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Trideuteromethyl\u2010containing compounds represent a substantial portion of both approved deuterated drugs and those in development. Traditional approaches to incorporate trideuterated methyl group with trideuterated methyl sources (such as iodomethane\u2010\n                    <jats:italic>d<\/jats:italic>\n                    <jats:sub>3<\/jats:sub>\n                    , dimethyl sulfate\u2010\n                    <jats:italic>d<\/jats:italic>\n                    <jats:sub>6<\/jats:sub>\n                    ) require preactivated synthetic precursor, limiting the application for the late\u2010stage trideuteromethyl group incorporation of pharmaceutical molecules. Herein, we develop an electrochemical approach for late\u2010stage trideuteromethyl incorporation of thioether by using stoichiometric methanol\u2010\n                    <jats:italic>d<\/jats:italic>\n                    <jats:sub>4<\/jats:sub>\n                    as the trideuteromethyl isotopic source via a sulfide alkyl displacement. This protocol features operational simplicity, selectivity, and scalability, enabling direct alkyl modification of various aryl alkyl sulfides as well as gram\u2010scale production of trideuteromethyl drugs without the need for synthetic precursors. Mechanistic studies show that the in\u2010situ generated sulfonium salt was the key intermediate. A series of control experiments reveals that alkanes as the departing moiety are the key to alkyl displacement and precise late\u2010stage trideuteration.\n                  <\/jats:p>","DOI":"10.1002\/anie.202512612","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T07:06:34Z","timestamp":1753340794000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Electrochemical Alkyl Displacement of Thioethers for Streamlined Trideuteromethylation"],"prefix":"10.1002","volume":"64","author":[{"given":"Hongshuai","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Green Chemistry and Engineering Suzhou Key Laboratory of Green Intelligent Manufacturing of New Energy Materials and Devices School of Frontier Sciences State Key Laboratory of Coordination Chemistry School of Chemistry and Chemical Engineering Nanjing University  Suzhou 215163 P.R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8220-9187","authenticated-orcid":false,"given":"Minghao","family":"Feng","sequence":"additional","affiliation":[{"name":"Institute of Green Chemistry and Engineering Suzhou Key Laboratory of Green Intelligent Manufacturing of New Energy Materials and Devices School of Frontier Sciences State Key Laboratory of Coordination Chemistry School of Chemistry and Chemical Engineering Nanjing University  Suzhou 215163 P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"e_1_2_5_1_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026615666150915111741"},{"key":"e_1_2_5_2_1","first-page":"376","volume":"5","author":"Scott K. A.","year":"2018","journal-title":"Top. Curr. 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