One-pot cascade reactions for the synthesis of dinitroalkanes in aqueous buffer

Abstract

Dinitroalkanes are powerful synthetic building blocks because of the versatility of the 1,3-dinitro motif. Here, we show that dinitroalkanes can be synthesized from aliphatic aldehydes in a three-step cascade reaction catalysed by phosphate buffer and the amino acid lysine. We further show that this methodology can be expanded to limited alcohol substrates (1-butanol and 1-pentanol) with the inclusion of a biocatalysed alcohol oxidation. Simultaneous addition of all reagents gives a maximal yield of 52% of 3-(nitromethyl)hexane, derived from 1-butanol and nitromethane, whereas staggering the introduction of the amino acid catalyst and nitromethane substrate boosts the yield to 71% of 3-(nitromethyl)hexane with near-quantitative consumption of the n-butyraldehyde intermediate. Taken together, this work presents a mild synthetic method that couples multi-step catalytic cascades to generate 1,3-dinitroalkanes.