Hantzsch Ester Research Articles

N-Iminopyridinium Compounds in Giese Reaction: Photoinduced Homolytic N-N and C-C Bond Cleavage for Cyanoalkyl Radical Generation.

We present an innovative photoinduced cyanoalkyl radical addition methodology using N-iminopyridinium reagents derived from cyclic ketones. Mechanistic investigations reveal the association of the excited Hantzsch ester and iminopyridinium with pyridyl radical generation. The ensuing cascade involving homolytic N-N bond and C-C bond cleavage of the pyridyl radical ultimately leads to the formation of cyanoalkyl radical species, leading to diverse Giese-type products. The method showcases versatility and synthetic utility in late-stage functionalization.

Computational Insights into the Photoinduced Dimeric Gold-Catalyzed Divergent Dechloroalkylation of gem-Dichloroalkanes with Alkenes.

The employment of dinuclear Au(I) catalysts in photomediated modern organic transformations has attracted significant attention over the past decade, which commonly demonstrates unique catalytic performance compared with the corresponding mononuclear gold complexes. Nevertheless, detailed mechanisms of dinuclear gold catalysis remain ambiguous, and further mechanistic understanding is highly desirable. Herein, computational studies were carried out to gain mechanistic insights into the photoinduced dinuclear gold-catalyzed divergent dechloroalkylation of gem-dichloroalkanes. Computational results suggest that a proton transfer from the additive, Hantzsch ester (HE), to the base, guanidine, could lead to an ionic pair complex, which is ready to undergo excitation under blue light irradiation to result in the corresponding triplet excited state. Then, the excited complex might undergo oxidative quenching with the dinuclear gold photocatalyst [AuI-AuI]2+, via a single-electron-transfer (SET) step to afford an unusual [Au1/2-Au1/2]+ dinuclear species. The corresponding mononuclear gold catalyst, [AuI]+, however, is not ready to enable the analogous step to give a [Au0] species, which might account for the unique characteristics of dinuclear gold catalysis. Subsequently, the formed [Au1/2-Au1/2]+ intermediate could trigger a Cl-atom transfer from dichloromethane in an inner-sphere manner to furnish a critical chloromethyl radical. Next, the resulting chloromethyl radical could attack the alkenyl moiety of substrates to generate the corresponding alkyl radicals. Then, three possible mechanistic pathways were explored to rationalize the substrate-dependent divergent transformations in this protocol. The main factors responsible for the diversified transformations were discussed.

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles.

A convenient and efficient method for the synthesis of optically active difluoro-substituted indoline derivatives starting from the corresponding 3H-indoles by chiral phosphoric acid-catalyzed transfer hydrogenation was developed. Using Hantzsch ester as the hydrogen source under mild reaction conditions, the target products can be obtained with excellent yield and enantioselectivity.

Visible‐Light‐Photocatalyzed Pinacol Coupling in Water

AbstractWe present a green and efficient approach for synthesizing vicinal diols via a metal‐free photocatalyzed pinacol coupling reaction in water or aqueous media. The mild and practical reaction conditions, including a commercially available organic photocatalyst and a nontoxic solvent, provide wide functional group tolerance while furnishing the corresponding vicinal diols in high yields. Mechanistic studies reveal the crucial role of Hantzsch ester (HEH), which undergoes single‐electron oxidation and subsequently acts as a proton donor to aldehydes for proton‐coupled electron transfer (PCET). This work contributes to the development of environmentally friendly methodologies for carbon−carbon bond formation, aligning with the principles of green and sustainable chemistry.

Radical Cross Coupling and Enantioselective Protonation through Asymmetric Photoredox Catalysis.

An unprecedented enantioselective protonation reaction enabled by photoredox catalytic radical coupling is developed. Under cooperative dicynopyrazine-derived chromophore (DPZ) as a photosensitizer and a chiral phosphoric acid catalyst, and Hantzsch ester as a sacrificial reductant, the transformations between α-substituted enones and cyanoazaarenes or 2-(chloromethyl)azaaren-1-iums can proceed a tandem reduction, radical coupling, and enantioselective protonation process efficiently. Two classes of pharmaceutically important enantioenriched azaarene variants, which contain a synthetically versatile ketone-substituted tertiary carbon stereocenter at the β- or γ-position of the azaarenes, are synthesized with high yields and ees.

