{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T22:08:31Z","timestamp":1782511711375,"version":"3.54.5"},"reference-count":68,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The substituted tetrahydrofuran core is a structural motif in many biologically active and natural compounds. However, the scarcity of enantioselective methods developed towards its synthesis makes this field challenging and attractive to explore. Herein, the first Br\u00f8nsted\u2010base catalyzed enantioselective (3+2) annulation of donor\u2010acceptor cyclopropanes with aldehydes and ketones affording enantioenriched 2,3,5\u2010substituted tetrahydrofurans is reported. The reaction concept is based on activation of racemic \u03b2\u2010cyclopropyl ketones by a chiral bifunctional Br\u00f8nsted base which catalyzes the (3+2) annulation for a range of aldehydes and ketones. For aldehydes, the annulation furnished tetrahydrofurans in excellent yield, good diastereoselectivity and with excellent enantioselectivity up to &gt;99\u2009% <jats:italic>ee<\/jats:italic>. Surprisingly, aromatic aldehydes afforded the <jats:italic>cis<\/jats:italic>\u20102,5\u2010substituted tetrahydrofurans as the major diastereoisomer, while for aliphatic aldehydes the <jats:italic>trans<\/jats:italic>\u2010cycloadduct was favored. The reaction also proceeds well for ketones affording spiro tetrahydrofurans in excellent yields and enantioselectivities (up to 99\u2009% <jats:italic>ee<\/jats:italic>). Hammett studies have been conducted to elucidate the influence of the electronic nature of benzaldehydes on the stereoselectivity. Based on the diastereochemical outcome for the aldehydes, two reaction paths for aromatic and aliphatic aldehydes are proposed. Finally, two diastereoselective synthetic transformations have been conducted to demonstrate the synthetic potential of the obtained products.<\/jats:p>","DOI":"10.1002\/anie.202410524","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T09:15:51Z","timestamp":1721034951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Enantioselective (3+2) Annulation of Donor\u2010Acceptor Cyclopropanes with Aldehydes and Ketones Catalyzed by Br\u00f8nsted Bases"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3723-6776","authenticated-orcid":false,"given":"Erlaitz B.","family":"Obreg\u00f3n","sequence":"first","affiliation":[{"name":"Department of Chemistry Aarhus University  8000 Aarhus C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7664-7423","authenticated-orcid":false,"given":"Louise G.","family":"Rost","sequence":"additional","affiliation":[{"name":"Department of Chemistry Aarhus University  8000 Aarhus C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8326-3882","authenticated-orcid":false,"given":"Ida R.","family":"Kocemba","sequence":"additional","affiliation":[{"name":"Department of Chemistry Aarhus University  8000 Aarhus C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8746-7273","authenticated-orcid":false,"given":"Anne","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Department of Chemistry Aarhus University  8000 Aarhus C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4908-5554","authenticated-orcid":false,"given":"David A.","family":"McLeod","sequence":"additional","affiliation":[{"name":"Department of Chemistry Aarhus University  8000 Aarhus C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3482-6236","authenticated-orcid":false,"given":"Karl Anker","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Department of Chemistry Aarhus University  8000 Aarhus C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"e_1_2_3_1_1","doi-asserted-by":"crossref","first-page":"3778","DOI":"10.3390\/molecules24203778","volume":"24","author":"Lu Q.","year":"2019","journal-title":"Molecules"},{"key":"e_1_2_3_2_1","unstructured":"\u00a0"},{"key":"e_1_2_3_3_2","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3390\/md20020120","volume":"20","author":"Fern\u00e1ndez-Pe\u00f1a L.","year":"2022","journal-title":"Mar. Drugs"},{"key":"e_1_2_3_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr3004778"},{"key":"e_1_2_3_5_1","unstructured":"\u00a0"},{"key":"e_1_2_3_6_2","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1002\/asia.202000753","volume":"15","author":"Fernandes R. A.","year":"2020","journal-title":"Chem. Asian J."