Base-catalyzed Research Articles

Metal and Ligand‐Free Approach Towards the Efficient One‐Pot Synthesis of Dipyridopyrimidinimine Derivatives

AbstractWe report a facile, expeditious, user‐friendly, and convenient metal‐free synthesis employing base catalysis in a one‐pot procedure to construct 11H‐dipyrido[1,2‐a : 3′,2′‐d]pyrimidin‐11‐imine derivatives. This protocol involves a domino process leading to the formation of double C−N bonds utilising KOtBu as the base and DMAc as the superior solvent at 25 °C for 2 h. The versatility of this methodology was demonstrated by its successful application to substrates with both electron‐withdrawing and electron‐donating functional groups, yielding novel functionalized stable 11H‐dipyrido[1,2‐a : 3′,2′‐d]pyrimidin‐11‐imine derivatives in good to excellent yields. Additionally, we have discussed a plausible reaction pathway for the synthesis.

Competing Reaction Mechanisms of Peptide Bond Formation in Water Revealed by Deep Potential Molecular Dynamics and Path Sampling.

The formation of an amide bond is an essential step in the synthesis of materials and drugs, and in the assembly of amino acids to form peptides. The mechanism of this reaction has been studied extensively, in particular to understand how it can be catalyzed, but a representation capable of explaining all the experimental data is still lacking. Numerical simulation should provide the necessary molecular description, but the solvent involvement poses a number of challenges. Here, we combine the efficiency and accuracy of neural network potential-based reactive molecular dynamics with the extensive and unbiased exploration of reaction pathways provided by transition path sampling. Using microsecond-scale simulations at the density functional theory level, we show that this method reveals the presence of two competing distinct mechanisms for peptide bond formation between alanine esters in aqueous solution. We describe how both reaction pathways, via a general base catalysis mechanism and via direct cleavage of the tetrahedral intermediate respectively, change with pH. This result contrasts with the conventional mechanism involving a single pathway in which only the barrier heights are affected by pH. We show that this new proposal involving two competing mechanisms is consistent with the experimental data, and we discuss the implications for peptide bond formation under prebiotic conditions and in the ribosome. Our work shows that integrating deep potential molecular dynamics with path sampling provides a powerful approach for exploring complex chemical mechanisms.

K2CO3-catalyzed highly efficient O and N-acylation under mild conditions

An eco-friendly, mild and efficient acylation of various nucleophiles with alkenyl carboxylates via inorganic base catalysis is described. Among five inorganic base species examined, K2CO3 was proved to be the most efficient catalyst for the acylation. A broad variety of acylated products were achieved within 15 min at room temperature in high yields. In addition, we found that the 3-position of indoles should have a suitable substituent group under this procedure.

Sustainable synthesis of chromene derivatives catalysed by magnetite nanoparticle cored polyamine dendrimer

Chromene derivatives are naturally occurring heterocyclic compounds used as cosmetic agents, food additives, and potential biodegradable agrochemicals. Normally, its synthesis is carried out with three component/substrates with a suitable base. Dendrimer with amine functionality has several applications in catalysis, more specifically, dendrimers having enriched amino groups with accessible void makes a significant impact in base catalysis. Moreover, polar periphery of the dendrimers may enhance the solubility of material in the reaction medium. Therefore, herein we report the base catalytic efficiency of magnetite nanoparticle supported polyamine dendrimer with enriched amine groups and peripheral carboxyl groups. Actually, magnetite supported polyamine dendrimer synthesis involves the synthesis of PAMAM G3 on magnetite nanoparticle core, followed by reduction of amide group with subsequent functionalization of carboxylic acid terminals. Further, it is used as versatile polyvalent base for the synthesis of chromene derivatives. The magnetite supported dendritic scaffold has accessible voids and polar periphery which enables them dispersible in the reaction medium. The recycle efficiency study confirms, the competency of the material to work in industrial catalysis.

