Obtaining enantiomerically pure compounds is of major importance in modern organic chemistry, and this PhD thesis outlines new advances made in this area. Two new enantioselective synthetic methodologies have been designed using isothiourea based- organocatalysts. A brief introduction to the recent literature involving this catalyst architecture is presented. Then, the results of the structure-activity relationship study carried out on a range of isothiourea catalysts for the kinetic resolution of (±)-1-naphthylethanol 16 is described. Chiral isothiourea HBTM 2.1 58 was identified as the optimum catalyst and was further employed in the resolution of a range of secondary alcohols. Good levels of conversion (c~50%) and selectivity (S up to 100) were achieved delivering alcohols in high levels of enantioselectivity (up to 98% ee). The synthetic utility of this process was subsequently demonstrated through isolation of a range of enantiopure alcohols (>99% ee) on a preparative scale, using low catalyst loading of HBTM 2.1 (0.10 mol%). Secondly, a new organocatalytic asymmetric transformation involving the generation of a C1-ammonium enolate using isothiourea is described. An intramolecular Michael addition-lactonisation (IMAL) of enone-acid substrates was developed using (‒)-tetramisole 37 as a catalyst. The generality of this protocol was probed via structural variation of the enone-acid substrates, providing a range of highly functionalised syn-polycyclic carbo- and heterocycles in excellent yields, diastereo- and enantioselectivities (up to 99% yield, 99 : 1 dr and 99% ee). Whilst investigating this process, we discovered that using cinchona alkaloid derivatives as catalysts gave preferential access to the diastereomeric anti-products. Therefore, a range of anti-dihydrobenzofurans was synthesised from readily available starting materials in good yield and stereoselectivities (up to 73%, 20 : 80 dr and 99% ee) using OTMS-quinidine catalyst. These two complementary synthetic strategies allowed facile and controllable access to both syn- and anti-diasteroisomers of a product in high enantioselectivity via judicious choice of catalyst. Subsequently, two telescoped procedures combining the synthesis of the enone-acid through olefination and asymmetric functionalisation were designed, giving rapid access to stereodefined pyrrolidines in high levels of diastereo- and enantioselectivitiy (up to 99 : 1 dr and 99% ee). The last part of this thesis describes preliminary studies toward the development of a doubly diastereoselective intramolecular Michael addition-lactonisation process, opening new avenues for the construction of complex molecular architectures.

[Rh(CO]2Cl]2 has been shown to catalyze sequential, mechanistically- distinct transformations in one pot. Tandem allylic alkylation/cycloisomerization sequences have been developed to access valuable, complex structures from relatively simple substrates. A methodology for the enantioselective conjugate addition of 2-heteroaryl nucleophiles to a variety of Michael acceptors has been developed. This method was used successfully in an ongoing approach to the synthesis of cortistatin A. 10 linear steps have been completed towards the synthesis of cortistatin A, including a highly regioselective propargylation to install a quaternary carbon and a diastereoselective intramolecular Diels-Alder reaction. / text

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Thesis advisor: James P. Morken / This dissertation describes the development of four metal-catalyzed carbon-carbon bond forming methods. The first project presented is a palladium-catalyzed proparyl-allyl cross-coupling which proceeds via a kinetic resolution to give enantioenriched 1,5-enynes. Next the asymmetric rhodium-catalyzed hydroformylation of 1-alkenes is described. This reaction delivers synthetically useful a-chiral aldehydes in up to 98:2 er and up to 15:1 branched to linear ratio. The development of a unique nickelcatalyzed asymmetric Kumada coupling of cyclic sulfates is presented. Mechanistic studies reveal the reaction proceeds via an SN2 oxidative addition of a chiral nickelcomplex. Finally, a-Substituted allyl bis(boronic) esters, which are derived from 1,2-diboration of 1,3-dienes are shown to undergo allylation and subsequent Suzuki coupling with aldehydes tethered to sp2 electrophiles. The carbocycle products obtained bear three contiguous stereocenters and were used as intermediates in the synthesis of complex molecules. / Thesis (PhD) — Boston College, 2017. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: James P. Morken / This dissertation will describe the development of three transition metal-catalyzed syntheses of nonracemic organoboronates. The first chapter explains the development of a palladium-catalyzed enantiotopic-group-selective cross-coupling of geminal bis(boronates) with alkenyl electrophiles. This process enables the synthesis of highly valuable nonracemic disubstituted allylic boronates. Chapter two describes a palladium-induced 1,2-metallate rearrangement of vinylboron “ate” complexes. The newly developed process incorporates an alternative route for the transmetallation step of Suzuki-Miyaura cross-couplings. Lastly, an enantioselective platinum-catalyzed hydrosilylation of alkenyl boronates is disclosed. This reaction enables the synthesis of nonracemic geminal silylboronates for the divergent synthesis of functionalized / Thesis (PhD) — Boston College, 2018. