Ph.D. (Chemistry) / Please refer to full text to view abstract

Ph.D. (Chemistry) / The bridged chiral benzopyrans were strategically ring opened via acetolysis to yield either galactose based chromenes or chromans, depending on the reaction conditions. A proposal relating to the mechanism of this selective ring opening acetolysis is discussed. The benzopyrans (chromenes, chromans and bridged chiral benzopyrans) were de-acetylated via triethyl amine catalysed transesterification. Interestingly, the chromenes did not yield the anticipated hydrolysis product (triol) but a new class of bridged chiral benzopyrans which were a result of intramolecular oxa-Michael addition. A chromene that formed during the selective ring opening of the bridged chiral benzopyrans was employed to develop a method for the synthesis of a carbohydrate derived oxepane. The oxepane synthesis was achieved, albeit in the face of numerous challenges from side reactions. The difficulties encountered in the synthesis are discussed...

Catalytic enantioselective desymmetrization of meso-epoxides is widely used in many areas of chemistry. Such process is usually catalyzed by a transition metal complex with a chiral ligand. Recently, a synthesis of an analogue of Bolm's 2,2'-bipyridine ligand was developed and its combination with metal salts were tested in various reactions. In this master's thesis, a catalytic system composed of Sc(OTf)3/Bolm's ligand analogue was studied in alcoholysis and aminolysis of the meso- epoxides. The reaction has been extended to a broad range of alcohols providing 1,2-diol monoethers in excellent enantioselectivity up to 99% ee. The aminolysis of meso-epoxides has been optimized, as well. The catalyst loading could be lowered to 1 mol% with only marginal effects on the enantioselectivity. Key words: epoxides, enantioselective catalysis, chiral ligands.

Thesis advisor: Masayuki Wasa / This dissertation describes the development of novel catalyst systems that could promote the regio- and enantioselective transformations of C-H bonds contained in N-alkylamines and ethers through Lewis acid-mediated hydride abstraction processes. The progress made in C-H functionalization of N-alkylamines and ethers that served as the intellectual foundation of this dissertation research are summarized in Chapter 1. Despite notable advances, the development of broadly applicable, enantioselective, and catalytic protocols to functionalize C-H bonds in N-alkylamines and ethers with high regio- and stereo-selectivity was regarded as an unsolved problem when we started this dissertation research. In an effort to overcome these fundamental limitations, we first identified a B(C6F5)3/Cu-PyBOX cooperative catalyst system for the enantioselective conversion of a-amino C-H bonds through the generation of an iminium by (F5C6)3B-catalyzed hydride abstraction process (Chapter 2). We then envisioned that in situ generated iminium ions could be further deprotonated to furnish an enamine intermediate, which may react with electrophilic species for a-amino C-H functionalization. The design and development of such a catalyst system were discussed in Chapter 3. Finally, we disclose enantioselective Cu–BOX-catalyzed hetero Diels-Alder reactions of enol ethers generated through Ph3C+-mediated oxidation of alkyl ethers. (Chapter 4). / Thesis (PhD) — Boston College, 2022. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: James P. Morken / This dissertation presents the development of catalytic enantioselective synthesis and selective functionalization of geminal or vicinal borylsilanes and bis(boronates). In the first chapter, a modular approach to the catalytic synthesis of enantioenriched anti-1,2-borylsilanes will be described, which is enabled by the stereospecific 1,2-metallate shift that occurs during Pd-catalyzed conjunctive cross-coupling reaction. In the second chapter, the Cu-catalyzed site-selective cross-coupling of vicinal bis(boronates) to an array of electrophiles is developed to provide a new method to construct complex boron-containing products from terminal alkenes. A dramatic rate acceleration in transmetalation to copper is enabled by the neighboring activating boronate group in the substrate. Mechanistic experiments suggest that the formation of a chelated cyclic ate complex may play a role in facilitating the transmetalation. As a follow-up project, the site-selective cross-coupling of vicinal diborylsilanes is also investigated. A Pt-catalyzed enantioselective hydrosilylation of (Z)-1,2-diborylethylene provides access to a vicinal 1,2-diboryl-1-silylalkane that can be used in catalytic cross-coupling reactions. Depending on the catalyst employed and the electrophile class, the coupling reaction can occur at either the α or β carbon relative to the silane center. In the last chapter, a practical method is developed to prepare a TiO2 supported gold nanoparticle catalyst that facilitates the cis-diboration of terminal alkynes. The resulting products can undergo a practical Cu-catalyzed site-selective cross-coupling with proton or other non-aryl/alkenyl electrophiles to yield α-substituted alkenyl boronates with excellent yield and site-selectivity. / Thesis (PhD) — Boston College, 2024. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

A set of five new C3-symmetric phosphites were synthesized and tested in palladium-catalyzed asymmetric Suzuki coupling. The observed reactivity and selectivity were dependent upon several factors. One of the phosphites was able to achieve some of the highest levels of enantioselectivity in asymmetric Suzuki couplings with specific substrates. Different hypotheses have been made for understanding the ligand effects and reaction selectivities, and those hypotheses were tested via various methods including DOSY NMR experiments, X-ray crystallography, and correlation of catalyst selectivity with Tolman cone angles. Although only modest enantioselectivities were observed in most reactions, the ability to synthesis these phosphites in only three steps on gram scales and to readily tune their properties by simple modification of the binaphthyl 2´-substituents makes them promising candidates for determining structure-selectivity relationships in asymmetric transition metal catalysis, in which phosphites have been previously shown to be successful. A series of novel chiral oxazoline-based carbodicarbene ligands was targeted for synthesis. Unfortunately, the chosen synthetic route could not be completed due to unwanted reactivity of the oxazoline ring. However, a new and efficient route for Pd-catalyzed direct amination of aryl halides with oxazoline amine was developed and optimized during these studies. Chiral binaphthyl based Pd(II) ADC complexes with different substituent groups have been synthesized and tested in asymmetric Suzuki coupling reactions. Although only low enantioselectivities were observed in Suzuki coupling, this represents a new class of chiral metal-ADC catalysts that could be tested in further catalytic.

