Synthesis Of Heterocycles Via Palladium Catalyzed Carbonylative Annulation Of Internal And Terminal Alkynes

Author : Gerardo Martin Torres
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (119 download)

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Download or read book New Palladium Catalyzed Carbonylative Approaches to Heterocycle and Acid Chloride Synthesis written by Gerardo Martin Torres and published by . This book was released on 2020 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Metal catalyzed carbonylation reactions are heavily exploited in synthetic chemistry. These include not only high volume industrial reactions, but also a plethora of catalytic small molecule syntheses. This thesis will describe our efforts to develop such reactions. In these, palladium catalyzed carbonylations are exploited to build-up reactive products such as acid chlorides or carbonyl-containing 1,3-dipoles. Coupling this with the ability of the products undergo other spontaneous reactions can offer new routes to build up products from combinations of available reagents or be used to expand the scope of carbonylation chemistry. In chapter 2, we describe how the palladium catalyzed carbonylation of aryl iodides in the presence of imines can allow the overall generation of a 1,3-dipole: a Münchnone. A variety of mechanistic studies were performed on this reaction and show that it proceeds via a tandem catalytic process: the first involving the Pd catalyzed coupling of aryl iodides with carbon monoxide and a chloride salt to form an acid chloride, which can react with an imine and then undergo a second spontaneous cyclocarbonylation to afford the product. Coupling their formation with alkyne cycloaddition can be used to develop a novel method to assemble broad families of pyrroles from aryl iodides, imines, carbon monoxide and alkynes. In Chapter 3 we develop a strategy to apply our palladium catalyzed carbonylative synthesis of Münchnones to construct more complex pyrrole structures. In this, the combination of alkyne-tethered imines, aryl iodides, and carbon monoxide generates a Münchnone that can undergo intramolecular 1,3-dipolar cycloaddition to generate polycyclic pyrroles. This approach allows the modular and regioselective synthesis of complex pyrrole structures, and is compatible with less activated alkynes. In addition, we show that this reaction can be used in tandem with the palladium catalyzed Sonogashira functionalization of terminal alkynes with aryl iodides.In Chapter 4 we describe our efforts to take advantage of the ketene-like reactivity of Münchnones to generate [beta]-lactams. This transformation occurs via the palladium catalyzed formation of Münchnones from imines, aryl iodides, and carbon monoxide, followed by a cycloaddition to a second equivalent of imine to afford amide substituted [beta]-lactam products. Moreover, applying the conditions described in Chapter 2 for the synthesis of Münchnones allowed us to construct more diversely substituted [beta]-lactams by reacting the Münchnone with a different imine. Alternatively, the palladium catalyzed carbonylation of imine-tethered aryl iodides leads to the formation of novel spirocyclic [beta]-lactams.The palladium catalyzed synthesis of acid chlorides is a key component to the synthetic approaches to heterocycles presented in Chapters 2-4. However, the specific features that enable the catalyst to mediate the challenging reductive elimination of acid chlorides also inhibit the reverse oxidative addition step. In Chapter 5 we address these limitations by approaching this palladium catalyzed reaction from a different perspective. In this, visible light is used to drive both key steps in palladium catalysis: oxidative addition and reductive elimination. Analogous to other reports, we show that visible light excitation of a Pd complex can drive oxidative addition of a wide variety of aryl and alkyl halides. In addition, we find that visible light can induce a new reaction step the reductive elimination of acid chlorides. The latter occurs via the excitation in this case of the palladium-acyl intermediate. Together, this offers a platform to perform palladium catalyzed carbonylations at ambient temperature, with a wide array of organic halide substrates that have proven to be challenging in traditional palladium catalysis, and form from these acid chloride electrophiles that can allow the use of nucleophiles that are typically incompatible with carbonylations"--