Browsing by Subject "Cyanoamidation"

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    Carbon-carbon sigma bond activation: functionalizing C-C and C-CN Bonds via carboacylation and cyanoamidation
    (2015-01) Dreis, Ashley Michelle
    Chapter One. The content of this chapter broadly describes the growing area of carbon¬-carbon (C-C) sigma bond activation. The barriers to bond activation and the strategies employed to overcome these barriers will be summarized. Examples of stoichiometric and catalytic reactions utilizing strained systems and other thermodynamic driving forces are presented in addition to kinetic strategies enforced through cyclometalation.Chapter Two. The focus of the second chapter is on my discoveries in quinoline-directed C-C bond activation. A series of catalytic intramolecular carboacylation reactions with both alkenes and alkynes will be discussed. The mechanism(s) of such transformations were elucidated by researchers at Hope College and will be presented. The intermolecular carboacylation with norbornenes discovered by other Douglas group members will be acknowledged, and preliminary investigations into the idea of migratory insertion (or sigma-bond metathesis) across cyclopropane will be provided.Chapter Three. The third chapter of this thesis describes my efforts to uncover a synthetically viable directing group for C-C bond activation. Directing groups that are anticipated to be removable and reusable, such as quinoline esters, pyridyl esters, and azaindoles, will be described. Efforts to promote C-C activation with versatile triazene directing groups will be discussed. The strategy of metal-organic cooperative catalysis (MOCC) was explored with guanidines and 2-amino pyrimidine diol derivatives, and the concept of Lewis acid or hydrogen-bond-mediated directing groups will be proposed. Chapter Four. Chapter four provides a selected review of carbon-nitrile (C-CN) bond activation. Cleavage of alkyl, allyl, alkenyl, aryl, acyl, and carbamoyl C-CN bonds that undergo subsequent functionalization will be reported. Intramolecular variations of such reactions are highlighted in complex molecule syntheses.Chapter Five. The final chapter will explain my efforts in developing enantio- and diastereoselective routes to 3,3-disubstituted lactams via C-CN bond activation (cyanoamidation). β-, λ-, and δ-lactams are shown to be effectively prepared through this methodology, and attempts to access ε-lactams will be discussed.
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    Development of Stereoselective Cyanoamidation Reactions and Their Application to Natural Product Total Synthesis
    (2019-12) Eastwood, Matthew
    Chapter 1. A survey of the literature to date on the palladium-catalyzed cyanoamidation reaction, both in terms of synthesis and mechanism. Details of work expanding the substrate scope of diastereoselective alkene cyanoamidation, as well as studies toward the removal of the chiral directing group, which necessitated development of a method for chemoselective reduction of hindered lactams in the presence of nitriles. Chapter 2. A review of the literature regarding the synthesis of asymmetric Aspidosperma alkaloids quebrachamine and eburnamonine. Approaches to scalemic material by a wide variety of routes. Chapter 3. A discussion of work towards an enantioselective cyanoamidation of a highly functionalized aliphatic-tethered alkene towards the synthesis of Aspidosperma alkaloids is presented. Efforts toward the functionalization of cyanoamidation products towards quebrachamine, including attempts at forming the alkaloid’s nine-membered ring and the application of diastereoselective cyanoamidation, are discussed. A successful total synthesis of (+)-eburnamonine in four steps from the scalemic cyanoamidation product. Chapter 4. A review of the literature published to date on the synthesis of madangamine alkaloids, including approaches to the diazatricyclic core, macrocyclic rings, and completed total syntheses of various members of the madangamine family. Chapter 5. A discussion of the variety of approaches undertaken towards the synthesis of a di(cyanoformamide) thought to be a viable substrate for a cyanoamidation-based C–C bond activation cascade for making the madangamine core. Details of the development of said cascade reaction and successful synthesis of a madangamine core derivative.
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    Studies of Intramolecular Cyanoamidation with Alkenes and Application Toward the Total Synthesis of Natural Products
    (2017-10) Otte, Sadie
    Chapter One. A brief discussion of the relevant background in intramolecular cyanoamidation. Examples from successive methodology studies are given. The proposed mechanism and published mechanistic experiments are presented, along with its applications in the synthesis of complex molecules. Chapter Two. A summary of the design, discovery, and optimization of the diastereoselective intramolecular cyanoamidation reaction is presented. Significant findings are discussed along with a preliminary substrate scope. A detailed description of our attempts to cleave the chiral directing group is given. Chapter Three. An overview of the Aspidosperma alkaloid family with an emphasis on quebrachamine is presented. A discussion is given of the isolation, biological activity, and previous total syntheses of quebrachamine. Strategies for the synthesis of the all–carbon quaternary center and formation of the nine–membered ring are specified. Chapter Four. A novel strategy for the total synthesis of quebrachamine via intramolecular cyanoamidation is proposed. Three routes to the key cyanoformamide intermediate are presented. Optimization of the intramolecular cyanoamidation is described along with reproducibility studies. Progress toward the final ring closure between indole and nitrile groups via one– and two–step methods is discussed, along with future work. Chapter Five. The application of a serendipitously discovered Bischler–Napieralski-type reaction toward the total synthesis of eburnamonine is proposed. Optimization of the reaction is discussed along with attempts to grow high-quality crystals of the product. Subsequent efforts to hydrogenate the iminium ion product are presented.