},{"key":"e_1_2_3_7_2","doi-asserted-by":"publisher","DOI":"10.1039\/D0OB01542C"},{"key":"e_1_2_3_8_1","unstructured":"\u00a0"},{"key":"e_1_2_3_9_2","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.1039\/C4OB00423J","volume":"12","author":"Nasir N. M.","year":"2014","journal-title":"Org. Biomol. Chem."},{"key":"e_1_2_3_10_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3390\/md14040065","volume":"14","author":"Fuwa H.","year":"2016","journal-title":"Mar. Drugs"},{"key":"e_1_2_3_11_2","doi-asserted-by":"crossref","first-page":"6890","DOI":"10.1002\/ejoc.201901067","author":"Chavan L. N.","year":"2019","journal-title":"Eur. J. Org. Chem."},{"key":"e_1_2_3_12_1","doi-asserted-by":"crossref","first-page":"5003","DOI":"10.1016\/j.tet.2016.06.076","volume":"72","author":"Torre A.","year":"2016","journal-title":"Tetrahedron"},{"key":"e_1_2_3_13_1","unstructured":"\u00a0"},{"key":"e_1_2_3_14_2","doi-asserted-by":"crossref","first-page":"3283","DOI":"10.1021\/ol051058r","volume":"7","author":"Shin C.","year":"2005","journal-title":"Org. Lett."},{"key":"e_1_2_3_15_2","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1055\/s-1992-21280","author":"Kotsuki H.","year":"1992","journal-title":"Synlett"},{"key":"e_1_2_3_16_2","doi-asserted-by":"crossref","first-page":"14538","DOI":"10.1021\/jacs.6b09129","volume":"138","author":"Xie Y.","year":"2016","journal-title":"J. Am. Chem. Soc."},{"key":"e_1_2_3_17_1","unstructured":"\u00a0"},{"key":"e_1_2_3_18_2","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1021\/cs4002332","volume":"3","author":"Lu Y.","year":"2013","journal-title":"ACS Catal."},{"key":"e_1_2_3_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c03182"},{"key":"e_1_2_3_20_1","unstructured":"For a review with hydroalkoxylations with alkenes:"},{"key":"e_1_2_3_21_2","doi-asserted-by":"crossref","first-page":"12029","DOI":"10.1039\/C5DT00280J","volume":"44","author":"Rodriguez-Ruiz V.","year":"2015","journal-title":"Dalton Trans."},{"key":"e_1_2_3_22_2","doi-asserted-by":"crossref","first-page":"15024","DOI":"10.1021\/ja055659p","volume":"127","author":"F\u00fcrstner A.","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"e_1_2_3_23_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1021\/ja8072462","volume":"131","author":"Seo S.","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"e_1_2_3_24_1","unstructured":"\u00a0"},{"key":"e_1_2_3_25_2","doi-asserted-by":"crossref","first-page":"11439","DOI":"10.1002\/ange.201407013","volume":"126","author":"Khan A.","year":"2014","journal-title":"Angew. Chem."},{"key":"e_1_2_3_26_2","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1021\/acs.joc.5b02524","volume":"81","author":"Yuan X.","year":"2016","journal-title":"J. Org. Chem."},{"key":"e_1_2_3_27_2","doi-asserted-by":"crossref","first-page":"6716","DOI":"10.1021\/acs.orglett.2c02437","volume":"24","author":"Li M.","year":"2022","journal-title":"Org. Lett."},{"key":"e_1_2_3_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja201181g"},{"key":"e_1_2_3_29_1","unstructured":"\u00a0"},{"key":"e_1_2_3_30_2","doi-asserted-by":"crossref","first-page":"16014","DOI":"10.1021\/ja055777c","volume":"127","author":"Pohlhaus P. D.","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"e_1_2_3_31_2","doi-asserted-by":"crossref","first-page":"8642","DOI":"10.1021\/ja8015928","volume":"130","author":"Pohlhaus P. D.","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"e_1_2_3_32_2","doi-asserted-by":"crossref","DOI":"10.1002\/anie.202214390","volume":"62","author":"Ahlburg N. L.","year":"2023","journal-title":"Angew. Chem. Int. Ed."