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Despite this potential, current benzene bioisosteres based on bicyclo[n.1.1]alkanes are confined to three\u2010dimensional scaffolds with fixed exit vectors at their rigid bridgehead positions. As a critical piece for mimicking substituted arenes, the development of C(sp\n                    <jats:sup>3<\/jats:sup>\n                    )\u2010enriched bioisosteres bearing two flexible vectors has been thwarted by the lack of stereoselective synthetic routes. Herein, we report a photochemical nickel\u2010catalyzed selective 1,7\u2010difunctionalization of tricyclo[4.1.0.0\n                    <jats:sup>2,7<\/jats:sup>\n                    ]heptane using readily available organohalides. This sequential protocol generates previously elusive\n                    <jats:italic>anti<\/jats:italic>\n                    \u2010stereoselective 6,7\u2010difunctionalized bicyclo[3.1.1]heptanes with high stereocontrol, broad coupling\u2010partner scope, and built\u2010in handles for post\u2010functionalization. Biological assays and computational modeling on drug analogues demonstrate the bioisosteric potential of these dual\u2010flexible\u2010vector bicyclo[3.1.1]heptane scaffolds. This methodology unlocks previously unexplored chemical space with broad implications for drug discovery and beyond.\n                  <\/jats:p>","DOI":"10.1002\/anie.9614011","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:23:18Z","timestamp":1792070598000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modular Synthesis of Bridge\u2010Disubstituted Bicyclo[3.1.1]heptanes via Stereoselective Difunctionalization of Tricyclo[4.1.0.0\n                    <sup>2<\/sup>\n                    <sup>,<\/sup>\n                    <sup>7<\/sup>\n                    ]heptane"],"prefix":"10.1002","author":[{"given":"Zhenda","family":"Fu","sequence":"first","affiliation":[{"name":"Institute of Frontier Chemistry School of Chemistry and Chemical Engineering Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Frontier Chemistry School of Chemistry and Chemical Engineering Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Gu","sequence":"additional","affiliation":[{"name":"Institute of Frontier Chemistry School of Chemistry and Chemical Engineering Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3014-6719","authenticated-orcid":false,"given":"Xueping","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Frontier Chemistry School of Chemistry and Chemical Engineering Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzi","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Chemical Research of Catalonia (ICIQ)  Tarragona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3671-5951","authenticated-orcid":false,"given":"Wei\u2010Qiao","family":"Deng","sequence":"additional","affiliation":[{"name":"Institute of Frontier Chemistry School of Chemistry and Chemical Engineering Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1153-1558","authenticated-orcid":false,"given":"Xingwei","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Frontier Chemistry School of Chemistry and Chemical Engineering Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9156-8774","authenticated-orcid":false,"given":"Songjie","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Frontier Chemistry School of Chemistry and Chemical Engineering Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm901241e"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570\u2010025\u201000688\u20105"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201603951"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c08206"},{"key":"e_1_2_8_6_1","first-page":"1539","article-title":"Conquering the Synthesis and Functionalization of Bicyclo[1.1.1]Pentanes","volume":"3","author":"Shire B. 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