{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:11:20Z","timestamp":1789067480359,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P32607"],"award-info":[{"award-number":["P32607"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P37182"],"award-info":[{"award-number":["P37182"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["CoG 682002"],"award-info":[{"award-number":["CoG 682002"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2024,5,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The nature of protecting group chemistry necessitates a deprotection step to restore the initially blocked functionality prior to further transformation. As this aspect of protecting group manipulation inevitably adds to the step count of any synthetic sequence, the development of methods enabling simultaneous deprotection and functionalization (\u201cdeprotective functionalization\u201d\u2014distinct from \u201cdeprotection followed by functionalization\u201d) is appealing, as it has the potential to improve efficiency and streamline synthetic routes. Herein, we report a deprotective functionalization of the newly introduced Nms\u2010amides guided by density functional theory (DFT) analysis, which exploits the inherent Nms reactivity. Mechanistic studies further substantiate and help rationalize the exquisite reactivity of Nms\u2010amides, as other commonly used protecting groups are shown not to exhibit the same reactivity patterns. The practicality of this approach was ultimately demonstrated in selected case studies.<\/jats:p>","DOI":"10.1002\/anie.202318304","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T09:11:31Z","timestamp":1710839491000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Deprotective Functionalization: A Direct Conversion of Nms\u2010Amides to Carboxamides Using Carboxylic Acids"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2674-0165","authenticated-orcid":false,"given":"Philipp","family":"Spie\u00df","sequence":"first","affiliation":[{"name":"Institute of Organic Chemistry University of Vienna  W\u00e4hringerstra\u00dfe 38 1090 Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Brze\u015bkiewicz","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry University of Vienna  W\u00e4hringerstra\u00dfe 38 1090 Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Meyrelles","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry University of Vienna  W\u00e4hringerstra\u00dfe 38 1090 Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Just","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry University of Vienna  W\u00e4hringerstra\u00dfe 38 1090 Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3643-0718","authenticated-orcid":false,"given":"Nuno","family":"Maulide","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry University of Vienna  W\u00e4hringerstra\u00dfe 38 1090 Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,19]]},"reference":[{"key":"e_1_2_3_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/9783527828166.ch11"},{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo501924u"},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.216"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja305261h"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01409"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c09637"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b03404"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja0177049"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo1006812"},{"key":"e_1_2_3_10_1","doi-asserted-by":"crossref","unstructured":"P. G. M. Wuts T. W. Greene InGreene's Protective Groups in Organic Synthesis John Wiley & Sons Inc. Hoboken NJ USA 2006 pp. 696\u2013926.","DOI":"10.1002\/0470053488"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/b311203a"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo049862z"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c06636"},{"key":"e_1_2_3_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202301312"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.3c00299"},{"key":"e_1_2_3_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr100048w"},{"key":"e_1_2_3_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.202301018"},{"key":"e_1_2_3_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10702"},{"key":"e_1_2_3_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202112668"},{"key":"e_1_2_3_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201402147"},{"key":"e_1_2_3_21_1","unstructured":"For a proposed mechanism of this reaction see the Supporting Information."},{"key":"e_1_2_3_22_1","unstructured":"In the Supporting Information a number of different tested examples is shown. It has been shown that tertiary sulfonamides react very sluggishly (130\u2009\u00b0C or higher) and do not produce ureas."},{"key":"e_1_2_3_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/00397919508011779"},{"key":"e_1_2_3_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(98)00017-3"},{"key":"e_1_2_3_25_1","unstructured":"This concept has been further applied in more specialized contexts such as peptide- and glycochemistry enabling the mild and selective construction of new peptide bonds using thioacids."},{"key":"e_1_2_3_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol701583t"},{"key":"e_1_2_3_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.9b00688"},{"key":"e_1_2_3_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo900532e"},{"key":"e_1_2_3_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200903050"},{"key":"e_1_2_3_30_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8OB00512E"},{"key":"e_1_2_3_31_1","unstructured":"Lower yields are reported with benzylic and secondary amines (30\u201350\u2009%). See the following references for some examples:"},{"key":"e_1_2_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.04.048"},{"key":"e_1_2_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2013.04.063"},{"key":"e_1_2_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(97)01334-8"},{"key":"e_1_2_3_35_1","doi-asserted-by":"publisher","DOI":"10.1039\/b810189b"},{"key":"e_1_2_3_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/b515623h"},{"key":"e_1_2_3_37_1","doi-asserted-by":"publisher","DOI":"10.1039\/b508541a"},{"key":"e_1_2_3_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar1000956"},{"key":"e_1_2_3_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41557-018-0079-7"},{"key":"e_1_2_3_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b12911"},{"key":"e_1_2_3_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201809606"},{"key":"e_1_2_3_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-3897(199902)341:2<186::AID-PRAC186>3.0.CO;2-6"},{"key":"e_1_2_3_43_1","unstructured":"Since9\u2009iconsists of 4 rotamers this was demonstrated by preparing an authentic sample of9\u2009iusing classical amide coupling. See the Supporting Information for more details."},{"key":"e_1_2_3_44_1","unstructured":"Increasing the reaction temperature to 100\u2009\u00b0C was necessary to ensure complete conversion of the starting sulfonamide."},{"key":"e_1_2_3_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.2c01041"},{"key":"e_1_2_3_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(96)00206-4"},{"key":"e_1_2_3_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.9b00375"},{"key":"e_1_2_3_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.3c00269"},{"key":"e_1_2_3_49_1","doi-asserted-by":"publisher","DOI":"10.1201\/9780429291166"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202318304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T01:25:46Z","timestamp":1731979546000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202318304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,19]]},"references-count":49,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2024,5,6]]}},"alternative-id":["10.1002\/anie.202318304"],"URL":"https:\/\/doi.org\/10.1002\/anie.202318304","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,19]]},"assertion":[{"value":"2023-11-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202318304"}}