Abstract
This Thesis presents the development of multiple Ir(I)-catalysed hydrofunctionalisation methodologies. Following the introduction of enantioselective intermolecular Murai-type hydroarylation reactions in Chapter 1, Chapter 2 describes the synthesis of chiral bisphosphonite and bisphosphite ligands. Building upon previous work in the group, Chapter 3 begins by exploring the use of these ligands in enantioselective hydroheteroarylation reactions of styrene to promote high enantio- and branch-selectivity.Chapter 3 proceeds to describe the optimisation of hydroheteroarylation reactions of styrene using furan substrates through judicious modification of the directing group. This process exhibits broad substrate scope for a wide variety of styrenes and aliphatic alkenes and the products were obtained in high: (i) yield, (ii) site-selectivity, (iii) branch-selectivity and (iv) enantioselectivity. Further utility of this reaction was demonstrated by use of an α-chiral alkene to deliver a product bearing contiguous 1,2- stereocentres in a catalyst-controlled, diastereoselective process. A methodology for the hydro(hetero)arylation of 1,1-disubstituted alkenes was also developed and exemplified to install challenging quaternary stereocentres.
Chapter 4 discusses the development of hydroheteroarylation reactions using alkenyl silanes by extensive screening of a range of phosphine-derived ligands. The methodology is applicable to a range of vinyl and allyl silanes using a broad scope of furan, thiophene and pyrrole substrates. The products are formed in excellent yields and in very high alkene regiocontrol.
Finally, Chapter 5 begins by disclosing investigations into enantioselective hydroalkylation reactions using 1,3-dicarbonyl compounds. A related process for enantioselective hydroalkylations using α-aminoamides is then described. This tolerates of a wide variety of styrenes to form branched products with excellent control over absolute and relative stereochemistry. Further investigations demonstrate the catalysis products can be further derivatised into various α-amino analogues (such as α-amino acids) as well as other pharmaceutically-active motifs.
| Date of Award | 20 Jun 2023 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | John Bower (Supervisor) & Natalie Fey (Supervisor) |