Multiple Structure-Reactivity Correlations in the Hydrolysis of Epimeric 2-(Aryloxy)-2-oxydioxaphosphorinanes. Stereoelectronic Effects

Article abstract of DOI:10.1021/ja00409a046

The epimeric 2-(aryloxy)-2-oxo-trans-5,6-tetramethylene-1,3,2-dioxaphosphorinanes 1-4 (ArO = p-methoxyphenoxy, p-nitrophenoxy, phenoxy, and 2,4-dinitrophenoxy) and isomeric 2-(p-nitrophenoxy)-2-oxo-trans-5,6-tetramethylene-1,3,2-oxazaphosphorinane (5) were hydrolyzed in 30percent dioxane/water at 70 deg C with a variety of nucleophiles.The reactivities were sensitive to changes in both the nucleophile and leaving group.The Broensted β_nuc's for the equatorial leaving groups 2,4-DNP, PNP, and Ph are 0.48, 0.64, and 0.75, respectively.The Broensted β_lg's are -0.96, -1.04, -0.85, -0.66, -0.64, -0.57, -0.46, and -0.35 for nucleophiles water, methoxyacetate, acetate, phosphate, hexafluoroisopropoxide, carbonate, trifluoroethoxide, and hydroxide, respectively, for the equatorial triesters.These results are best interpreted in terms of a change in mechanism from a concerted S_N2(P) process to a stepwise one.The stepwise mechanism via a pentacovalent intermediate is supported by the stereochemistry of reaction and epimeric rate ratios.Thus, some retention of configuration at phosphorus was observed in the methanolysis of all triesters except 4b and 5b.Also the hydroxide-catalyzed hydrolysis of 4a and 1b yielded some retention at phosphorus, and, therefore, a pentacovalent intermediate is required for attack by very basic nucleophiles.This agrees with the kinetic results if one considers the fact that β_lg for hydroxide is only 0.35.Solvent deuterium isotope effects, k_H2O/k_D2O, for acetate-catalyzed hydrolysis of the dinitrophenyl triesters were determined to be 1.08.Thus, these triesters hydrolyze mostly via nucleophilic catalysis.The isotope effects for phosphate-catalyzed hydrolysis of the equatorial p-nitrophenyl and phenyl triesters are 1.19 and 1.8, respectively.This indicates an increasing amount of hydrolysis via general-base catalysis toward the poorer leaving groups.