Use of polymeric supports for the synthesis of structurally defined oligomers
The aims of this project were firstly to develop a protocol for the iterative synthesis of polyethers on a polymeric support, using suitably protected monomers. The synthesis of cyclic ethers by an intramolecular cyclisation/cleavage from the polymeric support, utilising a sulfonyl chloride linker, was also desired. The final aim was to develop a method for reductive amination on a polymeric support, with a view to forming mixed amine/ether oligomers. Chapter 1 is a review of the range of polymers that have been used as supports in organic synthesis, various linkers that have been used to immobilise molecules onto supports, the synthesis of polyethers and cyclic ethers in solution and on polymeric supports, and reductive amination in solution and on polymeric supports. Chapter 2 describes the protecting group strategies that were developed for the synthesis of linear, singly branched and dibranched monomers. These strategies gave monomers in very high yields, which were suitably protected for use in the synthesis of oligomers and cyclic ethers in later chapters. Chapter 3 describes the synthesis of novel linkers on a soluble PEG support PEG sulfonyl chloride and PEG Wang trichloroacetimidate. Both linkers were synthesised in high yields, and were successfully utilised in the PEG supported reactions described in later chapters. Chapter 4 describes the synthesis of oxetanes by mono-activation of a branched diol as a sulfonate ester in solution, on cross-linked polystyrene and on PEG, followed by intramolecular cyclisation/cleavage. Oxetanes were afforded in good yields, under mild conditions, with rapid purification. Chapter 5 describes the development of an iterative polyether synthesis, initially on cross-linked polystyrene, and then on a PEG support. This provided access to a range of structurally defined oligoethers and avoided the laborious purification techniques associated with classical solution based methods. Chapter 6 describes the mild and selective oxidation of an immobilised alcohol to an aldehyde on a PEG support, followed by reductive amination with secondary amines. A strategy is also proposed for the synthesis of mixed amine/ether oligomers. The final chapter describes the experimental techniques employed.