No description available.

No description available.

Thesis advisor: James P. Morken / 1,1-Bis(boronic) esters have attracted significant attention these days due to their unique reactivity. In this thesis, I will show that readily available reagents can undergo deborylative alkylation to deliver synthetically useful primary, secondary and tertiary boronic esters. 1,1-Diboryl alkanes can also engage in base-promoted deborylative cyclization to afford diversified cyclopentane rings with boron motifs attached. This transformation is very appealing because of the prevalence of five-membered rings in natural products. Lastly, it will be showed that geminal bis(boronic) esters can act as an important cornerstone in constructing relatively complicated structures such as natural product Arenolide. / Thesis (PhD) — Boston College, 2018. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Boronic acids are key reagents in a host of chemical applications. In particular, they have been utilised in a range of metal-catalysed coupling reactions, involving the facile formation of carbon-carbon or carbon-heteroatom bonds under mild conditions that often boasts high yields and selectivity, thus becoming a vital tool in the design of complex molecules. Alongside the increased application of boronic acids, there has been a substantial increase in their commercial availability and now a wide range of elaborate boronic acids exist. However, many of these motifs are prone to undesired and troublesome side reactions, namely protodeboronation. Although many efforts have been made towards mitigating decomposition during coupling, the general mechanistic understanding of in situ protodeboronation is remarkably limited and outdated. pH-rate profiles for the protodeboronation of many heterocyclic, vinyl and cyclopropyl boronic acids (1:1 H2O/dioxane, pH 1-13, 70 °C) have been constructed using NMR spectroscopy. A general model was constructed to allow the simulation of pH-rate profiles and allow facile extrapolation of equilibrium and rate constants. With computational support, a range of novel protodeboronation mechanisms have been elucidated. Concentration-dependent processes (self-/auto-catalytic protodeboronation and disproportionation of boronic acid into borinic acid and boranes) are present when both boronic acid and boronate are present in high concentrations. Non-basic heterocyclic, vinyl and cyclopropyl boronic acids display common acid- and base-catalysed protodeboronation mechanisms, however basic heterocyclic boronic acids exhibit additional pathways. The formation and subsequent fragmentation of zwitterion water adducts (particularly for 2-pyridyl, 5-thiazolyl and 5- pyrazolyl boronic acids) leads to surprisingly rapid protodeboronation at neutral pH values, which can be attenuated (2-pyridyl) or accelerated (5-thiazolyl/5-pyrazolyl) with various Lewis acid additives. Protodeboronation of a series of polyfluorophenyl boronic acids under alkaline conditions revealed an immense range of reactivity, spanning several orders of magnitude (phenyl boronic acid, t½ ≈ months; pentafluorophenyl boronic acid, t½ ≈ milliseconds). Ortho-fluorine substituents were found to heavily influence the reactivity of such substrates. Detailed KIE and computational studies indicate the presence of a unique mechanism involving rate-limiting fragmentation of aryl boronate to form an aryl anion intermediate. Strong correlations with LFER and computational parameters indicate this mechanism is predominant with extremely electron deficient or ortho-fluoro substituted substrates, and can be used as a predictive model for the reactivity of aryl and polyfluorophenyl boronic acids.

Amine-functionalized boronic acids have revolutionized the field of carbohydrate sensing in recent years. Capable of rapidly and reversibly forming cyclic boronate esters with of 1,2- and 1,3-diols, polyols, catechols, and α-hydroxycarboxylic acids, boronic acids have found applications spanning from lipid transport to Hydrogen fuel cells. The majority of the work presented in this dissertation will be aimed at gaining a better understanding of the Boron-Nitrogen interactions in ortho-aminomethyl functionalized boronic acids. Chapter 2 will provide an overview of the mechanistic understanding of boronic acid-diol interactions with a special focus on amine-functionalized boronic acids. Chapters 3 – 5 report the progress made by the Anslyn group to develop a more thorough understanding of Boron-Nitrogen interactions and how they affect boronate ester formation. The first introductory chapter will present a the recent advances that have been made in the development of pattern-based sensor systems. Finally, chapter 6 will present the synthesis of a series of bicycloguanidinium hosts, which will be used in a sensing array for chiral carboxylates. / text

