Scalable, Green Synthesis of Heteroaromatic Amine-boranes

In situ generated, transient sodium monohydroxyborohydride readily reacts with a present amine to form amineborane adducts in ethyl acetate at room temperature. Synthesis of heteroaromatic pyridine-, 2-picoline-, and 5-ethyl-2methylpyridine-boranes, those relevant to large-scale reductive aminations, has been demonstrated at 100 mmol scale, and pyridineborane at 1.1 mole scale. This first report substituting ethyl acetate for tetrahydrofuran, the traditional solvent for amine-borane synthesis, allows for activation of sodium borohydride by the aqueous portion of the heterogeneous dual-solvent system. These factors make this green protocol more economical than those currently available for the large-scale production of amine-boranes as demonstrated, quantitatively, by the computed green chemistry metrics.

Automated summary

In this study, a novel method for the synthesis of amineborane adducts using in situ generated, transient sodium monohydroxyborohydride in ethyl acetate was reported. The synthesis of heteroaromatic pyridine-, 2-picoline-, and 5-ethyl-2-methylpyridine-boranes was successfully demonstrated at 100 mmol scale, as well as pyridineborane at 1.1 mole scale. The substitution of ethyl acetate for tetrahydrofuran as the solvent allows for the activation of sodium borohydride by the aqueous portion of the dual-solvent system, making this green protocol more economically feasible for large-scale production of amine-boranes, as quantitatively demonstrated by the computed green chemistry metrics.