Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.

Thesis (Ph. D.)--University of Texas at Austin, 2002. / Vita. Includes bibliographical references. Available also from UMI Company.

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references (leaves 212-220). Available also in a digital version from Dissertation Abstracts.

Thesis (Ph. D.)--Hong Kong University of Science and Technology, 2003. / Includes bibliographical references. Also available in electronic version. Access restricted to campus users.

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

Two syntheses of non-cross-linked polystyrene-supported TADDOL-based phosphoric acid organocatalyst have been developed. The optimal polymer-supported catalyst 2.29d exhibited comparable catalytic activity to its small molecule counterpart in asymmetric Mannich-type reactions, and the syntheses of several chiral β-amino esters were demonstrated using 2.29d as catalyst. However, when this TADDOL-based phosphoric acid was immobilized on a polystyrene cross-linked with 1,4-bis(4-vinylphenoxy)butane, ie. JandaJelTM, the catalytic activity diminished in the first recycling and reuse of the catalyst. Building on the success of the immobilization of chiral phosphoric acid, a more robust phase-tagged BINOL-based phosphoric acid organocatalyst was developed. By taking advantage of a tetraarylphosphonium salt as a solubility-controlling group, a widely-used BINOL-based phosphoric acid, TRIP (3.1), was introduced onto a tetraphenylphosphonium salt to produce a phosphonium salt-tagged phosphoric acid catalyst 3.3e. After systematic optimizations of reaction conditions, it was found that the catalyst 3.3e with PF6 as counteranion exhibited the best performance in terms of enantioselectivity. Catalyst 3.3e was proved to be highly effective in asymmetric Friedel-Crafts reaction of indoles because it was shown to be recyclable and reusable after six cycles without loss of catalytic activity. Based on our previous studies on the reduction of unsaturated thioesters catalyzed by (BDP)CuH, further investigation of ligand effects revealed that in addition to BDP, dppf was also an effective ligand for the simple reduction of 5.8. In the stoichiometric reduction of unsaturated thioester 5.8, dppe and dppf were both efficient ligands for copper hydride that could convert 5.8 to aldehyde 5.18 in the presence of TMSCl, without the formation of the undesired enol ester 5.17, which was a major product when stoichiometric amounts of Stryker’s reagent was employed. When 5.30 bearing both a saturated and unsaturated thioester was reduced under these conditions, only the enethioate functional group underwent reaction to yield the mono-reduced product 5.31 while the saturated thioester functional group remained inert. The desymmetrizing reductive aldol reactions of symmetrical keto-enethioates 6.19, 6.22, 6.24 and 6.26 catalyzed by in situ generated chiral copper hydride were investigated. After a screening of the reaction conditions, TaniaPhos L8 was found to be the most effective chiral ligand to achieve high ee and yields. Under the optimum reaction condition (5 mol% Cu(OAc)-H2O and L8 with 2.0 eq. PhSiH3), a range of keto-enethioates smoothly underwent desymmetrizing reductive aldol cyclizations, offering bicyclic or polycyclic β-hydroxythioesters (6.28a-6.32a, 6.37a-6.47a) in 35- 84% yield and 30-97% ee with high diastereoselectivity. The addition of 5 mol% of bipyridine as additive resulted in an accelerated reaction rate in all of the reductions of keto-enethioates. The crystal structure of the L8-copper bromide complex allowed the rationalization of the major enantiomer (eg. 6.48a), in which all of the substituents are cis, to be a result of a reductively generated (Z)-thioester enolate reacting through a Zimmerman-Traxler transition state. This stereochemical outcome is in contrast to the reduction of the analogous oxoesters, which yield trans β-hydroxyesters, (eg. 6.54b), as the major products. Several proposals to explain the divergent stereochemistry, including the predominance of a Zimmerman-Traxler transition state of (E)-enolates or subsequent retroaldol rearrangements, were discussed. The retroaldol rearrangement has been observed in the conversion of 6.48a to 6.57c, in which there was retention of the configuration at C5 and a perfect conservation of enantiomeric purity. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

