| The work developed in this dissertation consists in the development of new methodologies for the preparation of H-phosphinic acid derivatives and their P-chiral counterparts. Special emphasis is given to the role of H-phosphinates as useful synthons for organophosphorus compounds via tandem processes. A review of the most relevant literature in terms of the preparation methodologies and reactivity of H-phosphinic acid derivatives is provided in Chapter I. The following chapter describes the addition of hypophosphorous compounds to unsaturated substrates in presence of metal-catalysts. The mechanism, regioselectivity on alkynes, and reactivity of substituted alkenes, allenes, allenols, and 1,3-dienes as substrates in a palladium-catalyzed hydrophosphinylation was investigated. A novel alkyne hydrophosphinylation catalyzed by nickel chloride or its hydrate in the absence of added ligand was discovered and exploited in the synthesis of various important organophosphorus compounds. The third chapter details a tandem esterification---cross-coupling reaction of alkyl phosphinates with aryl, heteroaryl, alkenyl, and benzylic halides and triflates. Thus the reaction of the electrophilic substrate with a hypophosphorous acid salt, in the presence of a silicate, a base and the palladium catalyst provided directly a wide variety of H-phosphinates, which were not accessible previously. In the following chapter, transition metal-catalyzed reactions of hypophosphorous compounds with allylic electrophiles are disclosed. Allylic acetates, benzoates and carbonates undergo an effective cross-coupling in the presence of palladium catalysts where pure H-phosphinic acids can be isolated by a simple acidic work-up or esterified in situ to the corresponding H-phosphinate esters. Chapter V describes a palladium-catalyzed dehydrative allylation of hypophosphorous acid with allylic alcohols, in the absence of additives. The next chapter focuses on P-H bond activation of H-phosphinates through catalytic allylation and oxidation strategies, which lead to disubstituted phosphinic acid and phosphonic acids, respectively. In the last chapter, desymmetrization strategies to access P-chiral H-phosphinates are reported. Two different avenues are explored: the use of chiral ligands in palladium-catalyzed reactions and the use of chiral auxiliaries by means of esterification of hypophosphorous acid with chiral alcohols, where 8-phenylmenthol provides, in a palladium-catalyzed hydrophosphinylation reaction, our best result with around 70% diastereomeric excess. |
