The Use of Reversible Covalent Bonding and Induced Intramolecularity to Achieve Selectivity and Rate Acceleration in Organic Reactions

Abstract

Chapter 1. Catalytic directing group, I, which was designed with the ability to form a reversible covalent bond with a substrate and bind a metal, was shown to direct the hydroformylation of allylic amines. The efficient regioselective hydroformylation of a variety of 1,2-disubstituted allylic sulfonamides to form β-amino-aldehydes under mild conditions has been shown. Chapter 2. Building off of the successful application of I, enantioenriched catalytic directing group, II, was designed and synthesized. It retained the essential features to direct hydroformylation to obtain good regioselectivity while also providing a chiral environment to induce absolute stereocontrol. Under mild conditions, a variety of disubstituted olefins react to give good yields and excellent enantioselectivites. Thus, the first enantioselective reaction performed with a catalytic directing group was demonstrated. Chapter 3. A new set of organocatalysts was developed that benefits from reversible covalent bonding and induced intramolecularity. The desymmetrization of meso-1,2-diols was accomplished using organocatalyst III, which was synthesized easily and cheaply. Experimental results indicate that the selectivity and increased reactivity are a result of the ability of III to pre-organize the substrate through a reversible, covalent bond. A variety of cyclic and acylic substrates were shown to react efficiently with good enantioselectivities under mild conditions. The catalyst's ability to functionalize cis-1,2-diols selectively indicated it might be successfully applied to site selective catalysis. Thus, the selective functionalization of a secondary alcohol in the presence of a primary alcohol was developed using a combination of binding selectivity and stereoselectivity. The (S)-enantiomer forms the secondary functionalized product while the (R)-enantiomer forms the primary functionalized product with high selectivity. As the enantiomers preferentially form different functionalized products, a regiodivergent reaction on a racemic mixture resulted giving two valuable enriched products.