Conformational Analysis of (2-Substituted-alkyl)phosphoryl Compounds. 1. NMR Spectroscopic Studies of Dialkyl (2-Hydroxyalkyl)phosphonates and Their Carboxylic Esters

Abstract

Twelve (2-substituted-alkyl)phosphonates (2, 3) were synthesized and conformational analyses carried out by NMR spectroscopy. The conformational populations in six solvents with different polarities and in the presence of metal ions (Li+, Na+, Zn2+), were studied. Steric effects were studied by variation of the sizes of alkyl groups R1 and R2 and intramolecular interactions studied by derivatization of the hydroxy group X. In (2-hydroxyalkyl)phosphonates the most stable conformer ga, in which the phosphoryl group is gauche to the hydroxy group and anti to the alkyl group (R1), is favored particularly in less polar solvents such as C6D6 and CDCl3. In polar solvents the population of the less stable conformer ag, in which the phosphoryl group is gauche to the alkyl group (R1) and anti to the hydroxy group, is increased. Smaller alkyl groups R1 (Me, Prn) allow more conformational freedom. Conversion of the hydroxy group to its carboxylic ester reduces the population of conformer ga so that, for R1 = Prn, conformers ga and ag are approximately equally populated. The presence of metal salts in the acetone-d6 solutions causes an increase in the population of conformer ga in both (2-hydroxyalkyl)phosphonates and their carboxylic ester derivatives. The chemical shift difference between the diastereotopic α-methylene protons has been shown to be proportional to the population of conformer ga.