A simple four-component synthesis of ferrocenyl amidodiesters and ferrocenyl triamides

Synthesis, Crystal Structures and Properties of Ferrocenyl Bis-Amide Derivatives Yielded via the Ugi Four-Component Reaction

“…The U-4CR is becoming the most efficient strategy for the construction of dipeptide-like compounds [ 14 , 15 , 16 , 22 ]. We found that ferrocenecarboxylic acid can react smoothly with a mixture of diverse amines, aldehydes, and isocyanides in the absence of any catalyst in methanol solution ( Scheme 1 ) and afford new ferrocenyl bis-amides 1 – 10 in moderate to excellent yields.…”

“…In most cases, the types of amines and isocyanides exhibited less effect on the reaction. Based on the known results [ 14 , 15 , 23 ], a possible mechanism ( Scheme 2 ) was suggested for the formation of ferrocenyl bis-amides 1 – 10 : firstly, the reaction of amine with aldehyde yields an imine I , which further interacts with ferrocenecarboxylic acid to give an imine salt II ; secondly, it reacts with isocyanide to form an intermediate product III , which then rearranges into the final product bis-amide via an acyl transfer process (Mumm rearrangement). It should be noted that the U-4CR strategy provides an efficient synthesis of novel dipeptide-like molecules containing one or two ferrocenyl moieties.…”

“…Recently, incorporating a ferrocenyl group into peptide structures has received considerable attention [ 10 , 11 , 12 , 13 ] as ferrocene was extensively exploited as a potential probe to identify non-covalent interactions between peptide structures, and the electron-transfer properties of different peptide secondary units. Although versatile ferrocenyl peptides or peptide-like derivatives have been reported [ 2 , 14 , 15 , 16 , 17 , 18 , 19 ], the majority of such compounds were generally obtained via a time-consuming stepwise strategy, which is usually inefficient and reduces the overall greenness of the synthesis.…”

“…In particular, the Ugi four-component reaction (U-4CR) [ 21 ] is now a powerful tool for the construction of diverse dipeptide-like molecules in combinatorial chemistry [ 22 ]. Bazgir et al firstly reported ferrocenyl bis/tri-amide compounds generated via the U-4CR using ferrocenealdehyde [ 14 , 15 ]. Very recently, utilizing the U-4CR [ 16 ], we have successfully synthesized two novel ferrocenyl bis-amide molecules from ferrocenecarboxylic acid and ferrocene-1,1′-dicarboxylic acid, respectively.…”