Browsing by Subject "Amination"
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Item The allylic amination of silyl enol ethers using N, N-bis-(trichloroethoxycarbonyl) sulfur diimide and efforts towards the synthesis of proaporphine alkaloids(2012-12) Roberts, James Jackson; Magnus, Philip D.This doctoral dissertation described herein will be comprised of two parts. The first portion will address our efforts towards the synthesis of [alpha]-amino carbonyls from silyl enol ethers and the second portion will describe our unrelated efforts towards the synthesis of proaporphine alkaloids. A full discussion of the relevant literature, experiments and development of the methodologies will be provided along with all relevant experimental data. Part I: The [alpha]-amino carbonyl moiety has great potential for being a very useful synthetic intermediate for the incorporation of nitrogen owing to the synthetic utility and versatility of the carbonyl functional group. Despite this potential the synthesis has long been problematic owing to their tendency to undergo condensation reactions. We aimed to synthesize them utilizing a protected carbonyl in the form of a triisopropylsilyl enol ether and an electrophilic nitrogen source that could incorporate the nitrogen via an ene-[2,3] sigmatropic reaction sequence. To this end we used an N-sulfinyl carbamate as an electrophilic source of nitrogen that could be utilized for a regiospecific allylic amination of alkenes or could be used to form a highly reactive sulfur diimide that could be used for the allylic amination of alkenes or silyl enol ethers. Part II: Many pharmacologically important and synthetically interesting alkaloids have been formed in nature by the o,p oxidative phenolic coupling of various benzyl-tetrahydroisoquinoline alkaloids. One major class of alkaloids derived from this generalized oxidation is the proaporphine alkaloids and they possess an acid labile spirocyclic-dienone system obtained from this coupling. These compounds have great potential for being used for their anesthetic properties. Despite the relative ease of synthesizing the benzylisoquinoline alkaloids the application of the biomimetic oxidative coupling to make the quaternary center of these compounds gives very poor yields. We opted to form this spiro-dienone system by using a two step Suzuki coupling-para phenolate alkylation methodology that had been used to synthesize the related alkaloids codeine and narwedeine. In doing this we opted to extend the practical application of this methodology by the displacement of an alcohol derived leaving group.Item Development of new synthetic methodologies(Texas Tech University, 2001-12) Kim, Sun HeeSeveral 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.