| Description |
Transforming simple starting materials into complex products with high selectivity is a longstanding goal in the Sigman group with efforts partially focusing on the enantioselective functionalization of alkenes. Research described herein reveals mechanistic insight into three distinct palladium-catalyzed reactions that promote the enantioselective arylation or diarylation of various types of alkenes. Thus, Chapter 1 provides a brief review of several classical and modern techniques that are available for interrogating reaction mechanism. As described in Chapter 2, the redox-relay Heck reaction couples alkenyl, aryl, or other nucleophiles with di- or trisubstituted alkenyl alcohols in high enantioselectivity using pyridine oxazoline (PyrOx) ligands, after which the alkene unsaturation is translated through the alkyl chain, ultimately oxidizing the terminal alcohol. In order to better understand this reaction's robust ability to generate stereocenters in excellent enantiomeric ratios, mechanistic studies were initiated to identify the origins of site and enantioselectivity and determine the stereochemical consequences of the relay process. By using various classical strategies, such as transition state calculations, kinetic experiments, and deuterium labeling studies, detailed information regarding the fundamental reaction steps was gained. Chapter 3 describes the analysis of the redox-relay Heck reaction of 1,1-disubstituted alkenes, the reactivity of which is distinct from the former case as studied in Chapter 2. Specifically, a phenyl substituted PyrOx ligand in combination with styrenyl homoallylic alcohols are required for high enantioselectivity. Deviations from these scaffolds result in diminished selectivity. Consequently, the ligand and substrate effects on the stereodefining step in this reaction were examined using multidimensional parameterization, wherein molecular properties are related to the reaction outcome in mathematical equations. This analysis led to a proposal of a stereo-controlling attractive interaction between the substrate and the ligand in the selectivity determining step. A similar approach was utilized in Chapter 4, which details both the development and analysis of the enantioselective 1,1-diarylation reaction of benzyl acrylates using a chiral anion phase transfer (CAPT) strategy. In this case, the enantioselectivity is affected significantly by the substituents on the benzyl acrylate and the CAPT catalyst, the influences of which were also analyzed using multidimensional parameterization. The resulting analysis suggests that specific noncovalent interactions are required in order to achieve high enantioselectivity. |
