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However, conventional isothiocyanation reactions typically require highly electrophilic reagents or strongly oxidative conditions, rendering them unsuitable for complex molecular systems. Herein, we present a robust and nonchemist\u2010friendly protocol for the isothiocyanation of primary alkyl amines using CS\n                    <jats:sub>2<\/jats:sub>\n                    under ambient aerobic oxidation conditions, eliminating the need for additional promoters. These mild conditions not only ensure broad compatibility with endogenous functional groups in biorelevant molecules but also unlock a powerful new capability: selective differentiation between primary and secondary alkyl amines. Notably, the unique suppression of homo\u2010linking for both primary and secondary amines under these conditions enables near\u2010perfect hetero\u2010selectivity in cross\u2010linking two different biorelevant molecules via their abundant amino handles in a one\u2010pot operation, offering a streamlined, thiol\u2010independent, and small\u2010footprint approach to biocompatible conjugation.\n                  <\/jats:p>","DOI":"10.1002\/anie.202507734","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T10:47:52Z","timestamp":1748342872000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hetero\u2010Selective Cross\u2010Linking of Primary and Secondary Alkyl Amines with CS\n                    <sub>2<\/sub>\n                    Under Ambient Aerobic Oxidation for Bioconjugation"],"prefix":"10.1002","volume":"64","author":[{"given":"Shuai","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chu","sequence":"additional","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangmei","family":"Kong","sequence":"additional","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xintao","family":"Miao","sequence":"additional","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxi","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"Xuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Synthetic Biology School of Life Sciences Faculty of Medicine Tianjin University  Tianjin 300072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanzheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianfei","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5067-9889","authenticated-orcid":false,"given":"Gong","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Nankai University  Tianjin 300071 China"},{"name":"Frontiers Science Center for New Organic Matter Nankai University  Tianjin 300071 China"},{"name":"Haihe Laboratory of Sustainable Chemical Transformations  Tianjin 300192 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.9b00828"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4CS00388H"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.268"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01530"},{"key":"e_1_2_7_5_1","volume-title":"Bioconjugate Techniques","author":"Hermanson G. 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