EDA Complexes Research Articles

Sunlight-induced three-component synthesis of α-aminoketones: a green and sustainable pathway through an EDA complex

We reported a sunlight-promoted, three-component reaction involving glyoxal hydrates, anilines, and 4-alkyl DHPs for the synthesis of α-aminoketones with high yields under ambient conditions without additional photocatalysts or additives.

Controllable tertiary amine-promoted photoactivation metal-free carbonylation of aryl sulfonium salts to aryl carboxylic acid derivatives

This paper describes a new method for the activation of aryl radicals via EDA complexes without metals and photosensitizers for carbonylation with various nucleophilic reagents under visible light.

Photoinduced selective perfluoroalkylation of terminal alkynes via electron donor-acceptor complexes.

Herein, we report a photoinduced selective perfluoroalkylation of terminal alkynes driven by the noncovalent interaction between a thymol anion and fluoroalkyl iodides. By precisely tuning the reaction solvent, a wide range of 37 structurally diverse perfluoroalkylated alkynes and alkenes, including ibuprofen, empagliflozin, galactose, isoxepac and indomethacin, were obtained in up to 92% yields. Mechanistic studies reveal the formation of EDA complexes between the thymol anion and fluoroalkyl iodides. This strategy may provide an important complement to traditional approaches to prepare useful perfluoroalkylated alkynes and alkenes.

Catalyst-free C–H methylation of heteroarenes enabled by electron donor–acceptor complex photoactivation

A visible-light-induced direct C–H methylation of heterocycles (including quinoxalinones, pyrazinones, quinolinones and coumarins) with methylamines via EDA complex photoactivation was developed.

Zwitterions as catalytic electron donor species for visible light-induced photoactivation of oxime esters and direct C3-alkylation of quinoxalin-2(1H)-ones

A novel ternary EDA complex catalysis strategy has been developed for the photoactivation of oxime esters. By augmenting the electron-donating properties of zwitterions with a base, a ternary EDA complex...

An Expanded EDA Complex Profile: Construction of Aza-arenes and Their Synthetic Application as Fluorescence Probes.

We developed a visible-light-driven expanded EDA complex profile for the synthesis of aza-arenes via aza-6π electrocyclization of 2-styrylanilines with aromatic aldehydes. This protocol relies on the EDA complexes of AlCl3 with imine to induce the absorption red-shift to visible light from ultraviolet light. An array of 2,3-disubstituted quinolines were constructed smoothly after excitation with blue-light-emitting diodes at room temperature. In addition, the resultant product, used as a cell permeable lipid droplet-specific probe, shows a low working concentration, a short staining time, and functionality in living and fixed cells.

The Synthesis of (E)‐Vinyl and Alkynyl Sulfones by the Formation of an Electron Donor‐Acceptor Complex Using Thiosulfonates and Sodium Iodide Under Visible Light

AbstractA method for the synthesis of (E)‐vinyl sulfones and alkynyl sulfones through the cleavage of thiosulfonate promoted by the formation of EDA complexes under visible light irradiation at room temperature without the need for other metal catalysts is described. The mechanism study shows that sodium iodide and thiosulfonate form EDA complexes under visible light irradiation, resulting in a single‐electron transfer cleavage to generate sulfonyl radicals, which then react with olefins or alkynes to produce (E)‐vinyl sulfones or alkynyl sulfones, respectively. This method is applicable to 44 olefin and alkyne substrates, with yields ranging from 38% to 90%, providing a radical synthesis approach for the preparation of sulfonylated compounds.

Visible Light‐Induced EDA‐Complex Triggered Annulative Difunctionalization via Olefin‐Olefin Coupling and Radical Truce‐Smiles Rearrangement

AbstractAn EDA complex comprising N‐allyl bromodifluoroacetamides and tertiary alkyl amine was exploited to facilitate annulative difunctionalization reaction under visible‐light irradiation. This external photocatalyst‐free methodology garners olefin‐olefin coupling featuring a radical Truce‐Smiles rearrangement and produced long‐chain functionalized gem‐difluoropyrrolidones from N‐substituted methacryloyl sulfonamides, while simple N‐aryl methacrylamides furnished pyrrolidinone‐oxindole hybrid lactams in high yields. Mechanistic investigations substantiate a combined reaction mechanism, involving charge‐transfer EDA complex‐based radical cascade, alongside an α‐aminoalkyl radical‐triggered XAT process, exhibiting a quantum yield value of 1.48.