Crystal structure of activating sulfotransferase SgdX2 involved in biosynthesis of secondary metabolite sungeidine

Microorganisms synthesize a plethora of complex secondary metabolites, many of which are beneficial to human health, such as anticancer agents and antibiotics. Among these, the Sungeidines are a distinct class of secondary metabolites known for their bulky and intricate structures. They are produced by a specific biosynthetic gene cluster within the genome of the soil-dwelling actinomycete Micromonospora sp. MD118. A notable enzyme in the Sungeidine biosynthetic pathway is the activating sulfotransferase SgdX2. In this pathway, SgdX2 mediates a key sulfation step, after which the product undergoes spontaneous dehydration to yield a Sungeidine compound. To delineate the structural basis for SgdX2's substrate recognition and catalytic action, we have determined the crystal structure of SgdX2 in complex with its sulfate donor product, 3′-phosphoadenosine 5′-phosphate (PAP), at a resolution of 1.6 Å. Although SgdX2 presents a compact overall structure, its core elements are conserved among other activating sulfotransferases. Our structural analysis reveals a unique substrate-binding pocket that accommodates bulky, complex substrates, suggesting a specialized adaptation for Sungeidine synthesis. Moreover, we have constructed a substrate docking model that provides insights into the molecular interactions between SgdX2 and Sungeidine F, enhancing our understanding of the enzyme's specificity and catalytic mechanism. The model supports a general acid-base catalysis mechanism, akin to other sulfotransferases, and underscores the minor role of disordered regions in substrate recognition. This integrative study of crystallography and computational modeling advances our knowledge of microbial secondary metabolite biosynthesis and may facilitate the development of novel biotechnological applications.

A method for basicity determination of thermally labile samples

BackgroundLayered double hydroxides (LDH) belong to the group of catalytic materials used in basic catalysis. Their basicity is the most important property for catalytic performance. Our work presents a possible method for the determination of such thermally labile materials' basicity using liquid phase sorption of a specific probe. ResultsAnthranilic acid was chosen as an optimal probe, and two methods were used for measuring the basic site amount – HPLC-MS and DRUV–Vis. The chosen methods described exactly the behavior of the tested LDHs in the model reaction. The basicity of LDHs increased in the row LDH2 < LDH3 < LDH2.5 which was the same trend for the conversion of reactant achieved in a model reaction. The important parameter in the model reaction and in the basicity determination was the particle size of the materials. The amount of adsorbed anthranilic acid on LDHs was in the range 197.8–199.7 mg/g, which was ten times higher than the amount adsorbed on mixed oxides (MO, the precursor for LDH preparation, adsorbed amount of anthranilic acid 13.8–18.5 mg/g). The MO adsorption of anthranilic acid showed differences in overall basicity that were not visible under conventionally used method (TPD). SignificanceThe developed method seems to be promising in the determination of the basicity of especially thermally labile materials for which the conventional methods cannot be used.

Catalytic Generation and Intermolecular Addition of Diarylmethyl Anions Utilizing [1,2]‐Phospha‐Brook Rearrangement Under Brønsted Base Catalysis

AbstractAn intermolecular addition reaction involving an unconventional combination of a diarylmethyl anion and an electrophile, which is mediated by the [1,2]‐phospha‐Brook rearrangement under Brønsted base catalysis, was developed. Diarylmethyl anions having a benzofuran moiety were generated through the rearrangement with the aid of a catalytic amount of phosphazene base P2‐tBu. The resulting carbanion intermediates were trapped by various electrophiles, such as α,β‐unsaturated ketones, aryl aldehydes, α‐ketoesters, and N‐Boc imines, providing the corresponding diarylalkane derivatives in good yields.

Palladium(0) π-Lewis Base Catalysis: Concept and Development.

The development of a new catalytic strategy plays a vital role in modern organic chemistry since it permits bond formation in an unprecedented and more efficient manner. Although the application of preformed metal complexes as π-base-activated reagents have enabled diverse transformations elegantly, the concept and strategy by directly utilizing transition metals as efficient π-Lewis base catalysts remain underdeveloped, especially in the field of asymmetric catalysis. Here, we outline our perspective on the discovery of palladium(0) as an efficient π-Lewis base catalyst, which is capable of increasing the highest occupied molecular orbital (HOMO) energy of both electron-neutral and electron-deficient 1,3-dienes and 1,3-enynes upon flexible η2-complexes formed in situ and resultant π-backdonation. Thus, fruitful carbon-carbon-forming reactions with diverse electrophiles can be achieved enantioselectively in a vinylogous addition pattern, which is conceptually different from the classical oxidative cyclization mechanism. Emphasis will be given to the concept and mechanism elucidation, catalytic features, and reaction design together with perspective on the further development of this emerging field.

