{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:14:17Z","timestamp":1788437657485,"version":"build-2803163510"},"reference-count":87,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["758710"],"award-info":[{"award-number":["758710"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201021\u2010CE07\u20100035\u201002"],"award-info":[{"award-number":["ANR\u201021\u2010CE07\u20100035\u201002"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201022\u2010CE92\u20100083"],"award-info":[{"award-number":["ANR\u201022\u2010CE92\u20100083"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018696","name":"R\u00e9gion Normandie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018696","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fluorinated (hetero)cyclic compounds have garnered attention over the years, offering key building blocks in medicinally relevant molecules. However, the synthesis of fluorinated tetrahydrofurans remains a synthetic challenge to reach. Herein, we developed an efficient and robust approach for the synthesis of\n                    <jats:italic>cis<\/jats:italic>\n                    \u2010(ethoxycarbonyl)difluoromethylated tetrahydrofurans. Using the inexpensive Pd\/C catalyst, the diastereoselective hydrogenation of functionalized CF\n                    <jats:sub>2<\/jats:sub>\n                    CO\n                    <jats:sub>2<\/jats:sub>\n                    Et\u2010containing furans was achieved under mild reaction conditions. Access to unprecedented\n                    <jats:italic>cis<\/jats:italic>\n                    \u2010fluorinated tetrahydrofurans with isolated yields of up to 74% and diastereomeric ratios up to 95:5 (12 examples) was reached. Pleasingly, under slightly modified reaction conditions, 5\u2010arylated CF\n                    <jats:sub>2<\/jats:sub>\n                    CO\n                    <jats:sub>2<\/jats:sub>\n                    Et\u2010containing furans were smoothly converted into the valuable \u03b1,\u03b1\u2010difluoro\u2010\u03b2\u2010hydroxyesters (five examples, up to 66% yield). Overall, the protocol exhibited good functional\u2010group tolerance and was easily scaled up. The synthetic utility of the CF\n                    <jats:sub>2<\/jats:sub>\n                    CO\n                    <jats:sub>2<\/jats:sub>\n                    Et moiety was further illustrated by its conversion into various other fluorinated groups.\n                  <\/jats:p>","DOI":"10.1002\/chem.71545","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:23:09Z","timestamp":1788434589000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Access to Uncharted (Ethoxy)difluoromethylated\u2010Containing Tetrahydrofurans by Hydrogenation"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4181-4310","authenticated-orcid":false,"given":"Thibaud","family":"Charvillat","sequence":"first","affiliation":[{"name":"INSA Rouen Normandie, Univ Rouen Normandie Univ Caen Normandie ENSICAEN, CNRS, Institut CARMeN (UMR 6064)  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Levet","sequence":"additional","affiliation":[{"name":"INSA Rouen Normandie, Univ Rouen Normandie Univ Caen Normandie ENSICAEN, CNRS, Institut CARMeN (UMR 6064)  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7969-7837","authenticated-orcid":false,"given":"Patrick","family":"Bernardelli","sequence":"additional","affiliation":[{"name":"Sanofi R&amp;D, 13 Quai Jules Guesde  Vitry\u2010sur\u2010Seine France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Daumas","sequence":"additional","affiliation":[{"name":"Responsable De C&amp;BD Science &amp; innovation, Sanofi\u2010Aventis R&amp;D  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5813-1482","authenticated-orcid":false,"given":"Hassan","family":"Oulyadi","sequence":"additional","affiliation":[{"name":"INSA Rouen Normandie, Univ Rouen Normandie Univ Caen Normandie ENSICAEN, CNRS, Institut CARMeN (UMR 6064)  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Sebban","sequence":"additional","affiliation":[{"name":"INSA Rouen Normandie, Univ Rouen Normandie Univ Caen Normandie ENSICAEN, CNRS, Institut CARMeN (UMR 6064)  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Ferey","sequence":"additional","affiliation":[{"name":"Sanofi Winthrop Industrie\/MSAT\/ Site d'Aramon, Route d'Avignon  Aramon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4877-5270","authenticated-orcid":false,"given":"Tatiana","family":"Besset","sequence":"additional","affiliation":[{"name":"INSA Rouen Normandie, Univ Rouen Normandie Univ Caen Normandie ENSICAEN, CNRS, Institut CARMeN (UMR 6064)  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022\u20101139(01)00375\u2010X"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","DOI":"10.1002\/9780470281895","volume-title":"Bioorganic and Medicinal Chemistry of Fluorine","author":"B\u00e9gu\u00e9 J.\u2010P.","year":"2008"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1039\/B711844A"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.5b00392"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr500706a"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6CS00351F"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43586\u2010021\u201000042\u20101"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.0c00830"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr4002879"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101467"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115476"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.4c00661"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.3c00199"},{"key":"e_1_2_7_15_1","first-page":"2345","article-title":"An Overview of the Uses of Per\u2010 and Polyfluoroalkyl Substances (PFAS)","volume":"22","author":"Gl\u00fcge J.","year":"2020","journal-title":"Environmental Science: Processes & Impacts"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1007\/s00044-023-03094-y","article-title":"Future Challenges and Opportunities With Fluorine in Drugs?","volume":"32","author":"O'Hagan D.","year":"2023","journal-title":"Medicinal Chemistry Research"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.0c00030"},{"key":"e_1_2_7_18_1","volume-title":"Emerging Fluorinated Motifs: Synthesis, Properties and Applications","author":"Besset T.","year":"2020"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CS00360G"},{"key":"e_1_2_7_20_1","doi-asserted-by":"crossref","first-page":"4549","DOI":"10.1055\/s-0039-1690027","article-title":"Recent Progress on the Synthesis of CF2H\u2010Containing Derivatives","volume":"51","author":"Levi