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The utilization of the homogeneous (S)-2-pyrrolidine-tetrazole organocatalyst (Ley catalyst) in the self-condensation of ethyl pyruvate and cross-aldol reactions of ethyl pyruvate donor with non-enolizable pyruvate acceptors, namely the sterically hindered ethyl 3-methyl-2-oxobutyrate or the highly electrophilic methyl 3,3,3-trifluoropyruvate, is described as the key enantioselective step toward the synthesis of the corresponding biologically relevant isotetronic acids featuring a quaternary carbon functionalized with ester and alkyl groups. The transition from homogeneous to heterogeneous flow conditions is also investigated, detailing the fabrication and operation of packed-bed reactors filled with a silica-supported version of the pyrrolidine-tetrazole catalyst (SBA-15 as the matrix). [ABSTRACT FROM AUTHOR]

Amino acids have a crucial role in the field of asymmetric organocatalysis for the production of chiral compounds with high added value and specific biological activity. In particular, proline offers high activity and stereoselectivity for catalyzing aldol reactions in organic solvents. However, proline‐based catalysts often lack water‐solubility, accessibility, catalytic performance, or recovery in aqueous media. This work reports the design of proline‐functionalized poly(methyl methacrylate) (PMMA) nanoparticles with a magnetic core that offer high availability of chiral units in water and high recyclability. A proline‐based copolymerizable surfactant is designed and integrated onto the surface of PMMA nanoparticles through a miniemulsion polymerization process without using additional surfactants. The miniemulsion technique allows the incorporation of magnetite to the system to create a magnetically separable catalyst. The chiral nanocatalyst presents a high diastereoselective catalytic activity for the intermolecular aldol reaction between p‐nitrobenzaldehyde and cyclohexanone in water. [ABSTRACT FROM AUTHOR]

Proline‐catalyzed aldol reaction of aromatic aldehydes with cyclohexanone was successfully carried out in water without any cosolvent in presence of catalytic amounts of bile acid salt surfactants. The bile acid salts, acting as surfactants, facilitate the dispersion of nonpolar substrates, enabling efficient reaction conditions "in presence of water" which exploit the role of water beyond its simple characteristic as a solvent. While enantioselectivity is moderate, the high yields achieved reflect the potent synergy between proline and sodium deoxycholate (NaDC), underscoring the feasibility of water‐exclusive processes in synthetic organic chemistry. [ABSTRACT FROM AUTHOR]

A hydroxyl‐tagged porous aromatic framework PAF‐NBU2‐OH was task‐specifically designed and successfully synthesized targeted toward immobilizing chiral catalysts. Using proline‐type compound as model chiral organocatalyst, PAF‐NBU2‐OH was used as a platform to covalently link proline‐type group. The obtained PAF‐immobilized organocatalyst PAF‐NBU2‐OPro featured high chemical stability in different solvents even under very harsh conditions. PAF‐NBU2‐OPro showed excellent catalytic activity, diastereoselectivity and enantioselectivity with complete and easy recyclability when catalyzing the aldol reaction between p‐nitrobenzaldehyde and cyclohexanone, which could undergo at least 30 cycles without any activity, diastereoselectivity or enantioselectivity loss for catalyzing the current reaction. [ABSTRACT FROM AUTHOR]

Highly efficient one‐pot synthesis of a series of indeno[2,1‐b]quinolin‐6‐ones 10 and indolo[1,2‐b]isoquinoline‐6,12‐diones 12 is portrayed from easily accessible starting materials such as indan‐1‐ones 7 and 2‐nitrobenzaldehydes 9. The reaction mechanism studies by control experiments and computational analysis reveal that the reactions are initiated by attack of a conjugate base of indanones 7 to the aldehyde group or the adjacent nitro group of 2‐nitrobenzaldehydes 9 followed by intramolecular cyclization involving a second anion to furnish the appropriate products. The heterocyclic compounds were obtained in moderate to good yields. [ABSTRACT FROM AUTHOR]

