Microwave-Assisted Palladium-Catalyzed Cross-Coupling of Aryl and Vinyl Halides with H-Phosphonate Diesters

Abstract

A general and efficient method for the microwave-assisted formation of the C-P bond was developed. Using a prevalent palladium catalyst, Pd(PPh3)4, a quantitative cross-coupling of various H-phosphonate diesters with aryl and vinyl halides was achieved in less than 10 min. The reactions occurred with retention of configuration at the phosphorus center and in the vinyl moiety. Using this protocol, several C-phosphonates, including those bearing nucleoside and cholesteryl moieties, were prepared in high yields.

The Use of MW in Organophosphorus Chemistry

“…The series of arylphosphonates (30), alkyldiphenylphosphinates (31) and diaryl-phenylphosphine oxides (33) The P-ligand-free approaches are environmentally-friendly as save costs and environmental burdens. Other MW-assisted variations of the Hirao-reaction were also described, but they applied P-ligands [46][47][48][49].…”

“…Dialkyl phosphites were also added to the carbonyl function of α-ketophosphonates (46) to result in the formation of dronate analogue α-hydroxybisphosphonates (47) in the presence of diethylamine and in the absence of any solvent. Under optimum conditions, the formation of the rearranged by-product 48 could be avoided (Scheme 3.32) [64,65].…”

Microwave-assisted Hirao reaction: recent developments

“…In 2008, Stawinski and co-workers [28] developed a general and efficient microwave-assisted method for the preparation of a broad spectrum of aryl-and vinylphosphonates (15 and 17, respectively) based on a Pd-catalyzed cross-coupling of aryl/vinyl halides (13/16) with H-phosphonate diesters (14) using Pd(PPh 3 ) 4 as a prevalent palladium catalyst and either cesium carbonate or triethylamine as base in THF; the reaction was completed within 10 min furnishing good yields (Scheme 7). It is also noteworthy that the reaction is completely stereospecific with retention of configuration at the phosphorus center and at the same time, the configuration in the vinyl moiety remains unaltered.…”

“…To overcome such a limited scope of the reaction, they used microwave (MW) heating, instead of conventional heating, and became successful in their endeavor. The operational simplicity, fastness of the process, simple workup, and high purity of the desired compounds (28) are some of the key features of the present protocol, which make it a good candidate for application in both laboratory and large-scale synthesis.…”

“…aryl-and vinyl-phosphonates, phosphine oxides and related derivatives) are compounds of practical importance in industry, agriculture, and medicine as well as in everyday life [34][35][36][37][38][39]. In addition to their applications as pesticides, detergents, or anticorrosive agents, these phosphorus-containing synthetic compounds Scheme 10 Pd/C-catalyzed synthesis of aryl diphenylphosphine oxides (28) in water Scheme 11 Ligand-free synthesis of arylphosphonates/phosphine oxides (30) have received a lot of attention both in drug research and in medicinal chemistry due to their great potential in combating diseases and pathological conditions, and curing parasitic infections [40].…”