Thesis (Ph.D.) - University of St Andrews, June 2007.

Thèse Doct.-ing.--Paris, 1982. / 1983 d'après la déclaration de dépôt légal. Notes bibliogr.

Th. doct.-ing.--Trait. et valorisation des ressources d'origine végétale--Toulouse--I.N.P., 1983. N°: 249.

Thesis advisor: Kian L. Tan / 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. / Thesis (PhD) — Boston College, 2014. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Kian L. Tan / Scaffolding ligand, 14, was designed to direct the hydroformylation of 1,2 disubstituted alkenes, such that the aldehyde forms at the carbon distally from the directing group. The ligand has the ability to form reversible covalent bonds with the substrate and bind to the metal to achieve high conversion, regio- and diastereoselectivity of homoallylic alcohol products. / Thesis (MS) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Kian L. Tan / Chapter 1. Directing groups are a powerful means of controlling the selectivity in reactions. The field of hydroformylation has used directing group strategies to control regio- and diastereoselectivity with much success. However, directing groups are inherently inefficient as they must be installed and removed from the molecule of interest, and generate a stoichiometric byproduct in the process. Strategies to solve this problem have included the use of exchange reactions that allow for transient binding of substrate to a molecule that can direct the course of the reaction. This allows the use of catalytic quantities of the directing functionality to effect the desired transformation, and obviates the need for installation and removal of the directing functionality in separate steps. Chapter 2. Our lab has developed a phosphorous based ligand that incorporates an N,O-acetal moiety that allows for reversible binding of both alcohol substrates and a metal catalyst. These ligands rapidly exchange with alcohols in the presence of catalytic amounts of p-TsOH. The racemic ligand was found to undergo epimerization on exchange with a chiral alcohol in an effort to isolate enantioenriched material. However, a strategy using a thermodynamic gearing effect of adjacent stereocenters was found to be successful in producing a chiral ligand. Chapter 3. Using catalytic quantities of our scaffolding ligand we are able to effect branch- and diastereoselective hydroformylation of homoallylic alcohols. We offer a model based on A1,3 strain for the origin of the diastereoselectivity, and tested substrates to lend support to the model. We also investigated the use of chiral scaffolding ligands in the enantioselective hydroformylation of homoallylic alcohols, and preliminary results show modest enantioselectivity. Chapter 4. We have expanded the substrate scope of our scaffolding ligand strategy to include the hydroformylation of allylic alcohols. We are able to produce β-hydroxy carbonyl compounds in good yields and with excellent selectivities, which offers an alternative to the formaldehyde aldol reaction. We show that our strategy is successful in the hydroformylation of trisubstituted olefins, which are a difficult class of hydroformylation substrates, where we are able to produce single diastereomers in good yields under mild conditions. We investigated the enantioselective hydroformylation of allylic alcohols and found that while racemization may be a problem with these substrates, in-situ hemi-acetal protection may offer a solution to the problem. / Thesis (PhD) — Boston College, 2011. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Kian L. Tan / Utilization of directing groups in a general and efficient manner for highly regioselective hydroformylation of 1,1-disubstituted olefins. / Thesis (MS) — Boston College, 2011. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: James Morken / Asymmetric hydroformylation (AHF) is a metal-catalyzed reaction in which CO and H2 are added across an olefin to form a new carbon-carbon bond. AHF has perfect atom-economy and is an ideal way to form a chiral aldehyde. However, the utility of branch selective hydroformylation is limited due to a lack of readily available ligands and restrictions on a wide variety of terminal olefins. Herein, Rh-catalyzed asymmetric hydroformylation of 1-alkenes is reported using commercially available Ph-BPE ligand to generate α-chiral aldehydes. A wide range of terminal olefins were explored and all showed high enantioselectivity (up to 98:2 er) and good regioselectivity (up to 15:1 branched to linear ratio). / Thesis (MS) — Boston College, 2015. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

In this work the synthesis of new potentially trans-chelating biphosphine ligands is described and their value in rhodium catalysed hydroformylation evaluated. The reactions of biphosphine diolefin rhodium complexes with hydrogen in methanol, monitored by ¹H- and ³¹P-NMR spectroscopy were used to determine trans-chelating ability. Complexes of 1,5-bis(diphenylphosphino)-3-oxapentane and 1,3-bis- (4-diphenylphosphinobenzyl)benzene formed rhodium dihydrides solely whereas the more flexible 1,7-bis(diphenylphosphino)-4-oxaheptane gave isomeric rhodium dihydrides and a solvate complex. The reaction of diolefin complexes with hydrogen and carbon monoxide in dichloromethane was also investigated. The 3-oxapentane ligand, readily synthesized from 3-oxapentane-1,5-diol, as its rhodium complex gave a n—/iso aldehyde ratio of 9:1 for 1-octene hydroformylation (100°, 80 psi, 1:1 hydrogen/carbon monoxide). Secondly, reactive intermediates relevant to hydroformylation were identified using ¹³C- and ²H-labelling and ¹H, ¹³C and ³¹P-NMR spectroscopy. Hydridocarbonylbis(triphenylphosphine)rhodium(I), the probable catalytic cycle initiator, was conclusively shown to be the initial product of hydridocarbonyltris(triphenylphosphine)rhodium(I) under hydroformylation conditions. The kinetics of interconversion of these latter two complexes were examined by saturation transfer ³¹P-NMR. On reaction of the dicarbonyl complex with styrene no alky1-rhodium complexes were observed, but an iso-acyl intermediate which isomerizes rapidly at ambient temperature was identified and a structure proposed. A similar n-acyl complex, from 1-octene, shows dynamic NMR behaviour explained in terms of triphenylphosphine isomerization at lower temperature and acyl-alkyl interconversion at high temperature.

Thesis (M.S.)--Rutgers University, 2010. / "Graduate Program in Chemistry." Includes bibliographical references.