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.

The asymmetric Michael reaction of nitroalkanes and β,β-disubstituted α,β-unsaturated aldehydes was catalyzed by diphenylprolinol silyl ether to afford 1,4-addition products with an all-carbon quaternary stereogenic center with excellent enantioselectivity. The reaction is general for β-substituents such as β-aryl and β-alkyl groups, and both nitromethane and nitroethane can be employed. The addition of nitroethane is considered a synthetic equivalent of the asymmetric Michael reaction of ethyl and acetyl substituents by means of radical denitration and Nef reaction, respectively. The short asymmetric synthesis of (S)-ethosuximide with a quaternary carbon center was accomplished by using the present asymmetric Michael reaction as the key step. The reaction mechanism that involves the E/Z isomerization of α,β-unsaturated aldehydes, the retro-Michael reaction, and the different reactivity between nitromethane and nitroethane is discussed.

The formation of amides and peptides often necessitates powerfuly et mild reagent systems.T he reagents used, however,a re often expensive and highly elaborate.N ew atom-economical and practical methods that achieve such goals are highly desirable.I deally,t he methods should start with substrates that are readily available in both chiral and non-chiral forms and utilize cheap reagents that are compatible with awide variety of functional groups,steric encumberance, and epimerizable stereocenters.Adirect oxidative method was developed to form amide and peptide bonds between amines and primary nitroalkanes simply by using I 2 and K 2 CO 3 under O 2 .C ontrary to expectations,a1:1h alogen-bonded complex forms between the iodonium source and the amine,w hich reacts with nitronates to form a-iodo nitroalkanes as precursors to the amides.

The title reaction becomes possible in the presence of molecular oxygen and either NIS or I2.

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