Abstract
The inherent strain of highly constrained ring systems has enabled their exploitation in organic synthesis for decades. However, methods utilising modern photoredox catalysis remain underexplored. The studies presented in this thesis detail efforts to employ highly strained rings in various strain-induced ring-opening and cyclisation sequences using visible light photocatalysis.Chapter 1 introduces and summarises previous efforts for [3+2] cycloadditions of cyclopropylamines, highlighting numerous inter- and intramolecular processes through both traditional and modern photoredox strategies. Most avenues utilise cyclopropylanilines and styrenes, limiting the potential for access to diverse products, and few examples exhibit high diastereoselectivity. In Chapter 2, studies towards the improvement of previous cycloaddition sequences are discussed. An operationally simple strategy employing N-sulfonyl cyclopropylamines is used, featuring facile oxidation of an aza-anion for accessing the key nitrogen-centered radical. The methodology enables access to sulfonyl-protected amino-cyclopentanes in high yields with excellent trans-selectivity. Various electron-deficient olefins are tolerated, and alteration of the sulfone substitution was also achieved. Analogues bearing fully substituted quaternary centres are obtained, however expansion onto the synthesis of highly functionalised products proved more challenging. Disubstituted olefins gave issues of poor diastero- or regiocontrol, and fused cyclopropylamine substrates were incompatible. Mechanistic investigations confirmed the key stereo-defining cyclisation step to be anionic in nature (rather than radical) in nature. Product derivatisations showcased the synthetic utility of the process and X-ray crystallography validated trans-selectivity.
Chapter 3 introduces previously reported routes to access derivatives of the spiro[3.4]octane family, and highlights key reactions which employ electron-deficient bicyclobutanes (BCBs). In Chapter 4, studies towards the use of alkene-tethered BCBs in a photoredox-mediated spirocyclisation is discussed. The developed methodology permitted the modular construction of unique spirocycles in high yields and as a mixture of diastereomers, from a range of radical precursors and substituted BCBs. Incorporation of heteroatoms was tolerated in the cyclisation to afford rare aza- and oxospiro[3.4]octanes. Furthermore, novel scaffolds bearing adjacent spirocyclic centres were achieved. The successful exploitation of BCBs in the synthesis of spirocyclic compounds serves as an interesting foundation for future endeavours.
| Date of Award | 9 May 2023 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Varinder K Aggarwal (Supervisor) & Chris L Willis (Supervisor) |