Fe-Catalyzed Oxidative Cleavage of Unsaturated Fatty Acids

Abstract

The oxidative cleavage of unsaturated fatty acids into aldehydes or carboxylic acids gives access to valuable products. The products can be used as chemical building blocks, as emulsifiers or in the paint or polymer industry. Ozonolysis is applied industrially to cleave the fatty acid oleic acid into the aldehydes nonanal and 9-oxo-nonanoic acid or into pelargonic and azelaic acid. Considerable hazards, including explosion risks, are associated with the use of ozone, and alternative processes are desired. Catalytic alternatives typically comprise systems based on second- and third-row transition metals. Alternatively, Fe-catalysts would be attractive, as this first-row metal is non-toxic, cheap and abundant. In this thesis, the first examples of iron-based catalysts for the oxidative cleavage of unsaturated fatty acids were developed. Chapter 1 gives a comprehensive review of the reported transition metal-catalyzed oxidative cleavage methods. Many examples involve methods using second- and third-row transition metals; first-row transition metal systems have almost exclusively been used for the oxidative cleavage of styrene derivatives. No examples had been reported of the oxidative cleavage of unsaturated fatty acids with first row transition metal complexes. The main strategy for the development of such an oxidative cleavage process in the subsequent chapters aims at a sequence of reactions consisting of alkene epoxidation, followed by hydrolysis into trans-diols, and further oxidation into either the aldehydes or carboxylic acids. Chapter 2 introduces a metal-free method for the oxidative cleavage of unsaturated fatty acids into their corresponding carboxylic acids. The combination of oxone and periodate is shown to mediate this reaction in a clean and selective manner. The method involves a straightforward procedure and allows for the facile isolation of the product. In Chapter 3 an Fe-(BPBP)-based (N,N’-bis(2-picolyl)-2,2’-bipyrrolidine) system is presented that is capable of catalytic oxidative cleavage of unsaturated fatty acids to the corresponding aldehydes using hydrogen peroxide and sodium periodate. No over-oxidation to the carboxylic acids is observed. The system operates at low catalyst loadings, under mild reaction conditions and at low temperatures. Chapter 4 explores the regioselectivity of the system developed in Chapter 3. The system is shown to be capable of regioselective oxidative cleavage of the electron-rich double bond in substrates containing multiple double bonds towards aldehydes. Trace amounts of acetic acid are added to improve selectivity and the rate of alkene epoxidation. The protocol outperforms those based on Ru, Os or W-salts, which are generally strongly oxidizing and lack regioselectivity as they oxidize multiple bonds in polyenes. Chapter 5 reports the Fe-(6-Me-PyTACN)-based (1-[(6-methyl-2-pyridyl)methyl]-4,7-dimethyl-1,4,7-triazacyclononane) oxidative cleavage of unsaturated fatty acids and esters to the carboxylic acids with hydrogen peroxide and sodium periodate. Indeed, the Fe-catalyst is capable to oxidize the aldehyde intermediates to the carboxylic acids. Chapter 6 finally presents a study of new non-heme Fe-based complexes of the bapbpy (N6,N6’-bis(pyridine-2-yl)-[2,2’-bipyridine]-6,6’-diamine) ligand family including structural, spectroscopic, electrochemical and spin-crossover features of two Fe(II) complexes. The reaction with peroxides is studied by computational means and through mechanistic studies at low temperature. Such complexes are able to epoxidize alkenes with hydrogen peroxide under oxidant-limiting conditions.