"K\u00f6nigs C. D. F.","year":"2013","journal-title":"Angewandte Chemie International Edition"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.organomet.4c00224"},{"key":"e_1_2_8_64_1","unstructured":"Deposition numbers 2559107 (3pp) and 2559108 (13) contain the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures Service."},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201409617"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202301168"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44160\u2010025\u201000745\u20103"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.1059611","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.1059611","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.1059611","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T06:44:40Z","timestamp":1793342680000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.1059611"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,29]]},"references-count":66,"alternative-id":["10.1002\/anie.1059611"],"URL":"https:\/\/doi.org\/10.1002\/anie.1059611","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,29]]},"assertion":[{"value":"2026-09-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1059611"}}