Oxidative Amidation of Nitroalkanes with Amine Nucleophiles using Molecular Oxygen and Iodine

Abstract

The formation of amides and peptides often necessitates powerful yet mild reagent systems. The reagents used, however, are often expensive and highly elaborate. New atom-economical and practical methods that achieve such goals are highly desirable. Ideally, the methods should start with substrates that are readily available in both chiral and non-chiral forms and utilize cheap reagents that are compatible with a wide variety of functional groups, steric encumberance, and epimerizable stereocenters. A direct oxidative method was developed to form amide and peptide bonds between amines and primary nitroalkanes simply by using I2 and K2 CO3 under O2 . Contrary to expectations, a 1:1 halogen-bonded complex forms between the iodonium source and the amine, which reacts with nitronates to form α-iodo nitroalkanes as precursors to the amides.

Dioxoiodane Compounds as Versatile Sources for Iodine(I) Chemistry

“…Finally, a recent report by Hayashi on the possible activation of N ‐iodosuccinimide with amine groups (Scheme ) prompted the investigation on related reactivity in the present system. While allylamine turned out to be incompatible with iodine(I) reagent 3 c , related acetamides promoted the iodooxygenation of 4‐fluorostyrene 4 g to the corresponding product 6 t in a way that is comparable to activation with 2‐chlorobenzoic acid.…”

Role of Lewis‐Base‐Coordinated Halogen(I) Intermediates in Organic Synthesis: The Journey from Unstable Intermediates to Versatile Reagents

“…An example of the formation of a halogen‐bonded iodine(I) intermediate in situ can be seen in the recent report by Hayashi et al on the oxidative amidation of nitroalkanes with amines and NIS in the presence of molecular oxygen (Scheme ) …”

Mechanism of Oxidative Amidation of Nitroalkanes with Oxygen and Amine Nucleophiles by Using Electrophilic Iodine

“…Later mechanistic studies supported such tetrahedral intermediates 3′ coupling with molecular oxygen in a homogenic manner to eventually form the amide products 4 (Figure a) . Through a systematic study of our recently developed oxidative amidation procedure on unsubstituted nitroalkanes 1 , we now provide evidence that the tetrahedral intermediates are more likely α,α‐dihalogenated nitroalkanes derived from α‐halonitroalkanes like 1′ or 3 (Figure b). Under our reaction conditions, we propose that there is no umpolung of reactivity in the amine component and an extra equivalent of iodonium source is generated in the process.…”