The principal goal is the development of a methodology for the synthesis of chiral alpha-substituted phosphorous acid derivatives, considered the most important structure for the substitution of the corresponding amino acids in biological systems. Attempts to develop a more general and flexible approach for the synthesis of chiral phosphorous derivatives by asymmetric induction has been an active research area, however, with only few promising results. The attractiveness of such target molecules is related to their varied structure and broad range of biological and medicinal applications such as in protease inhibition and as antibacterials. The goal will be achieved by developing a new 3-component coupling (3-cc) approach based on the 1,4-addition of a functionalized zinc reagent to a vinyl phosphorous oxide followed by the asymmetric alkylation of the resulting phosphorous-stabilized carbanion, all in """"""""one-pot"""""""". This approach is based on the use of a catalytic amount of copper reagent and the rapid transmetallation between copper and zinc that will provide the """"""""in-situ"""""""" generation of the zinc phosphorous-stabilized carbanion. In this way, chiral alpha-substituted phosphorous acid derivatives are to be synthesizeable with a wide range of functionalized alpha-substituents by a flexible """"""""one pot"""""""" approach. This methodology will allow the synthesis of more elaborated and novel biomedically interesting phosphorous compounds.
