A Four-Step Biocatalytic and Organocatalytic Cascade for Single-Flask Production of Dinitroalkanes from Alcohols in Aqueous Buffer



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.


Thumbnail image of Dinitroalkane_main text_ChemRxiv.pdf

Supplementary material

Thumbnail image of Dinitroalkane SI_final.pdf
Supplementary Information
Includes full amino acid catalyst screen, toxicity effects of nitromethane on K. pastoris, time-course production of nitroalcohol and dinitroalkane from butyraldehyde, experimental procedures, syntheses, and characterization data.