Novel derivatives of diazadioxocalix[2]arene[2]triazine were synthesized and evaluated for their catalytic effects on direct asymmetric Aldol reactions in organic solvents. Chiral groups were attached to the heteroatom-bridged calix[2]triazine scaffold through reactions involving (R)/(S)-1,2,3,4-tetrahydro-1-naphthylamine with diazadioxocalix[2]arene[2]triazine. Diazadioxocalix[2]arene[2]triazine derivatives were found to be effective catalysts for the reaction of acetone with aromatic aldehydes. According to the obtained results, it has been determined that the moiety of the catalyst affects the configuration of the Aldol product. The Aldol adducts were obtained in excellent yields (93%) and enantioselectivities (96%). [ABSTRACT FROM AUTHOR]

We report a convenient and diastereoselective copper‐catalyzed reductive alkynone aldol addition to aldehydes, with pinacolborane as stoichiometric reductant, that results in the generation of densely functionalized, trisubstituted (Z)‐enone products analogous to Morita‐Baylis‐Hillman adducts. We demonstrate that the reaction proceeds via an allenolborate, which we have characterized by NMR spectroscopy. A range of aromatic and aliphatic aldehydes can be reductively coupled with various non‐terminal alkynones. [ABSTRACT FROM AUTHOR]

A novel helical polymer (compound poly-1200) containing side chains of L-leucine was synthesized. This chiral L-leucine polymer catalyst exhibited excellent catalytic activity and stereoselectivity in Aldol reaction. Poly-1200 catalyzed Aldol reaction of cyclopentanone and 4-nitrobenzaldehyde in saturated brine solution with a high enantiomeric excess (ee) value of up to 99% and a diastereomeric selectivity (dr) value of 58/42. Furthermore, the chiral polymer catalyst could be recycled three times in the asymmetric Aldol reaction without significant loss of catalytic activity. [ABSTRACT FROM AUTHOR]

The use of high catalyst loading is required for most of the organocatalyzed asymmetric aldol reactions in organic synthesis, and this often presents challenges during purification and difficulties in catalyst recovery from the reaction mixture. The immobilization of the catalyst onto gold nanoparticles (AuNPs) can change the structural conformations of the catalyst, thereby improving its catalytic activity and reusability. Herein we report on the synthesis of aldolase mimetic peptide coupled to gold nanoparticles (AuNPs) as efficient organocatalysts for asymmetric aldol reaction. AuNPs were synthesized using the Turkevich method. The conjugation of the peptide to AuNPs was characterized using surface plasmon resonance (SPR), Raman and X-ray photoelectron spectroscopy, and transmission electron microscopy (TEM) was used for particle size determination. The produced nanoparticles, whose sizes depended on the reduction method, were quasi-spherical with a relatively narrow size distribution. The peptide–AuNP conjugates were evaluated for aldol reaction catalytic activity between carbonyls p-nitrobenzaldehyde and cyclohexanone. The products were obtained with good yields (up to 85%) and enantioselectivity (up to 94%). The influence of organic solvents, pH and buffer solutions was also investigated. The results showed that the buffer solutions regulated the colloidal stability of AuNPs, resulting in a significant enhancement in the catalytic rate of the peptide–AuNP conjugate. [ABSTRACT FROM AUTHOR]

An atom‐economical sequential‐flow synthesis of donepezil, a widely prescribed drug for Alzheimer's disease, was accomplished using inexpensive, commercially available precursors. This achievement was made possible by reconfiguring the synthetic route to include only heterogeneous catalytic addition and condensation reactions, with a particular emphasis on skeletal transformation and bond formation through hydrogenation processes. Notably, water was the sole byproduct in this synthesis. A crucial aspect of this work was the development of appropriate continuous‐flow processes to achieve a one‐flow synthesis. This was accomplished by implementing in‐line treatments of the main reaction stream to eliminate inhibitory factors that could affect catalyst performance in the hydrogenation steps. [ABSTRACT FROM AUTHOR]