CsPbBr3 Quantum Dots Promoted Depolymerization of Oxidized Lignin via Photocatalytic Semi‐Hydrogenation/Reduction Strategy

AbstractDue to the demanding depolymerization conditions and limited catalytic efficiency, enhancing lignin valorization remains challenging. Therefore, lowering the bond dissociation energy (BDE) has emerged as a viable strategy for achieving mild yet highly effective cleavage of bonds. In this study, a photocatalytic semi‐hydrogenation/reduction strategy utilizing CsPbBr3 quantum dots (CPB‐QDs) and Hantzsch ester (HEH2) as a synergistic catalytic system was introduced to reduce the BDE of Cβ−O−Ar, achieving effective cleavage of the Cβ−O−Ar bond. This strategy offers a wide substrate scope encompassing various β‐O‐4 model lignin dimers, preoxidized β‐O‐4 polymers, and native oxidized lignin, resulting in the production of corresponding ketones and phenols. Notably, this approach attained a turnover frequency (TOF) that is 17 times higher than that of the reported Ir‐catalytic system in the photocatalytic depolymerization of the lignin model dimers. It has been observed via meticulous experimentation that HEH2 can be activated by CPB‐QDs via single electron transfer (SET), generating HEH2⋅+ as a hydrogen donor while also serving as a hole quencher. Moreover, HEH2⋅+ readily forms an active transition state with the substrates via hydrogen bonding. Subsequently, the proton‐coupled electron transfer (PCET) from HEH2⋅+ to the carbonyl group of the substrate generates a Cα⋅ intermediate.

CsPbBr3 Quantum Dots Promoted Depolymerization of Oxidized Lignin via Photocatalytic Semi-Hydrogenation/Reduction Strategy.

Due to the demanding depolymerization conditions and limited catalytic efficiency, enhancing lignin valorization remains challenging. Therefore, lowering the bond dissociation energy (BDE) has emerged as a viable strategy for achieving mild yet highly effective cleavage of bonds. In this study, a photocatalytic semi-hydrogenation/reduction strategy utilizing CsPbBr3 quantum dots (CPB-QDs) and Hantzsch ester (HEH2 ) as a synergistic catalytic system was introduced to reduce the BDE of Cβ -O-Ar, achieving effective cleavage of the Cβ -O-Ar bond. This strategy offers a wide substrate scope encompassing various β-O-4 model lignin dimers, preoxidized β-O-4 polymers, and native oxidized lignin, resulting in the production of corresponding ketones and phenols. Notably, this approach attained a turnover frequency (TOF) that is 17 times higher than that of the reported Ir-catalytic system in the photocatalytic depolymerization of the lignin model dimers. It has been observed via meticulous experimentation that HEH2 can be activated by CPB-QDs via single electron transfer (SET), generating HEH2 ⋅+ as a hydrogen donor while also serving as a hole quencher. Moreover, HEH2 ⋅+ readily forms an active transition state with the substrates via hydrogen bonding. Subsequently, the proton-coupled electron transfer (PCET) from HEH2 ⋅+ to the carbonyl group of the substrate generates a Cα ⋅ intermediate.

K2S2O8‐Mediated Access to Alkylsulfonated Spiro[4,5] Trienones from N‐Arylpropiolamides with the Insertion of Sulfur Dioxide

AbstractA four‐component reaction of N‐arylpropiolamides, Hantzsch esters, Na2S2O5 and water via a radical cascade cyclization process with the insertion of sulfur dioxide mediated by K2S2O8 is reported. A series of alkylsulfonated spiro[4,5] trienones are prepared up to 86% yield with a good functional group tolerance and substrate applicability. Preliminary mechanism experiments indicate that carbonyl oxygen of spiro[4,5] trienones originated from water.

Photoredox-catalyzed carbonylative acylation of styrenes with Hantzsch esters.

Ketones exist widely in naturally occurring products and are indispensable building blocks in organic synthesis. Carbonylation represents one of the most straightforward methods for ketone preparation and has become an attractive field in modern organic chemistry as well. Among the strategies, photocatalytic carbonylation is also worthy of further exploration. Herein, we developed a three-component carbonylation that provides a new method for the synthesis of ketones from Hantzsch esters, CO and styrenes. The reaction was performed under a blue light environment and yields a series of ketones with moderate to good yields.

