Reductive Amination Revisited: Reduction of Aldimines with Trichlorosilane Catalyzed by Dimethylformamide-Functional Group Tolerance, Scope, and Limitations
Abstract
Aldimines, generated in situ from aliphatic, aromatic, and heteroaromatic aldehydes and aliphatic, aromatic, and heteroaromatic primary or secondary amines, can be reduced with trichlorosilane in the presence of dimethylformamide (DMF) as an organocatalyst (=2:1) allows second alkylation, giving rise to tertiary amines. Reductive N-alkylation of alpha-amino acids proceeds without racemization; the resulting products, containing a CC triple bond or N3 group, are suitable for click chemistry.
This reaction thus offers advantages over the traditional methods (borohydride reduction or catalytic hydrogenation) in terms of efficiency and chemoselectivity. Solubility of some of the reacting partners appears to be the only limitation.
The byproducts generated by the workup with aqueous NaHCO3 (i.e., NaCl and silica) are environmentally benign. As a greener alternative, DMA can be employed as a catalyst instead of DMF.