Phosphorus Hydrides in Radical Chemistry David Sharpe University of York

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

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

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

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.

Addition of a phosphite to an alkene

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

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

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

The synthesis of phosphorus hydrides

Reactions using Ph(EtO)P(S)H

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

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

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

α-Functionalisation

Horner-Wadsworth-Emmons reaction

Horner-Wittig reaction

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

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

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

Suplementary info for questions

Overview of Et 3 B chemistry

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

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

Phosphites and electron-poor alkenes

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