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The \u03b1-carbon of gem-difluoroalkenes is inherently electrophilic, which typically precludes their utility in nucleophilic assemblies. Herein, we report an umpolung strategy that utilizes low-valent Ni(0) as a \u03c0-Lewis base activator for gem-difluorodienes and leverages d \u2192 \u03c0* backdonation to effectively reverse their intrinsic electrophilicity, thereby enabling the addition to aldehydes and imines stereoselectively. Two distinct transformative pathways for the resultant difluoro \u03c0-allylnickel(II) species are developed: exclusively (Z)-defined defluorination and reductive coupling, finally furnishing chiral fluoroalkenyl and gem-difluoro homoallylic derivatives, respectively. In addition, stereodivergent control over vicinal fluorine-containing stereocenters is achievable under the identical catalysis, by simply using geometric isomers of 1-fluorodienes. The current Ni(0)-based umpolung paradigm of fluorodienes establishes a powerful framework for constructing structurally diverse and enantioenriched fluorinated compounds with pharmaceutical significance.<\/jats:p>","DOI":"10.1021\/jacs.6c17168","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:01:45Z","timestamp":1792069305000},"page":"46287-46297","source":"Crossref","is-referenced-by-count":0,"title":["Construction of Divergent\nEnantioenriched 3D-Fluoro\nScaffolds via Ni(0) \u03c0-Lewis Base-Mediated Umpolung of\nFluorodienes"],"prefix":"10.1021","volume":"148","author":[{"given":"Shun-Zhong","family":"Tan","sequence":"first","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan-Xu","family":"Chen","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang-Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1161-5102","authenticated-orcid":true,"given":"Qin","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Army Medical University , , Shapingba, ,","place":["Chongqing, China, 400038"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4162-1471","authenticated-orcid":true,"given":"Wei","family":"Du","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1902-0979","authenticated-orcid":true,"given":"Ying-Chun","family":"Chen","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610041"]},{"name":"Frontiers Medical Center , , ,","place":["Chengdu, China, 610213"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"2026102809075519500_cit1a","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1126\/science.1131943","article-title":"Fluorine in\nPharmaceuticals: Looking Beyond Intuition","volume":"317","author":"Mu\u0308ller","year":"2007","journal-title":"Science"},{"key":"2026102809075519500_cit1b","doi-asserted-by":"publisher","first-page":"2432","DOI":"10.1021\/cr4002879","article-title":"Fluorine in Pharmaceutical Industry: Fluorine-Containing Drugs Introduced\nto the Market in the Last Decade (2001\u20132011)","volume":"114","author":"Wang","year":"2014","journal-title":"Chem. 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