Dimethyl 1-Hydroxy-3,7-dimethyl-2,6-octadienylphosphonate. Development of Synthetic Procedures

Abstract

SHORT COMMUNICATIONSWith the goal of simulating phosphorylation of natural polyisoprenyl aldehydes which are promising low-molecular bioregulators [1-3], we examined reactions of citral (3,7-dimethyl-2,6-octadienal, a mixture of E and Z isomers) with trimethyl phosphite and dimethyl phosphonate in the presence of third-party reagents. We previously succeeded in reacting trimethyl phosphite with citral under fairly mild conditions (50°C, 1.5 h) in the presence of acid catalysts, e.g., acetic acid [4]. While developing methods of synthesis of unsaturated α-hydroxy phosphonates we tried to use other initiating agents. It is known that phosphorylation of lower aldehydes and ketones with neutral phosphites successfully occurs in the presence of an equimolar amount of water [5][6][7]. The behavior of dienals toward trialkyl phosphites in the presence in water remains unexplored. We examined the reaction of citral (I) with trimethyl phosphite (II) in the presence of an equimolar amount of water. According to the 31 P NMR data, under these conditions (~20°C) trimethyl phosphite undergoes hydrolysis to dimethyl phosphonate. Therefore, the same reaction was carried out following the Abramov version in the presence of a base catalyst. For this purpose, a dilute solution of triethylamine in ethanol was added to the reaction mixture, and the mixture was heated for 13.5 h at 60°C. As a result, we isolated dimethyl 1-hydroxy-3,7-dimethyl-2,6-octadienylphosphonate (III) as a mixture of E and Z isomers in an overall yield of 71% (Scheme 1); the physical constants and IR, 31 P and 13 C NMR, and mass spectra of the product were in agreement with the data reported in [4].Taking into account that the formation of compound III in the above reaction involves intermediate conversion of II into dimethyl phosphonate (IV), we examined the reaction of IV with citral I in the presence of triethylamine at a reactant molar ratio of 4 : 2 : 8 in a dilute solution in methanol (Scheme 2). The reaction was complete in 16 h at 40-55°C, and phosphonate III was isolated in 88% yield.