Reagents containing a H-P bond, such as diethyl phosphite&dimethyl phosphite, have recently been reported as effective radical reducing agents for organic halides, thioesters, and isocyanides, affording high yields of the corresponding hydrocarbons. These reagents are ideal alternatives to organic tin hydrides as hydrogen sources. They are less toxic, and have a simple workup procedure for purification of the products, whereby the excess reagent and phosphorus-containing byproducts can be washed out from the reaction mixture after the radical reaction. Some applications of these reagents are as follows i. Reductive deconjugation of a-bromo a,b-unsaturated esters in the presence of triethylamine. ii. Reduction of bromoacetyl groups to the corresponding acetyl groups. iii. Diethyl phosphite/Et3N reduction of gem-dibromo compounds to the mono-bromo derivatives. iv. Reduction of trichloro or triiodo derivatives cleanly to only dichloro or diiodo derivatives. v. Conversion of trichlorofluorocarbons into dichlorofluorohydrocarbons. To explore if these reagents have potential as tritio-reducing reagents, we have investigated the labelling and some of the applications of diethyl phosphite. When a-bromoacetophenone, a,p-dibromoacetophenone and a-bromo,p-nitroacetophenone were reduced with commercial diethyl phosphite in the presence of triethylamine in benzene at room temperature, they all gave the corresponding acetophenones as the only product of the reaction. The p-bromo and p-nitro functional groups remained intact and only the aliphatic bromo was reduced. The extraction of the organic layer with water removed the triethylamine hydrobromide. In a deuterium labelling experiment, the H-P hydrogen of diethyl and dimethyl phosphite underwent facile exchange with deuteriated water and generated DP(O)(OMe)2 and DP(O)(OEt)2 with close to 90% deuterium incorporation at room temperature in 5 hours. We then searched for an alternative synthesis of these reagents for application to tritium labelling techniques. We have recently investigated the deuterium labelling of the reagent via the synthesis of its lithium salt from commercial diethyl phosphite and n-butyllithium in THF at 0oC, followed by D2O quench. The result of this experiment was very encouraging. The 1H and 2H NMR analyses of the product indicated synthesis of the reagent with close to 76% deuterium incorporation in the D-P bond. The JP,H in diethyl phosphite and JP,D in the deuteriated reagent were measured to be 603 and 106 Hz respectively. Further characterization and application of the deuteriated reagent is underway.
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