Strong and Confined Acids Enable a Catalytic Asymmetric Nazarov Cyclization of Simple Divinyl Ketones

We report a catalytic asymmetric Nazarov cyclization of simple, acylic, alkyl-substituted divinyl ketones using our recently disclosed strong and confined imidodiphosphorimidate Brønsted acids. The corresponding monocyclic cyclopentenones are formed in good yields and excellent regio-, diastereo-, and enantioselectivities. Further, the chemical utility of the obtained enantiopure cyclopentenones is demonstrated

The Development of Strong Chiral Brønsted Acids for Asymmetric Hydrofunctionalizations of Olefins

The main objective of this thesis is to design and synthesize chiral Brønsted acids capable of catalyzing the functionalization of weakly basic olefins. Olefins are a particularly intriguing substrate class because while they are widely available, many being considered feedstock chemicals, they have so far eluded asymmetric organocatalysis. In our efforts to resolve this major limitation of the field, our group recently reported an intramolecular asymmetric hydroalkoxylation using highly confined and chiral Brønsted acids, imidodiphosphorimidates (IDPi), to provide enantioenriched tetrahydrofurans and tetrahydropyrans in high yields and excellent enantioselectivities. Mechanistic investigations, including computational and kinetic analyses, suggest that the reaction proceeds via a concerted, though asynchronous pathway, in which the reaction is initiated by protonation of the olefin followed by C−O bond formation. The PhD studies described herein have focused on accessing similar reactivity in intermolecular systems. Namely, in chapter 2 of this thesis, the development of an intermolecular hydroalkoxylation reaction of styrenyl olefins with oxygenated nucleophiles is described. In particular, we report the hydroalkoxylation of styrene with benzyl alcohol to afford the corresponding ether in 95% yield with a very promising enantioselectivity (er = 76.5:23.5). The reaction is tolerant of a range of nucleophilic partners, including alcohols, carboxylic acids, and phenols to yield the corresponding functionalized products with moderate degrees of enantioinduction. Our efforts to increase the enantioselectivity of these transformations through catalyst optimization are delineated. Further, we report preliminary investigations into the asymmetric hydroalkoxylation of structurally-simple olefins. In chapter 3, we report the development of a new class of highly acidic chiral catalysts, deemed imido-(N,Nʹ-bis(sulfonimidoyl))-diphorphorimidates (I2DPi’s). This development was inspired by the work of Yagupolskii, who, among others, has described dramatic increases in the acidity of neutral molecules toward superacids by substituting S=O bonds with S=NSO2CF3 (S=NTf) bonds. These novel scaffolds not only enable significantly increased reactivity in both Brønsted and Lewis acid catalysis, but uniquely provide two additional chiral handles for tuning enantioselectivity within the catalyst pocket, potentially offering new avenues in acid catalyzed transformations

Catalytic Asymmetric Hydroalkoxylation of C–C Multiple Bonds

Asymmetric hydroalkoxylation of alkenes constitutes a redox-neutral and 100% atom-economical strategy toward enantioenriched oxygenated building blocks from readily available starting materials. Despite their great potential, catalytic enantioselective additions of alcohols across a C–C multiple bond are particularly underdeveloped, especially compared to other hydrofunctionalization methods such as hydroamination. However, driven by some recent innovations, e.g., asymmetric MHAT methods, asymmetric photocatalytic methods, and the development of extremely strong chiral Brønsted acids, there has been a gratifying surge of reports in this burgeoning field. The goal of this review is to survey the growing landscape of asymmetric hydroalkoxylation by highlighting exciting new advances, deconstructing mechanistic underpinnings, and drawing insight from related asymmetric hydroacyloxylation and hydration. A deep appreciation of the underlying principles informs an understanding of the various selectivity parameters and activation modes in the realm of asymmetric alkene hydrofunctionalization while simultaneously evoking the outstanding challenges to the field moving forward. Overall, we aim to lay a foundation for cross-fertilization among various catalytic fields and spur further innovation in asymmetric hydroalkoxylations of C–C multiple bonds

Transition metal-catalyzed olefin functionalization for highly regio-, enantio-, and chemoselective C–X bond formation

