In 1984, Ram and Ehrenkaufer, Tetrahedron Lett. 1984, 25, 3415, reported that nitro compounds could be easily converted into the corresponding amines by transfer hydrogenation using ammonium formate catalyzed by palladium on carbon. The preparation of ammonium formate was described in 1941 by S. Zuffanti in J. Am. Chem. Soc.1941, 63, 3123. It has been generally used in the precipitation of base metals from the salts of the noble metals. The use of ammonium formate in organic synthesis was first illustrated by Leucart in Ber-Disch. Chem. Ges. 1885, 18, 2341, in which various carbonyl compounds were reacted with ammonium formate to afford the corresponding amines. This process was later named as the "Leucart Reaction".
Ram et al. Tetrahedron Letter, supra, and Ram et al. Synthesis, 1986, 138, disclose the conversion of nitro compounds to the corresponding amines by transfer hydrogenation using ammonium formate in the presence of a palladium on carbon catalyst without concern directed to steric configuration. Reduction of nitro compounds to the corresponding amine has been generally thought, by those skilled in the art, to entail the loss of stereo configuration and production of racemic mixtures when the starting nitro compound is an enantiomercially pure material. This involved deprotonation of untreated nitro compound to form a nitronate anion which is planar and, therefore, one which forms a racemic mixture of nitro compound on reprotonation (an equilibrium reaction). The reduction of the thus formed reprotonated racemic nitro compound provides the corresponding racemic amino compound.
Conventional prior art processes for converting .beta.-nitro alcohols into the corresponding hydroxy amines with retention of configuration were usually carried out by hydrogenation over Raney nickel or platinum catalysts. These procedures frequently required elevated temperatures and pressures and cannot be carried out at room temperature in a relatively mild procedure.
The present invention is directed to an improvement in the prior art process wherein the reduction protocol is clearly demonstrated to show that the ammonium formate transfer hydrogenation method is stereospecific and provides retention of configuration to the amines produced from functionalized nitro compounds as shown in FIG. I.