Hantzsch Ester Research Articles

Reductive Alkylation of Quinolines to N-Alkyl Tetrahydroquinolines Catalyzed by Arylboronic Acid.

A boronic acid catalyzed one-pot tandem reduction of quinolines to tetrahydroquinolines followed by reductive alkylation by the aldehyde has been demonstrated. This step-economcial synthesis of N-alkyl tetrahydroquinolines has been achieved directly from readily available quinolines, aldehydes, and Hantzsch ester under mild reaction conditions. The mechanistic study demonstrates the unique behavior of organoboron catalysts as both Lewis acids and hydrogen-bond donors.

Atom-transfer radical cyclization of α-bromocarboxamides under organophotocatalytic conditions

The atom-transfer radical cyclization (ATRC) reaction gives halogenated heterocycles from the corresponding halocarbonyls that possess a C–C double bond. In contrast, the reductive ATRC reaction gives non-halogenated heterocycles in the presence of a reductant. In this research, we successfully control the ATRC and reductive ATRC reactions of N-allyl-α-haloamides under visible-light irradiation in the presence/absence of the Hantzsch ester as a reductant.

Carbene-Catalyzed Alkylation of Carboxylic Esters via Direct Photoexcitation of Acyl Azolium Intermediates

A carbene-catalyzed reductive coupling reaction of carboxylic esters and substituted Hantzsch esters is disclosed. Key steps of this reaction include one-electron reduction of a carbene catalyst-bound acyl azolium intermediate to generate the corresponding radical intermediate for subsequent alkylation reactions. The reaction is promoted by irradiation with visible light without the involvement of transition-metal photocatalysts. Mechanistic studies suggest that direct photoexcitation of the in situ formed acyl azolium intermediate is likely responsible for this light-induced one-electron-reduction process. Photoexcitation converts the acyl azolium intermediate to a single-electron oxidant, enabling single-electron oxidation of Hantzsch esters to generate radical intermediates. Our reactions work well for a broad range of aryl carboxylic ester and Hantzsch ester substrates. Sophisticated structures, including those present in medicines, can be incorporated into ketone molecules using our approach via very mild conditions that tolerate various functional groups.

Dendrons containing boric acid and 1,3,5-tris(2-hydroxyethyl)isocyanurate covalently attached to silica-coated magnetite for the expeditious synthesis of Hantzsch esters

A new multifunctional dendritic nanocatalyst containing boric acid and 1,3,5-tris(2-hydroxyethyl)isocyanurate covalently attached to core–shell silica-coated magnetite (Fe3O4@SiO2@PTS-THEIC-(CH2)3OB(OH)2) was designed and properly characterized by different spectroscopic or microscopic methods as well as analytical techniques used for mesoporous materials. It was found that the combination of both aromatic π–π stacking and boron–oxygen ligand interactions affords supramolecular arrays of dendrons. Furthermore, the use of boric acid makes this dendritic catalyst a good choice, from corrosion, recyclability and cost points of view. The catalytic activity of Fe3O4@SiO2@PTS-THEIC-(CH2)3OB(OH)2, as an efficient magnetically recoverable catalyst, was investigated for the synthesis of polyhydroacridines (PHAs) as well as polyhydroquinolines (PHQs) via one-pot multicomponent reactions of dimedone and/or ethyl acetoacetate, different aldehydes and ammonium acetate in EtOH under reflux conditions. Very low loading of the catalyst, high to quantitative yields of the desired PHAs or PHQs products, short reaction times, wide scope of the substrates, eliminating any toxic heavy metals or corrosive reagents for the modification of the catalyst, and simple work-up procedure are remarkable advantages of this green protocol. An additional advantage of this magnetic nanoparticles catalyst is its ability to be separated and recycled easily from the reaction mixture with minimal efforts in six subsequent runs without significant loss of its catalytic activity. This magnetic and dendritic catalyst can be extended to new two- and three-dimensional covalent organic frameworks with different applications.

Lewis Acid Activation of Fragment-Coupling Reactions of Tertiary Carbon Radicals Promoted by Visible-Light Irradiation of EDA Complexes.

