Sodium cyanoboronhydride (NaBH3(CN)) as a reducing agent for reductive amination has lower solubility in aprotic solvents, restricting its application when these solvents are required. To overcome this limitation, Hutchins introduced tetrabutylammonium cyanoborohydride (TBAC), a soluble compound not only in protic and polar solvents, but also in most aprotic solvents such as DCM, hexane, benzene, and THF. Notably, TBAC, being a white crystalline solid, possesses excellent stability in air and moisture, rendering it an ideal reagent choice.
TBAC exhibits comparable reactivity to its precursor NaBH3(CN), when facilitating reductive amination between unhindered aldehydes/ketones and basic amines in aprotic solvents. Nevertheless, the reaction duration is prolonged, particular in cases involving ketones and secondary amines. Furthermore, there are challenges when working with aldehydes/ketones and weaker or neutral amines, limiting the common use of TBAC in reductive amination.