Presented herein is the development, optimization and mechanistic investigation of an Cu catalytic system for the oxidation of sp 3 C-H bond of simple arenes to form C-N bond in a direct manner. Due to the prevalence of nitrogen containing molecules among biologically active synthetic and natural compounds, synthetic chemists have always been motivated to develop new efficient ways to directly transform ubiquitous carbonhydrogen (C-H) bonds into carbon- nitrogen (C-N) bonds. Recent advances in transition metal catalyzed C-H amination has demonstrated that it is not only possible but also practical to functionalize C-H bonds that are often considered inert in one step, circumventing more classical, sequential functional group interconversion approaches. Existing catalytic systems that promote the transition metal-catalyzed, amination of sp 3 C-H bonds displayed certain limitations, especially the lack of built-in versatility and stability in their amination reagents. To overcome these drawbacks of these existing catalytic system, our group developed a new Cu amination protocol that deployed versatile hydroxylamine-based with general structure RSO 2 NH-OAc as amination reagents. Although the reactivity of the catalytic system ranges from moderate to good, the catalytic system provided promising results using simple arene substrates. Further detailed mechanistic studies revealed that the reaction undergoes an unprecedented two subsequent cycles divided by a major intermediate PhCH 2 (NTsOAc). The proposed mechanism is consistent with radical clock experiments, observed reaction profiles, the need for excess of substrate, and the documented role of the ligand in the catalytic system. The exciting proposed mechanism led to a new type of copper catalyzed amination reaction using N- fluorobenzenesulfonimide (NFSI) as oxidant, which overcomes the need to use an excess of substrate. A wide range of unactivated amines HNR 1 R 2 , including sulfonamide and benzamide, can be used as amine sources, which enables the installation of different nitrogen groups on benzylic sp 3 C-H bond of a variety of substrates in moderate to excellent yield. Moreover, mechanistic experiments and critical analysis of related reactivity in the literature provide insight into the catalytic cycle, resulting in a proposal that details the role of both oxidant and amine source in the new system.

Catalyst-Controlled Divergent C–H Functionalization of Unsymmetrical 2-Aryl Cyclic 1,3-Dicarbonyl Compounds with Alkynes and Alkenes A problem faced within the area of C–H functionalization is achieving siteselectivity when several similar C–H bonds are present within a given compound. One solution to this problem is the development of reactions that employ different catalytic systems to control the required selectivity. Herein, it is shown that such catalyst-controlled selectivity could be achieved on 2-aryl cyclic 1,3-dicarbonyl compounds where there exist two potential, non-adjacent sites for C–H functionalization. Examples demonstrate the palladium- and ruthenium-catalysed oxidative annulations of the 2-aryl cyclic 1,3-dicarbonyl substrates with alkynes, as well as with alkenes, where initial C–H bond cleavage occurs at one of two potential sites, depending on the catalyst used, which give unique products. 1,4-Rhodium(III) Migration in the One-Carbon Oxidative Annulations of 2-Arylphenols, Benzamides, and Benzoic Acids with 1,3-Enynes Oxidative annulations of 2-arylphenols, benzamides, and benzoic acids with alkynes and enynes are precedented and provide a range of heterocyclic products. However, in these examples, either the alkyne or enyne acts as a two-carbon annulation partner, reacting only across the alkynyl moiety. Herein, a more expansive scope of a previously published process in which 1,3-enynes, possessing allylic hydrogen atoms cis to the alkyne, undergo oxidative annulations with the three aforementioned classes of substrates as a one-carbon annulation partner is described. Proposed to occur via the 1,4-migration of a rhodium(III) species, annulated products were formed from a range of 1,3-enynes and substrates possessing a variety of functional groups.

No description available.

The C-H amination and olefin aziridination chemistry of iron supported by dipyrromethene ligands (RLAr, L=1,9-R2-5-aryldipyrromethene, R = Mes, 2,4,6-Ph3C6H2, tBu, Ad, 10-camphoryl, Ar = Mes, 2,4,6-Cl3C6H2) was explored. The weak-field, pyrrole-based dipyrrinato ligand was designed to generate an electrophilic, high-spin metal center capable of accessing high valent reactive intermediates in the presence of organic azides. Isolation of the reactive intermediate in combination with a series of mechanistic experiments suggest the N-group transfer chemistry proceeds through a rapid, single-electron pathway and maintains an overall S=2 electronic configuration throughout the catalytic cycle. We have established the catalysts' strong preference for allylic amination over aziridination with olefin containing substrates. Aziridination is limited to styrenyl substrates without allylic C-H bonds, while allylic amination has been demonstrated with both cyclic and linear aliphatic alkenes. Notably, the functionalization of &alpha-olefins to linear allylic amines occurs with outstanding regioselectivity. / Chemistry and Chemical Biology

No description available.

