Unusual Conformational Aspects of Some Novel Chiral Non-Racemic Pyridinyl-2-phosphonates

摘要

Reaction of pyridinyl-2-phosphonyl dichloride (6) with 1-phenyl-2,2-dimethylpropane-1,3-diol (9) leads to the two epimeric 2-oxo-2-(2-pyridinyl)-4-phenyl-5,5-dimethyl-1,3,2-dioxaphosphorinanes (10a,b). These can be separated and the stereochemistry assigned on the basis of 31P NMR spectroscopy. For 10a the pyridinyl substituent is arranged axially at phosphorus. Arguments derived from 2D NMR experiments indicated that the nitrogen of pyridine is locked in a conformation whereby the pyridinyl nitrogen points over the six-membered ring; in other words it is locked between the two ring oxygen substituents. This conclusion is substantiated by an X-ray crystal determination. Oxidation of 10a with hydrogen peroxide leads to the N-oxide (12). The crystal structure of 12 reveals that despite serious steric overcrowding the N-O bond is also oriented over the six-membered ring. Methylation of 10a with methyl trifluoromethanesulfonate affords the N-methyl pyridinium salt (13). NMR experiments indicate that in this case the methylated nitrogen has turned “outside” of the six-membered ring. The borane adduct of 10a appears on the basis of NMR data to have a conformation wherein the complexed borane is located just outside of the six-membered ring. Although crystal structures have not been obtained the pyridinyl-2-thiophosphonates (15a,b) obtsined from treatment of 10a and 10b with [(4-MeOC6H4)2PS]2 appear to have the same conformational properties as 10a and 10b. Restricted Hartree-Fock geometry optimizations have been carried out to aid in clarifying this unexpected conformational behaviour. These calculational results are in excellent accord with the experimental observations, and provide insight into the reasons for the conformational behaviour.