The development of alkene functionalizations is an important challenge in modern catalysis.1 This thesis specifically focuses on using transition metal-catalysis to form C–X bonds from C–C double bonds with high degrees of regio-, chemo-, and stereoselectivity. In chapter 1, a regiodivergent Rh-catalyzed hydrothiolation of allyl amines to form 1,2- or 1,3-aminothioethers with excellent degrees of regioselectivity is reported. Bidentate phosphine ligands with larger natural bite angles (βn ≥ 99°) promote a Markovnikov-selective hydrothiolation in up to 88% yield and >20:1 regioselectivity. Conversely, when smaller bite angle ligands (βn ≤ 86°), are employed, the anti-Markovnikov product is formed in up to 74% yield and >20:1 regioselectivity. Initial mechanistic investigations are consistent with an oxidative addition/olefin insertion/reductive elimination mechanism for each pathway. We hypothesize that the change in regioselectivity is an effect of diverging coordination spheres to favor either Rh–S or Rh–H insertion to form the branched or linear isomer, respectively. In chapter 2, initial studies on an asymmetric hydroamination method for the highly enantioselective formation of a chiral 1,2-diamine are discussed. To our delight, we have identified a MeO-BIPHEP-type ligand that promotes the hydroamination of allyl amines in moderate yield with excellent enantioselectivity. Ligand discovery and initial optimization are described. Finally, in chapter 3, an anti-Markovnikov oxidative amination reaction of terminal olefins with pendent aryl- or alcohol functionality is presented. Alkenes are shown to react with imides in the presence of a palladate catalyst to afford the terminally aminated product. Following an anti-Markovnikov selective trans-aminopalladation, a thermodynamically-driven redox relay process occurs away from the newly formed C–N bond to afford a terminal Csp3–N bond and a ketone or styrene moiety. The functional group tolerance is explored and results of preliminary mechanistic investigations are shown

Hydrolytic Degradation of 3D-Printed Poly (Lactic Acid) Structures

Hydrolytic degradation of commercially available 3D printing filament, i.e. poly (lactic acid) with broad molecular weight distribution was induced by incubating 3D-printed parts in deionized water at 3 temperatures. Small changes in orthogonal dimensions occurred due to relaxation of printing stresses, but no mass or volume loss were detected over the time-frame of the experiments. Molecular weight decreased while polydispersity remained constant. The most sensitive measure of degradation was found to be nondestructive, small-amplitude oscillatory tensile measurements. A rapid decay of tensile storage modulus was found with an exponential decay time constant of about an hour. This work demonstrates that practical monitoring of commercially available PLA degradation can be achieve with linear viscoelastic measurements of modulus

Microphase separation of highly amphiphilic, low N polymers by photoinduced copper-mediated polymerization, achieving sub-2 nm domains at half-pitch

The lower limit of domain size resolution using microphase separation of short poly(acrylic acid) homopolymers equipped with a short fluorinated tail, posing as an antagonist 'A block' in pseudo AB block copolymers has been investigated. An alkyl halide initiator with a fluorocarbon chain was utilized as a first 'A block' in the synthesis of low molecular weight polymers (1400-4300 g mol -1) using photoinduced Cu(ii)-mediated polymerization allowing for very narrow dispersity. Poly(tert-butyl acrylate) was synthesized and subsequently deprotected to give very low degrees of polymerization (N), amphiphilic polymers with low dispersity (D = 1.06-1.13). By exploiting the high driving force for demixing and the well-defined 'block' sizes, we are able to control the nanostructure in terms of domain size (down to 3.4 nm full-pitch) and morphology. This work demonstrates the simple and highly controlled synthesis of polymers to push the boundaries of the smallest achievable domain sizes obtained from polymer self-assembly

Porous Hollow TiO2 Microparticles for Photocatalysis: Exploiting Novel ABC Triblock Terpolymer Templates Synthesised in Supercritical CO2

