Scalable, Green Synthesis of Heteroaromatic Amine-boranes

Abstract

In situ generated, transient sodium monohydroxyborohydride readily reacts with a present amine to form amine-borane adducts in ethyl acetate at room temperature. Synthesis of heteroaromatic pyridine-, 2-picoline-, and 5-ethyl-2-methylpyridine-boranes, those relevant to large-scale reductive aminations, has been demonstrated at 100 mmol scale, and pyridine-borane 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.

Borane-Pyridine: An Efficient Catalyst for Direct Amidation

“…The lower yields obtained when using 1i and 1j, and the drawbacks associated with 1k, including cost and difficulty in separation from the reaction mixture due to high boiling point and low water solubility, led to the selection of borane-pyridine (1l) as the optimal catalyst. Additional benefits of 1l include the fact that it is a liquid, it works at a lower (5 mol%) catalyst loading, and our recently described large-scale, green synthesis of 1l eliminates the use of tetrahydrofuran from its preparation [19]. Standardization of conditions led to the use of 1 eq.…”

“…Procedure for the preparation of borane-pyridine [ 19 ] consisted of sodium borohydride (2 eq, 0.2 mole, 7.566 g) being charged to a 200 mL round-bottom flask containing a stir-bar followed by the addition of 100 mL ethyl acetate (1 M w.r.t. amine).…”

Catalyst- and Stoichiometry-Dependent Deoxygenative Reduction of Esters to Ethers or Alcohols with Borane–Ammonia

“…The reductant was examined using a series of synthesized , borane–amines, including 1°- (borane– n -propylamine, 1b ) 2°- (borane–dimethylamine, 1c ), 3°- (borane–triethylamine, 1d ), and heteroaromatic (borane–pyridine, 1e ), and carrying out each reaction for 6 h. The transformations were incomplete (Table , entries 12–15), confirming the superiority of 1a for the reduction of esters to ethers. The widely varying product outcomes obtained for the various borane–amines are believed to be a result of variations in reducing strength arising from the differences in sterics and basicity of the coordinated amine.…”