{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T03:51:40Z","timestamp":1791604300340,"version":"4.3.4"},"reference-count":68,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001703","name":"\u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001703","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["SNSF 200021\u2013219764"],"award-info":[{"award-number":["SNSF 200021\u2013219764"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Medium\u2010sized rings and macrocycles constitute a privileged class of scaffolds in medicinal chemistry, providing unique access to challenging biological targets through their preorganized, semi\u2010rigid architectures. However, their synthesis remains challenging due to the unfavorable kinetic and thermodynamic constraints during ring closure. Herein, we report the efficient cyclization of \u03c9\u2010isocyano aldehydes via Passerini and Ugi multicomponent reactions (MCRs), alongside related variants. These transformations provide rapid access to structurally diverse medium\u2010sized and macrocyclic \u03b1\u2010acyloxy, \u03b1\u2010hydroxy, \u03b1\u2010acetamido, and \u03b1\u2010keto lactams, as well as tetrazole\u2010fused macrocycles, under mild conditions. Notably, this macrocyclization strategy relies on C(sp\n                    <jats:sup>3<\/jats:sup>\n                    )\u2500C(sp\n                    <jats:sup>2<\/jats:sup>\n                    ) bond formation while simultaneously generating \u03b1\u2010functionalized amide motifs. By avoiding the need to pre\u2010synthesize \u03b1\u2010functionalized carboxylic acids, this approach offers a complementary alternative to traditional macrolactamization.\n                  <\/jats:p>","DOI":"10.1002\/anie.6516584","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T03:03:38Z","timestamp":1791601418000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrocyclization of \u03c9\u2010Isocyano Aldehydes"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0045-4529","authenticated-orcid":false,"given":"Baochao","family":"Yang","sequence":"first","affiliation":[{"name":"Laboratory of Synthesis and Natural Products (LSPN) Institute of Chemical Sciences and Engineering Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne  Lausanne Switzerland"},{"name":"Shanghai Key Laboratory of Green Chemistry and Chemical Processes School of Chemistry and Molecular Engineering East China Normal University  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teerawat","family":"Songsichan","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis and Natural Products (LSPN) Institute of Chemical Sciences and Engineering Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6062-7137","authenticated-orcid":false,"given":"Cyril","family":"Piemontesi","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis and Natural Products (LSPN) Institute of Chemical Sciences and Engineering Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis and Natural Products (LSPN) Institute of Chemical Sciences and Engineering Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8390-6689","authenticated-orcid":false,"given":"Jieping","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis and Natural Products (LSPN) Institute of Chemical Sciences and Engineering Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c01163"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CB00154J"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21639"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm1012374"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b13178"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.12.75"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm400887j"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.200400751"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.1062"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.0c00759"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.5b00056"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3CS01066J"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10702"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202317981"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aec8992"},{"key":"e_1_2_8_17_1","first-page":"1","article-title":"The Passerini Reaction","volume":"65","author":"Banfi L.","year":"2005","journal-title":"Organic Reactions"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1SC03810A"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3773(20000915)39:18<3168::AID-ANIE3168>3.0.CO;2-U"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2008.12.002"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3762\/bjoc.10.50"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.201201660"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6CS00444J"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.200390167"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr0505728"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1QO00313E"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr8003407"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/7081_2010_47"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1139\/v79-533"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol702521g"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.5b00858"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201704426"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja910544p"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5SC01958C"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2636"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.5b02419"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.6b01430"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7OB00459A"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2011.10.050"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201402428"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.c16-00182"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b07846"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202419383"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.7b02319"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200390216"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja060720r"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo7022125"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja809005k"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.3762\/bjoc.10.101"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00250a050"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00175a045"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr00021a007"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1039\/c39940001003"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo9718253"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)01287-4"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00042a053"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo00073a010"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.199417291"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00109a006"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200802005"},{"key":"e_1_2_8_61_1","unstructured":"Deposition numbers CCDC 1904494 (for5f) and CCDC 1904495 (for9b) contain the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service."},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3773(20000616)39:12<2054::AID-ANIE2054>3.0.CO;2-Z"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo00331a017"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr950025u"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200704840"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo100302y"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5RA11531K"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1021\/np010042g"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1080\/10286020500246741"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.6516584","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.6516584","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.6516584","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T03:03:46Z","timestamp":1791601426000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.6516584"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":68,"alternative-id":["10.1002\/anie.6516584"],"URL":"https:\/\/doi.org\/10.1002\/anie.6516584","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]},"assertion":[{"value":"2026-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e6516584"}}