Vinyl Carbocations Generated under Basic Conditions and Their Intramolecular C–H Insertion Reactions

Here we report the surprising discovery that high-energy vinyl carbocations can be generated under strongly basic conditions, and that they engage in intramolecular sp³ C–H insertion reactions through the catalysis of weakly coordinating anion salts. This approach relies on the unconventional combination of lithium hexamethyldisilazide base and the commercially available catalyst, triphenylmethylium tetrakis(pentafluorophenyl)borate. These reagents form a catalytically active lithium species that enables the application of vinyl cation C–H insertion reactions to heteroatom-containing substrates

Dancing in the office: A study of gestures as resistance

Following the art-body-ethics turn in management studies we use dance as an analogy in order to explore how the body can resist organisational control in office work contexts. We argue that in office work gestures can be a site of post-recognition resistance. Drawing on two art videos and on dance studies, we explain that this is operated either through arrest or through flow. In fact aesthetic experiments in gesturing disrupt the work rhythm needed for organisational efficiency and enforced by organisational control. This allows us to contribute primarily to the literature on resistance in organisation studies and relatedly to the growing literature on dance in organisation studies through demonstrating how dance can be a source of resistance

The Generation and Reactivity of Vinyl Carbocations

This dissertation describes efforts to generate vinyl carbocation intermediates to leveragetheir high–reactivity, with a particular focus on subsequent C–H insertion reactions to forge new C–C bonds. These intermediates have historically been difficult to generate using catalytic regimes, but in doing so their reactivity can be controlled to give high-yielding methodologies. Additionally, efforts to search for new means to generate these intermediates often leads to discovery of novel reactivity. A variety of conditions have been developed to generate these intermediates that will be highlighted in five chapters of this thesis. An initial overview will be given to demonstrate how access to vinyl carbocations has steadily increased in the past decades, allowing for discovery of novel reactivity particularly highlighted by C–H functionalization. Then, efforts of my colleagues and myself are partitioned into four main categories related to the generation of vinyl carbocations and their subsequent reactivity. In the first chapter current state-of-the-art and previous methods of vinyl carbocation generation are reviewed to shed light on the massive amount of work already dedicated to producing these reactive intermediates. The second and third chapters cover the development of Br�nsted basic conditions to generate these intermediates. These chapters detail the surprising discovery of utilizing lithium hexamethyl disilazide, a strong base, to generate vinyl carbocations that subsequently undergo C–H insertion reactions to yield olefinic products. These chapters will describe how these new basic conditions allowed for heteroatom containing substrates and additionally allowed for the use of much more easily accessible urea catalysts. The fourth chapter describes electrochemical means to gain access to these intermediates primarily for nucleophilic fluorination to produce fluoro-olefins. This work was a direct result of the annoyance in needing to use strong Lewis acids; while still allowing fairly diverse substrates, these conditions drastically limited the types of reagents that could be utilized and overall limited the methodology. Instead, Lewis-acid free conditions utilizing electrodes to oxidize substrates to the vinyl carbocation intermediate were developed. Finally, the fifth chapter details ongoing efforts to generate vinyl carbocations paired with chiral counterions to yield enantioselective C–H insertion reactions as well as the future outlook on other issues to tackle in developing new methodology. This work required small incremental discoveries in both catalyst and substrate design, and in all it took four PhD students almost two years to gain high levels of enantio- and regio- selectivity

Electrochemical Fluorination of Vinyl Boronates Through Donor-Stabilized Vinyl Carbocation Intermediates

The electrochemical generation of vinyl carbocations from vinyl boronic esters and boronates is reported. Using easy-to-handle nucleophilic fluoride reagents, these intermediates are trapped to form fully substituted vinyl fluorides. Mech-anistic studies support the formation of dicoordinated car-bocations through sequential single-electron oxidation events. Notably, this electrochemical fluorination features fast reaction times and mild conditions. This transfor-mation provides a complementary method to access vinyl fluorides with simple fluoride salts such as TBAF

Electrochemical Fluorination of Vinyl Boronates through Donor‐Stabilized Vinyl Carbocation Intermediates**

The electrochemical generation of vinyl carbocations from alkenyl boronic esters and boronates is reported. Using easy-to-handle nucleophilic fluoride reagents, these intermediates are trapped to form fully substituted vinyl fluorides. Mechanistic studies support the formation of dicoordinated carbocations through sequential single-electron oxidation events. Notably, this electrochemical fluorination features fast reaction times and Lewis acid-free conditions. This transformation provides a complementary method to access vinyl fluorides with simple fluoride salts such as TBAF

