Alkylations of Chiral, Phosphoryl- and Thiophosphoryl-Stabilized Carbanions

A general method for the preparation of enantiomerically enriched phosphonic acids and phosphonates with three different α-substitution patterns (aryl, alkyl, and alkoxy) has been developed. Anions derived from enantiomerically enriched thiophosphonamidates (2-thioxo-l,3,2-oxazaphosphorinanes) underwent smooth electrophilic substitutions with excellent diastereoselectivity for both cis and trans stereoisomers. Highly enantioselective synthesis of α-alkoxyphosphonates in either antipodal form can be achieved by the employment of highly diastereoselective alkylation with anions derived from the corresponding P-methoxymethyl analogs in the presence of HMPA or PMDTA. Implications for the aggregation states and reactive conformations of the anions are discussed.