The addition of tertiary carbon radicals generated from N-(acyloxy)phthalimide esters to cyclic α,β-unsaturated ketones and lactones is markedly enhanced by the addition of substoichiometric amounts of a Ln(OTf)3. The reaction is accomplished by irradiation with visible light in the absence of a photosensitizer and is suggested to proceed by excitation of a ternary electron donor-acceptor complex between the NHPI ester, Hantzsch ester, and a Ln(OTf)3.

Highly Chemoselective Deoxygenation of N-Heterocyclic N-Oxides Using Hantzsch Esters as Mild Reducing Agents.

Herein, we disclose a highly chemoselective room-temperature deoxygenation method applicable to various functionalized N-heterocyclic N-oxides via visible light-mediated metallaphotoredox catalysis using Hantzsch esters as the sole stoichiometric reductant. Despite the feasibility of catalyst-free conditions, most of these deoxygenations can be completed within a few minutes using only a tiny amount of a catalyst. This technology also allows for multigram-scale reactions even with an extremely low catalyst loading of 0.01 mol %. The scope of this scalable and operationally convenient protocol encompasses a wide range of functional groups, such as amides, carbamates, esters, ketones, nitrile groups, nitro groups, and halogens, which provide access to the corresponding deoxygenated N-heterocycles in good to excellent yields (an average of an 86.8% yield for a total of 45 examples).

Thermodynamic and kinetic studies of hydride transfer from Hantzsch ester under the promotion of organic bases

Thermodynamics and kinetics for base-promoted hydride transfer (BPHyT) were investigated with Hantzsch ester and acridinium derivatives as model compounds.

Photoactive electron donor-acceptor complex platform for Ni-mediated C(sp3)-C(sp2) bond formation.

A dual photochemical/nickel-mediated decarboxylative strategy for the assembly of C(sp3)–C(sp2) linkages is disclosed. Under light irradiation at 390 nm, commercially available and inexpensive Hantzsch ester (HE) functions as a potent organic photoreductant to deliver catalytically active Ni(0) species through single-electron transfer (SET) manifolds. As part of its dual role, the Hantzsch ester effects a decarboxylative-based radical generation through electron donor–acceptor (EDA) complex activation. This homogeneous, net-reductive platform bypasses the need for exogenous photocatalysts, stoichiometric metal reductants, and additives. Under this cross-electrophile paradigm, the coupling of diverse C(sp3)-centered radical architectures (including primary, secondary, stabilized benzylic, α-oxy, and α-amino systems) with (hetero)aryl bromides has been accomplished. The protocol proceeds under mild reaction conditions in the presence of sensitive functional groups and pharmaceutically relevant cores.

A heavy-metal-free desulfonylative Giese-type reaction of benzothiazole sulfones under visible-light conditions.

A visible-light-induced desulfonylative Giese-type reaction has been developed. Essential to the success is the employment of Hantzsch ester to activate benzothiazole sulfones without any heavy-metal additives. Not only benzylic benzothiazole sulfones but also alkyl ones were viable substrates and reacted with electron-deficient alkenes and a propiol amide.

Visible light-induced alkylpyridylation of styrenes via a reductive radical three-component coupling.

A visible light-induced and metal-free strategy for the intermolecular three-compoment alkylpyridylation of styrenes is reported. Hantzsch ester was found to be key to initiate the overall reductive radical coupling reaction. This radical process realized difunctionalization of styrenes, selectively yielding alkylated pyridines in good to excellent yields with a wide tolerance of functional groups, mild reaction conditions and simple operation. This new reaction complements existing visible light-induced variants of styrenes with NHP esters and expands the capabilities of radical-based cross-coupling reactions of pyridines.

Visible-light photocatalytic preparation of alkenyl thioethers from 1,2,3-thiadiazoles and Hantzsch esters: synthetic and mechanistic investigations

A visible-light-promoted S-alkylation of 1,2,3-thiadiazoles with C-radical precursors, 4-alkyl-1,4-dihydropyridines (DHPs), to produce alkenyl thioethers is disclosed.

G-C3N4@Ce-MOF Z-scheme heterojunction photocatalyzed cascade aerobic oxidative functionalization of styrene

A unique composite of the cerium-based metal–organic framework (Ce-UiO-66) modified with graphitic carbon nitride nanosheets (g-C3N4) has been synthesized. The g-C3N4@Ce-MOF as a photocatalyst was employed in photocatalytic aerobic oxidative Hantzsch pyridine synthesis of styrene.

