Szalai Zsuzsanna, Ábrányi-Balogh Péter, Keglevich György
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., Budapest 1111, Hungary.
Medicinal Chemistry Research Group, HUN-REN Research Centre for Natural Sciences, Budapest 1117, Hungary.
J Org Chem. 2025 Jan 10;90(1):439-447. doi: 10.1021/acs.joc.4c02355. Epub 2024 Dec 17.
The condensation of dialkyl α-hydroxy-benzylphosphonates with dialkyl phosphites and that of α-hydroxybenzyl-diphenylphosphine oxide with diphenylphosphine oxide unexpectedly gave the corresponding phosphorylated α-hydroxy derivatives. This new reaction proved to be general. The formation of the two products may be similar and involves the attack of the hydroxy group of the α-hydroxyphosphonate or α-hydroxyphosphine oxide on the phosphorus atom of the trivalent tautomer form (YPOH) of the YP(O)H reagent (Y= MeO, EtO, or Ph) going with the elimination of an alcohol and water molecule, respectively. The mechanism was supported by DFT computations at the M062/6-31G (d,p) level of theory, including suitable proton transfer networks. The condensations discussed are typical autocatalytic reactions promoted by the alcohol or water molecules formed. The initial promoters are the traces of water inevitably present in the mixture. In the reaction of α-hydroxyphosphonates with dialkyl phosphites, the -P(O)(OR)H derivative is the primary product that is partially hydrolyzed to the -P(O)(OH)H species by the traces of water under the conditions of the reaction. Arbuzov reaction of diethyl α-bromobenzylphosphonate with ethyl diphenyphosphinite afforded the target-like phenylmethylene-phosphine oxide─phosphonate derivative.
二烷基α-羟基苄基膦酸酯与亚磷酸二烷基酯的缩合反应，以及α-羟基苄基-二苯基氧化膦与二苯基氧化膦的缩合反应意外地得到了相应的磷酸化α-羟基衍生物。这一新反应被证明具有普遍性。这两种产物的形成可能相似，涉及α-羟基膦酸酯或α-羟基氧化膦的羟基对YP（O）H试剂（Y = MeO、EtO或Ph）的三价互变异构体形式（YPOH）的磷原子的进攻，分别伴随着一分子醇和一分子水的消除。该机理得到了理论水平为M062/6 - 31G（d，p）的DFT计算的支持，包括合适的质子转移网络。所讨论的缩合反应是由生成的醇或水分子促进的典型自催化反应。最初的促进剂是混合物中不可避免存在的微量水。在α-羟基膦酸酯与亚磷酸二烷基酯的反应中，-P（O）（OR）H衍生物是主要产物，在反应条件下会被微量水部分水解为-P（O）（OH）H物种。α-溴苄基膦酸二乙酯与二苯基次膦酸乙酯的Arbuzov反应得到了目标样的苯基亚甲基-氧化膦-膦酸酯衍生物。
