Copper-catalyzed 4-HO-TEMPOH mediated phosphorylation of alkenes

• Published in: Organic & biomolecular chemistry Vol. 21; no. 25; pp. 5171 - 5175
• Main Authors: Zhan, Jun-Long, Wang, Bing-Jie, Wang, Chen-Xi, Zhao, Xin-Ming, Zhou, Sai-Nan, Dou, Zao-Zao, Yang, Xin-Xin, Zhu, Lin, Ren, Wei
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 28.06.2023; Royal Society of Chemistry
• Subjects: Alkenes; Catalysis; Chemical synthesis; Chemistry; Chemistry, Organic; Copper; Functional groups; Oxidation; Phosphorylation; Physical Sciences; Regioselectivity; Science & Technology; HYDROPHOSPHORYLATION; PHOSPHONATES; ACIDS; H-PHOSPHINE OXIDES; VINYLPHOSPHINE OXIDES; BONDS; 1,1-DIBROMO-1-ALKENES; TERMINAL ALKYNES; SELECTIVE SYNTHESIS; DIPHENYLPHOSPHINE OXIDE
• ISSN: 1477-0520; 1477-0539; 1477-0539
• DOI: 10.1039/d3ob00607g

An efficient, practical and regioselective synthesis of ( E )-alkenylphosphine oxides has been developed starting from alkenes under copper catalysis and 4-HO-TEMPOH oxidation. Preliminary mechanistic studies clearly reveal that a phosphinoyl radical is involved in this process. Moreover, this method features mild reaction conditions, good functional group tolerance, and excellent regioselectivity and also promises to be efficient for the late-stage functionalization of drug molecular skeletons. The reaction will create an opportunity for the synthesis of complex phosphorus containing bioactive molecules. A copper-catalyzed unprotected hydroxylamine mediated phosphorylation of alkenes furnished structurally important ( E )-alkenylphosphine oxides under mild reaction conditions with good functional group tolerance and excellent regioselectivity.