Direct Access to Quinone-Fused 5-Substituted-1,4-Benzodiazepine Scaffolds from Azidoquinones with/without [1,2]-Azide-Nitrogen Migration: Mechanistic Insights.

Seven-membered nitrogen heterocycles have a strong influence in drug discovery due to their inherent 3D character, which allows the ability to explore a vast conformational space with a biological target. Notably, the privileged 1,4-benzodiazepine scaffold is dominant in treating the central nervous system due to its binding affinity with the GABAA receptor. Herein, we report a protocol for the transformation of azidoquinones to p-quinone fused 5-substituted-1,4-benzodiazepines (p-QBZDs) from InCl3-catalyzed intermolecular tandem cycloannulation of azidoquinones with amines and aldehydes. Detailed mechanistic studies reveal that the EDA complex between azidoquinones and InCl3 is crucial in determining the reaction pathway. In the absence of EDA complex formation, the reaction proceeds via the intermediacy of 2,3-bridged-2H-azirine followed by regiospecific addition of an amine to C═N/ring opening/cyclization to deliver p-QBZD with 1,2-azide-nitrogen migration. In the case of EDA complex formation, the reaction proceeds through regioselective aza-Michael addition/nitrene insertion with aldehyde and subsequent cyclization to deliver p-QBZD and p-quinone fused imidazole as a secondary product without 1,2-azide-nitrogen migration. This protocol provides straightforward access to redox-active quinone embedded 5-substituted-1,4-benzodiazepines from azidoquinones with diverse substrate scopes that would find potential applications in medicinal chemistry and drug discovery.

Photoinduced Trifluoromethylselenolation of Aryl Halides with [Me4N][SeCF3

A visible-light-induced metal-free trifluoromethylselenolation of aryl iodides and bromides with [Me4N][SeCF3] is described. The reaction was conducted at ambient temperature by successfully harnessing the light-sensitive SeCF3 reagent. Mechanistically, the EDA complexes between aryl halide and the -SeCF3 anion or the base might be formed and excited by light, which subsequently undergo intracomplex SET processes to generate aryl and •SeCF3 radicals as key intermediates, allowing a convenient and green access to various aryl trifluoromethyl selenoethers.

Three-Component Aminoheteroarylation of Alkenes via Photoinduced EDA Complex Activation.

A catalyst-free approach for the multicomponent aminoheteroarylation reaction of alkenes with N-aminopyridinium salts and heteroarenes is herein described. The reaction shows good functional group tolerance and allows the generation of valuable β-heteroarylethylamines in satisfying yields. In this transformation, N-aminopyridinium salts and heteroarenes are utilized to generate electron donor-acceptor complexes, which undergo a single-electron transfer process upon light irradiation to form key amidyl radicals and heteroaryl radical cations. The amidyl radical is subsequently captured by alkenes, followed by a Minisci-type reaction to yield the desired β-heteroarylamines as products.

Visible Light Induced EDA‐mediated Deaminative C‐2 Alkylation of Heterocyclic‐N‐Oxides using Katritzky salts

AbstractHerein, a direct C‐2 alkylation of Heterocyclic‐N‐oxides with alkyl amines as Katritzky salts via visible‐light induced deaminative approach was developed. Mechanistic studies revealed that Katritzky salts and base were involved to generate an EDA complex, which underwent intermolecular single electron transfer (SET) to give an alkyl radical intermediate. Finally, the alkyl radical intermediate further underwent‐addition with heterocyclic‐N‐oxide substrates to access the desired products with 63–94% yield. The method worked well with quinoline‐N‐oxides, pyridine‐N‐oxides, and benzopyrazine‐N‐oxides.

Aryl versus Alkyl Redox-Active Diazoacetates ─ Light-Induced C-H Insertion or 1,2-Rearrangement.

Diazo compounds with redox-active leaving groups are versatile reagents for orthogonal functionalizations, previously utilized in the Rh-catalyzed synthesis of highly substituted cyclopropanes. Photochemical activation of aryl-substituted diazoacetates generates carbenes, whereas redox-active esters can furnish C-radicals via the photoexcitation of EDA complexes. However, the photochemical behavior of these two functionalities, while present in one molecule, remains to be defined. We demonstrate that under light irradiation, reactions occur only on the diazo moiety, leaving the NHPI functionality intact. Not only aryl- but also alkyl-substituted NHPI diazoacetates are activated by blue light; either C-H insertion or the hydrogen/carbon 1,2-rearrangement occurs depending on the aryl/alkyl group.

