Towards the Development, Application and Understanding of Copper-Catalysed Alkene Functionalisation Processes Using Iodonium Salts

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Male, Henry Peter John 

This thesis comprises three projects focused on the use of the combination of catalytic copper and iodonium salts towards the functionalisation of alkenes. Chapter 2 details the development of an enantioselective and regiodivergent allylic amide arylation procedure using a specific copper(II)-bisoxazoline pre-catalyst and hexafluorophosphate diaryliodonium salts. The regioselectivity of the process was discovered to be controlled by the electronic properties of the iodane employed, allowing enamide production to be biased with electron-poor iodonium salts and oxazines to be produced with electron-rich analogues. An overall scope of 38 compounds was collaboratively elaborated, with 20 synthesised personally. All products were generated in useful yields and high levels of enantioselectivity. Chapter 3 describes efforts towards the application of a copper-catalysed oxy-alkenylation procedure to the production of the macrolidal natural product (-)-lyngbyaloside B. It is proposed that an elaborate homoallylic carbamate may be coupled with a complex polyoxygenated alkenyl(aryl)iodonium salt as a fragment coupling for polyketide synthesis. Following extensive investigations, it was discovered that the challenging vinyl-iodonium salt could be synthesised in good yields and then coupled with the desired homoallylic carbamate, albeit in limited yield and low d.r.. Chapter 4 presents initial studies towards a computational understanding of the copper-catalysed arylation of alkenes with iodonium salts. Evidence is presented to suggest that two functionalisation modes are energetically accessible, allowing the production of regioisomeric arylated products.

Gaunt, Matthew
Catalysis, Copper, Enantioselectivity, Total Synthesis, Regiodivergence, Hypervalent Iodine, High Valent Copper
Doctor of Philosophy (PhD)
Awarding Institution
University of Cambridge
University of Cambridge - CHESS Award, Magdalene College - Leslie Wilson Scholarship, Corness Bursary