|Amides are typically made from a nitrogen nucleophile (amine) and an activated electrophilic carbonyl compound (for example acid chloride) in the Schotten-Baumann reaction. This functional group is relevant to biochemistry as peptides and chemists are always on the lookout for new synthetic methods. A novel approach by Shen et al. reverses the parts played by nucleophile and electrophile in what is known in organic chemistry as umpolung (DOI).|
In the new scheme alpha bromo nitroalkane 1 forms a nucleophilic synthon after deprotonation by potassium carbonate to nitronate salt 2. At the same time 1-phenylethylamine 3 exchanges a proton for an iodine atom with NIS to N-iodiamine 4. The nucleophilic attack by the nitronate is similar to what can be seen in electrophilic amination by an enolate. Intermediate 5 after hydrolysis as in the Nef reaction gives amide 6.