No description available.

Thesis advisor: Amir H. Hoveyda / Chapter 1 Enantioselective Conjugate Additions of Carbon Nucleophiles to Activated Olefins: Preparation of Enantioenriched Compounds Containing All-Carbon Quaternary Stereogenic Centers. Methods for enantioselective conjugate addition of nucleophiles to activated olefins generating products containing all-carbon quaternary stereogenic centers are critically reviewed. Enantioselective conjugate addition has been shown to be a powerful and concise approach to construct carbon-carbon bonds to prepare compounds containing sterically hindered stereogenic centers and has seen great advances in the past several years. Owing to the difficult nature of additions to relatively unreactive conjugate acceptors, compared to additions generating tertiary stereogenic centers, and construction of a sterically-hindered bond, in many cases, new and active catalysts had to be developed. The review discusses the areas where significant advances have been made as well as current limitations and future outlook. Chapter 2 Development of New and Active Catalysts for Cu-Catalyzed Enantioselective Conjugate Addition of Alkyl- and Arylzinc Reagent. Through development of new chiral catalysts, we have found an active and enantiodiscriminating bidentate, sulfonate-containing NHC-Cu catalyst that effects enantioselective conjugate addition of alkyl- and arylzinc reagents on notoriously difficult trisubstituted cyclic enones. Products are prepared with high levels of selectivity and participate in a variety of further functionalizations. The enantioselective additions are efficient and practical, not requiring rigorously anhydrous or oxygen-free conditions. Chapter 3 Cu-Catalyzed Enantioselective Conjugate Addition of Alkyl- and Arylaluminum Reagents to Trisubstituted Enones. Outlined in this chapter is the first effective solution for Cu-catalyzed enantioselective addition of alkyl and aryl nucleophiles to trisubstituted cyclopentenones generating products bearing a &beta;-all-carbon quaternary stereogenic center. Products are obtained in up to 97% yield and 99:1 er, only requiring 5 mol % of an in situ generated Cu-NHC catalyst. The methodology was highlighted as one of the key steps in the total synthesis of clavirolide C. Not only five-membered rings, but six- and seven-membered rings serve as proficient partners in the enantioselective process. Moreover, in cases for the enantioselective aryl addition, in situ prepared Me₂AlAr can be used without purification, filtration, or isolation, only requiring the corresponding aryl halides. The additions have also been extended to trisubstituted unsaturated lactones and chromones. Chapter 4 Cu-Catalyzed Enantioselective Conjugate Addition of Vinylaluminum Reagents to Cyclic Trisubstituted Enones. An enantioselective protocol for the formation of &beta;,&beta;-disubstituted cyclic ketones containing a synthetically versatile vinylsilane is disclosed. Enantioselective conjugate addition of in situ prepared silyl-substituted vinylaluminum reagents to &beta;,&beta;-unsaturated ketones promoted by 5 mol % of chiral Cu-NHC complexes delivers desired products with high efficiency (up to 95% yield after purification) and enantioselectivities (up to >98:<2 er). Several functionalizations utilizing the vinylsilanes, vicinal to an all-carbon quaternary stereogenic center, are shown, including an oxidative rearrangement, vinyl iodide formation and protodesilylation, accessing products not previously attainable. Furthermore, the enantioselective protocol is demonstrated as the key transformation in the total synthesis of riccardiphenol B. / Thesis (PhD) — Boston College, 2011. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Amir H. Hoveyda / In the course of a total synthesis of quebrachamine, we were faced with a late-stage enantioselective ring-closing metathesis that could not be promoted by any of the state-of-the-art chiral metathesis catalysts. To overcome this deficiency, we designed and developed a new class of catalysts based on mechanistic and theoretical principles. The new catalysts contain a stereogenic metal center and display unprecedented levels of reactivity and selectivity in enantioselective olefin metathesis, enabling us to complete our planned synthesis of quebrachamine. We have also discovered that non-productive metathesis reactions with stereogenic-at-Mo catalysts, generated and used in situ as a mixture of diastereomers, are crucial to the efficiency and enantioselectivity of the ring-closing metathesis reactions. Specifically, our studies have indicated that the two diastereomers of catalyst are in rapid equilibrium due to non-productive metathesis with ethylene, generated as the desired ring-closing reaction proceeds, thereby establishing a reaction manifold that is under Curtin-Hammett control. Finally, in our efforts to prepare air-stable precursors to stereogenic-at-Mo olefin metathesis catalysts, we have examined the addition of N,N-chelating ligands to Mo bis-pyrrolide complexes. Upon addition of 2,2&#8242;-bipyridyl to bis-dimethylpyrrolide Mo complexes, rather than the expected octahedral chelate, a five-coordinate monopyrrolide alkylidyne complex is generated. The complex displays good air-stability and efficiently serves as a precursor to stereogenic-at-Mo alkylidene catalysts; several alkylidyne complexes have been prepared. / Thesis (PhD) — Boston College, 2010. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Amir H. Hoveyda / Formation of C-C bonds is an invaluable tool for the construction of materials, pharmaceuticals, natural products, and the building blocks of life. Although great strides in this area have been made, there remain several limitations in regio-, site-, and enantioselective additions of carbon-based nucleophiles. Solving these challenges by expanding the scope, efficiency, and selectivity of alkyl, aryl, heteroaryl, vinyl, and alkynyl additions to carbon-based electrophiles is the topic of this dissertation. / Thesis (PhD) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.