Photochemical approaches to azetidines

Baldwin, Kipp (2022) Photochemical approaches to azetidines. PhD thesis, University of Nottingham.

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This thesis concerns the application of continuous flow photochemistry to the 4 electrocyclisation of nitrogen-containing heterocycles, in particular 2-pyridinones and 1,2-dihydropyridines, for the synthesis of so-called Dewar heterocycles, which were envisaged as convenient starting materials for the synthesis of sp3-rich, highly substituted small molecules.

The introduction chapter covers a brief history of photochemistry in organic synthesis, as well as the basic principles of organic photochemistry. The synthesis and subsequent uses of various Dewar heterocycles is then discussed, with a focus on Dewar heterocycles derived from 2-pyrones, 2- pyridones and 1,2-dihydropyridines, the latter of which includes discussion on the chemical properties of 1,2-dihydropyridines and synthesis of derivatives by various methods.

The results and discussion chapter first describes construction of a continuous flow photochemical reactor based on the design developed by the Booker-Milburn group and its application to the synthetic goals.

Initially, commercially available 2-pyridones were transformed into azetidinone-bearing Dewar structures. Following optimisation of productivity, a novel route to a cyclobutane-containing -amino acid was achieved in 3 steps from the Dewar azetidinone, requiring no chromatographic purification in an overall 60% yield.

Subsequently, photosynthesis of azetidine bearing Dewar heterocycles from 1,2-dihydropyridines was investigated. A selection of 1,2- dihydropyridines were synthesised by addition of various nucleophiles to acyl pyridinium salts, and subsequently transformed by photoirradiation. Productivities of up to 1622 mg h-1 were achieved, which compared favourably with a batch method with maximum productivity of 67 mg h-1.

Next, a synthesis of dihydropyridines with quaternary substitution at the 2- position by heating propargyl vinyl ethers with primary amines was employed. Subsequent irradiation gave the corresponding Dewar azetidines with good productivity. This route was an interesting way to make novel spirocyclic azetidines.

Further transformations of the Dewar photoproducts were investigated with the aim of accessing highly substituted, sp3-rich small molecules. Of the methods investigated, a route involving epoxidation and further Lewis acid promoted substitution was the most productive.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Dowden, James
George, Michael
Keywords: Photochemical, Azetidines
Subjects: Q Science > QD Chemistry > QD450 Physical and theoretical chemistry
Faculties/Schools: UK Campuses > Faculty of Science > School of Chemistry
Item ID: 69782
Depositing User: Baldwin, Kipp
Date Deposited: 14 Dec 2022 04:40
Last Modified: 14 Dec 2022 04:40

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