Phosphinic acid synthesis

Chapter 1 gives a background to the importance of phosphinic acids, and a description of their physical properties and chemical reactivity. A review of the more useful methods towards synthesis is given. At the end of the chapter, trivalent silyl phosphonite esters are introduced as potentially useful synthetic reagents. However, only limited work has performed using these species. Chapter 2 introduces the novel addition of bis(trimethylsilyl) phosphonite to c-unsaturated esters under basic silylating conditions. This reaction is optimised and transformed into a useful synthetic method for the preparation of phosphinic acids, named the "triethylammonium phosphinate reaction." Various other electrophiles were used as substrates in this reaction, little success was obtained. Theories are provided to explain side reactions and products, some additional reactions were performed to give evidence to support these theories. A novel reaction between a Nannich base and silyl phosphonite esters, yielding a phosphinic acid, is introduced. The problems of phosphinic acid purification by physical and chemical methods are discussed. Chapter 3 is concerned with the development of the "triethylammonium reaction" to allow addition of silyl phosphonite esters to a,-unsaturated ketones. The novel "sodium phosphinate" reaction was developed but little success was achieved, however excellent yields of phosphinic acids were obtained when a,-unsaturated esters were used as substrates. Chapter 4 is about developing a new reaction to allow phosphinic acid synthesis using vinyl ketones as substrates, under controlled conditions. This mild reaction was then combined with a novel method of purification forming adamantanammonium phosphinate esters. This flexible methodology was established by the preparation of a variety of substituted phosphinic acids and phosphinate esters. In chapter 5 adaption of the reaction discovered in chapter 4 was undertaken which, allows the synthesis of phosphinic acids using alkyl iodides. A useful reaction was developed which gives similar products to the Arbuzov reaction, however it is demonstrated that this new reaction does not proceed by the same mechanism. Chapter 6 gives an account of work undertaken to the phosphinate analogue of platelet activating factor. The original route was unsuccessful, reasons for this are discussed. A shorter alternative route is given, which relies on chemistry developed in this thesis. I have made an attempt to show the utility of the novel methodology contained in this thesis, by giving my ideas on proposed routes to the synthesis of some interesting phosphinate analogues. I consider some of these analogues to be useful biochemical tools.