A stereochemical study of the dissociative substitution reactions of N-(S)-α-phenylethyl-P-t-butylphosphonamidic chloride with t-butylamine and isopropylamine

Abstract

The diastereoisomers of the title phosphonamidic chloride (8) have been separated and their substitution reactions with Bu^tNH₂ and PrⁱNH₂(MeCN solvent) have been examined. The reactions are entirely dissociative in nature, any contribution from S_N2(P) being insignificant. At very low concentrations of amine, reaction occurs mainly by simple elimination-addition with a free monomeric metaphosphonimidate intermediate (13). This mechanism is first-order in amine (base) and gives the phosphoric diamide product (14) with complete non-stereospecificity. As the concentration of amine is increased, preassociation elimination–addition becomes increasingly important. This mechanism is second-order in amine (base and nucleophile) and has variable stereochemistry. The degree of stereospecificity is very small at first, but it increases with the concentration of the amine. Even with neat amine, however, the preassociation elimination–addition mechanism is still substantially non-stereospecific. For both elimination–addition mechanisms, there is only weak discrimination between PrⁱNH₂ and Bu^tNH₂ under competitive conditions.