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Here, however, we show that fsDVKs bearing only electronically neutral alkyl or aryl groups actually undergo facile NC due to steric crowding in the pentadienyl cation intermediate, which raises its energy and reduces the barrier height to cyclization. Strongly ionizing and suitably bulky acid moieties further increase the energy of this intermediate cation, favoring cyclization. These features enable NCs of fsDVKs to be employed in the ready construction of multiple contiguous all\u2010carbon quaternary stereocenters under mild conditions, in the absence of electronically activating groups.<\/jats:p>","DOI":"10.1002\/chem.202402779","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T10:35:53Z","timestamp":1728902153000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Steric Activation in the Nazarov Cyclization of Fully Substituted Divinyl Ketones"],"prefix":"10.1002","volume":"30","author":[{"given":"Shuqi","family":"Chen","sequence":"first","affiliation":[{"name":"Medicinal Chemistry Monash Institute of Pharmaceutical Sciences Monash University  381 Royal Parade Parkville, Victoria 3052 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angus B.","family":"Keto","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences The University of Queensland  Brisbane, Queensland 4072 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad","family":"El\u2010Hawli","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Monash Institute of Pharmaceutical Sciences Monash University  381 Royal Parade Parkville, Victoria 3052 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence R.","family":"Gahan","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences The University of Queensland  Brisbane, Queensland 4072 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan M.","family":"White","sequence":"additional","affiliation":[{"name":"School of Chemistry Bio21 Institute University of Melbourne  Parkville, Victoria 3010 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth H.","family":"Krenske","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences The University of Queensland  Brisbane, Queensland 4072 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4410-2423","authenticated-orcid":false,"given":"Bernard L.","family":"Flynn","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Monash Institute of Pharmaceutical Sciences Monash University  381 Royal Parade Parkville, Victoria 3052 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"e_1_2_3_1_1","unstructured":"For reviews on bioactive cyclopentyl scaffolds see:"},{"key":"e_1_2_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.200801229"},{"key":"e_1_2_3_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/13852728113176660150"},{"key":"e_1_2_3_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/138527209788921738"},{"key":"e_1_2_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.1788"},{"key":"e_1_2_3_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr900169j"},{"key":"e_1_2_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2023.133747"},{"key":"e_1_2_3_8_1","unstructured":"For reviews on sp3-rich scaffolds in drug discovery"},{"key":"e_1_2_3_9_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1SC00161B"},{"key":"e_1_2_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2016.04.023"},{"key":"e_1_2_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2021.05.001"},{"key":"e_1_2_3_12_2","doi-asserted-by":"publisher","DOI":"10.1039\/C9CC09796A"},{"key":"e_1_2_3_13_2","doi-asserted-by":"publisher","DOI":"10.1039\/c2md20347b"},{"key":"e_1_2_3_14_2","doi-asserted-by":"publisher","DOI":"10.1039\/D3OB00351E"},{"key":"e_1_2_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40362-013-0014-7"},{"key":"e_1_2_3_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00829"},{"key":"e_1_2_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2020.07.017"},{"key":"e_1_2_3_18_1","unstructured":"For reviews on the Nazarov cyclization:"},{"key":"e_1_2_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2005.04.014"},{"key":"e_1_2_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/cctc.201100137"},{"key":"e_1_2_3_21_2","doi-asserted-by":"crossref","unstructured":"F.\u2005G. 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