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We report a simple and extremely versatile carbonyl reductive functionalization strategy achieving direct, highly selective, and efficient reductive amination, etherification, esterification, and phosphinylation reactions of (hetero)aryl aldehydes and ketones, which are extremely challenging or unattainable to achieve by traditional strategies, using only diphenylphosphine oxide and an inorganic base. It enables modular synthesis of functionally and structurally diverse tertiary amines, ethers, esters, phosphine oxides, etc., as well as related pesticides, drug intermediates, and pharmaceuticals. Compared to phosphorus-mediated name reactions, this strategy firstly transformed C\u2550O bonds into C-element single bonds. Mechanistically, phosphinates are formed as intermediates, which undergo unconventional nucleophilic substitution at the C atom within their C\u2500O\u2500P unit. Thus, this work provides important strides in the field of reductive functionalization of aldehydes\/ketones, phosphorus-mediated transformation, and various fundamental reactions.<\/jats:p>","DOI":"10.1126\/sciadv.ads4626","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T13:58:26Z","timestamp":1738936706000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":11,"title":["Direct carbonyl reductive functionalizations by diphenylphosphine oxide"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0511-0231","authenticated-orcid":true,"given":"Feng","family":"Liu","sequence":"first","affiliation":[{"name":"Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2161-1372","authenticated-orcid":true,"given":"Jianyu","family":"Dong","sequence":"additional","affiliation":[{"name":"School of Physics and Chemistry, Hunan First Normal University, Changsha 410205, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4086-2276","authenticated-orcid":true,"given":"Ruofei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Chemistry, FQRNT Centre for Green Chemistry and Catalysis, McGill University, 801 Sherbrooke Street W., Montreal, Quebec H3A0B8, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9857-9804","authenticated-orcid":true,"given":"Shuang-Feng","family":"Yin","sequence":"additional","affiliation":[{"name":"Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China."},{"name":"College of Science, Central South University of Forestry and Technology, Changsha 410004, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3106-8396","authenticated-orcid":true,"given":"Lang","family":"Chen","sequence":"additional","affiliation":[{"name":"Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1039-0308","authenticated-orcid":true,"given":"Lebin","family":"Su","sequence":"additional","affiliation":[{"name":"Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8423-9988","authenticated-orcid":true,"given":"Renhua","family":"Qiu","sequence":"additional","affiliation":[{"name":"Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3540-8618","authenticated-orcid":true,"given":"Yongbo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5566-9017","authenticated-orcid":true,"given":"Li-Biao","family":"Han","sequence":"additional","affiliation":[{"name":"Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3859-8824","authenticated-orcid":true,"given":"Chao-Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemistry, FQRNT Centre for Green Chemistry and Catalysis, McGill University, 801 Sherbrooke Street W., Montreal, Quebec H3A0B8, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"F. 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