UC Santa Cruz
EXPLORATION AND DEVELOPMENT OF INDIUM-MEDIATED REACTIONS: SYNTHESIS OF DICHLOROINDIUM HYDRIDE, BORANE, AND THEIR APPLICATION TO VARIOUS REDUCTIONS
- Author(s): Saavedra, Jaime Zendejas
- Advisor(s): Singaram, Bakthan
- et al.
Metal hydrides, since their inception, have proven to be invaluable to the organic chemist. As the complexity of chemical compounds has increased over time, the need for finely tuned reducing agents has also increased and is responsible for the development of other metal hydrides and reducing agents we have today. However, as the specific requirements of metal hydrides continues to increase in the future, so too will the need for hydrides with increased selectivity and ease of use. Dichloroindium hydride, with its unique reactivity and ability to affect a variety of reactions sits poised to become a prominent and widely used reagent. Among HInCl2's abilities, it possesses the ability to behave as an ionic as well as radical reducing agent making it useful to a variety of reactions that have in the past required less desirable reaction conditions and reagents. Additionally, there are exist a variety of methods for the generation of HInCl2, causing the reactivity and reducing ability to vary greatly depending on the method and conditions used in the synthesis of HInCl2. This versatility, allows for the tailoring of HInCl2. Thus, the generation of HInCl2 using a variety of reaction conditions and hydride sources, such as: Bu3SnH, DIBAL-H, Et3SiH, NaBH4, was comparatively reviewed.
The reductive capabilities of the InCl3/NaBH4 system and its dependence on the solvent used for reduction were explored. Investigation by 11B NMR spectroscopic analyses indicates that the reaction of InCl3 with NaBH4 in THF generates HInCl2 along with borane−tetrahydrofuran (BH3*THF) in situ. Nitriles undergo reduction to primary amines under optimized conditions at 25 °C using one equivalent of anhydrous InCl3 with three equivalents of NaBH4 in THF. A variety of aromatic, heteroaromatic, and aliphatic nitriles are reduced to their corresponding primary amines in 70−99% isolated yields.
Continued exploration of various applications of HInCl2, the InCl3/NaBH4 system was used in selective reductive deoxygenation of diaryl carbonyls to the corresponding methylene hydrocarbons in good to excellent yields using a simple and convenient procedure. In addition, the generation of borane using the InCl3/NaBH4 system, as well as the synthesis of various known and novel borane complexes using a simple and reliable method under mild reaction conditions.
Lastly, novel methods of preparing HInCl2 via the in situ reduction of InCl3 using lithium amino borohydride (LAB) were developed. The generation of HInCl2 from the reduction of InCl3 by NaBH4 was used for comparison. The formation of HInCl2 from the InCl3/NaBH4 system also generates borane that is trapped as BH3-tetrahydrofuran (THF). Both reducing agents were used to control the reactivity of the system. This allowed for the selective, tandem, and/or partial reduction of multi-functionalized compounds containing nitriles and halogens. The InCl3/NaBH4 system in THF was found to efficiently reduce both nitriles and carbon-halogen bonds in a tandem fashion utilizing both HInCl2 and BH3*THF. In comparison, the InCl3/NaBH4/MeCN system scavenges the in situ generated borane and affords the selective reduction of the carbon-halogen bond in halo nitriles. Similarly, the InCl3/MeLAB and the InCl3/DIBAL-H systems were also found to selectively reduce the carbon-halogen bond in halo nitriles, while DIBAL-H alone selectively reduced halo nitriles to the corresponding halo aldehyde. The sequential addition of two equivalents of DIBAL-H followed by the addition of an equivalent of InCl3 allows the partial reduction of halo nitriles to halo imines; subsequent reduction of the carbon-halogen bond affords the corresponding aldehyde in a one-pot procedure.