Potassium tert‐Butoxide‐Catalyzed Selective Synthesis of 1,4‐Benzodioxepines via 7‐exo/7‐endo‐dig Cyclization of Alkynol: Experimental and DFT Study

AbstractA new method utilizing base catalysis is outlined for the synthesis of 1,4‐benzodioxepines, introducing a unique scaffold containing a seven‐membered ring heterocycle. The reaction proceeded under thermal conditions, with no waste was generated during the transformation, highlighting its remarkable atom efficiency and environmental friendliness. A straightforward metal‐free reaction condition utilizing 2‐propynyloxy benzyl alcohols as starting material and a catalytic amount of t‐BuOK in mesitylene at 100 °C for 1 hour was employed for this intramolecular cyclization transformation, resulting in the formation of 1,4‐Benzodioxepines in good to excellent yields and high regio‐ and diastereo‐selectivity. The density functional theory (DFT) calculations yielded the relative internal energy (U), enthalpy (H), and Gibbs free energy (G) values for all possible products, aligning closely with our experimental data.

Comprehensive understanding of base catalysis derived from nitrogen species incorporated into the frameworks of silica and carbon porous materials

A base-catalytic nitrogen site in a specific and confined nanospace on the surfaces of silica and carbon was developed using mesoporous silica SBA-15 and its replicated porous carbon nitride PCN. Knoevenagel condensation reactions using differentially active methylene compounds and diffusion studies using CO2 as the probe molecule for the basic site revealed that the primary amine-based N component showed high activity for the base-catalyzed reaction. Among the samples investigated, primary amine-grafted SBA-15 showed the highest performance owing to the activity and location density of primary amines, as well as its surrounding hydrophobic nature. Although NSBA-15 showed moderate catalytic performance owing to an isolated active N species located on its mesopore surface, methylation of the N species led to enhanced catalytic performance because of its isolation effect. Carbonaceous PCN showed high hydrophobicity and durability during reaction and storage. A general design for N-based basic catalytic materials was also proposed.

Bifunctional two-dimensional copper-organic framework for high catalytic performance on cycloaddition of CO2 with epoxides and deacetalization-Knoevenagel condensation

Due to the larger external surface areas and more accessible active sites, two-dimensional (2D) metal-organic frameworks (MOFs) have aroused great interest in the catalytic field. Herein, the exquisite combination of Cu2+ and designed flexible tetracarboxylic acid of 1,1′-(1,3-phenylenebis(methylene))bis(1H-benzo[d]imidazole-5,6-dicarboxylic acid) (H4PBDA) under the solvothermal condition offers a highly robust 2D network of [Cu(H2PBDA)(H2O)]n (NUC-130), which are interlaced via hydrogen-bonding interactions to form a 3D skeleton. After removing associated solvent molecules by activation, NUC-130a is a scarcely reported Lewis acid/Brönsted acid mediated host framework, which can serve as a promising multifunctional catalyst due to the plentiful active sites including exposed penta-coordinated Cu2+ ions, Brønsted acidic sites of -COOH, and Lewis basic sites of Nbenzimidazole atoms and C=O groups. Performed experiments confirmed that NUC-130a had the high catalytic performance on the cycloaddition of CO2 with a series of epoxide derivatives under solvent-free mild conditions. Furthermore, for deacetalization-Knoevenagel condensation based on acid-base catalysis, NUC-130a also shows excellent catalytic activity, which should be ascribed to that dimethyl acetal can be more effectively hydrolyzed by free -COOH group into formyl group than simple Lewis acidic metal sites. Hence, this work not only provides a type of promising catalyst for efficient chemical fixation of CO2 and deacetalization-Knoevenagel condensation, but also opens up an avenue to creating multifunctional MOFs with integrating multiple active sites and larger external surface areas.

Facile Synthesis of Quinoline-Substituted 3-Hydroxy-2-oxindoles and 3-Amino-2-oxindoles via a Palladium-Catalyzed Cascade Intramolecular Cyclization/Intermolecular Nucleophilic Addition Reaction.

An efficient cascade intramolecular cyclization/intermolecular nucleophilic addition reaction of allenyl benzoxazinone with isatin or isatin-derived ketimine has been established by using Pd0-π-Lewis base catalysis. A series of 3-hydroxy-2-oxindoles and 3-amino-2-oxindoles with quaternary carbon atoms at the C3 position were synthesized in good yields under mild conditions through this protocol.

Flavin-N5OOH Functions as both a Powerful Nucleophile and a Base in the Superfamily of Flavoenzymes.