Reversible addition–fragmentation chain transfer (RAFT) mediated dispersion polymerisation in supercritical carbon dioxide (scCO2) is an efficient and green method for synthesising block copolymer microparticles with internal nanostructures. Here we report for the first time the synthesis of phase separated poly(methyl methacrylate-block-styrene-block-4-vinylpyridine) (PMMA-b-PS-b-P4VP) triblock terpolymer microparticles using a simple two-pot sequential synthesis procedure in scCO2, with high monomer conversions and no purification steps. The microparticles, produced directly and without further processing, show a complex internal nanostructure, appearing as a “lamellar with spheres” [L + S(II)] type morphology. The P4VP block is then exploited as a structure-directing agent for the fabrication of TiO2 microparticles. Through a simple and scalable sol–gel and calcination process we produce hollow TiO2 microparticles with a mesoporous outer shell. When directly compared to porous TiO2 particles fabricated using an equivalent PMMA-b-P4VP diblock copolymer, increased surface area and enhanced photocatalytic efficiencies are observed

Exploration and Optimization of a [2]Rotaxane Synthesis via Ring-Opening Cross Metathesis of a [2]Catenane and a Doubly-Stoppered Axle

In our efforts to develop a new route toward rotaxane synthesis, we have envisioned the insertion method. This rotaxane-forming transformation can be achieved by the ring-opening of a [2]catenane followed by its in situ “insertion” into a doubly-stoppered axle. The process incorporates two modern synthetic techniques, i.e. olefin metathesis and metal templation. The first step to study and optimize the insertion method is to synthesize three complex molecules i.e., a macrocycle, an α,ω-diene, and a doubly-stoppered axle. Our progress thus far includes the complete synthesis of both the macrocycle and the α,ω-diene, as well as the partial synthesis of the doubly-stoppered axle. Future work will include: (1) completing the synthesis of the doublystoppered axle via a cross-metathesis reaction, (2) synthesizing more α,ω-diene, (3) completing the synthesis of the [2]catenane via complexation followed by olefin metathesis, and finally, (4) optimizing the insertion method

The Development of Strong Chiral Brønsted Acids for Asymmetric Hydrofunctionalizations of Olefins

The main objective of this thesis is to design and synthesize chiral Brønsted acids capable of catalyzing the functionalization of weakly basic olefins. Olefins are a particularly intriguing substrate class because while they are widely available, many being considered feedstock chemicals, they have so far eluded asymmetric organocatalysis. In our efforts to resolve this major limitation of the field, our group recently reported an intramolecular asymmetric hydroalkoxylation using highly confined and chiral Brønsted acids, imidodiphosphorimidates (IDPi), to provide enantioenriched tetrahydrofurans and tetrahydropyrans in high yields and excellent enantioselectivities. Mechanistic investigations, including computational and kinetic analyses, suggest that the reaction proceeds via a concerted, though asynchronous pathway, in which the reaction is initiated by protonation of the olefin followed by C−O bond formation. The PhD studies described herein have focused on accessing similar reactivity in intermolecular systems. Namely, in chapter 2 of this thesis, the development of an intermolecular hydroalkoxylation reaction of styrenyl olefins with oxygenated nucleophiles is described. In particular, we report the hydroalkoxylation of styrene with benzyl alcohol to afford the corresponding ether in 95% yield with a very promising enantioselectivity (er = 76.5:23.5). The reaction is tolerant of a range of nucleophilic partners, including alcohols, carboxylic acids, and phenols to yield the corresponding functionalized products with moderate degrees of enantioinduction. Our efforts to increase the enantioselectivity of these transformations through catalyst optimization are delineated. Further, we report preliminary investigations into the asymmetric hydroalkoxylation of structurally-simple olefins. In chapter 3, we report the development of a new class of highly acidic chiral catalysts, deemed imido-(N,Nʹ-bis(sulfonimidoyl))-diphorphorimidates (I2DPi’s). This development was inspired by the work of Yagupolskii, who, among others, has described dramatic increases in the acidity of neutral molecules toward superacids by substituting S=O bonds with S=NSO2CF3 (S=NTf) bonds. These novel scaffolds not only enable significantly increased reactivity in both Brønsted and Lewis acid catalysis, but uniquely provide two additional chiral handles for tuning enantioselectivity within the catalyst pocket, potentially offering new avenues in acid catalyzed transformations