N.","year":"2019","journal-title":"Synthesis"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201702311"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajoc.201600509"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201801121"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr500193b"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11426\u2010018\u20109402\u2010x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202201776"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/sym13122380"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202202939"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/17568919.2024.2359358"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00604"},{"key":"e_1_2_7_31_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.4155\/fmc-2019-0309","article-title":"Utilizing the CF2H Moiety as a H\u2010Bond\u2010Donating Group in Drug Discovery","volume":"12","author":"Saphier S.","year":"2020","journal-title":"Future Medicinal Chemistry"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol4009377"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022\u20101139(00)82523\u20103"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.201300140"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/17568919.2024.2379229"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202200365"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5OB00997A"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b00876"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24203778"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol802711s"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040\u20104039(02)00042\u20104"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo9810765"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rser.2014.07.003"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17030281"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202500662"},{"key":"e_1_2_7_46_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/B978-0-12-812733-9.00002-7","volume-title":"Fluorine in Life Sciences: Pharmaceuticals, Medicinal Diagnostics, and Agrochemicals, Progress in Fluorine Science Series","author":"M\u00fcller K.","year":"2019"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01788"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100029\u20101218753"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2015.04.080"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja071380s"},{"key":"e_1_2_7_51_1","doi-asserted-by":"crossref","DOI":"10.1002\/ejoc.202501086","article-title":"Synthesis and Physicochemical Characterization of 5\u2010Trifluoromethyl\u2010Substituted Tetrahydrofurans and Tetrahydrothiophenes","volume":"29","author":"Redka M. O.","year":"2025","journal-title":"European Journal of Organic Chemistry"},{"key":"e_1_2_7_52_1","unstructured":"Cost for 1\u00a0g USD 1133.00 Enamine as supplier."},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7CS00334J"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CS00736F"},{"key":"e_1_2_7_55_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1055\/s-0040-1705939","article-title":"Recent Developments in Transition\u2010Metal\u2010Catalyzed Asymmetric Hydrogenation of Enamides","volume":"53","author":"Ponra S.","year":"2021","journal-title":"Synthesis"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9CS00138G"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201814471"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.8b00262"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b10690"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.6b00564"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.5b00027"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201500937"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr400037u"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1OB02331D"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3CS00329A"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200453942"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201907457"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10593\u2010023\u201003210\u20101"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b09540"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202004674"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c02038"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41557\u2010025\u201002008\u20102"},{"key":"e_1_2_7_73_1","article-title":"Pd\/C\u2010Catalyzed Hydrogenation of CF3\u2010, CF2H\u2010, and CF2CO2Et\u2010Containing Pyridines: A Robust Method for Highly Functionalized Containing Piperidines","volume":"66","author":"Charvillat T.","year":"2026","journal-title":"Angewandte Chemie International Edition"},{"key":"e_1_2_7_74_1","unstructured":"S.Durrant \u201cSubstituted Tetrahydrofurans as Modulators of Sodium Channels \u201d WO 2021\/113627 A1 2021."},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfluchem.2003.12.015"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201400542"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/cjoc.201300411"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo5010907"},{"key":"e_1_2_7_79_1","unstructured":"See Supporting information for more details especially Figures S2 to S11."},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00329a001"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00271a077"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo301873y"},{"key":"e_1_2_7_83_1","first-page":"343","volume-title":"Fluorine\u2010Containing Amino Acids","author":"Kirk K. L.","year":"1995"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlac.1995199508196"},{"key":"e_1_2_7_85_1","unstructured":"Analysis of the crude reaction mixture by 19F NMR indicated the presence of only one detectable diastereomer. However the stereochemical assignment of this product could not be established unambiguously from the available data."},{"key":"e_1_2_7_86_1","doi-asserted-by":"crossref","first-page":"5256","DOI":"10.1002\/cctc.202001025","article-title":"Copper\u2010Catalyzed C\u2212H Difluoroalkylation of Coumarins With Fluoroalkyl Bromides","volume":"12","author":"Rao M.","year":"2020","journal-title":"ChemCatChem"},{"key":"e_1_2_7_87_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.200600209"},{"key":"e_1_2_7_88_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201400557"}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.71545","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/chem.71545","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.71545","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:23:14Z","timestamp":1788434594000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.71545"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":87,"alternative-id":["10.1002\/chem.71545"],"URL":"https:\/\/doi.org\/10.1002\/chem.71545","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"assertion":[{"value":"2026-06-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71545"}}