Flavoenzymes can mediate a large variety of oxidation reactions through the activation of oxygen. However, the O2 activation chemistry of flavin enzymes is not yet fully exploited. Normally, the O2 activation occurs at the C4a site of the flavin cofactor, yielding the flavin C4a-(hydro)hydroperoxyl species in monooxygenases or oxidases. Using extensive MD simulations, QM/MM calculations and QM calculations, our studies reveal the formation of the common nucleophilic species, Flavin-N5OOH, in two distinct flavoenzymes (RutA and EncM). Our studies show that Flavin-N5OOH acts as a powerful nucleophile that promotes C-N cleavage of uracil in RutA, and a powerful base in the deprotonation of substrates in EncM. We reason that Flavin-N5OOH can be a common reactive species in the superfamily of flavoenzymes, which accomplish generally selective general base catalysis and C-X (X=N, S, Cl, O) cleavage reactions that are otherwise challenging with solvated hydroxide ion base. These results expand our understanding of the chemistry and catalysis of flavoenzymes.

Flavin‐N5OOH Functions as both a Powerful Nucleophile and a Base in the Superfamily of Flavoenzymes

AbstractFlavoenzymes can mediate a large variety of oxidation reactions through the activation of oxygen. However, the O2 activation chemistry of flavin enzymes is not yet fully exploited. Normally, the O2 activation occurs at the C4a site of the flavin cofactor, yielding the flavin C4a‐(hydro)hydroperoxyl species in monooxygenases or oxidases. Using extensive MD simulations, QM/MM calculations and QM calculations, our studies reveal the formation of the common nucleophilic species, Flavin‐N5OOH, in two distinct flavoenzymes (RutA and EncM). Our studies show that Flavin‐N5OOH acts as a powerful nucleophile that promotes C−N cleavage of uracil in RutA, and a powerful base in the deprotonation of substrates in EncM. We reason that Flavin‐N5OOH can be a common reactive species in the superfamily of flavoenzymes, which accomplish generally selective general base catalysis and C−X (X=N, S, Cl, O) cleavage reactions that are otherwise challenging with solvated hydroxide ion base. These results expand our understanding of the chemistry and catalysis of flavoenzymes.

A Water-Stable Boronate Ester Cage.

The reversible condensation of catechols and boronic acids to boronate esters is a paradigm reaction in dynamic covalent chemistry. However, facile backward hydrolysis is detrimental for stability and has so far prevented applications for boronate-based materials. Here, we introduce cubic boronate ester cages 6 derived from hexahydroxy tribenzotriquinacenes and phenylene diboronic acids with ortho-t-butyl substituents. Due to steric shielding, dynamic exchange at the Lewis acidic boron sites is feasible only under acid or base catalysis but fully prevented at neutral conditions. For the first time, boronate ester cages 6 tolerate substantial amounts of water or alcohols both in solution and solid state. The unprecedented applicability of these materials under ambient and aqueous conditions is showcased by efficient encapsulation and on-demand release of β-carotene dyes and heterogeneous water oxidation catalysis after the encapsulation of ruthenium catalysts.

N-Terminal Proline Editing for the Synthesis of Peptides with Mercaptoproline and Selenoproline: Mechanistic Insights Lead to Greater Efficiency in Proline Native Chemical Ligation.

Native chemical ligation (NCL) at proline has been limited by cost and synthetic access. In addition, prior examples of NCL using mercaptoproline have exhibited stalling of the reaction after thioester exchange, due to inefficient S → N acyl transfer. Herein, we develop methods, using inexpensive Boc-4R-hydroxyproline, for the solid-phase synthesis of peptides containing N-terminal 4R-mercaptoproline and 4R-selenoproline. The synthesis proceeds via proline editing on the N-terminus of fully synthesized peptides on the solid phase, converting an N-terminal Boc-4R-hydroxyproline to the 4S-bromoproline, followed by an SN2 reaction with potassium thioacetate or selenobenzoic acid. After cleavage from the resin and deprotection, peptides with functionalized N-terminal proline amino acids were obtained. NCL reactions with mercaptoproline proceeded slowly under standard NCL conditions, with the S-acyl transthioesterification intermediate observed as a major species. Computational investigations indicated that the bicyclic intermediates and transition states for S → N acyl transfer are sufficiently low in energy (10-15 kcal mol-1 above starting material) that ring strain cannot explain the slow S → N acyl transfer. Instead, the bicyclic zwitterionic tetrahedral intermediate has a low barrier for reversion to the S-acyl intermediate, causing reversion to the thioester (reverse reaction) to occur preferentially over elimination to generate the amide (forward reaction). We hypothesized that a buffer capable of general acid and/or general base catalysis could promote S → N acyl transfer and thus achieve greater efficiency in proline NCL. In the presence of 2 M imidazole at pH 6.8, NCL with mercaptoproline proceeded efficiently to generate the peptide with a native amide bond. NCL with selenoproline also proceeded efficiently to generate the desired products when a thiophenol thioester was employed as a ligation partner. After desulfurization or deselenization, the products obtained were identical to those synthesized directly, confirming that the solid-phase proline editing reactions proceeded stereospecifically and without epimerization.