Chiral monosubstituted cyclohexanediamine catalyst, namely (1R,2R)-2-(piperidin-1-yl)cyclo-hexan-1-amine (Cat1) has been efficiently synthesized and used to catalyze the aldol reaction of cyclohexanone and 2-(trifluoromethyl)benzaldehyde to obtain (R)-2-{(S)-hydroxy[2-(trifluoromethyl)phenyl]methyl}cyclo-hexan-1-one. The catalyst (20 mol %) provided high yield (up to 85%) and excellent enantioselectivity (95.6% ee) in water solution in three parallel tests. [ABSTRACT FROM AUTHOR]

A less hazardous, environmentally friendly, and energy-efficient Knoevenagel reaction performed using proline as a catalyst has been designed and implemented within a sophomore-level organic chemistry laboratory as a guided inquiry activity. The main learning objective is to enable students to identify and understand various green chemistry principles such as atom economy, use of safer chemicals, design for energy efficiency, and inherently safer chemistry for accident prevention. Students were successful in synthesizing α,β-unsaturated diesters using unknown substituted benzaldehydes (later identified by the students spectroscopically) and Meldrum’s acid at room temperature in the presence of proline as a catalyst without the need for an additional base. By analyzing 1H NMR spectroscopic data, infrared spectroscopy, and mass spectrometry to identify the synthesized product, the unknown benzaldehyde starting material, and the major reaction pathway, students have enhanced their spectroscopy skills and developed a deeper understanding of the mechanism of the reaction that may not be covered in the lecture course.

The key skeleton that could allow to access structurally intriguing mohangic acids A−E has been synthesized in stereoselective manner. The salient features of this synthesis include Evans syn‐aldol reaction to construct the C‐11 and C‐12 centers, HWE olefination to construct C14−C15 bond, Evans asymmetric methylation to install C‐14 center and Crimmins acetate aldol to generate C‐15 center whereas Wittig and Takai olefinations to prepare the C8–C9 & C6–C7 alkenes, respectively, and Heck reaction to couple C1–C5 & C6–C17 segments of the molecules. The developed route is highly modular and useful for accessing diverse natural product like molecules for future investigations. [ABSTRACT FROM AUTHOR]

The abundance and renewability of lignocellulosic biomass have made it a suitable alternative to fossil fuels in the reduction of global warming. The complex nature of the cellulose–hemicellulose–lignin bonds in the biomass makes it difficult to directly obtain platform chemicals. Pretreatment of the biomass has become a solution to remove lignin and obtain cellulose and or hemicellulose to produce platform chemicals. Platform chemicals such as hydroxymethylfurfural, furfural, and levulinic acid are viable feedstocks for aldol condensation to produce C8–C15 fuels. This review reports on deep eutectic solvents and microwave‐assisted pretreatment as green techniques for the delignification and platform chemicals production. Emphasis is placed on the use of hydrotalcites (HTs) as catalysts in platform chemicals production and aldol condensation for C8–C15 alkane fuels. Additionally, the hydrogenation of furfural into cyclopentanone and successive conversion into C10 and C15 alkanes with HTs was reviewed. [ABSTRACT FROM AUTHOR]

This article explores the advancements in stereodivergent carbon-carbon bond-forming reactions in organic chemistry. These reactions allow for the control of multiple stereogenic centers in a reaction, providing synthetic chemists with more flexibility and efficiency in constructing complex molecular structures. The article emphasizes the importance of these methods in drug discovery, where different stereoisomers of a drug can have different biological activities. The field of stereodivergent catalysis has grown significantly, with mono-catalytic and bifunctional catalytic methods contributing to the development of these reactions. Dual catalysis faces challenges, but progress has been made in finding compatible reaction types. The ultimate challenge lies in achieving high yields of multiple stereoisomers, but advancements in high-throughput experimentation and catalyst optimization may help overcome this challenge. [Extracted from the article]

