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...

Aldehydes are both versatile intermediates in chemical syntheses and used directly as pharmaceuticals, flavors, and fragrances. However, their synthetic preparation with traditional synthetic chemistry often requires harsh operating conditions and/or toxic metals, including osmium or chromium. To improve the sustainability of aldehyde synthesis, emerging efforts have focused on the production of bio-aldehydes via enzymatic oxidation, reduction, or de novo metabolic pathways. Here, we present a practical guide the different ways to synthesize aldehydes with enzymatic and whole-cell systems with an emphasis on circumventing common challenges, including product isolation and avoiding over-reduction or over-oxidation of the desired aldehyde.

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 alcohol substrates using a combination of biocatalysis and organocatalysis in a single-flask process. Alcohol oxidase oxidizes alcohol substrates to an intermediate aldehyde, which is sequentially converted to a nitroalcohol, then a nitroalkene, and finally, to a 1,3-dinitroalkane with a combination of phosphate buffer and lysine catalysis. Simultaneous addition of all reagents gives a maximal yield of 52%, whereas staggering the introduction of the amino acid catalyst and nitromethane substrate boosts the yield to 71% with near-quantitative conversion. Taken together, this work shows that biocatalysed oxidation can be coupled to multi-step catalytic cascades to expand the types of products available from bioprocesses.