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    Planar chiral oxazolines based on [2.2]paracyclophane : a new toolbox for asymmetric synthesis : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Chemistry at Massey University, Manawatū, New Zealand
    (Massey University, 2024-03-07) Tewari, Shashank
    This thesis contains total 7 chapters, dealing with the synthesis of planar chiral Oxazolines based on [2.2]paracyclophane, enantiopure products obtained from their resolution, synthesis of metal-based chiral complexes, studies on C-H activation field, namely selective remote β-C-H activation of cyclic amines, and future ideas towards the goal. As the main focus of this thesis is on the development of novel planar chiral [2.2]paracyclophane derivatives, Chapter 1 starts with a brief description of [2.2]paracyclophane chemistry. A short introduction about the synthesis of key enantioenriched [2.2]paracyclophane derivatives is given. Finally, a short introduction of the recent applications of [2.2]paracyclophane-based ligands in asymmetric catalysis is also mentioned. Chapter 2 outlines a brief overview of the role of 2-oxazolines. 2-Oxazolines have been utilized in the field of asymmetric catalysis as ligands and chiral auxiliaries. The chapter briefly discusses the synthesis and highlights some of the uses of 2-oxazolines as chiral ligands. Chapter 3 describes the concise synthesis of planar chiral oxazolines based on [2.2]paracyclophanes. Various oxazoline-based compounds that were synthesized are all discussed in Chapter 3. The synthesis of mono-oxazolines coupled to [2.2]paracyclophanes, based on the methodology developed in our lab was accomplished. The next were the synthesis of bis-oxazolines and tetra-oxazolines coupled to [2.2]paracyclophane. The chapter mentions all the details and substrate scope generated with oxazolines. Chapter 4 focuses on the resolution of [2.2]paracycoplane by the hydrolysis of the oxazolines. The enantiopure products like planar chiral mono-acids, bis-acids, and partial acids were obtained by hydrolysis of the oxazolines. Apart from them, a section in the chapter describes the decarboxylative phosphorylation that was achieved through our planar chiral acids. Synthesis of planar chiral diamines via Curtius rearrangement of the diacids is also described in the chapter, followed by phanol synthesis. A part of the above chapter describes about the rhodium paddle-wheel complex formed by partial chiral acids. An attempt to make dinuclear gold complexes was made that was also successful. Overall, chapter four is the highlight of the thesis, where a lot of pure chiral products are made and their utility is explained in the field of asymmetric catalysis. Chapter 5 describes the remote β-C-H activation of cyclic amines. Attempts were made to accomplish the functionalization through the directing group strategy. The directing groups based on heterocyclic piperidine and cyclic amines were synthesized successfully. These pre-made directing groups were used for the C-H bond functionalization but the functionalization possessed many challenges that made the functionalization difficult. Chapter 6 explains the future scope of the research work mentioned in this thesis. Finally, Chapter 7 describes the experimental procedures and characterization of the synthesized compounds mentioned in Chapters 3 to 5.
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    New routes to planar chiral ligands and their use in asymmetric catalysis : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Chemistry at Massey University, Manawatū, New Zealand
    (Massey University, 2021) Mungalpara, Maulik
    This thesis contains 8 chapters detailing 3 optimised methods to synthesise [2.2]paracyclophane derivatives and our studies in the C-H activation field, namely selective remote β-C-H activation of cyclic amines, and enantioselective γ-C(sp³)-H functionalisation of cyclic amines, as well as a future direction. As the main focus of this thesis is on the development of novel planar chiral [2.2]paracyclophane derivatives, Chapter 1 starts with a brief description of [2.2]paracyclophane chemistry. A short introduction about the synthesis of key enantioenriched [2.2]paracyclophane derivatives is given. Finally, a short introduction of the recent applications of [2.2]paracyclophane-based ligands in asymmetric catalysis is also mentioned. Chapter 2 describes the synthesis of (RSp,SRP)-4-tert-butyl[2.2]paracyclophane phosphine oxide (SPO) and attempts to synthesise its asymmetric variant. Further, its synthetic utility is investigated, mainly in Suzuki-Miyaura cross-coupling, Buchwald-Hartwig amination, and Au(I)-catalysed cyclisation reactions. Additionally, a general route to the P-stereogenic [2.2]paracyclophane-derived phosphines via the reduction of tertiary phosphine oxides is reported. Chapter 3 mainly outlines attempts for β-C(sp³)-H activation of cyclic amine to target the shortest route of epibatidine moiety. A stepwise approach is mentioned. Firstly, a range of heteroatom-substituted secondary phosphine oxides (HASPOs) is evaluated to access (chiral) indolines via intramolecular C(sp³)-H activation. Next, an intramolecular C(sp³)-H activation of 7-azanorbornane, a core skeleton of epibatidine, is investigated. The third approach is mainly targeted for the directing-group-assisted intermolecular C(sp³)-H activation of 7-azanorbornane. Lastly, enantioselective γ-C(sp³)-H activation of N-cyclohexylpicolinamide using various chiral Brønsted acids, again targeting the epibatidine moiety by the late-stage cyclisation, is described. In a search for suitable planar chiral Brønsted acid, an optimised single-step protocol for the synthesis of [2.2]paracyclophanes carboxylic acid derivatives is reported in Chapter 4. This protocol proceeds via C(sp²)-H activation of chiral oxazolines and their coupling with bromo[2.2]paracyclophanes. Chapters 5 & 6 are related to pyridine sulfinates. Chapter 5 describes an attempted regioselective C-H functionalisation of aromatic acids via desulfitative coupling with pyridine-2-sulfinate. A detailed study with catalytic Pd(OAc)₂ and pre-formed palladacycle is mentioned. The effect of catalytic Pd(OAc)₂ on homo-coupling of pyridine-2-sulfinates is also investigated. The potential of sulfinates as nucleophilic coupling partners is investigated in Chapter 6. A novel methodology to synthesise pyridyl[2.2]paracyclophanes is described. The method involves desulfitative cross-coupling reactions between pyridine sulfinates and bromo[2.2]paracyclophanes. One of the interesting results of the desulfitative coupling with the unreactive (±)-4-bromo-5-amino[2.2]paracyclophane is also mentioned. Chapter 7 explains the future scope of the research work mentioned in this thesis. Finally, Chapter 8 describes the experimental procedures and characterisation of the synthesised compounds mentioned in Chapters 2 to 6.