Synthesis and reactivities of titanocene-oxo complexes and rhodium-catalyzed oxidative amidation

Titanium complexes;Titanium oxo;Amidation

Nguyen, Trang Thi

关键词: Titanium complexes;    Titanium oxo;    Amidation;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/99222/NGUYEN-DISSERTATION-2017.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Oxo complexes of late transition metals have been used in a number of catalytic reactions such as C–H activation, epoxidation and water oxidation. In comparison, few studies have been published on terminal oxo complexes of group IV transition metals.The imido complexes of these metals, which are isoelectronic to the oxos, have also been shown to effectively catalyze various organic reactions, including hydroamination and carbonamination. Similar reactivity of [Ti]=O and [Zr]=O complexes has been relatively underdeveloped. The first part of this thesis focuses on the synthesis of terminal titanium–oxocomplexes supported by cyclopentadienyl ligands and their reactivity toward unsaturated organic substrates. The research objectives are: (i) Develop new methods for the preparation of Cp*2Ti=O(L) and Cp’2Ti=O(L) (Cp* = pentamethylcyclopentadienyl, Cp’ = tetramethylcyclopentadienyl, L = pyridine or pyridine derivative); (ii) Investigate the cycloaddition and cycloreversion reactions of these oxo complexes with alkynes, nitriles, aldehydes and imines, and unsaturated carbonyls; (iii) Develop a titanium-mediated alkyne-aldehyde coupling reaction for the synthesis of α,β-unsaturated carbonyl compounds. Early work focusing on oxo synthesis established that starting from titanocene ethylene complexes, pyridine N-oxide was an effective oxidant to generate Cp*2Ti=O(L) in high yield while styrene oxide was the oxidant of choice for Cp’2Ti=O(L). These complexes were then demonstrated to readily undergo cycloaddition with unsaturated organic compounds to generate isolable four- or six-membered metallacycles. The reversed reaction, retro-cycloaddition, occurred at room temperature and could achieve high conversion depending on the stereoelectronic properties of the titanacycles. This facile cycloreversion is significantly different from similar reactions of analogous zirconium complexes. With regard to the third objective, the development of an alkyne-aldehyde coupling reaction faced a major setback as one of the three proposed elementary steps, the insertion aldehyde of into an oxatitanacyclobutene complex, favored unproductive pathways. Studies conducted to provide insights into this process also discovered novel reactivity of oxatitanacyclobutenes: facile reductive elimination of the Cp*, which is usually considered an innocent ligand, followed by bond activation (C–H, C–X, or C–C) to generate a number of new titanium complexes, the structures of which were confirmed by X-ray crystallography.The second part of the thesis focuses on rhodium-catalyzed oxidative amidation reactions. Amides are an important functional group commonly found in natural products and pharmaceuticals, and are traditionally prepared via amidation reactions involving stoichiometric activation of carboxylic acids, either in the form of highly reactive acid chlorides and anhydrides, or with the use of stoichiometric, high molecular weight coupling reagents. The transition metal-catalyzed amidation of aldehydes and alcohols is a promising method for greener, more atom-economical amide synthesis and thus is of great interest to our group.The objective here is to address the current drawbacks in this research area, including: (i) low reactivity of sterically hindered substrates and aniline nucleophiles, and (ii) lack of asymmetric transformations. A rhodium-catalyzed oxidative amidation was developed for the synthesis of amides bearing a quaternary carbon at the alpha position from sterically hindered aldehydes and alcohols. A variety of amines, both aliphatic and aromatic, were effective nucleophiles and generated the amide products in good to excellent yields. The aldehyde substrate scope was very limited compared to alcohols, due to competing imine formation. Unlike in the case of less hindered substrates used in our previous study, these imines were not converted to the desired products under reaction conditions. Finally, to address the second drawback, our approach was to combine the amidation reaction with an earlier isomerization step in which the desired stereochemistry would be set. This approach was effective for the asymmetric synthesis of β-branched amides. In this rhodium-catalyzed reaction, prochiral trisubstituted allylic diethylamines first underwent a highly enantioselective isomerization to enamines, then oxidative amidation to chiral amides in good yield and excellent enantioselectivity. The synthesis of α,β-disubstituted amides proved to be much more challenging, as tetrasubstituted allylamine showed no reactivity and a related substrate, allylic alcohol, showed no diastereoselectivity.Starting with diallyl ethers, a tandem olefin isomerization – Claisen rearrangement – amidation reaction was developed and afforded the desired amides in moderate yields and diastereoselectivity. The results varied significantly with different substrates and nucleophiles.