Rhodium-Catalyzed Cyclocarbonylation Reactions: Construction of Unsaturated Six-Membered Rings and Enantioselective Pauson–Khand-Type Reactions of 1,6-Chloroenynes

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Burnie, Andrew
Rhodium , Cyclocarbonylation , Carbocyclization , Pauson–Khand
Transition metal-catalyzed higher-order carbocyclization reactions provide a versatile and atom-economical approach to the construction of carbo- and heterocyclic ring systems. The ability to efficiently assemble complex and often functionalized (poly)cyclic molecules from relatively simple starting materials in a highly regio-, diastereo- and/or enantioselective manner, depending on the substrate(s) and metal catalyst employed, provides an attractive method for target-directed synthesis. In this regard, rhodium-catalyzed cyclocarbonylation reactions afford a convenient route to the synthesis of various cyclic ketone derivatives, and the utility of these transformations is emphasized by the number of natural product syntheses incorporating this transformation as a key ring-forming step. The following thesis is divided into three key chapters, encompassing a literature review followed by two research chapters, further divided according to the type of transformation discussed. Chapter 1 commences with an overview of transition metal-catalyzed higher order carbocyclization reactions and an introduction to the Pauson–Khand reaction, which is followed by a detailed account of various rhodium-catalyzed semi-intermolecular [(m+n)+1] cyclocarbonylation processes. The final section in this chapter presents the application of rhodium-catalyzed cyclocarbonylation reactions to the total synthesis of several complex natural products. Chapter 2 describes the development of the rhodium-catalyzed [(3+2)+1] carbocyclization reaction of alkylidenecyclopropane (ACP) derivatives with carbon monoxide (CO). Following a brief introduction on the chemistry of three-carbon components in metal-catalyzed carbocyclization processes, our work on the carbocyclization reaction of ACPs with CO for the construction of bicyclic phenols will be presented. The last section in Chapter 2 will discuss the development of the cyclocarbonylation reaction of ACPs containing tetrasubstituted olefins with CO to provide bicyclohexa-2,5-dienones. Chapter 3 begins with an introduction to the enantioselective Pauson–Khand-type (PK-type) reaction of various 1,6-enyne derivatives with CO. The remainder of Chapter 3 is given to the discussion of our efforts towards the enantioselective rhodium-catalyzed PK-type reaction of 1,6-chloroenynes containing trisubstituted olefins for the preparation of bicyclopentenones containing vicinal quaternary and tertiary stereogenic centers. The preliminary scope and some of the limitations of this process will be outlined.
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