Rhodium-Catalyzed Allylic Substitution Reactions with Nitrile-Stabilized Carbanions: Construction of Acyclic Ternary and Quaternary Carbon Stereogenic Centers
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The transition metal-catalyzed allylic substitution reaction is a particularly versatile method for the construction of carbon-carbon and carbon-heteroatom bonds. Furthermore, owing to a number of developments over the past few decades, highly regio- and stereoselective reactions are now attainable with a variety of stabilized and unstabilized nucleophiles. In this regard, the rhodium-catalyzed allylic substitution reaction has been shown to be highly regio- and stereospecific, thus providing a complementary method to the asymmetric metal-catalyzed allylic substitution reaction. The following thesis is divided into three key chapters, which encompass a literature review followed by two research chapters, further divided based on the type of transformation discussed. Chapter 1 commences with a discussion of the mechanism of the transition metal-catalyzed allylic substitution reaction, with a particular focus on the factors that control the regio- and stereoselectivity, which is followed by a detailed account of the discovery and development of the rhodium-catalyzed variant. Chapter 2 highlights the development of the regio- and stereospecific rhodium-catalyzed allylic substitution reaction with an acyl anion equivalent. Following a brief introduction, our work with alkenyl cyanohydrins and tertiary allylic carbonates for the construction of α-quaternary α,β-unsaturated ketones shall be described. The last section in Chapter 2 will outline the development of a divergent allylic alkylation of aryl cyanohydrins with secondary allylic carbonates to furnish α-ternary ketones or trisubstituted enones. Chapter 3 will discuss our efforts toward using nitrile-stabilized carbanions in the enantioselective rhodium-catalyzed allylic substitution reaction. In this regard, the reaction of α-alkyl benzyl nitrile pronucleophiles with allyl benzoate has been shown to afford homoallylic nitriles bearing a quaternary carbon center in high enantioselectivity using a chiral complex derived from a cationic rhodium(I) complex and a chiral monodentate phosphite. Finally, our initial progress toward the development of an enantioselective allylic alkylation with a homoenolate equivalent shall be discussed. This approach offers a fundamentally novel method for the construction of acyclic β-functionalized carboxylic acids, which should provide the impetus for future advances in this area.