A direct diastereoselective aldol reaction of cyclic or acyclic α‐azido ketones with α‐trifluoromethyl (CF3) pyruvate catalysed by DABCO is developed, which allowed the facile access of CF3‐containing multifunctional organoazides with vicinal tetrasubstituted carbons in good to high yields and diastereoselectivities. Moreover, phenylethynyl trifluoro‐ and difluoromethyl ketones are also viable substrates. Up to 50 % enantioselectivity could be obtained in the initial exploration of the catalytic asymmetric variant. [ABSTRACT FROM AUTHOR]

Dihydroxyacetone phosphate (DHAP)-dependent aldolases catalyze the aldol addition of DHAP to a variety of aldehydes and generate compounds with two stereocenters. This reaction is useful to synthesize chiral acyclic nucleosides, which constitute a well-known class of antiviral drugs currently used. In such compounds, the chirality of the aliphatic chain, which mimics the open pentose residue, is crucial for activity. In this work, three DHAP-dependent aldolases: fructose-1,6-biphosphate aldolase from rabbit muscle, rhanmulose-1-phosphate aldolase from Thermotoga maritima, and fuculose-1-phosphate aldolase from Escherichia coli, were used as biocatalysts. Aldehyde derivatives of thymine and cytosine were used as acceptor substrates, generating new acyclic nucleoside analogues containing two new stereocenters with conversion yields between 70% and 90%. Moreover, structural analyses by molecular docking were carried out to gain insights into the diasteromeric excess observed. [ABSTRACT FROM AUTHOR]

The unique physicochemical properties of PEG-400 were imparted to (L)-prolinamide to afford a homogeneous, solvent-free, recyclable organocatalyst for scalable enantioselective aldol reaction between acetone and benzaldehyde to afford (R)-4-hydroxy-4-phenylbutan-2-one. The reaction was scaled up to afford 41 g of ketol in 95% yield and an ee of 91% using 30 mol% catalyst, 10 mol% trifluoroacetic acid (TFA), and 135 equivalent moles of acetone with respect to benzaldehyde. The catalyst was recycled 4 times with no obvious loss of activity. The role of PEG is discussed at the molecular level. This type of catalyst may provide new possibilities for the so-far-thwarted attempts at large-scale application of proline organocatalysis to asymmetric aldol reactions. [ABSTRACT FROM AUTHOR]

The Aldol reaction is a key and challenging topic in the foundational organic chemistry course. In our teaching practice, we have found that explaining the principles of the Aldol reaction based on its reversibility and providing mechanism problems can effectively deepen students’ understanding and awareness of the Aldol reaction, thus enhancing the teaching effectiveness. In this article, we share three typical examples of rearrangement reactions based on reversible Aldol reactions, which can serve as references for teachers and students in their teaching and learning endeavors. [ABSTRACT FROM AUTHOR]

Concise route for the synthesis of (-)-isoaltholactone and (±)-5-epi-OBn-Goniotriol were described. Key features for the (-)-isoaltholactone synthesis involved; a) diastereoselective and enantioselective aldol reaction between chiral pyrrolidine substituted γ-benzyloxy vinylogous urethane enolate and cinnamaldehyde afforded highly stereoselective syn δ-lactone, b) allylic 1,3-strain controlled epoxidation of styryl alkene following the stereospecific opening of the epoxide assisted by a proximal benzyloxy group completed the synthesis. Reaction of simple pyrrolidine substituted γ-benzyloxy vinylogous urethane enolate and cinnamaldehyde gave anti δ-lactone. Epoxidation and epoxide opening of the styryl alkene substrate of anti δ-lactone derivative was also investigated, which led to the synthesis of (±)-5-epi-OBn-Goniotriol. [ABSTRACT FROM AUTHOR]

This work investigated the cocatalytic activity of recently prepared guanidinium salts containing an oxanorbornane subunit in an (S)-proline-catalyzed aldol reaction. The activity was interpreted by the diastereoselectivity of the reaction (anti/syn ratio) and for the most interesting polycyclic guanidinium salt, the enantioselectivity of the reaction was determined. The results indicated a negative impact on the oxanorbornane unit if present as the flexible substituent. For most of the tested aldehydes, the best cocatalysts provided enantioselectivities above 90% and above 95% at room temperature and 0 °C, respectively, culminating in >99.5% for 4–chloro– and 2–nitrobenzaldehyde as the substrate. The barriers for forming four possible enantiomers were calculated and the results for two anti–enantiomers are qualitatively consistent with the experiment. Obtained results suggest that the representatives of furfurylguanidinium and rigid polycyclic oxanorbornane-substituted guanidinium salts are good lead structures for developing new cocatalysts by tuning the chemical space around the guanidine moiety. [ABSTRACT FROM AUTHOR]