Boronic acids, particularly those that carry an ortho-aminomethyl group, have been extensively utilized in the field of molecular recognition in recent years thanks to their ability to reversibly bind to a wide variety of polyol substrates. They have been shown to form cyclic boronate esters rapidly upon reaction with 1,2- and 1,3-diols, catechols, carbohydrates and hydroxycarboxylic acids, making them attractive as potential sensing units. While they have found broad application in this forum, the mechanism by which they work is still up for debate. This work begins in Chapter 1 with a review of the fundamentals of ¹¹B NMR spectroscopy and its application on the analysis of boronic acid-containing systems. The focus of Chapter 2 turns toward systems with an o-iminomethylphenylboronic acid moiety. This species can be formed easily through a three-component assembly, though physical understanding of this complex lags behind. With the fundamentals of ¹¹B NMR spectroscopy detailed previously, the results obtained when utilizing this technique to study both the structure and mode of interaction in these species will be presented. In Chapter 3 we give a comprehensive review of the data and conclusions that have been published by different groups about one of the most successful fluorescent sugar sensors of this kind, first introduced by Seiji Shinkai in 1994. Additionally, it delineates the experimental results obtained by our group when attempting to answer some of the remaining questions. In Chapter 4 we report the use of the aforementioned multi-component assembly as an enantioselective sensor for α-chiral primary amines. Using circular dichroism, the ee% of these analytes could be accurately determined with this system. Additionally, enantio- and chemodiscrimination was possible by employing chemometric tools like PCA and LDA. Finally, Chapter 5 is a compilation of efforts to expand the use of these sensing systems into synthetic organic chemistry research labs. In collaboration with Xumu Zhang at Rutgers University, we have implemented a previously developed system to analyze the product of an asymmetric hydrogenation of an imine to create a chiral amine. A proof of concept study on a novel automated circular dichroism plate reader prototype aimed to increasing sample throughput was completed at New York University with Professor Bart Kahr. / text

Boronic acids play an important role in the design and synthesis of chemosensors for carbohydrates due to their ability to reversibly bind with diol-containing compounds. Along this line, the availability of boronic acids that change fluorescence upon sugar binding is critical to a successful sensor design effort. Here, two boronic acids that show strong fluorescent intensity changes upon sugar binding are reported: isoquinoline-7-boronic acid (7-IQBA) and phenoxathiin-4-boronic acid (4-POBA).

Quartz crystal microbalances, (QCM), are high frequency oscillators, capable of nanogram mass resolution in both air and liquid environments. ~ work has produced data showing the feasibility of using the QCM for monitoring interactions in liquids for several types of systems and has allowed comparison with surface plasmon resonance (SPR) where appropriate. Bulk phase changes in viscosity and density have been used in the development of a QCM agglutination assay for the Staphylococcus epidermidis infection which has reduced diagnosis periods by a factor of twelve. Direct interactions at the crystal electrode have been employed when studying bacterial adhesion to protein treated gold surfaces. It was shown that suspensions containing as little as I x 10-2 cellsml-1 could be recognised using the QCM system. A novel boronic acid - vicinal diol interaction mechanism has been employed as a model for receptor-ligand binding. New boronic acid disulphide and short chain thiol derivatives have been synthesised and the formation of self assembled monolayers of the~e compounds monitored, both on the gold QCM electrodes and on the gold films of SPR slides, the assembly mechanism being shown to fit a two stage model shown by other workers for straight chain thiols. Monolayer orientation was confirmed using SPR, by the binding of a range of saccharides and the diol containing enzyme cofactor nicotinamide adenine dinucleotide. The enzymes lactate dehydrogenase and glucose-6-phosphate dehydrogenase have been shown to interact with bound NAD using both a novel flow injection system with QCM detection and SPR. The low molecular weight saccharide, glucose, was shown to bind reversibly to GDH on the surface of a QCM and the potential for kinetic stu4ies recognised. This was taken one step further with a preliminary investigation into sensing within real fluids, using diluted and spiked human seruin samples.

No description available.

The research presented herein is concerned with the exploration of rhodium-catalysed addition reactions with organoboranes encompassing the 1,4-addition enolate protonation to benzyl acrylate esters, and the synthesis of chiral organoboranes for use in the synthesis of natural products Hermitamides A and B. Chapter 1 introduces the area of rhodium-catalysed conjugate addition as a tool for asymmetric synthesis. An extensive discussion of this methodology is included and recent advances in the area will be highlighted. In addition to this some recently published alternatives to organoboranes are outlined and their use in rhodium-catalysed chemistry documented. Chapter 2 discusses the tandem process of rhodium-catalysed conjugate addition enolate protonation, a recently observed asymmetric development. By using a novel route to benzyl acrylic esters the synthesis of α,α′-dibenzyl esters is achieved in excellent yields and selectivity. This study highlights the fact that when dealing with 1,1-disubstituted activated alkenes it is more difficult to produce enantioselective results as the chirality is determined in the protonation step and not during insertion. Some insights into the mechanism are proposed based on the outcomes observed. Chapter 3 describes the total synthesis of Lyngbic Acid and related structures Hermitamides A and B. Synthesis of these natural products are achieved by synthesis of an enantiopure organoborane species and its subsequent coupling via rhodium catalysis. Some interesting insights into the addition of alkenyl organoborane species to unsubstituted 1,1-activated alkenes are detailed. Chapter 4 describes the synthesis and characterisation for the compounds discussed in the previous chapters.