},{"key":"e_1_2_3_33_1","unstructured":"\u00a0"},{"key":"e_1_2_3_34_2","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.1021\/ja809873u","volume":"131","author":"Parsons A. T.","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"e_1_2_3_35_2","doi-asserted-by":"crossref","first-page":"6239","DOI":"10.1021\/ja5024578","volume":"136","author":"Nanteuil F.","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"e_1_2_3_36_1","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1002\/cjoc.202000277","volume":"38","author":"Zheng Z.-B.","year":"2020","journal-title":"Chin. J. Chem."},{"key":"e_1_2_3_37_1","unstructured":"\u00a0"},{"key":"e_1_2_3_38_2","doi-asserted-by":"crossref","first-page":"11831","DOI":"10.1002\/anie.201706150","volume":"56","author":"Blom J.","year":"2017","journal-title":"Angew. Chem. Int. Ed."},{"key":"e_1_2_3_39_2","doi-asserted-by":"crossref","DOI":"10.1002\/anie.202206096","volume":"61","author":"McLeod D. A.","year":"2022","journal-title":"Angew. Chem. Int. Ed."},{"key":"e_1_2_3_40_2","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1039\/D4QO00002A","volume":"11","author":"Li S.","year":"2024","journal-title":"Org. Chem. Front."},{"key":"e_1_2_3_41_1","unstructured":"For a review:"},{"key":"e_1_2_3_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201309886"},{"key":"e_1_2_3_43_2","doi-asserted-by":"crossref","DOI":"10.1016\/j.tchem.2023.100041","volume":"7","author":"Reyes E.","year":"2023","journal-title":"Tetrahedron Chem"},{"key":"e_1_2_3_44_2","doi-asserted-by":"crossref","DOI":"10.1016\/j.tet.2020.131760","volume":"82","author":"Apel C.","year":"2021","journal-title":"Tetrahedron"},{"key":"e_1_2_3_45_1","doi-asserted-by":"crossref","first-page":"7148","DOI":"10.1021\/ja00389a043","volume":"104","author":"Wang K. K.","year":"1982","journal-title":"J. Am. Chem. Soc."},{"key":"e_1_2_3_46_1","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1002\/anie.201812880","volume":"58","author":"Kreft A.","year":"2019","journal-title":"Angew. Chem. Int. Ed."},{"key":"e_1_2_3_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja036972z"},{"key":"e_1_2_3_48_1","unstructured":"For a discussion of \u03c0-\u03c0-interactions:"},{"key":"e_1_2_3_49_2","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1039\/c2sc20045g","volume":"3","author":"Martinez C. R.","year":"2012","journal-title":"Chem. Sci."},{"key":"e_1_2_3_50_2","doi-asserted-by":"crossref","first-page":"10854","DOI":"10.1021\/ja802849j","volume":"130","author":"Wheeler S. E.","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"e_1_2_3_51_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja202932e"},{"key":"e_1_2_3_52_1","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1246\/cl.171231","volume":"47","author":"Kawamoto T.","year":"2018","journal-title":"Chem. Lett."},{"key":"e_1_2_3_53_1","doi-asserted-by":"crossref","first-page":"3040","DOI":"10.1002\/adsc.201500487","volume":"357","author":"Zou L.-X.","year":"2015","journal-title":"Adv. Synth. Catal."},{"key":"e_1_2_3_54_1","doi-asserted-by":"crossref","first-page":"15593","DOI":"10.1021\/jacs.1c08615","volume":"143","author":"Jones B. T.","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"e_1_2_3_55_1","doi-asserted-by":"crossref","first-page":"11956","DOI":"10.1021\/jo401997v","volume":"78","author":"Xin X.","year":"2013","journal-title":"J. Org. Chem."},{"key":"e_1_2_3_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.0c03674"},{"key":"e_1_2_3_57_1","unstructured":"\u00a0"},{"key":"e_1_2_3_58_2","unstructured":"Gaussian 09 Revision C.01 M.\u2005J. Frisch G.\u2005W. Trucks H.\u2005B. Schlegel G.\u2005E. Scuseria M.\u2005A. Robb J.\u2005R. Cheeseman G. Scalmani V. Barone G.\u2005A. Petersson H. Nakatsuji X. Li M. Caricato A. Marenich J. Bloino B.