{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:35:56Z","timestamp":1792204556016,"version":"4.4.0"},"reference-count":89,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21H01933"],"award-info":[{"award-number":["21H01933"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2022,6,13]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>gem<\/jats:italic>\u2010Difluoromethylene moieties are attractive in medicinal chemistry due to their ability to mimic other more ubiquitous functional groups. Thus, effective asymmetric methods for their construction are highly desirable, especially for the industrial production of chiral drugs. Using a Pd\u2010catalyzed asymmetric [4+2] cycloaddition between substituted\u20102\u2010alkylidenetrimethylene carbonates and <jats:italic>gem<\/jats:italic>\u2010difluoroalkyl ketones, we were able to easily access chiral 1,3\u2010dioxanes that contain a tetrasubstituted difluoroalkyl stereogenic center in cyclic and acyclic skeletons. A novel phosphoramidite ligand, which contains a bulky 1,1\u2010dinaphthylmethanamino moiety, was developed to provide the products in high yield with excellent enantio\u2010, diastereo\u2010, and regioselectivity. Strikingly, the <jats:italic>gem<\/jats:italic>\u2010difluoro substitution pattern promotes the reaction, and pentafluoroethylketone, an \u03b1,\u03b1\u2010difluorinated \u03b2\u2010ketoester, and a \u03b2\u2010ketosulfone are suitable substrates for this method.<\/jats:p>","DOI":"10.1002\/anie.202117635","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T13:38:39Z","timestamp":1648474719000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Enantio\u2010, Diastereo\u2010 and Regioselective Synthesis of Chiral Cyclic and Acyclic <i>gem<\/i>\u2010Difluoromethylenes by Palladium\u2010Catalyzed [4+2] Cycloaddition"],"prefix":"10.1002","volume":"61","author":[{"given":"Hiroto","family":"Uno","sequence":"first","affiliation":[{"name":"Department of Nanopharmaceutical Sciences &amp; Department of Life Science and Applied Chemistry Nagoya Institute of Technology  Gokiso, Showa-ku, Nagoya 466-8555 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koki","family":"Kawai","sequence":"additional","affiliation":[{"name":"Department of Nanopharmaceutical Sciences &amp; Department of Life Science and Applied Chemistry Nagoya Institute of Technology  Gokiso, Showa-ku, Nagoya 466-8555 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taichi","family":"Araki","sequence":"additional","affiliation":[{"name":"Department of Nanopharmaceutical Sciences &amp; Department of Life Science and Applied Chemistry Nagoya Institute of Technology  Gokiso, Showa-ku, Nagoya 466-8555 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoo","family":"Shiro","sequence":"additional","affiliation":[{"name":"Rigaku Corporation  3-9-12, Matsubara-cho Akishima-shi, Tokyo 196-8666 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3742-4064","authenticated-orcid":false,"given":"Norio","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Nanopharmaceutical Sciences &amp; Department of Life Science and Applied Chemistry Nagoya Institute of Technology  Gokiso, Showa-ku, Nagoya 466-8555 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,13]]},"reference":[{"key":"e_1_2_7_1_1","unstructured":"\u00a0"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1039\/B610213C"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr4002879"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00258"},{"key":"e_1_2_7_5_1","unstructured":"\u00a0"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cclet.2020.03.050"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01877"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.0c00830"},{"key":"e_1_2_7_9_1","unstructured":"\u00a0"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr1004293"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfluchem.2014.06.026"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr500368h"},{"key":"e_1_2_7_13_1","unstructured":"\u00a0"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr500277b"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.8b00230"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1QO00032B"},{"key":"e_1_2_7_17_1","unstructured":"\u00a0"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm1013693"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01788"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01540-1"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07525-y"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11758-w"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14254-3"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19387-4"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23504-2"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24596-6"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00528.2003"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2014.05.068"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002800050764"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1517\/14796694.1.1.7"},{"key":"e_1_2_7_31_1","unstructured":"\u00a0"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.3762\/bjoc.4.21"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201303551"},{"key":"e_1_2_7_33_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201303551"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajoc.201200131"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00778"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2019.09.012"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202111376"},{"key":"e_1_2_7_37_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202111376"},{"key":"e_1_2_7_38_1","unstructured":"\u00a0"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201501747"},{"key":"e_1_2_7_39_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201501747"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf8078"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.7b03826"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c02331"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.0c03406"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26667-0"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00197a060"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja0753389"},{"key":"e_1_2_7_47_1","unstructured":"\u00a0"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)89261-8"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo990430b"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja073997f"},{"key":"e_1_2_7_51_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja801742h"},{"key":"e_1_2_7_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201407013"},{"key":"e_1_2_7_52_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201407013"},{"key":"e_1_2_7_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202005313"},{"key":"e_1_2_7_53_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202005313"},{"key":"e_1_2_7_54_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c08348"},{"key":"e_1_2_7_55_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c11504"},{"key":"e_1_2_7_56_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1QO00273B"},{"key":"e_1_2_7_57_1","unstructured":"\u00a0"},{"key":"e_1_2_7_58_2","doi-asserted-by":"publisher","DOI":"10.1246\/bcsj.20120171"},{"key":"e_1_2_7_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2018.02.081"},{"key":"e_1_2_7_60_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.0c00152"},{"key":"e_1_2_7_61_2","doi-asserted-by":"publisher","DOI":"10.1039\/D0OB00458H"},{"key":"e_1_2_7_62_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.0c00160"},{"key":"e_1_2_7_63_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1OB00259G"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1039\/c0cc05308b"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.1c00420"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202002765"},{"key":"e_1_2_7_66_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202002765"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2021.04.037"},{"key":"e_1_2_7_68_1","unstructured":"\u00a0"},{"key":"e_1_2_7_69_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201300616"},{"key":"e_1_2_7_69_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201300616"},{"key":"e_1_2_7_70_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201807308"},{"key":"e_1_2_7_70_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201807308"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.0c03927"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c00790"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9OB01598A"},{"key":"e_1_2_7_74_1","unstructured":"Deposition Number2123342contains the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum KarlsruheAccess Structures service."},{"key":"e_1_2_7_75_1","unstructured":"Deposition Number2123343contains the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum KarlsruheAccess Structures service."},{"key":"e_1_2_7_76_1","unstructured":"Deposition Number2130769contains the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum KarlsruheAccess Structures service."},{"key":"e_1_2_7_77_1","unstructured":"\u00a0"},{"key":"e_1_2_7_78_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201403754"},{"key":"e_1_2_7_78_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201403754"},{"key":"e_1_2_7_79_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.8b03665"},{"key":"e_1_2_7_80_1","unstructured":"Deposition Number2123344contains the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum KarlsruheAccess Structures service."}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202117635","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.202117635","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202117635","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T00:47:28Z","timestamp":1692751648000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202117635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,13]]},"references-count":89,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2022,6,13]]}},"alternative-id":["10.1002\/anie.202117635"],"URL":"https:\/\/doi.org\/10.1002\/anie.202117635","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,13]]},"assertion":[{"value":"2021-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202117635"}}