Using cinchonine as a raw material, a cinchonine-based isonitrile monomer was prepared after multistep transformation, and finally cinchonine-based catalyst was prepared by polymerization initiated by 4-methoxyphenylethynyl(chloro)bis(triethylphosphine)palladium(II). The new catalyst was used to catalyze asymmetric aldol reactions between cyclohexanone and aromatic aldehydes with different substituent groups. The reaction of cyclohexanone and 3-nitrobenzaldehyde in methanol afforded an enantiomeric excess (ee) value of up to 55% and a diastereomeric ratio (dr) of up to 30:70, indicating high performance of the catalyst. The synthesized compounds were characterized by HPLC, IR, and 1H NMR. [ABSTRACT FROM AUTHOR]

The preparation of a new class of six bifunctional thiourea organocatalysts having a D-fructose scaffold and a primary amino group was demonstrated. In the present study, the novel organocatalysts exhibited excellent enantio- and moderate diastereoselectivities in the asymmetric Michael addition of aliphatic ketones and 1,3-diketone to substituted nitroolefins at room temperature. In addition, the direct asymmetric aldol reaction between cyclic aliphatic ketone and aromatic aldehydes was also studied in the presence of the saccharide-thiourea organocatalysts giving excellent yield with moderate enantioselectivity.

A zinc(II)‐templated catalyst assembling terpyridine and bipyridine organocatalytic ligands has been developed for the asymmetric aldol reaction. The system has been optimized to maximize the formation of the heteromeric bifunctional species through the determination of the equilibrium constants leading to the formation of all the species present. A practical, easy to synthesize catalytic system providing high stereoselectivity has been achieved in this way. [ABSTRACT FROM AUTHOR]

Chiral 2‐hydroxy‐4‐arylbut‐3‐enoic acid derivatives are important precursors for the synthesis of angiotensin converting enzyme (ACE) inhibitors, such as enalapril, lisinopril, cilapril or benazepril. In this work, we take advantage of the unexplored promiscuous ketoreductase activity of Δ1‐piperidine‐2‐carboxylate/Δ1‐pyrroline‐2‐carboxylate reductase from Pseudomonas syringae pv. tomato DSM 50315 (DpkAPsyrin) for the synthesis of (S,E)‐2‐hydroxy‐4‐arylbut‐3‐enoic acids. The strategy was designed as an enzymatic cascade comprising an aldol condensation between pyruvate with aryl aldehydes, catalyzed by the trans‐o‐hydroxybenzylidene pyruvate hydratase‐aldolase from Pseudomonas putida (HBPAPputida), for the construction of carbon scaffold, and an ensuing asymmetric reduction of the carbonyl group catalyzed by DpkAPsyrin. The enzymatic cascade provided quantitative conversions, with global isolated yields between 57–85%. A total of nine structurally diverse (S,E)‐2‐hydroxy‐4‐arylbut‐3‐enoic acids were prepared in ee between 87–99%. [ABSTRACT FROM AUTHOR]

