Visible Light‐induced Decarboxylative Alkylations Enabled by Electron Donor‐Acceptor Complex

Abstract

We demonstrated herein a versatile protocol for visible-light-induced decarboxylative alkylations enabled by electron-donor acceptor complex. An array of primary, secondary, tertiary and amino acid-derived redox-active esters (RAEs) were all amenable substrates to undergo radical decarboxylation to be coupled with a diverse range of nucleophiles, creating diverse C(sp 3 )À C(sp 3 ) and C(sp 3 )À C(sp 2 ) bonds with high efficiency. It is worth noting that Katritzky's salt and Togni's reagent were also suitable substrates, affording deaminative alkylation and trifluoromethylation products in high yields. Additionally, a one-pot two-step telescoped procedure and continuous-flow process further increase the synthetic utility of this catalytic system.

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).…”

“…Possibly because of the reaction suspension’s suitable and effective light absorption in the blue LED emission region (Figures S22 and S23, see the Supporting Information), only β-ketoenamine-linked 2D-COF-4 gave the satisfactory desired product yield (entry 4). Then, several previously documented homogeneous or heterogeneous photocatalysts in visible light-driven α-C­(sp 3 )–H bond alkylation − or arylation − of glycine derivatives, such as Eosin Y, Ru­(bpy) 3 Cl 2 , and g-C 3 N 4 , were incorporated into the reaction system to evaluate their compatibility (Table S1, entries 1–3, see the Supporting Information). Regrettably, the results revealed that all these catalysts demonstrated relatively diminished catalytic activity.…”

“…Subsequently, several common solvents used in previous protocols, − water, and ethanol were verified for compatibility with this heterogeneous photocatalytic system. Dimethylacetamide (DMA), as a critical solvent in some EDA-complex-catalyzed visible light-driven α-C­(sp 3 )–H bond alkylations, − still performed well and gave 3da in 79% yield (entry 6). Delightfully, water and ethanol were both applicable, and ethanol provided a comparative reaction efficiency with DMSO (entries 10, 11).…”

“…(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.…”