Asymmetric Hydrophosphonylation of α-Ketoesters Catalyzed by Cinchona-Derived Thiourea Organocatalysts

A study was conducted to demonstrate asymmetric hydrophosphonylation of αketoesters, catalyzed by cinchona-derived thiourea organocatalysts. It was demonstrated that chiral cinchona-derived thioureas are a type of bifunctional organocatalyst that combine a basic bridge-head nitrogen, with a tunable hydrogen-bonding group that originates from the 9-amino functionality. It was also demonstrated that these organocatalysts have emerged as powerful tools for the asymmetric construction of chiral molecules. The investigation proceeded by screening the organocatalysts, derived from cinchona alkaloids, to evaluate their ability to promote the addition of methyl phenylglyoxylate with dimethyl phosphite at 0°C in toluene. A variety of variables, including the choice of solvent, catalyst loading, reaction concentration, and the ester group of phosphite and phenylglyoxylate were investigated, to obtain the optimal conditions for the investigations.