The choice of solvent plays a crucial role in aldol reactions, often affecting both the conversion rate and stereoselectivity. In this study, we investigated the influence of solvents (water, methanol and hydroalcoholic) on the proline-catalyzed aldol reactions. We focused on elucidating the solute–solvent interactions at the rate-determining step and the stereoselective step. Our theoretical finding suggests, hydroalcoholic-mediated reaction exhibits a higher conversion rate as compared to pure water and pure methanol-mediated system with the generation of most stable transition state structure. This can be attributed to the existence of strong hydrogen bonding and the formation of stable six-membered transition state structures in hydroalcoholic-mediated system. In addition to this, our research demonstrates that the choice of solvent plays a crucial role in determining the percentage of enantiomeric excess in the reaction. Theoretical finding suggest that the anti-product is preferentially formed in the presence of water and hydroalcoholic media as solvents. Pure water and hydroalcoholic solvents surprisingly showed a higher enantiomeric excess for the anti-product due to formation of strong hydrogen bonding between reaction moiety and solvents. In contrast, methanol-assisted reactions resulted in a racemic mixture, consistent with experimental observations. Results reported in the present study contribute to the broader understanding of solvent effects in organic reactions and offer valuable insights for the design of organic reactions. [ABSTRACT FROM AUTHOR]

Kinetic data is most commonly collected through the generation of time‐series data under either batch or flow conditions. Existing methods to generate kinetic data in flow collect integral data (concentration over time) only. Here, we report a method for the rapid and direct collection of differential kinetic data (direct measurement of rate) in flow by performing a series of instantaneous rate measurements on sequential small‐scale reactions. This technique decouples the time required to generate a full kinetic profile from the time required for a reaction to reach completion, enabling high throughput kinetic experimentation. In addition, comparison of kinetic profiles constructed at different residence times allows the robustness, or stability, of homogeneously catalysed reactions to be interrogated. This approach makes use of a segmented flow platform which was shown to quantitatively reproduce batch kinetic data. The proline mediated aldol reaction was chosen as a model reaction to perform a high throughput kinetic screen of 216 kinetic profiles in 90 hours, one every 25 minutes, which would have taken an estimated continuous 3500 hours in batch, an almost 40‐fold increase in experimental throughput matched by a corresponding reduction in material consumption. [ABSTRACT FROM AUTHOR]

In the presence of different nucleophilic Knoevenagel competitors, cyclic and acyclic ketones have been shown to undergo highly chemoselective aldol reactions with aldehydes. In doing so, the substrate breadth for this emerging methodology has been significantly broadened. The method is also no longer beholden to proline-based catalyst templates, e.g., commercially available O-t-Bu-L-threonine is advantageous for acyclic ketones. The key insight was to exploit water-based mediums under conventional (in-water) and non-conventional (deep eutectic solvents) conditions. With few exceptions, high aldol-to-Knoevenagel chemoselectivity (>10:1) and good product profiles (yield, dr, and ee) were observed, but only in DESs (deep eutectic solvents) in conjunction with ball milling did short reaction times occur. [ABSTRACT FROM AUTHOR]

Over the recent years, the pharmaceutical field has been under significant pressure to adapt to the principles of green chemistry. The industry is facing the challenge of environmental protection and securing people's health while sustaining its fundamental goals of efficiency and selectivity optimization. In this work, the reaction processes optimization has been acheived through the microfluidic approach to the widely used aldol condensation reaction. In accordance with the green chemistry principles, we have found that the best conditions include aqueous ethanol solvent and easily available amino acids used as catalysts. Asymmetric aldol condensation of para -nitrobenzaldehyde with cyclohexanone catalyzed by L- tert -Leu under microfluidic conditions provided the product with high yield and diastereoselectivity (anti/syn = 28:1) and 98% enantiomeric excess. The microfluidic reactor process, compared to the classical batch method (in a flask), provides comparable product yield, while the reaction time was reduced by an order of magnitude. It should be noted that this approach allows to carry out the reactions at low (below zero) temperatures with greater enantioselectivity. [Display omitted] • A microfluidic approach has been successfully applied to optimize asymmetric aldol condensation. • The reaction conditions meet the principles of green chemistry. • The reaction mechanism was suggested to explain the regularities in the observed values of stereoselectivity. • Reaction time was reduced by an order of magnitude compared to conventional methods. • The reaction can be carried out even at temperature below zero with greater enantioselectivity. [ABSTRACT FROM AUTHOR]

