1. Phosphorus Hydrides in Radical Chemistry David Sharpe University of York

2. Outline of talk Introduction Phosphorus hydride chemistry Previous work Development of new phosphorus hydride reagents Radical reactions of phosphorus hydride reagents Chemistry of Organophosphorus adducts Oxidation chemistry Formation C=C and C-C bonds Conclusions Future Work

3. Introduction Ageing Poor selectivity Toxicity Disease Novel reactivity E.g. Anti-Markovnikov addition of HBr to alkenes Mild reaction conditions -OH and –NH functionalities do not need to be protected

4. Traditional radical reagents Bu 3 SnH Toxicity Difficult to remove tin by-products SmI 2 Difficult to prepare Toxicity Radioactive

5. Cleaning up radical chemistry We need to consider Recovery/disposal of waste Reaction conditions (i.e. solvents, temperature) Project aims To generate organophosphorus adducts by radical addition of phosphorus hydride reagents to alkenes. To use organophosphorus compounds in synthetically useful reactions.

6. Addition of a phosphite to an alkene

7. Diethyl phosphite Advantages Cheap Non-toxic Easily removed from reaction mixture Disadvantages Poor H-atom donor Requires large excess of phosphite Requires significant amounts of initiator

8. Reactivity of phosphorus hydrides C. M. Jessop, A. F. Parsons, A. Routledge and D. Irvine, Tetrahedron Lett., 2003, 44, 497

9. Computational calculations BDE (kJ mol -1 )365.0337.4316.5302.3 Calculations performed by Dr J. E. McGrady, University of York

10. The synthesis of phosphorus hydrides

11. Reactions using Ph(EtO)P(S)H

12. Ph 2 P(S)H and electron-rich alkenes

13. Ph 2 P(S)H and electron-poor alkenes

14. Oxidation of phosphonothioates Two step procedure (radical addition/oxidation) reaction 92% overall yield. One step radical addition 36%

15. α-Functionalisation

16. Horner-Wadsworth-Emmons reaction

17. Horner-Wittig reaction

18. Conclusions We have been able to add To both Electron-rich alkenes Electron-poor alkenes The resulting organophosphorus compounds undergo Alkylation Acylation HWE

19. Future Work Development of HWE chemistry of phosphinothioates Different aldehydes/ketones Different phosphinothioates Diphenylphosphine sulfide in other reactions Reduction of halides

20. Acknowledgments Dr A. F. Parsons Dr P. Taylor ICI Paints and E.P.S.R.C. for funding Members of the AFP group past and present. Gillian Allen Gregory Bar Nicola Chessum Nathalie Huther Chris Jessop Jaouad El Harfi Tom Hunt Jim Rawlinson Ruth Bingham Tony Wright No technicians were harmed during this project. Thank you for listening

21. Suplementary info for questions

22. Overview of Et 3 B chemistry

23. Peroxydisulfates Extremely cheap (K 2 S 2 O 8, 100g, £8.40) Strong oxidising agents (E = 1.92 V, SO 4 2- /SO 4 - ) Half-life at 80 o C ~1 h Possible to make organosoluble peroxydisulfates

24. Advantages of radical chemistry Mild reaction conditions Low temperature Acid/base sensitive functionalities are unreactive Novel reactivity Anti-Markovnikow addition of HBr Umpolung chemistry Electrophilic radical Nucleophilic radicalElectrophile Nucleophile Radicals are uncharged.But…. They have a polarity

25. Phosphites and electron-poor alkenes

26. Horner-Wadsworth-Emmons reaction Potent inhibitor of factor Xa and factor IIa Role in blood clotting Thrombosis