Development of new synthetic methodologies

Several new synthetic methodologies of chemically and biologically importance are described in this dissertation. These include electrophilic aminohalogenation, electrophilic diamination, Baylis-Hillman type bond formations and Mukaiyama aldol type reactions. These reactions are for either carbon-nitrogen or carbon-carbon bond formations and can result in multifunctionalized products.

Efficient nitrogen/halogen sources are studied as electrophiles for electrophilic aminohalogenation and diamination. Transition metals or their complexes with ligands are utilized as catalysts to control the regio- and stereoselectivity. A/-Arylsulfonyl-A/-chloroaziridinium ions are confirmed as novel intermediates to exist in electrophilic additions of alkenes. The resulting haloamine and vicinal diamine derivatives have been converted into aziridines and a,p-differentiated amino acids.

Baylis-Hillman type adducts are obtained by the treatment of aldehydes with acetylenic carbonyl compounds in the presence of TiCI4 as the Lewis acid promoter. The reaction proceeds through the formation of halo aldol adducts. These adducts have been isolated in good yields, which extends the application of classical aldol reaction. A similar reaction system has also been applied for new C=C bond formations.

Asymmetric versions of Baylis-Hillman type reactions and aldol reactions have been systematically studied. New chiral auxiliaries are employed to direct the chirality of products. Chiral sulfinimines are successfully utilized as electrophilic acceptors for the asymmetric synthesis of multifunctionalized Baylis- Hillman adducts, p-halo, p-monosubstituted, and p,p-disubstituted Baylis-Hillman olefines. Among these products, a-alkylidene p-amino acids have been found to serve as novel leads for the design of anf/-cancer drugs by NIH. Finally, novel synthesis of oxazaborolidine auxiliaries is demonstrated in which unique solutionto- solid and solid-to-solid techniques are applied. For the later case, no solvent is required; therefore, the reaction is environmentally friendly.