MOF-derived nanocarbon materials for electrochemical catalysis and their advanced characterization

Because of the demand for clean and sustainable energy sources, nanocarbons, modified carbons and their composite materials derived from metal-organic frameworks (MOFs) are emerging as distinct catalysts for electrocatalytic energy conversion. These materials not only inherit the advantages of MOFs, like customizable dopants and structural diversity, but also effectively prevent the aggregation of nanoparticles of metals and metal oxides during pyrolysis. Consequently, they increase the electrocatalytic efficiency, improve electrical conductivity, and may play a pivotal role in green energy technologies such as fuel cells and metal-air batteries. This review first explores the carbonization mechanism of the MOF-derived carbon-based materials, and then considers 3 key aspects: intrinsic carbon defects, metal and non-metal atom doping, and the synthesis strategies for these materials. We also provide a comprehensive introduction to advanced characterization techniques to better understand the basic electrochemical catalysis processes, including mapping techniques for detecting localized active sites on electrocatalyst surfaces at the micro- to nano-scale and in-situ spectroscopy. Finally, we offer insights into future research concerning their use as electrocatalysts. Our primary objective is to provide a clearer perspective on the current status of MOF-derived carbon-based electrocatalysts and encourage the development of more efficient materials.

Manganese/CaCO3-based dual functional catalyst facilitating basic catalysis activity and stability for the selective oxidation of aromatics

The pore engineering of alkaline earth metal carbonates with significant specific surface area (SSA) provides promising opportunities for the optimization of surface bases and further construction of bifunctional catalysts. Herein, Mn/CaCO3, with a high dispersion of Mn species and massive basic sites, is successfully synthesized utilizing a one-pot NaCl-assisted mechanochemistry protocol. To be astonished, the SSA of Mn25/CaCO3 reaches 77 m2/g, nearly ten times more than Mn/CaCO3-Pr (prepared by precipitation). Mn25/CaCO3 exhibits unique synergetic catalysis of basic and redox catalysis in the selective oxidation of ethylbenzene (EB) to acetophenone (AP), illustrating the turnover frequency (TOF) of EB is 3 and 7.1-fold compared to Mn/CaCO3-DP (synthesized by deposition precipitation) and Mn/CaCO3-Pr. The low energy barriers in activating EB for Mn25/CaCO3 are disclosed by density functional theory (DFT), further explaining the interactions of base-redox synergetic effect. This research lays a solid foundation for the exploration of highly efficient selective aerobic oxidation catalysts.

Fluorescent 5H‐Pyrano[3,2‐c]chromenes: Synthesis, Photophysical Properties and Sensing of Nucleophilic Anions

AbstractWe report the development of a convenient organocatalytic method for the synthesis of 5H‐pyrano[3,2‐c]chromenes from chromone‐containing acrylates and ethyl cyanoacetate. The synthesis is characterized by simple conditions (ethanol, basic catalysis) and good yields (up to 90 %). The synthesized pyrano[3,2‐c]chromenes are a promising new class of fluorescent compounds. They have intense fluorescence in the yellow‐green region of the spectrum (495–554 nm) with high quantum yields (up to 72 %) and exhibit large Stokes shifts (3514–5856 cm−1). We have demonstrated the possible application of the obtained pyrano[3,2‐c]chromenes as selective “turn‐off” sensors for nucleophilic anions, such as cyanide, sulfide and sulfite.

Lewis Base Catalyzed C−S Bond Formation Through Methyl C(sp3)‐H Thiocyanation of Indoles

AbstractA Lewis base catalyzed C−S bond formation through thiocyanation of methyl C(sp3)−H bond is reported. The method involves a sequential chlorination and thiocyanation reaction. This simple yet effective protocol works with diverse array of indoles to furnish thiocyanated products in good yield (up to 85 %). The developed method is also applied for the synthesis of phercaptoline (hypotensive agent) and umifenovir (antiviral drug).