Binary reducing agents containing dichloroindium hydride for the selective, partial, or tandem reductions of bifunctional compounds consisting of halo-nitriles, halo-esters and halo-carboxylic acids

Abstract

The selective, partial, or tandem reductions of bifunctional compounds containing primary alkyl or benzyl bromides can generate a variety of different products using a mixture of dichloroindium hydride (HInCl₂) and an additional hydride, such as borane–tetrahydrofuran (BH₃ : THF) or diisobutylaluminum hydride (DIBAL-H). Binary metal hydride systems, containing HInCl₂ and BH₃ : THF, are readily generated from anhydrous indium trichloride (InCl₃) and sodium borohydride (NaBH₄) in THF. Dichloroindium hydride can reduce primary halides and in the presence of another hydride, either generated in situ or added to the single-pot reaction, can perform tandem reductions of a variety of bifunctional bromides. Together, the hydrides reduce carbon–halogen bonds as well as an electrophilic group, such as a nitrile, an ester, or a carboxylic acid. The reduction of 4-(bromomethyl)benzonitrile using the HInCl₂ and BH₃ : THF binary metal hydride system affords 4-methylbenzylamine in an excellent yield under ambient conditions and short reaction times. By using the binary metal hydride system consisting of HInCl₂ and DIBAL-H, the tandem reduction of 4-(bromomethyl)benzonitrile was achieved affording para-tolualdehyde in an excellent yield, also under ambient conditions. The reduction of 4-(bromomethyl)phenyl acetic acid by HInCl₂ selectively reduced the carbon–halogen bond generating para-tolylacetic acid. When using either of the binary hydride systems, both functional groups were reduced generating 4-methylphenethyl alcohol. Methyl 4-(bromomethyl) benzoate underwent a selective or tandem reduction to generate [4-(bromomethyl)phenyl]methanol, methyl 4-methyl benzoate or para-tolylmethanol depending on the hydride system used. Consequently, a single bifunctional compound was transformed into a variety of different compounds by the simple manipulation of the binary hydride system used without the need for protecting groups, and in most cases, by a one-pot procedure.