Cascade cyclization of glycine derivatives with β-ketoesters for polysubstituted 1,4-dihydropyridines by visible light photoredox catalysis

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

“…Delightfully, water and ethanol were both applicable, and ethanol provided a comparative reaction efficiency with DMSO (entries 10, 11). This result broke the limitation of alcohol solvents in the visible light-driven α-C(sp 3 )–H bond alkylation of glycine derivatives, − leaving an infinite space to enhance the reaction sustainability and workup simplicity. The screening of light sources revealed that the changes in light wavelength all led to a decrease in reaction efficiency (entries 15–17).…”

“…(2) The catalyst (2D-COF-4) was easily reused, maintaining the catalytic activity even after 10 recycle runs with unfaded basic structure and micro appearance. (3) The reaction is compatible with a green solvent (ethanol), which has always encountered failures in previous works. − This solvent led to a straightforward scale-up and easy workup procedures for the alkylation. The desired product and byproduct are obtained quickly and efficiently with standard solvent removal and filtration.…”

“…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.…”

α-C–H functionalization of glycine derivatives under mechanochemical accelerated aging en route the synthesis of 1,4-dihydropyridines and α-substituted glycine esters

“…12 Their synthesis mostly relies on the multicomponent reactions of aldehydes, β-ketoesters, and specific amine sources, which is known as Hantzsch-type synthesis. 12 a , c ,13 Recently, the development of cascade cross dehydrogenative coupling (CDC) 14 -cyclization strategy 15 has provided an efficient alternative for the synthesis of 1,4-DHPs using glycines as accessible building blocks. For example, Jia 15 a developed the first Fe/TMSCl-TBPA + /O 2 promoted cascade CDC between glycinates and β-ketoesters in acetonitrile solvent to achieve 1,4-DHPs, where the cleavage of the C–N bonding and the reassembly of amine fragments led to the bond formation in an atom- and step-economic fashion.…”

Copper‐Catalyzed Oxidative [1+2+1+2] Cascade Cyclization of N,N‐Dimethyl Enaminones with Benzylamines: A Facile Access to Functionalized 1,4‐Dihydropyridines

“…In contrast to the above well-established methods, the construction of 1,4-DHPs by using the C(sp 3 )À H bond substrates as the C4 source still encounters challenges. Indeed, in terms of C(sp 3 )À H bond functionalization cascade cyclization to access 1,4-DHPs, there are only two cases of C(sp 3 )À O bond cleavage cascade cyclization from benzyl alcohols described by Ranjbar et al [15] and two cases of C(sp 3 )À N cleavage cascade cyclization from N-arylglycine esters described by Le et al [16] Recently, the cleavage of C(sp 3 )-N bond has been successfully applied as an important type of chemical transformation for constructing new CÀ C bonds or CÀ X bonds. [17] However, to the best of our knowledge, no example of the C(sp 3 )À H bond functionalization and C(sp 3 )À N bond cleavage of alkylamines through cascade cyclization reaction for the synthesis of 1,4-DHPs has been described.…”