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: James P. Morken / The first examples of an enantioselective allene diboration and diene diboration are reported. The asymmetric palladium-catalyzed allene diboration afforded 1,2- bis(boronate)esters in up to 98% ee. The reaction development for the allene diboration, as well as the expansion of the substrate scope, and elucidation of the reaction mechanism are reported. Following the development of the enantioselective allene diboration, the first enantioselective diene diboration was disclosed. 1,4-Dihydroxylation products resulting from a tandem diene diboration/oxidation sequence are obtained in up to 92% ee. / Thesis (PhD) — Boston College, 2008. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Shih-Yuan Liu / The first three chapters of this dissertation elaborate on certain facets of the isosteric relationship between different types of boron-nitrogen-containing heterocycles and the corresponding all-carbon compounds. In this vein, Chapter 1 describes selective photoisomerization of aromatic 1,2-dihydro-1,2-azaborines to BN-analogues of bicyclo[2.2.0]hexa-2,5-diene (Dewar benzene). In one instance, the photoisomer product was further derivatized into a series of disubstituted cyclobutanes through manipulations of the boron functionality. Chapter 2 discloses a combined experimental/theoretical mechanistic investigation of preliminary hydrogen release from the amine borane unit in a pair of BN-cycloalkanes. In Chapter 3, the kinetics of complementary dehydrogenation of the alkyl units in a BN-cyclohexene derivative are compared with those of related six-membered carbocycles. Chapter 4 treats with the separate subject of enantioselective silylation of glycerol by a catalytic strategy centered around reversible covalent binding of substrate hydroxyl groups. / Thesis (PhD) — Boston College, 2018. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Amir H. Hoveyda / Thesis (PhD) — Boston College, 2008. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Amir H. Hoveyda / Chapter 1: We disclose an Al-catalyzed enantioselective method for additions of Me2Zn and Et2Zn to α-ketoesters bearing aromatic alkenyl, and alkyl substituents. These transformations are promoted in the presence of a readily available amino acid-based ligand, and afforded the desired products in excellent yields and in up to 95% ee. In addition, we discovered a remarkable enhancement of efficiency and selectivity in the presence of an achiral phosphoramidate additive. Chapter 2: An efficient diastereo- and enantioselective Ag-catalyzed method for additions of a commercially available siloxyfuran to α-ketoimine esters is disclosed. Catalytic transformations require an inexpensive metal salt (AgOAc) and an air stable chiral ligand that is readily prepared in three steps from commercially available materials in 42% overall yield. Aryl- as well as heterocyclic substituted ketoimines can be used effectively in the Ag-catalyzed process. Additionally, two examples regarding reactions of alkyl-substituted ketoimines are presented. An electronically modified N-aryl group is introduced that is responsible for high reaction efficiency (>98% conversion, 72–95% yields after purification), diastereo- (up to >98:2 dr) and enantioselectivity (up to 97:3 er or 94% ee). The new N-aryl unit is also crucial for conversion of the asymmetric vinylogous Mannich products to the unprotected amines in high yields. Spectroscopic and X-ray data are among the physical evidence provided that shed light on the identity of the Ag-based chiral catalysts and some of the mechanistic subtleties of this class of enantioselective C–C bond forming processes. / Thesis (PhD) — Boston College, 2008. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: James P. Morken / This dissertation details the development of several enantioselective or stereospecific transformations involving organoboronic esters. Chapter one will introduce electrophile-induced boronate rearrangements which underpins much of the reactivity that will be discussed in subsequent chapters. In chapter two the conjunctive cross-coupling reaction is presented. Its development and application to the synthesis of non-racemic boronic esters, along with its application to the synthesis of enantioenriched allylic boronic esters, will be discussed. In chapter three the cross-coupling of geminal bis(boronic) esters is introduced and the development of a method to employ them in cross-coupling with alkenyl bromides, affording enantioenriched substituted allylic boronic esters is outlined. In chapter four we highlight the utility of allylic boronic esters, and detail the development of a cross-coupling reaction that involves the use of these substrates and halide electrophiles to furnish enantiomerically enriched products containing all carbon quaternary stereocenters. Finally, in chapter five we describe the development of a metalfree amination reaction of organoboron compounds, which is able to deliver otherwise difficult-to-access enantiomerically enriched α-tertiary amines. / Thesis (PhD) — Boston College, 2018. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.