Oxocarbenium ions are common intermedates or transition states for a variety of biological and synthetic transformations. Due to the fact that oxocarbenium ions are typically much more reactive than iminium ions, their reactivity is difficult to control. Especially challenging reactions of oxocarbeniums are stereoselective transformations. While there are several approaches to perform reactions of oxocarbeniums asymetrically, the Nagorny group is particularly interested in using chiral hydrogen bond donors and Brønsted acids as catalysts for these reactions.
Chapter 1 of this thesis provides an introduction to chemistry of oxocarbenium ions, their generation and use in asymmetric reactions. Both anion activation and protonation of acetals and vinyl ethers with chiral hydrogen bond donors and chiral Brønsted acids are covered in this chapter.
Chapter 2 discusses ionic Diels-Alder reaction as well as the use of thiophosphoramide as a co-catalysts for promoting this transformation. Thiophosphoramide catalyst was found to bind sulfonate anions and was used to separate the vinyl oxocarbenium/sulfonate ion pair. This effect leads to acceleration of the Diels-Alder reaction of unsaturated acetals. Thiophosphoramides are the most effective cocatalysts because of the stronger counterion activation effect resulting from three, rather than two, hydrogen bonds involved in anion binding.
Chapter 3 of this manuscript describes development of the first chiral catalyst-controlled enantioselective ionic Diels-Alder reaction of unsaturated acetals. Chiral BINOL-based N-triflylphosphoramides were used as catalysts for this transformation. Moderate enantioselectivities (up to 80:20 e.r.) have been obtained when α,β-unsaturated dioxolanes were employed as the dienophiles. These reactions demonstrate strong dependence on the counterion coordinating properties and solvent polarity, a behavior characteristic of oxocarbenium ions.
Finally, Chapter 4 describes attempts of stereo- and regioselective aminoglycosides via desymmetrization of meso-2-deoxystreptamine using chiral phosphoric acids as catalysts. We showed that chiral phosphoric acids facilitate desymmetrization of meso-diols via glycosylation reactions using mannose-α-trichloroacetimidate. Chiral phosphoric acid-promoted mannosylation of 2-deoxystreptamine produces a mixture of two α-mannosides with up to 1:5 (O-4 : O-6) regioselectivity. This is the first report of desymmetrization of meso-diols via glycosylation using chiral phosphoric acids as catalysts. This method has a potential to be applied for glycodiversification of 2-deoxystreptamine and synthesis of new aminoglycoside antibiotics.
PHD
Chemistry
University of Michigan, Horace H. Rackham School of Graduate Studies
http://deepblue.lib.umich.edu/bitstream/2027.42/113511/1/mealina_1.pdf