Lithiation and Trapping of Acyclic Sulfoximines: Scope and Diastereoselectivity

This thesis describes the diastereoselective synthesis of a wide range of α-functionalised acyclic sulfoximines via lithiation-trapping methodology. The diastereoselective synthesis of some tetrasubstituted sulfoximines is also presented. Chapter 2.1 describes the synthesis of a range of N-TBDPS acyclic sulfoximines bearing different aliphatic and aromatic substituents at sulfur. A range of lithiation-trappings with different electrophiles is presented in Chapter 2.2. N-TBDPS acyclic sulfoximines generally showed high diastereoselectivity and yields, particularly when the sulfoximine was substituted with a bulky group (R1 = t-butyl and adamantyl). Across most examples, the anti-diastereomer was produced as the major product and a model for this is proposed. Benzylic sulfoximines (R2 = Ph) (Chapter 2.2.3) were also explored and exhibited different and unpredictable diastereoselectivity. The synthesis of tetrasubstituted sulfoximines by lithiation-trapping is presented in Chapter 2.3 using t-Bu-substituted sulfoximines. High yields and diastereoselectivity were obtained for some examples and the same outcome was observed with benzaldehyde when employing either diastereomeric starting sulfoximine. The best results were obtained when small, reactive electrophiles were used, presumably due to the sterically demanding substrate. It was not possible to assign the stereochemistry of the major diastereomers.