Highly efficient electrogeneration of oxygen centered radicals from N-alkoxyphthalimides employing rapid alternating polarity (RAP) electrolysis. Transferring the photoredox catalytic conditions to organic electrosynthesis

The first electrogeneration of O-centered radicals from N-alkoxyphthalimides via rapid alternating polarity (RAP) electrolysis, using previous experimental conditions of photoredox catalysis (PRC) is reported. The electrochemical methodology emulates satisfactorily the redox cycle behavior accepted to explain the PRC technique. Notably, the contribution of oxidized Hantzsch ester produced during the anodic reaction is emphasized, which behaves as an efficient proton donor to facilitate N–O cleavage and to extinguish the radical sequence efficiently. The reaction is conducted in a practical way using an undivided cell fitted with glassy carbon electrodes, allowing the same reactions to occur on both electrodes during the overall transformation reaching a 77% yield of the corresponding alcohol. This yield is higher than the electrochemical protocol using direct current electrolysis, confirming that the use of RAP electrolysis favors the proximity where the reactive intermediates are produced, facilitating their reaction to promote the desired reaction pathway.

Diastereoselective 1,2-difunctionalization of 1,3-enynes enabled by merging photoexcited Hantzsch ester with chromium catalysis

We present a comprehensive account of the regio- and diastereoselective radical multicomponent 1,2-dialkylation of 1,3-enynes via photoexcited Hantzsch ester and chromium co-catalysis to furnish highly valuable homopropargylic alcohols.

2.2]Paracyclophane-based coumarins: effective organo-photocatalysts for light-induced desulfonylation processes.

Herein, we demonstrate for the first time that coumarins derived from [2.2]paracyclophane (pCp) can act as effective organo-photocatalysts and promote the reductive cleavage of sulfonamides under light-irradiation. In the presence of these original compounds, photodesulfonylation reactions occur under mild conditions at low catalyst loadings in the presence of Hantzsch ester. Theoretical and experimental investigations are described, which elucidate the reaction mechanism and the nature of the active species involved in the photocatalytic process. This proof-of-concept study paves the way for further application of pCps in the field of photocatalysis.

Visible-light-induced catalyst-free reductive coupling of aldehydes, ketones and imines with cyanopyridines.

This article introduces a reductive coupling driven by visible-light, facilitating the synthesis of pyridine-substituted alcohols and amines through the reaction of aldehydes, ketones and imines with cyanopyridines. Hantzsch esters serve as reductants in this process, eliminating the need for transition-metals or photosensitizers. The method demonstrates extensive compatibility and finds utility in the late-stage functionalization of both natural and pharmaceutical products, offering a sustainable pathway for the diversification of chemical compounds.

Quantification of Nitric Oxide in Single Cells Using the Single-Probe Mass Spectrometry Technique.

Nitric oxide (NO) is a small molecule that plays important roles in biological systems and human diseases. The abundance of intracellular NO is tightly related to numerous biological processes. Due to cell heterogeneity, the intracellular NO amounts significantly vary from cell to cell, and therefore, any meaningful studies need to be conducted at the single-cell level. However, measuring NO in single cells is very challenging, primarily due to the extremely small size of single cells and reactive nature of NO. In the current studies, the quantitative reaction between NO and amlodipine, a compound containing the Hantzsch ester group, was performed in live cells. The product dehydro amlodipine was then detected by the Single-probe single-cell mass spectrometry technique to quantify NO in single cells. The experimental results indicated heterogeneous distributions of intracellular NO amounts in single cells with the existence of subpopulations.

Hantzsch Esters Enabled [2π+2σ] Cycloadditions of Bicyclo [1.1.0] butanes and Alkenes under Photo Conditions.

Hantzsch esters (HEs) are widely recognized as sources of hydride ions (H-) and sacrificial electron donors in their ground state. Here, we report the application of HE as a mediator in [2π+2σ] cycloaddition of bicyclo[1.1.0]butanes (BCBs) with alkenes under photo conditions. Through this strategy, various substituted bicyclo[2.1.1]hexanes can be efficiently prepared.

Isocyanides as Catalytic Electron Acceptors in the Visible Light Promoted Oxidative Formation of Benzyl and Acyl Radicals.

The recent disclosure of the ability of aromatic isocyanides to harvest visible light and act as single electron acceptors when reacting with tertiary aromatic amines has triggered a renewed interest in their application to the development of green photoredox catalytic methodologies. Accordingly, the present work explores their ability to promote the generation of both alkyl and acyl radicals starting from radical precursors such as Hantzsch esters, potassium alkyltrifluoroborates, and α-oxoacids. Mechanistic studies involving UV-visible absorption and fluorescence experiments, electrochemical measurements of the ground-state redox potentials along with computational calculations of both the ground- and the excited-state redox potentials of a set of nine different aromatic isocyanides provided key insights to promote a rationale design of a new generation of isocyanide-based organic photoredox catalysts. Importantly, the green potential of the investigated chemistry has been herein demonstrated by a direct and easy access to deuterium labeled compounds.

