Recent Advances in the α-C(sp³)-H Bond Functionalization of Glycine Derivatives

Abstract

α-Amino acids are the units of proteins, which not only widely occur in many biological important compounds and natural products, but also are useful as organic catalysts or ligands for asymmetric synthesis. Among them, glycines are particularly useful building blocks in organic synthesis. Direct C(sp 3)-H bond functionalization of glycine derivatives provided an attractive synthesis strategy for the construction of a variety of α-substituted α-amino acids. The recent progress in the α-C(sp 3)-H bond activation of glycine derivatives, with various reagents to form carbon-carbon and carbon-heteroatom bond, and oxidative coupling/cyclization reaction involving glycine derivatives is reviewed.

Visible Light-Driven Flexible Synthesis of α-Alkylated Glycine Derivatives Catalyzed by Reusable Covalent Organic Frameworks

“…Glycine is the most elementary α-amino acid. Its direct derivatization and modification hold significant relevance in synthesizing unnatural amino acid-containing bioactive peptides and pharmaceuticals. , Past decades have witnessed a booming interest in functionalizing glycine derivatives. − Among them, visible light-driven α-C­(sp 3 )–H bond alkylation of glycine derivatives is outstanding as it could deliver diverse alkylated glycine derivatives precisely and efficiently in a green and sustainable manner. − Regarding the photocatalysts involved in initiating the reaction, reported visible light-driven approaches toward this objective can be categorized into the following three types (Scheme a): (1) the external photocatalyst (PC) needed visible light-driven C­(sp 3 )–H bond alkylation, in which transition-metal complexes, organic dyes, or quantum dots acted as photocatalysts to absorb visible light and initiate the reaction. − (2) photocatalyst-free visible light-driven C­(sp 3 )–H bond alkylation, in which electron donor–acceptor (EDA) complexes always formed and served as internal photocatalysts. − (3) visible light-driven C­(sp 3 )–H bond asymmetric alkylation, in which transition-metal asymmetric catalysis and photocatalysis merged to fulfill the synthesis of C­(sp 3 )-alkylated glycine derivatives stereo selectively. − The protocols above have demonstrated significant advancements concerning reaction efficiency, selectivity, and the range of applicable substrates. Nevertheless, substantial room exists for further enhancement in various facets of environmentally benign characteristics, including but not limited to catalyst reusability, reaction flexibility, and simplification of postreaction workup procedures.…”

Visible-Light-Driven α-C(sp3)–H Bond Functionalization of Glycine Derivatives

“…Many pioneering works toward this target have been intensively reported. Among them, the direct α-C(sp 3 )-H bond functionalization of glycine derivatives is privileged, owing to the inherent advantages of the atom economy, chemoselectivity, and reaction simplicity [8][9][10][11][12][13][14]. To date, according to the reaction modes, the strategies for accomplishing this process could be classified into four types: (1) Strong base-assisted functionalization of α-carbanions [15]; (2) Traditional radical precursors involved or UV light promoted direct radical coupling [16][17][18][19][20]; (3) Transition-metal catalyzed or thermal catalytic crossdehydrogenative coupling (CDC) [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]; (4) Visible-light-driven α-C(sp 3 )-H bond functionalization [37][38][39][40][41][42].…”

Synthesis of Chiral Spin-Labeled Amino Acids

“…Although chiral synthesis of α-amino acids is highly developed, , the spin-labeled targets 6 – 8 present some special challenges. In addition to the nitroxyl radical broadening conventional NMR signals, which makes direct structural analysis more difficult, the tetrasubstitution of carbons attached to nitrogen enables potential cation formation under acidic conditions with subsequent undesired decomposition (e.g., elimination).…”