Visible light induced deaminative alkylation of difluoroenoxysilanes: a transition metal free strategy

Visible-light-promoted deaminative alkylation of difluoroenoxysilanes utilizing Hantzsch ester as a catalyst or through substrate-induced pathway have been demonstrated.

Visible-light-promoted photocatalyst-free alkylation and acylation of benzothiazoles.

Herein we report a protocol for the visible-light-mediated alkylation/acylation reaction of benzothiazoles. Alkyl/acyl substituted Hantzsch esters are easily prepared and rationally used as radical precursors. In the presence of BF3·Et2O and Na2S2O8, various benzothiazole derivatives were readily obtained in good yields. Our user-friendly protocol can proceed by simple irradiation with blue LEDs (λ = 465 nm) and without the assistance of external photocatalysts. The reaction is also characterized by mild conditions and scalability, thus offering an alternative and efficient tool for the synthesis of 2-functionalized benzothiazoles.

Anti-Markovnikov hydroarylation of alkenes via polysulfide anion photocatalysis.

A protocol for anti-Markovnikov hydroarylation of alkenes with aryl halides has been developed using polysulfide anions as photocatalysts in the presence of the Hantzsch ester and water under irradiation with visible light.

Ring-contraction of hantzsch esters and their derivatives to pyrroles via electrochemical extrusion of ethyl acetate out of aromatic rings

Cut an acetate ester out of a Hantzsch ester. With a 4-electron electrochemical reduction, the Hantzsch-ester-derived pyridine was converted to a polysubstituted pyrrole in one step by dearomatization, ring-contraction, and rearomatization process.

Correction: Ring-contraction of hantzsch esters and their derivatives to pyrroles via electrochemical extrusion of ethyl acetate out of aromatic rings

Correction for ‘Ring-contraction of hantzsch esters and their derivatives to pyrroles via electrochemical extrusion of ethyl acetate out of aromatic rings’ by Xu Liu et al., Green Chem., 2021, 23, 3468–3473, DOI: 10.1039/D1GC00487E.

Synergistic photoredox and tertiary amine catalysis: generation of allylic sulfones from Morita–Baylis–Hillman acetates and sulfur dioxide

The first example of the synthesis of allylic sulfones through synergistic photoredox and tertiary amine catalysis, starting from MBH acetates, DABCO·(SO2)2 and 4-substituted Hantzsch esters or potassium alkyltrifluoroborates via a radical pathway, is reported.

Enantioselective Alkylamination of Unactivated Alkenes under Copper Catalysis.

An enantioselective addition reaction of various alkyl groups to unactivated internal alkenes under Cu catalysis has been developed. The reaction uses amide-linked aminoquinoline as the directing group, 4-alkyl Hantzsch esters as the donor of alkyl radicals, and rarely used biaryl diphosphine oxide as a chiral ligand. β-lactams featuring two contiguous stereocenters at Cβ and the β substituent can be obtained in good yield with excellent enantioselectivity. Mechanistic studies indicate that a nucleophilic addition of the alkyl radical to CuII-coordinated alkene is the enantio-determining step.

Self‐Reporting of Folding and Aggregation by Orthogonal Hantzsch Luminophores Within a Single Polymer Chain

AbstractSelf‐reporting fluorescence methods for monitoring folding and aggregation of proteins have a long history in biochemistry. Placing orthogonal luminophores within individual synthetic polymer chains for self‐reporting both folding (i.e., its intramolecular compaction to isolated single‐chain nanoparticles, SCNPs) and unbidden aggregation (i.e., the intermolecular association of SCNPs) remains a great challenge. Herein, a simple and efficient platform to identify both single‐chain compaction and intermolecular aggregation phenomena via photoluminescence is presented based on simultaneous synthesis through Hantzsch ester formation of orthogonal luminophores within the same polymer chain. Starting from non‐luminescent β‐ketoester‐decorated chains, intramolecular compaction is visually detected through fluorescence arising from Hantzsch fluorophores generated as intra‐chain connectors during folding. Complementary, intermolecular association is identified via aggregation‐induced emission (AIE) from orthogonal luminophores displaying intense photoluminescence at redshifted wavelengths after formation of multi‐SCNPs assemblies.