Synthesis of P(V)-Stereogenic Phosphorus Compounds via Organocatalytic Asymmetric Condensation
Year: 2024
Type: article
Abstract: Enantioenriched phosphorus(V)-stereogenic compounds, featuring a pentavalent phosphorus atom as the stereogenic center, are crucial in various natural products, drugs, bioactive molecules, and catalysts/ligands. While a handful of stereoselective synthetic approaches have been developed, achieving direct stereocontrol at the phosphorus atom through catalytic generation of phosphorus(V)-heteroatom bonds continues to be a formidable challenge. Here, we disclose an organocatalytic asymmetric condensation strategy that employs a novel activation mode of stable feedstock phosphinic acids by the formation of mixed phosphinic anhydride as the reactive species to facilitate further catalyst-controlled asymmetric P-O bond formations, involving a dynamic kinetic asymmetric transformation (DYKAT) process with alcohol nucleophiles via a cinchonidine-derived bifunctional catalyst. The resulting H-phosphinate intermediates allow further stereospecific derivatizations, affording modular access to a diverse library of chiral phosphonates and phosphonamidates with notable antibacterial activity. Furthermore, this synthetic platform facilitates P-O/N coupling with various natural products and drugs, presenting a valuable tool for medicine and agrochemical discovery.
DOI: 10.1021/jacs.4c11956
Authors: Fengrui Che, Junyuan Hu, Minghong Liao, Zhongfu Luo, Hongyan Long, Benpeng Li, Yonggui Robin Chi, Xingxing Wu
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: bronze
Funders: Universität Basel, National Research Foundation, National Research Foundation Singapore, Ministry of Education - Singapore, Nanyang Technological University, National Natural Science Foundation of China, Guizhou University, Guizhou Science and Technology Department, Ministry of Education, India, Young Scientists Fund, National Key Research and Development Program of China, National Science Fund for Distinguished Young Scholars
Awards: G114603890, G1482925484, G15845779, G1969097282, G2212741405, G2306326986, G3048563442, G332915675, G3641044699, G3913016970, G446957705, G4485291696, G4517617984, G4709341370, G4975014406, G5069063760, G518567468, G5503778186, G577023881, G6630121638, G6854926366, G8383952663, G8621933135, G967454774
OpenAlex ID: W4404719354