The Preparation of Deuterated Organic Compounds from Activated Organic Halides by Reduction with Zinc-Deuterium Oxide

Reductive elimination of halogen from α-halo esters with zinc and deuterium oxide in polar aprotic solvents provides a convenient method for the preparation of the corresponding α-deuterated substances. The procedures developed for carrying out these transformations can be applied to the synthesis of large quantities of either mono- or dideuterated esters with good isotopic purity. Several isolated experiments suggest that this method should also be applicable to the conversion of α-halogenated nitriles and amides to the corresponding α-deuterated materials; when applied to the reductive deuteration of α-halogenated ketones and acid chlorides, the isotopic purities of the deuterated products are lower. This technique for the synthesis of α-deuterated esters is superior to the base-catalyzed exchange techniques in general use when the prerequisite α-halogenated analogs are available, both in its economical use of deuterium oxide and in its ability to introduce a single deuterium atom into a methyl or methylene group containing multiple equivalent exchangeable protons.