The synthesis of useful chiral skeletons from simple achiral starting materials is always the dream of organic chemists. In the past decades, organocatalysis has been rapidly developed and has become one of the most important methods in asymmetric catalysis. The aim of this thesis is to develop asymmetric methods for the construction of useful chiral skeletons based on organocatalytic chemistry. Many natural products and biologically important compounds contain the hydrogenated dibenzofuran (Figure 1) as a common sub-structure. In the first part of this thesis, the first amine-catalysed asymmetric synthesis of a dihydrodibenzofuran species from bisenal substrates has been demonstrated. After a systematic screening of various reaction parameters, the optimal conditions have been found to be as follows: 0.1 M of substrate in solution with toluene with 0.2 equiv of (S)-di(2-naphthyl)pyrrolinol TMS ether (C2.8) and 0.2 equiv of 2-nitrobenzoic acid at 50 ℃ for 7 h under an argon atmosphere (Scheme 1). The first step product, an aldehyde, can be reduced in one pot to an alcohol by NaBH4. This two-step protocol gives exclusive cis selectivity. Many chiral cis-dihydrodibenzofuran species have been synthesized from the corresponding bisenal substrates in moderate to good yield with good to excellent ee (Scheme 1). The resulting cis-dihydrodibenzofuran species have promising synthetic applications. As shown in Scheme 2, the less hindered face of the newly formed C ring is more reactive and highly regioselective functionalizations of the C ring have been achieved. In the second part of this thesis, the first asymmetric aziridination of trans-α-nitroalkenes via a phase-transfer catalysis strategy has been systematically studied. The chiral phase-transfer catalysts screened are derivatives of the cinchona alkaloids. The new cinchonidine-derived phase-transfer catalyst CD17 has been found to be optimal for the aziridination (Figure 2). Addition of a small amount of water is crucial to achieve complete conversion of the reaction. Both trans-1-nitro-2-arylalkenes and trans-1-nitro-2-alkylalkenes are suitable substrates (Scheme 3). The reaction can be run on the gram-scale without significant loss of efficiency and ee. Mechanistic studies have revealed that the aziridination proceeds through an aza-Michael addition followed by an intramolecular SN 2 type three-membered ring formation (Scheme 4). / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

The research on asymmetric organocatalysis has been intensifying since the beginning of 2000. The growing interest in this research area is driven by the importance of the chemical synthesis of enantiomerically pure products. While the general field of asymmetric organocatalysis has been explored intensively, the recyclability of organocatalysts has not really been considered. The attachment of phosphonium ion phase tags to chiral binaphthyl-based phosphoric acid catalyst and the use of these materials in a range of organocatalytic asymmetric Friedel-Crafts reactions of indoles have been studied. Placement of tags at the 3 and 3’ positions of the binaphthyl core, so that they could serve as steric blocking groups, failed to produce an active catalyst. However, moving the phosphonium ion groups to the 6 and 6’ positions produced an efficient and enantioselective catalyst. Aided by the presence of the phase tags, the chiral catalyst was easily recovered at the end of the reactions, and could be reused several times, albeit with somewhat decreased efficiency and enantioselectivity. Furthermore, the synthesis of 1,1’-spirobiindane-7,7’-diol and their spiroindane-based derivatives have been explored. The (R)-1,1’-spirobiindane- 7,7’-diamine was successfully applied in exo selective asymmetric Diels-Alder reactions of -unsaturated aldehyde with cyclopentadiene. However, moderate results aspire further studies in assay of (R)-1,1’-spirobiindane-7,7’-diamine derivatives, which bear various bulky groups at the 6 and 6’ positions. Moreover, the conversion of the SPINOL into a spiroindane ketone unfortunately failed, which was caused by the sterically crowded structure of the SPINOL skeleton. / published_or_final_version / Chemistry / Master / Master of Philosophy

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