Practical Protocol for the Palladium-Catalyzed Synthesis of Arylphosphonates from Bromoarenes and Diethyl Phosphite

Abstract

A greatly improved, reliable protocol for the palladium-catalyzed cross-coupling of dialkyl phosphites with aryl bromides has been developed. The use of an alcoholic solvent was the key to high yields in the synthesis of a broad variety of arylphosphonates, with Pd(OAc)₂/PPh₃ as the catalyst and a sterically demanding ­tertiary amine as the base.

Key words

palladium - catalysis - arylphosphonates - cross-coupling - aryl halides

References

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1

New correspondence address: Rheinisch-Westfälische Technische Hochschule Aachen, Institut für Organische Chemie, Professor-Pirlet-Straße 1, 52074 Aachen, Germany.

13

Synthesis of Diethyl p -Toluenephosphonate (Representative Experimental Procedure).
A 200 mL round bottom flask equipped with a reflux condenser and a magnetic stirring bar was charged with Pd(OAc)₂ (45 mg, 0.2 mmol) and PPh₃ (157 mg, 0.6 mmol). The reaction vessel was evacuated and purged with argon. Subsequently, EtOH (40 mL), p-bromotoluene (1.71 g, 10 mmol), dicyclohexylmethylamine (2.93 g, 15 mmol) and diethyl phosphite (1.55 mL, 12 mmol) were added via syringe. The reaction mixture was stirred at reflux for 16 h, and the resulting yellow solution was diluted with EtOAc (300 mL) and washed with 1 N HCl, sat. aq NaHCO₃ and brine. The organic layer was dried over MgSO₄, filtered, the volatiles were removed in vacuo and the residue was purified by column chromatography (SiO₂, hexanes-EtOAc, 1:3), yielding 2.06 g (90%) of 3e as a colorless oil. The reactions in Table [2] were performed on 1 mmol scale, the products were purified by flash chromatography (SiO₂, hexanes-EtOAc) and characterized by means of ¹H NMR and ¹³C NMR, GC-MS and HRMS.