Reactions of Chiral Phosphorous Acid Diamides: The Asymmetric Synthesis of Chiral .alpha.-Hydroxy Phosphonamides, Phosphonates, and Phosphonic Acids

Abstract

Addition of aldehydes to the anions of chiral phosphorous acid diamides in THF solution gave a-hydroxy phosphonamides in good yield. The diastereoselectivity was strongly dependent upon the diamide used and ranged from poor to good. The phosphorous acid diamides 2a and 2b (R* 1 = -(CH2)4~, R2 = CH2PI1 and CH2CMe3, respectively) gave the best selectivity, and their reactions with a range of aldehydes were studied. Diamide 2b consistently gave good selectivities, whereas diamide 2a was only moderately selective. Aromatic, aliphatic, and unsaturated aldehydes are tolerated under the reaction conditions. The phosphonamides were hydrolyzed with aqueous HC1 in dioxane to give a-hydroxy phosphonic acids. While direct methanolysis of the phosphonamides was unsuccessful, methylation of the phosphonic acids with diazomethane gave a-hydroxy dimethylphosphonates.

C3-symmetric trialkyl phosphites as starting compounds of asymmetric synthesis

“…100% stereochemical purity. The structures of compounds 4 have been confirmed by 1 H, 13 C, and 31 P NMR spectroscopy. The diastereoisomer ratio and stereochemical purity of the compounds have been determined by means of HPLC and 31 P-{ 1 H} NMR spectroscopy.…”

“…The hydrolysis of the dimenthyl ether 4b by heating it in a water-dioxane solution of 6N hydrochloric acid leads to the formation of ␣-hydroxybenzylphosphonic acid 5, which has been isolated as the crystalline dicyclohexylammonium salt. The (R) configuration of 5 has been defined by comparison of its optical rotation with the data described earlier by Spilling [13] for SCHEME 3 SCHEME 4 the dextrorotatory dicyclohexylammonium salt of (R)-␣-hydroxybenzylphosphonic acid.…”

Enantioselective reduction of ketophosphonates using adducts of chiral natural acids with sodium borohydride

“…The dimenthyl esters were hydrolysed to free hydroxyphosphonic acids whose configuration was determined earlier. [25][26][27][28][29][30][31][32] For example, the hydrolysis of dimenthyl 2-hydroxy-3-chloropropylphosphonate 4b with conc. hydrochloric acid in dioxane afforded the enantiopure (S)-2-Hydroxy-3-chloropropylphosphonic acid (S)-6b with high yield.…”

“…15,25 (R)-1-Phenyl-1-hydroxymethylphosphonic acid (R)-(5a) (Method a). A solution of hydroxymethylphosphonate 3a (1 g, 2 mmol) in 50 mL of dioxane was placed in a flask and 25 mL of 6N hydrochloric acid was added.…”

Ammonium metavanadate: an effective catalyst for synthesis of α-hydroxyphosphonates

“…8 Field. 12 These methods are based on the reaction of aldehydes or ketones with dialkyl phosphonates in the presence of various bases such as, sodium alkoxide, 10,11 triethylamine, 12,13 ethyl magnesium bromide, 14 potassium or cesium fluoride, 15 potassium fluoride on alumina, 16 quinine, 17 LDA, 18 MgO, 19 TMG, 20 DBU. 21 There are some disadvantages over the use of base for the activation of dialkyl phosphonates.…”