Design and Synthesis of Scaffolding Ligands for Regio- and Stereoselective Hydroformylation

by Candice Lee Joe

Institution: Boston College
Year: 2014
Keywords: Hydroformylation; Scaffolding Ligands
Record ID: 2028137
Full text PDF: http://hdl.handle.net/2345/bc-ir:103550


Chapter 1. The use of directing groups is a powerful way to control selectivity in organic chemistry. Due to their ability to install new functionality in a reliable fashion, directing groups have had a profound impact on stereoselective, site-selective, and regioselective transformations. More recently, catalytic directing groups have been developed and utilized in a variety of metal-catalyzed transformations, including C-H activation and hydroacylation, and have the potential to be more broadly applied to other transformations. Chapter 2. Catalytic directing groups have recently been designed for hydroformylation. Based on the design of racemic scaffolding ligand 2.5, enantioenriched ligand 2.42 was synthesized for the asymmetric hydroformylation of para-methoxyphenyl (PMP) protected allylic amines. Under mild conditions, a variety of 1,2-disubstituted olefins underwent directed hydroformylation to afford the proximal β-amino alcohol products in good yields and excellent enantioselectivities. The substrate scope has been extended to electronically modified allylic anilines. A modest resonance effect was seen upon the aniline substrate binding to the ligand, which, in turn, manifested in the hydroformylation reaction results. Thus the first enantioselective reaction performed with a catalytic directing group was demonstrated. Chapter 3. Ligand 3.67 was developed, which promotes aldehyde formation on the distal olefinic carbon relative to the directing functionality on the substrate. This is in contrast to other phosphorus-based directing groups that have been successful at placing the aldehyde on the proximal olefinic carbon. Ligand 3.67 has been applied to the diastereoselective hydroformylation of homoallylic alcohols to afford δ-lactones selectively. Altering the distance between the alcohol and olefin revealed that homoallylic alcohols afford the distal lactone with the highest levels of regioselectivity. Taken together with previous examples of proximal-selective hydroformylation, these results being to more fully address the challenge of controlling regioselectivity in hydroformylation. Chapter 4. The harvesting of energy from light to power chemical transformations is an underdeveloped area. Utilizing p-type silicon nanowires (SiNWs) as a photocathode, the photoelectrochemical carboxylation of aromatic ketones has been developed to afford α-hydroxy carboxylic acids. Utilizing low operating potentials, the direct reduction of carbon dioxide (CO2) is avoided. Highlighting the synthetic utility of this transformation, two precursors to the NSAID compounds ibuprofen and naproxen were synthesized using CO2, and abundant C1 feedstock, and light, a crucial source of energy in nature.