New methodologies for the synthesis of organophosphorus compounds

Abstract

The work presented in this dissertation focus on the development of new methodologies for the preparation of organophosphorus compounds. A review of the most relevant literature in terms of the preparative methodologies and reactivity of H-phosphinic acid, phosphonic acids and phosphine-borane derivatives is provided in Chapter I. The following chapter describes the addition of hypophosphorous compounds to unsaturated substrates in the presence of metal-catalysts or radical initiators. A novel alkyne hydrophosphinylation catalyzed by nickel chloride or its hydrate, in the absence of added ligand, was discovered and explored in the synthesis of various important organophosphorus compounds. The AIBN-initiated radical addition of alkyl phosphinates to alkenes and alkynes provides alkyl-H-phosphinates in good yield and more importantly offers one of the best synthetic approach for the preparation of trans-alkenyl-phosphinates. Straightforward application to the synthesis of biologically active GABA (?-aminobutyric acid) analogs using AIBN-initiated radical hydrophosphinylation is also demonstrated. The synthesis of novel GABA analogs using methods developed in the Montchamp group and their biological evaluation is discussed in Chapter III. In Chapter IV the synthesis of a various functionalized organophosphorus compounds via organoboranes is reported. In some cases, selective migration of one group attached to boron can be observed. Phosphonite-borane complexes are introduced as novel synthons for the synthesis of phosphinic esters. The synthesis and the reactivity of these novel complexes are expanded in Chapter V.