Transamidation and Decarbonylation of N-Phthaloyl-Amino Acid Amides Enabled by Palladium-Catalyzed Selective C–N Bond Cleavage

Abstract

Amides are important functional synthons that have been widely used in the construction of peptides, natural products, and drugs. The C–N bond cleavage provides the direct method for amide conversion. However, amides, especially secondary amides, tend to be chemically inert due to the resonance of the amide bond. Here, we describe an efficient Pd-catalyzed transamidation and decarbonylation of multiamide structure molecules through C–N bond cleavage with excellent chemoselectivity. The transamidation of secondary amides and the decarbonylation of phthalimide provide meaningful tools for the modification of amino acid derivatives. Moreover, further transformations of azidation and C­(sp3)–H monoarylation emphasized the potential utility of this selective C–N bond cleavage method.

PhNCO-enabled synthesis of secondary amides from N-(2-aminophenyl)benzamides

“…These compounds are indispensable precursors for the synthesis of highly important amides. [27][28][29] In this regard, Bode et al documented a protocol for the synthesis of hindered and electron-deficient secondary amides by the direct coupling of isocyanates with Grignard reagents. 30 Inspired by these reports and building on our ongoing research interest in the chemoselective cleavage of C-N bonds in amides, [31][32][33] our recent work reported an N-H/C-H carbonylation reaction using phenyl isocyanate to facilitate the versatile synthesis of diverse Nheterocycles (Scheme 1b).…”

Catalyst-free activation of N–C(O) Amide bonds – efficient cascade synthesis of N-acyl thiocarbamides in batch and continuous-flow

“…24,25 In addition, transamidation, which is the transformation of one amide to another, has been reported by numerous groups. [26][27][28] The Szostak group spearheaded groundbreaking research on amide N-C bond reactions, unveiling the first instance of metal-free transamidation under LiHMDS in both activated and unactivated amides. 29,30 Recently, Lee et al have developed a couple of methods for transamidation involving activated amides, employing (NH 4 ) 2 CO 3 as the ammonia source to synthesize primary amides.…”

Direct C(sp3)–H Polyfluoroarylation: Access to Polyfluoroaryl Amino Acids via Rh-Catalyzed Selective C–F Bond Cleavage

“…In view of the important value, the efficient synthesis of polyfluoroaryl amino acids through the coupling reaction of amino acids with polyfluoroarenes will be of great significance. As part of our efforts to modify amino acids, herein, we report an Rh-catalyzed selective C–F bond alkylation of polyfluoroarene with glycinates and derivatives (Scheme b).…”