\u2005G. Janesko R. Gomperts B. Mennucci H.\u2005P. Hratchian J.\u2005V. Ortiz A.\u2005F. Izmaylov J.\u2005L. Sonnenberg D. Williams-Young F. Ding F. Lipparini F. Egidi J. Goings B. Peng A. Petrone T. Henderson D. Ranasinghe V.\u2005G. Zakrzewski J. Gao N. Rega G. Zheng W. Liang M. Hada M. Ehara K. Toyota R. Fukuda J. Hasegawa M. Ishida T. Nakajima Y. Honda O. Kitao H. Nakai T. Vreven K. Throssell J.\u2005A. Montgomery Jr. J.\u2005E. Peralta F. Ogliaro M. Bearpark J.\u2005J. Heyd E. Brothers K.\u2005N. Kudin V.\u2005N. Staroverov T. Keith R. Kobayashi J. Normand K. Raghavachari A. Rendell J.\u2005C. Burant S.\u2005S. Iyengar J. Tomasi M. Cossi J.\u2005M. Millam M. Klene C. Adamo R. Cammi J.\u2005W. Ochterski R.\u2005L. Martin K. Morokuma O. Farkas J.\u2005B. Foresman D.\u2005J. Fox Gaussian Inc. Wallingford CT 2016;"},{"key":"e_1_2_3_59_2","unstructured":"Gaussian 16 Revision B.01 M.\u2005J. Frisch G.\u2005W. Trucks H.\u2005B. Schlegel G.\u2005E. Scuseria M.\u2005A. Robb J.\u2005R. Cheeseman G. Scalmani V. Barone G.\u2005A. Petersson H. Nakatsuji X. Li M. Caricato A.\u2005V. Marenich J. Bloino B.\u2005G. Janesko R. Gomperts B. Mennucci H.\u2005P. Hratchian J.\u2005V. Ortiz A.\u2005F. Izmaylov J.\u2005L. Sonnenberg D. Williams-Young F. Ding F. Lipparini F. Egidi J. Goings B. Peng A. Petrone T. Henderson D. Ranasinghe V.\u2005G. Zakrzewski J. Gao N. Rega G. Zheng W. Liang M. Hada M. Ehara K. Toyota R. Fukuda J. Hasegawa M. Ishida T. Nakajima Y. Honda O. Kitao H. Nakai T. Vreven K. Throssell J.\u2005A. Montgomery Jr. J.\u2005E. Peralta F. Ogliaro M.\u2005J. Bearpark J.\u2005J. Heyd E.\u2005N. Brothers K.\u2005N. Kudin V.\u2005N. Staroverov T.\u2005A. Keith R. Kobayashi J. Normand K. Raghavachari A.\u2005P. Rendell J.\u2005C. Burant S.\u2005S. Iyengar J. Tomasi M. Cossi J.\u2005M. Millam M. Klene C. Adamo R. Cammi J.\u2005W. Ochterski R.\u2005L. Martin K. Morokuma O. Farkas J.\u2005B. Foresman D.\u2005J. Fox Gaussian Inc. Wallingford CT 2016."},{"key":"e_1_2_3_60_1","unstructured":"Schr\u00f6dinger Release 2019\u20131: MacroModel Schr\u00f6dinger LLC New York NY 2019."},{"key":"e_1_2_3_61_1","unstructured":"Schr\u00f6dinger Release 2019\u20131: Maestro Schr\u00f6dinger LLC New York NY 2019."},{"key":"e_1_2_3_62_1","unstructured":"\u00a0"},{"key":"e_1_2_3_63_2","doi-asserted-by":"crossref","first-page":"6615","DOI":"10.1039\/b810189b","volume":"10","author":"Chai J.","year":"2008","journal-title":"Phys. Chem. Chem. Phys."},{"key":"e_1_2_3_64_2","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1021\/ct401026a","volume":"10","author":"Jensen F.","year":"2014","journal-title":"J. Chem. Theory Comput."},{"key":"e_1_2_3_65_2","doi-asserted-by":"crossref","first-page":"6378","DOI":"10.1021\/jp810292n","volume":"113","author":"Manerich A. V.","year":"2009","journal-title":"J. Phys. Chem. B"},{"key":"e_1_2_3_66_1","doi-asserted-by":"crossref","first-page":"9955","DOI":"10.1002\/chem.201200497","volume":"18","author":"Grimme S.","year":"2012","journal-title":"Chem. Eur. J."},{"key":"e_1_2_3_67_1","doi-asserted-by":"crossref","first-page":"6074","DOI":"10.1021\/jo060755+","volume":"71","author":"McCann D. M.","year":"2006","journal-title":"J. Org. Chem."},{"key":"e_1_2_3_68_1","unstructured":"CYLview 20; Legault C.\u2005Y. Universit\u00e9 de Sherbrooke 2020(http:\/\/www.cylview.org)."}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202410524","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T16:02:25Z","timestamp":1725552145000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202410524"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,5]]},"references-count":68,"alternative-id":["10.1002\/anie.202410524"],"URL":"https:\/\/doi.org\/10.1002\/anie.202410524","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,5]]},"assertion":[{"value":"2024-06-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202410524"}}