Visible-Light-Mediated Synthesis of α-Aryl Ester Derivatives via an EDA Complex.

We report an efficient radical-based and photocatalyst-free method for the C(sp2)-C(sp3) cross-coupling reaction to synthesize α-aryl ester derivatives. The process starts from a β-keto ester and an electron-deficient halogenated aryl halide under alkaline conditions to form an electron donor-acceptor complex and is driven by visible light. From the synthetic point of view, this newly established method represents a simple way to access arylpropionic acids from commercially available and cheap starting materials.

Visible light-mediated photocatalyst-free N-demethylation of aryl tertiary amines

A visible light-mediated photocatalyst-free N-demethylation of aryl tertiary amines via EDA mechanism is described here. The N-demethylation of the arylamine is effectively enabled by forming an EDA complex of amine and PIDA, giving the corresponding secondary amines in moderate to good yields under irradiation with visible light. Relevant mechanistic experiments have demonstrated the reaction process is mediated by EDA complexes.

Visible-Light-Promoted Radical Cross-Dehydrogenative Coupling of C(sp3)-H/C(sp3)-H and C(sp3)-H/C(sp2)-H via Intermolecular HAT.

Cross-dehydrogenative coupling has emerged as a robust tool to construct C-C and C-heteroatom bonds. Herein, we reported an interesting visible-light-mediated radical CDC of C(sp3)-H/C(sp3)-H and C(sp3)-H/C(sp2)-H, enabled by a phenyl radical guided intermolecular HAT process. This strategy allowed the efficient coupling of a wide range of inert C(sp3)-H and C(sp2)-H with α-N C(sp3)-H of amines in good regioselectivities and yields. Mechanistic studies indicate that the EDA complex triggered an intermolecular HAT process.

Thianthrenium-Enabled Phosphorylation of Aryl C-H Bonds via Electron Donor-Acceptor Complex Photoactivation.

An efficient strategy for the preparation of aryl phosphonates via blue-light-promoted single electron transfer process of an EDA complex between phosphites and thianthrenium salts has been demonstrated. The corresponding substituted aryl phosphonates were obtained in good to excellent yields, and the byproduct thianthrene can be recovered and reused in quantity. This developed method realizes the construction of aryl phosphonates through the indirect C-H functionalization of arenes, which has potential application value in drug discovery and development.

Visible Light-Induced Metal-Free Fluoroalkylations.

Fluoroalkylation is a crucial synthetic process that enables the modification of molecules with fluoroalkyl groups, which can enhance the properties of compounds and have potential applications in medicine and materials science. The utilization of visible light-induced, metal-free methods is of particular importance as it provides an environmentally friendly alternative to traditional methods and eliminates the potential risks associated with metal-catalyst toxicity. This Account describes our studies on visible light-induced, metal-free fluoroalkylation processes, which include the use of organic photocatalysts or EDA complexes. We have utilized organophotocatalysts such as Nile red, tri(9-anthryl)borane, and an indole-based tetracyclic complex, as well as catalyst-free EDA chemistry through photoactive halogen bond formation or an unconventional transient ternary complex formation with nucleophilic fluoroalkyl source. A variety of π-systems including arenes/heteroarenes, alkenes, and alkynes have been successfully fluoroalkylated under the developed reaction conditions.

Sulfonium-Based EDA Complexes Grant Access to Electronically Diverse Aryl Radicals

Sulfonium-Based EDA Complexes Grant Access to Electronically Diverse Aryl Radicals

Synthesis of Sulfur-Containing Oxindoles by Photoinduced Alkene Difunctionalization via Sulfur 1,2-Relocation.

Organosulfur compounds are prevalent in various natural products, which have been widely applied in agrochemicals and pharmaceuticals. Herein, a new approach for the efficient construction of sulfur-containing oxindoles by photoinduced alkene difunctionalization via sulfur 1,2-relocation is developed. The method exhibited a high functional group tolerance and broad substrate compatibility. A library of sulfur-containing oxindole derivatives were synthesized under mild conditions (metal-, photocatalyst-, and additive-free). Mechanistic investigations revealed this photochemical process was triggered by the formation of an EDA complex of oxindole enolates with a redox-active ester, and the in situ generation of alkenes from the C-S bond cleavage of β-sulfanyl radicals was a key step in this transformation.