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Distinct from previous activation modes, this transformation proceeds under purely thermal conditions and does not require external irradiation or photoredox catalysis. Readily accessible nicotinic acid derivatives undergo efficient intramolecular [4 + 2] cycloaddition to furnish polyfused aza-bicyclo[2.2.2]octane frameworks with high levels of enantiocontrol. This work addresses the longstanding challenge associated with the functionalization of monocyclic pyridines and represents the first example of an asymmetric [4 + 2]-cycloaddition-based dearomatization of pyridines.<\/jats:p>","DOI":"10.1021\/acs.orglett.6c03541","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:01:44Z","timestamp":1789455704000},"page":"12022-12026","source":"Crossref","is-referenced-by-count":0,"title":["Direct Pyridine\nDearomatization via Organocatalytic\nEnantioselective [4 + 2] Cycloaddition Accessing Polyfused Aza-[2.2.2]\nScaffolds"],"prefix":"10.1021","volume":"28","author":[{"given":"Shuo","family":"Ma","sequence":"first","affiliation":[{"name":"Ocean University of China , , ,","place":["Qingdao, China, 266003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Li","sequence":"additional","affiliation":[{"name":"Ocean University of China , , ,","place":["Qingdao, China, 266003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Ocean University of China , , ,","place":["Qingdao, China, 266003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Chun","family":"Han","sequence":"additional","affiliation":[{"name":"Southern University of Science and Technology , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6571-5915","authenticated-orcid":true,"given":"Haiyong","family":"Yu","sequence":"additional","affiliation":[{"name":"Ocean University of China , , ,","place":["Qingdao, China, 266003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5868-4407","authenticated-orcid":true,"given":"Tao","family":"Xu","sequence":"additional","affiliation":[{"name":"Ocean University of China , , ,","place":["Qingdao, China, 266003"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"2026092510101944400_cit1a","doi-asserted-by":"publisher","first-page":"5671","DOI":"10.1039\/D3OB00799E","article-title":"C\u2013H functionalization of pyridines","volume":"21","author":"Maity","year":"2023","journal-title":"Org. 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