Organocatalytic Biomimetic Reduction of Conjugated Nitroalkenes

Abstract

A thiourea-catalyzed biomimetic reduction of conjugated nitroalkenes has been developed. Various aromatic and aliphatic conjugated nitroalkenes can be reduced to give the respective nitroalkanes with good yields under mild conditions. This protocol is not only practical, but may also provide insight into the mechanisms of redox transformations in biological systems.Aliphatic nitroalkanes are valuable building blocks and intermediates in organic synthesis as well as in carbohydrate chemistry. 1 They are very useful tools for carboncarbon bond formation or carbon skeleton elongation because the high electron-withdrawing power of the nitro group stabilizes a-carbanions and enables their reactions with electrophiles under mild conditions. Moreover, the nitro group itself can be transformed into other functionalities such as, amongst others, carbonyl, amino, oxime, and hydrogen moieties. 2 The preparation and subsequent reduction of conjugated nitroalkenes has been widely accepted as a straightforward route to nitroalkanes, thus, there are quite a number of reducing reagents and reduction methodologies employed in this transformation. 3 Commonly used reductants include borohydride derivatives, metal hydrides, and metal halides. However, the selective reduction of the conjugated double bond is rather difficult because nitro-group reduction often takes place simultaneously. 4 Though sodium borohydride primarily furnishes the corresponding nitroalkanes, these reactions are often accompanied by the formation of polymeric side products through Michael addition of the nitronate intermediate to the starting nitroalkene. 5 Zinc borohydride is reported to be an efficient reagent with which to convert nitroalkenes smoothly into the corresponding nitroalkanes. 6 Metal-catalyzed hydrogenations and transfer hydrogenation are also very effective, however, due to the difficulties in handling or the toxicity of metal ions, new efficient and environmentally friendly methods remain desirable. 7In contrast to the chemical conversions described above, biological redox transformations using reduced nicotinamide adenine dinucleotide (NADH) as a coenzyme to reduce unsaturated functionalities, proceeds smoothly under very mild conditions. The ease with which such reactions takes place has been a stimulus for the development of a wide range of NADH models for a variety of reductions. 8 Among these, Hantzsch esters are one of the most widely investigated biomimetic reductants because they are inexpensive, stable and readily available. 9 Recent advances in organocatalysis have shown considerable promise for employing Hantzsch esters as the hydrogen source in asymmetric reductions as well as reductive aminations; 10 however, there is no organocatalytic method for the reduction of conjugated nitroalkenes. 11 Developments in biological and enzymatic catalysis have shown that isolated enzymes from baker's yeast or Old Yellow Enzyme (OYE), which was termed as nitroalkene reductase, can efficiently catalyze the NADPH-linked reduction of nitro-olefins...