α-Functionalisation of Cyclic Sulfoximines via Lithiation-Trapping

This thesis describes the development of a general synthetic approach for the diastereoselective synthesis of a wide range of α-functionalised sulfoximines via lithiation-trapping reactions. In addition, studies for the synthesis of 2,2- and 2,5/2,6-disubstituted cyclic sulfoximines are reported.
The synthesis of cyclic and acyclic sulfoximines with different N-substituents is described in Chapter 2.1. Chapter 2.2 explores the scope and diastereoselectivity of lithiation-trapping reactions of 5- and 6-membered ring sulfoximines with a range of electrophiles (including benzophenone, benzaldehyde, benzyl bromide and methyl iodide) and N-substituents (TBDPS, Boc, Me and CN). Our results show high α-diastereoselectivity with the N-TBDPS group, giving mostly cis diastereomers in high yields. Good yields and diastereoselectivity were also observed for the lithiation-trapping reactions of N-Boc, N-Me and N-CN sulfoximines. It is proposed that the sterically bulky TBDPS group is able to block one face of the sulfoximine preventing electrophilic attack on one side. Therefore, the trapped sulfoximine adopts a configuration where the new α-substituent is cis to the sulfoximine oxygen.

In Chapter 2.3, the synthesis of disubstituted sulfoximines is reported. The two routes detail the diastereoselective synthesis of 2,2- and 2,5/2,6-disubstituted sulfoximines. The approach to 2,2-disubstituted sulfoximines was far less successful than that to the 2,5/2,6-disubstituted sulfoximines.