Reaction of InCl₃with Various Reducing Agents: InCl₃–NaBH₄-Mediated Reduction of Aromatic and Aliphatic Nitriles to Primary Amines

Abstract

While alternative methods of preparing dichloroindium hydride (HInCl(2)) via the in situ reduction of InCl(3) using lithium amino borohydride (LAB) were explored, generation of HInCl(2) from the reduction of InCl(3) by sodium borohydride (NaBH(4)) was also re-evaluated for comparison. The reductive capability of the InCl(3)/NaBH(4) system was found to be highly dependent on the solvent used. Investigation by (11)B NMR spectroscopic analyses indicated that the reaction of InCl(3) with NaBH(4) in THF generates HInCl(2) along with borane-tetrahydrofuran (BH(3)·THF) in situ. Nitriles underwent reduction to primary amines under optimized conditions at 25 °C using 1 equiv of anhydrous InCl(3) with 3 equiv of NaBH(4) in THF. A variety of aromatic, heteroaromatic, and aliphatic nitriles were reduced to their corresponding primary amine in 70-99% isolated yields. Alkyl halide and nitrile functional groups were reduced in tandem by utilizing the reductive capabilities of both HInCl(2) and BH(3)·THF in a one-pot reaction. Finally, the selective reduction of the carbon bromine bond in the presence of nitriles was achieved by generating HInCl(2) via the reduction InCl(3) with NaBH(4) in CH(3)CN or with lithium dimethylaminoborohydride (MeLAB) in THF.

Synthesis of dichloroindium hydride and exploration of its reactivity with organic functional groups. Tandem, selective and partial reductions of halo-nitriles

“…32 It was also found that the HInCl 2 produced using the MeLAB/InCl 3 reagent system possesses similar reductive capabilities to that of HInCl 2 prepared via other methods. For example, we were able to reduce aliphatic halides like (3-bromopropyl)benzene to n-propylbenzene in 77% yield (Scheme 29).…”

“…It was discovered that the ratio of InCl 3 to MeLAB played a significant role in the formation of the reducing species (Table 4). 32 When an excess of MeLAB was used (Table 4, entries 1 and 2), the reaction mixture quickly turned dark grey and precipitated colloidal indium metal which aggregated to form a shiny indium nugget. From the weight of the indium metal, it was deduced that indium metal was formed essentially quantitatively in these reactions.…”

“…InCl 3 /NaBH 4 reduction of aromatic, heteroaromatic and aliphatic nitriles to primary amines. 32 The InCl 3 /NaBH 4 system was able to reduce a variety of aromatic nitriles, including aromatic nitriles with electron-donating groups in good to excellent yields (70-99%). A variety of halogen-substituted aromatic nitriles were also reduced using this simple procedure.…”

“…30 Since previous reports had not elucidated the origin of these solvent effects, we decided to explore the InCl 3 /NaBH 4 reagent system further by monitoring the boron species formed during the reaction via 11 B NMR spectroscopy. 32 Consequently, we reacted a 1:1 molar ratio of InCl 3 to NaBH 4 in both THF and MeCN and analyzed the supernatant solution by 11 B NMR spectroscopy to probe the identity of the boron species formed in situ (Scheme 27). We suggest that the poor reduction of alkyl halides using a catalytic amount of InCl 3 along with one equivalent of NaBH 4 in THF that was previously reported 23 is likely to have been due to the inhibition of the catalytic cycle by the in situ generated BH 3 ·THF.…”

“…While our previous study demonstrated the ability of InCl 3 /NaBH 4 to reduce nitriles to primary amines utilizing in situ generated BH 3 ·THF, 32 we also sought to explore the reductive capabilities of the mixture of HInCl 2 and BH 3 ·THF. This was achieved by investigating a tandem reduction sequence that utilized both the HInCl 2 and BH 3 ·THF generated in situ from the InCl 3 /NaBH 4 system (Scheme 31).…”