Diastereoselective α- and β-Functionalisation of Cyclic Sulfoximines

In this thesis, the diastereoselective α- and β-functionalisation of cyclic sulfoximines via lithiation-trapping and various cross-coupling reactions is described. Chapter 1 details recent developments in synthetic methodology used to obtain sulfoximine compounds. Chapter 2, covers the diastereoselective lithiation and trapping of four different cyclic sulfoximines with a range of electrophiles, giving the cis diastereomers. Further functionalisation of these compounds was explored using sequential lithiation-trapping reactions to give tri- and tetra-substituted sulfoximines.

The diastereoselective synthesis of α- and β-aryl sulfoximines with cis stereochemistry is described in Chapter 3. Negishi cross-coupling of cyclic sulfoximines with aryl bromides was successful, giving a range of α-aryl sulfoximines. A second set of Negishi conditions was needed for the cross-coupling of heteroaromatic bromides. Different routes to vinyl sulfoximines and their cis-diastereoselective β-arylation via Hayashi-Miyaura cross-coupling are also presented in Chapter 3.

Chapter 4 details the trans-diastereoselective synthesis of α- and β-aryl sulfoximines. α-Bromination of a vinyl sulfoximine and Suzuki-Miyaura cross-coupling was explored. Diastereoselective hydrogenation of the alkene gave the trans α-aryl sulfoximines. A route for the synthesis of a β-iodo vinyl sulfoximine is described. Suzuki-Miyaura cross-coupling and hydrogenation of the sulfoximine gave the trans β-aryl sulfoximines.