Cross-Dehydrogenative Coupling Reactions for the Functionalization of α-Amino Acid Derivatives and Peptides

Abstract

The functionalization of typically unreactive C(sp3)–H bonds holds great promise for reducing the reliance on existing functional groups while improving atom-economy and energy efficiency. As a result, this topic is a matter of genuine concern for scientists in order to achieve greener chemical processes. The site-specific modification of α-amino acid and peptides based upon C(sp3)–H functionalization still represents a great challenge of utmost synthetic importance. This short review summarizes the most recent advances in ‘Cross-Dehydrogenative Couplings’ of α-amino carbonyl compounds and peptide derivatives with a variety of nucleophilic coupling partners.1 Introduction2 C–C Bond-Forming Oxidative Couplings2.1 Reaction with Alkynes2.2 Reaction with Alkenes2.3 Reaction with (Hetero)arenes2.4 Reaction with Alkyl Reagents3 C–Heteroatom Bond-Forming Oxidative Couplings3.1 C–P Bond Formation3.2 C–N Bond Formation3.3 C–O and C–S Bond Formation4 Conclusions

Enantioselective cross-dehydrogenative coupling enabled by organocatalysis

“…143,144 The direct α-functionalization of glycine derivatives has proven to be a powerful tool to access α-amino acids and their derivatives, and the corresponding asymmetric reaction has also been developed. [145][146][147][148] In 2020, Zhang and co-workers reported a CDC between glycine derivatives and ketones or aldehydes under cooperative photoredox catalysis and organocatalysis conditions (Scheme 16). 149 Under optimal conditions using Ru(bpy) 3 Cl 2 as a photoredox catalyst and a triflimide-derived chiral secondary amine C12 as a organocatalyst, a variety of glycine derivatives containing esters, ethers, amides, halogens, and aromatic rings underwent a wide array of ketones and aldehydes bearing sulfides, ethers, and esters groups to form enantiopure unnatural α-alkyl α-amino acid derivatives in 29-84% yields with 76-97% ees and 77 : 23->99 : 1 drs.…”

Oxidative Cross-Coupling of α-Amino Ketones with Alcohols Enabled by I2-Catalyzed C–H Hydroxylation

“…This condition limits the practical scope of these reactions to simple, inexpensive alcohols. Based on the high atom economy and environmentally friendly character, the oxidative cross-coupling of α-amino carbonyl compounds with nucleophiles has lately become a powerful and practical means for the assembly of structurally diversified α-amino acid derivatives. , The direct oxidative C–O bond formation of α-amino carbonyl compounds has been well studied by employing O -nucleophiles including phenols and carboxylic acids; however, methods that enable the direct oxidative C–H alkoxylation of α-amino carbonyl compounds with alcohols have been rarely reported. In 1981, Proctor and co-worker revealed oxidative cross-coupling of N -benzoyl-2-aminoacetophenone with methanol in low yields, which required manganese dioxide as oxidant and alcohols as solvent .…”

Direct annulation between glycine derivatives and thiiranes through photoredox/iron cooperative catalysis

“…Direct α-C(sp 3 )–H functionalization of glycine derivatives has recently emerged as the most straightforward method to synthesize UAAs and modify oligopeptides. 6 In this regard, several groups have successfully achieved the rapid synthesis of new UAAs by constructing C–C, 7 C–O, 8 C–N, 9 and C–P 10 bonds. However, such a reaction to provide the corresponding sulfur-containing UAAs through the direct construction of C–S bonds has not yet been achieved, and constitutes a formidable challenge, because of the easy oxidation of thiols.…”