Synthesis of Adamantyl H‐Phosphinate Esters

Abstract

AbstractAdamantyl H‐phosphinate esters have been described by Leclaire, Giordano, and coworkers as “universal precursors of P‐stereogenic compounds” after resolution by chiral HPLC, because these esters resist racemization during displacement with organometallics. In that work, the racemic esters were prepared from phosphorus trichloride or dichlorophosphines (RPCl2). We decided to investigate alternative methods for the preparation of these important precursors. Esterification methods included EDC, PivCl, and T3P. A protocol to avoid chromatographic purification was also developed and used for multigram‐scale synthesis. Finally, adamantyl hypophosphite 1‐AdOP(O)H2 was also prepared and used in the synthesis adamantyl H‐phosphinate esters, thereby providing an alternative to the esterification of H‐phosphinic acids, although 1‐AdOP(O)H2 was much less reactive than other hypophosphite esters.