Chemocatalytic Amplification Probes Enable Transcriptionally-Regulated Au(I)-Catalysis in E. coli and Sensitive Detection of SARS-CoV-2 RNA Fragments

The union of transition metal catalysis with native biochemistry presents a powerful opportunityto perform abiotic reactions within complex biological systems.(1,2) However, several chemicalcompatibility challenges associated with incorporating reactive metal centers into complexbiological environments have hindered efforts in this area, despite the many opportunities it maypresent. More challenging than chemical compatibility is biocommunicative transition metalcatalysis, where the reactivity of the metal species is regulated by native biological stimuli, akinto natural biocatalytic processes. Here we report a novel Au(I)-DNAzyme that is activated by shortnucleic acids in a highly sequence-specific manner and that is compatible with complex biologicalmatrices. The active Au(I)-DNAzyme catalyzes the formation of a fluorescent molecule with >10turnovers. This functional allostery, resulting in chemocatalytic signal amplification, is competentin complex biological settings, including within recombinant E. coli cells, where the catalyticactivity of the Au(I)-DNAzyme is regulated by transcription of an inducible plasmid. We furtherdemonstrate the potential of this transition metal oligonucleotide complex as a highly sensitive andselective hybridization probe, permitting the detection of attomolar concentrations (ca. 60molecules/µL) of SARS-CoV-2 RNA gene fragments in simulated biological matrices with ≥85%accuracy. Notably, this sensitive detection platform avoids expensive and poorly-scalablebiochemical components (e.g. post-synthetically modified oligonucleotides or enzymes) andutilizes small molecule fluorophores, inexpensive Au salts and oligonucleotides composed ofcanonical bases. This discovery highlights promising opportunities to perform abiotic catalysis incomplex biological settings under transcriptional regulation, as well as a chemocatalytic strategyfor PCR-free, direct-detection of RNA and DNA.The union of transition metal catalysis with native biochemistry presents a powerful opportunity to perform abiotic reactions within complex biological systems. However, several chemical compatibility challenges associated with incorporating reactive metal centers into complex biological environments have hindered efforts in this area, despite the many opportunities it may present. More challenging than chemical compatibility is biocommunicative transition metal catalysis, where the reactivity of the metal species is regulated by native biological stimuli, akin to natural biocatalytic processes. Here we report a novel Au(I)-DNAzyme that is activated by short nucleic acids in a highly sequence-specific manner and that is compatible with complex biological matrices. The active Au(I)-DNAzyme catalyzes the formation of a fluorescent molecule with >10 turnovers. This functional allostery, resulting in chemocatalytic signal amplification, is competent in complex biological settings, including within recombinant E. coli cells, where the catalytic activity of the Au(I)-DNAzyme is regulated by transcription of an inducible plasmid. We further demonstrate the potential of this transition metal oligonucleotide complex as a highly sensitive and selective hybridization probe, permitting the detection of attomolar concentrations (ca. 60 molecules/ L) of SARS-CoV-2 RNA gene fragments in simulated biological matrices with ≥85% accuracy. Notably, this sensitive detection platform avoids expensive and poorly-scalable biochemical components (e.g. post-synthetically modified oligonucleotides or enzymes) and utilizes small molecule fluorophores, inexpensive Au salts and oligonucleotides composed of canonical bases. This discovery highlights promising opportunities to perform abiotic catalysis in complex biological settings under transcriptional regulation, as well as a chemocatalytic strategy for PCR-free, direct-detection of RNA and DNA.</p

Urea-Catalyzed Functionalization of Unactivated C–H Bonds

Herein we report the 3,5bistrifluoromethylphenyl urea-catalyzed functionalization of unactivated C–H bonds. In this system, the urea catalyst mediates the formation of high-energy vinyl carbocations that undergo facile C–H insertion and Friedel–Crafts reactions. We introduce a new paradigm for these privileged scaffolds where the combination of hydrogen bonding motifs and strong bases affords highly active Lewis acid catalysts capable of ionizing strong C–O bonds. Despite the highly Lewis acidic nature of these catalysts that enables triflate abstraction from sp2 carbons, these newly found reaction conditions allow for the formation of heterocycles and tolerate highly Lewis basic heteroaromatic substrates. This strategy showcases the potential utility of dicoordinated vinyl carbocations in organic synthesis.<br /