No description available.

Thesis advisor: Shih-Yuan Liu / Described herein are four projects focused on the elaboration of aromatic 1,2-azaborine core structures through late-stage functionalization strategies. In the first chapter, the gram scale, protecting group-free synthesis of the direct BN isostere of benzene is developed. This protocol is used to produce large quantities of pure 1,2-azaborine suitable for use in fundamental investigations. Second, the first general solution for the functionalization of the C4, C5, and C6 ring positions of 1,2-azaborines is described, featuring iridium catalyzed C-H borylation as the key strategy. Azaborine boronates produced via this method are successfully elaborated through cross coupling and oxidation to access azaborines that serve as N,N-ligands for electrophilic boron sources. The third project is an extension of the borylation/cross coupling project, and introduces the first polymer consisting of repeating azaborine units that displays highly efficient extension of conjugation along the azaborine chain. Finally, a copper catalyzed radical process is developed that enables removal of azaborine boron protecting groups during synthetic routes to simple azaborine targets of high interest. / Thesis (PhD) — Boston College, 2016. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

The field of metal-catalyzed C–H bond functionalizations is an incredibly vibrant and spans beyond the formations of biaryl motifs. The introduction chapter will cover the mechanistic aspects of the C–H bond functionalization with metal-carboxylate complexes. The mechanistic facets of this reaction will be the main conducting line between the different sections and chapters of the first part of this thesis. In the second chapter, will be described additives that can readily promoted C–H bond arylation of poorly reactive substrates. More specifically, we will revisit the intramolecular direct arylation reaction we will demonstrate the effect of pivalic acid as a co-catalyst by developing milder reaction conditions. In the third chapter we be described experimental and computational studies which suggested that the a single pathway might be involved in the palladium-catalyzed C–H bond functionalization of a wide range of (hetero)arene. Following this we will describe a general set of conditions for the direct arylation of wide range of heteroarenes. Also, we will present two different strategies to selectively and predictably arylate substrates containing multiple functionalizable C–H bonds. In the fourth chapter will be presented our efforts toward the development of new C–H bond functionalization methods in which we could apply our knowledge on the C–H bond cleavage and apply it to the formation of new scaffolds. The development of two new palladium-catalyzed methods were also described. In the fifth chapter, our effort toward the development of ligands to specifically promoted C–H bond cleavage will be presented. In the sixth chapter will be presented the latest results on the study of the mechanism of the C–H bond cleavage combining experimental and computational studies. In part B of this thesis will be presented our strategy toward the total synthesis of ginkgolide C that included two gold(I)-catalyzed reactions as key steps in the preparation of the spiro[4.4]nonane core of this natural product. The first studies on the feasibility of the key steps of the synthesis will be described.

The development of a novel palladium-catalyzed domino reaction with indole-based gem-dibromoolefin substrates is described. The reaction allowed access to a new class of polycyclic nitrogen heterocycles: N-fused benzo[c]carbazoles. A key feature of this domino reaction was the participation of both bromides in C–H functionalization processes, a hitherto unprecedented reactivity. Various substituents and substitution patterns were tolerated in this reaction, allowing for a highly modular approach to these challenging synthetic targets. Mechanistic studies were performed to gain further insight into the reactivity of these systems and elucidate the sequence of reaction steps. The results indicate that isomerization of reaction intermediates likely played a key role in promoting a successful reaction.

The development of a novel palladium-catalyzed domino reaction with indole-based gem-dibromoolefin substrates is described. The reaction allowed access to a new class of polycyclic nitrogen heterocycles: N-fused benzo[c]carbazoles. A key feature of this domino reaction was the participation of both bromides in C–H functionalization processes, a hitherto unprecedented reactivity. Various substituents and substitution patterns were tolerated in this reaction, allowing for a highly modular approach to these challenging synthetic targets. Mechanistic studies were performed to gain further insight into the reactivity of these systems and elucidate the sequence of reaction steps. The results indicate that isomerization of reaction intermediates likely played a key role in promoting a successful reaction.