The reaction of unprotected 1,4-dihydropyridine Hantzsch esters with Grignard reagents: Preparation of unsymmetrical 1,4-dihydropyridine derivatives

The mild bromine-magnesium exchange reaction using i-PrMgBr in THF on the 2-bromomethyl-1,4-dihydropyridine Hantzsch esters allowed the synthesis of highly functionalized magnesiated 1,4-dihydropyridines with ester groups tolerance. Treatment of the resulting anionic intermediates with hard electrophile methyl iodide gave N-methylated product 6 and pyridine derivative 7 in 60 % and 10 % yields, respectively. In trapping the reaction mixture of magnesiated 1,4-dihydropyridine with ethyl bromide, pyridine derivative 8, and dimer 9 were obtained. Also, FeCl3-catalyzed cross-coupling reaction of allylMgBr, i-PrMgBr, and n-BuMgBr Grignard reagents with 2-bromomethyl-1,4-dihydropyridine derivative 2 afforded unsymmetrical 1,4-dihydropyridine derivatives 10a-c in good yields.

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins.

A visible-light-induced nickel-catalyzed cross coupling of alkyl carboxylic acids with N-trifluoroethoxyphthalimide is described. Under purple light irradiation, an α-hydroxytrifluoroethyl radical generated from a photoactive electron donor-acceptor complex between Hantzsch ester and N-trifluoroethoxyphthalimide was subsequently engaged in a nickel-catalyzed coupling reaction with in situ-activated alkyl carboxylic acids. This convenient protocol does not require photocatalysts and metal reductants, providing a straightforward and efficient access to trifluoromethyl alkyl acyloins in good yields with broad substrate compatibility. The complex bioactive molecules were also compatible with this catalytic system to afford the corresponding products.

Hantzsch Ester Modified Asymmetric BODIPY Probe with Ultra‐high Sensitivity for Ultra‐fast Detection of Endogenous Hypochlorite in Living Cells

Comprehensive SummaryHypochlorite (ClO–) is an important reactive oxygen species produced by the immune system to fight off invading pathogens, but its over‐expression can interfere with normal physiological process and induce serious diseases. Although a variety of molecular probes have been reported for detecting ClO–, the development of advanced fluorescent tools with faster response and higher sensitivity to precisely monitor ClO– remains a challenge. In this work, two Hantzsch ester (a derivative of 1,4‐dihydropyridine) derived fluorescent probes MeDHP‐BCl and MeDHP‐PhBCl were constructed based on asymmetric BODIPY‐matrix. These probes exhibit significant fluorescence turn‐on in the ultra‐sensitive (detection limit < 1 nmol/L) and ultra‐fast response (≤ 5 s) to ClO–. The reaction has been determined to be a highly selective N‐chlorination of Hantzsch ester which cannot be activated by various common bioactive species, including nitric oxide (NO) that could oxidize Hantzsch ester under aerobic physiological conditions in most reports. MeDHP‐PhBCl possessed a relatively longer fluorescence emission wavelength and higher quantum yield after activation, while more notably, MeDHP‐BCl displayed lower cytotoxicity and more remarkable fluorescence increment in the response to ClO–, enabling selective and precise visualization of endogenous ClO– over‐expression in living RAW264.7 cells.

A Dual Photoredox‐ and Cp2TiCl2‐Catalyzed Approach for the Direct Access to α‐Vinyl‐β‐hydroxy Esters

AbstractFor the first time, a dual photoredox‐ and titanocene‐catalyzed methodology for the regioselective access to α‐vinyl‐β‐hydroxy esters towards aldehyde allylation with 4‐bromobut‐2‐enoate is reported. The protocol is based on the Barbier‐type properties of the inexpensive and available Cp2TiCl2 in catalytic amount (5 mol%). The developed mild reaction conditions gave access to a library of differently functionalized α‐vinyl‐β‐hydroxy esters in moderate diastereoselectivity, employing the commercially available ethyl 4‐bromobut‐2‐enoate and both aromatic and aliphatic aldehydes. The reaction was realized under visible light irradiation, in the presence of an organophotocatalyst (3DPAFIPN, 2 mol%) combined with Hantzsch's ester as the sacrificial reductant. In contrast to other Barbier‐type reactions employing ethyl 4‐bromobut‐2‐enoate, the photoredox system ensures a better regioselectivity. Moreover, the use of preformed organometallic nucleophilic species (e. g., dienolborinates), and the need of metal reductants or stoichiometric amount of transition metals in low oxidation state for Barbier‐type reactions, is avoided. To support the experimental evidence, a detailed photophysical study shed light on the mechanism of the reaction.