General principles of ortho-lithiation in arylphosphinamides

Abstract

The development of alternatives to render the ortho-lithiation reaction of arylphosphinamides a diastereoselective and enantioselective process turned this class well explored among the organophosphorus compounds. The use of organolithium bases is the most suitable method for ortho functionalization in aromatic systems. In general, the reaction proceeds in two stages. Firstly, the removal of the ortho hydrogen promoted by the organolithium base takes place, followed by electrophilic neutralization leading to the formation of 1,2-disubstituted product. The improvement of the potential of the organolithium bases is often achieved by using chelating agents, such as N,N,N',N'- tetramethylethylenediamine (TMEDA) and (-)sparteine. Despite being subject of many theoretical and experimental studies, the mechanism of ortho-metallation remains controversial. Therefore, this paper will discuss the main mechanisms involved in the ortho-metallation of arylphosphinamides as well as the processes of synthesis of this class of organophosphorus compounds.