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- Creators: School of Life Sciences
- Creators: Hindemith, Paul, 1895-1963
The development of novel aqueous cross-coupling strategies has emerged as a rapidly expanding area of research within organic synthesis. However, many of these cross-coupling reactions require the pre-formation of an organohalide substrate, which often involves toxic halogenating reagents and harsh reaction conditions. This work details the development of a tandem halogenation/cross-coupling procedure in which an electron-rich arene or heteroarene is brominated through an enzymatic halogenation reaction catalyzed by a vanadium dependent haloperoxidase (VHPO) and then used without workup in a subsequent aqueous Suzuki cross-coupling reaction. This sequential process allows the arylated product to be accessed in a single pot from the unfunctionalized substrate via the brominated intermediate. Optimization of the enzymatic halogenation step was performed for three different substrates, resulting in the discovery of conditions for the bromination of 2,3-dihydrobenzofuran, chromane, and anisole in high yield (>95%). The scope of the reaction was then investigated for a range of electron-rich arene and heteroarene substrates. Next, Suzuki cross-coupling conditions were developed in a reaction mixture of pH 5 citrate buffer and acetonitrile and applied to the arylation of 2,3-dihydrobenzofuran utilizing an array of arylboronic acid coupling partners. Finally, the two procedures were combined to perform a tandem enzymatic halogenation/aqueous Suzuki cross-coupling of 2,3-dihydrobenzofuran to give the arylated product in 74% yield.
The trifluoromethyl group is an essential chemical motif in pharmaceutical and agrochemical industries. The trifluoromethyl group has similar steric bulk to a methyl group, but exhibits strongly electron withdrawing properties. As a result, a trifluoromethyl group can provide a molecule with enhanced lipophilicity, bioavailability, and metabolic stability, which makes it a commonly used tool to tune activity of agrochemicals and pharmaceutical candidates. There are many methods to generate a new trifluoromethyl moiety, but many of these methods rely on stoichiometric metal reagents or harsh reaction conditions. One strategy to install the trifluoromethyl group under benign conditions is with photoredox catalysis. In the field of photocatalysis, iron has emerged as an alternative for precious metals due to its low cost, earth-abundance, and environmentally benign nature. Methods of trifluoromethylation utilizing iron catalysis do exist, but they often rely on expensive CF3 precursors such as Togni’s Reagent and trifluoromethyl iodide. This thesis demonstrates a method using iron photocatalysis for decarboxylative trifluoromethylation of alkenes using trifluoroacetic acid. We have successfully enabled trifluoromethylation of select methoxy-substituted benzene derivatives as well as a number of alkenes, including those bearing sulfone and ketone groups.
The status of Earth’s diversity is deteriorating quickly which will continue to impact humans’ way of life, as well as every other living creature, in all regions of the world. However, there are organizations taking action to protect biodiversity on our planet. The Convention on Biological Diversity (CBD) is one of those organizations and includes 196 signatories from around the world who are committed to strategies to preserve their biodiversity (Secretariat). Indeed, 98% of the parties which have participated in the Convention on Biological Diversity (CBD) have created national biodiversity strategies (NBS) and action plans (NBSAPs) (Secretariat). Yet, there are still countries that have yet to partake in these efforts. America continues to hold out against ratifying the CBD and remains the only developed country without a National Biodiversity Strategy. As an NBS for the U.S. is under consideration, my goal is to understand what works from previous plans. In particular, I focus on stakeholder engagement in Conservation Biodiversity Action Plans. Stakeholder engagement is important because, without it, there may be insufficient levels of integration of the action plans, which can lead to the failure of the CBDs conservation efforts. To address this question, I analyze the 193 strategies created for countries across the globe. My review describes the ways that stakeholders are engaged in National Biodiversity Strategies for CBD member countries. All plans mention some form of engagement. The most common types mentioned are ‘Education’, ‘Communication’, and ‘Training’. Examining the plans further reveals that most forms of engagement often are just mentioned and not completed. Close to 58% of the engagement forms are only completed about 50% of the time. Exceptions are surveys, interviews, and workshops, which are each completed in over 70% of plans that mention them. I then use this information to provide practical recommendations for creating an effective NBSAP for the United States.