A less hazardous, environmentally friendly, and energy-efficient Knoevenagel reaction performed using proline as a catalyst has been designed and implemented within a sophomore-level organic chemistry laboratory as a guided inquiry activity. The main learning objective is to enable students to identify and understand various green chemistry principles such as atom economy, use of safer chemicals, design for energy efficiency, and inherently safer chemistry for accident prevention. Students were successful in synthesizing α,β-unsaturated diesters using unknown substituted benzaldehydes (later identified by the students spectroscopically) and Meldrum's acid at room temperature in the presence of proline as a catalyst without the need for an additional base. By analyzing 1H NMR spectroscopic data, infrared spectroscopy, and mass spectrometry to identify the synthesized product, the unknown benzaldehyde starting material, and the major reaction pathway, students have enhanced their spectroscopy skills and developed a deeper understanding of the mechanism of the reaction that may not be covered in the lecture course. [ABSTRACT FROM AUTHOR]

Highly enantio‐ and diastereoselective (Ipc)2BOTf mediated aldol reactions of morpholine carboxamides are described. A wide variety of α‐substituted N‐acyl morpholine carboxamides were successfully employed, including α‐bromo, α‐chloro, α‐vinyl and para‐methoxyphenyl morpholine carboxamides which provided the corresponding aldol products in moderate to excellent yields, and generally with high enantio‐ and diastereoselectivities. [ABSTRACT FROM AUTHOR]

The preparation of a new class of six bifunctional thiourea organocatalysts having a d-fructose scaffold and a primary amino group was demonstrated. In the present study, the novel organocatalysts exhibited excellent enantio- and moderate diastereoselectivities in the asymmetric Michael addition of aliphatic ketones and 1,3-diketone to substituted nitroolefins at room temperature. In addition, the direct asymmetric aldol reaction between cyclic aliphatic ketone and aromatic aldehydes was also studied in the presence of the saccharide-thiourea organocatalysts giving excellent yield with moderate enantioselectivity. [ABSTRACT FROM AUTHOR]

β‐Silyl ketones reacted with aldehydes by treatment with KMMDS in the presence of 18‐crown‐6 to give β,γ‐unsaturated ketones accompanied with a skeletal rearrangement. The reactions proceeded by aldol reaction of β‐silyl ketones with aldehydes followed by [1,4]‐Brook rearrangement and intramolecular 1,2‐addition to form cyclopropanol derivatives, in which carbon‐carbon bond cleavage took place to afford β,γ‐unsaturated ketones. The β,γ‐unsaturated ketones were prepared in a one‐pot manner by conjugate addition of silyl anions to α,β‐unsaturated ketones followed by reactions with aldehydes. The Brook rearrangement proceeded with complete inversion of configuration at the carbon center. [ABSTRACT FROM AUTHOR]

In this work, a gold nanoparticle (AuNP)-embedded composite polymer membrane for dip-catalysis is developed. Primarily, a polyvinylpyrrolidone-stabilized AuNP (PVP-AuNP) with an average size of 6.50 nm was synthesized by the reduction of a composite solution of Au salt and PVP. Next, the composite membrane was fabricated by simply depositing the PVP-AuNP on the Nylon membrane followed by UV cross-linking. The composite membrane having the cross-linked PVP-AuNP was utilized as a dip-catalyst for the aerobic oxidation of alcohols to carbonyl compounds under oxygen and clean reaction conditions. The catalyst was further tested for performing cross-aldol reactions. The PVP-AuNP-catalyzed oxidation reaction also has other noteworthy characteristics, such as a low catalyst loading (Au, 1.2 mol %), high yield, and selectivity with a broad substrate scope (aliphatic, aromatic, biphenyl, and heterocyclic alcohols). The turnover number (TON) and turnover frequency (TOF) for the oxidation reaction of the alcohol are calculated to be 74.5 and 12.41 h–1, respectively. The P4VP-AuNP dip-catalysts are highly stable under the reaction conditions without significant leaching of Au into the solution. The dip-catalyst demonstrates outstanding reusability up to 10 catalytic cycles while maintaining high catalytic performance and structural features. It can be easily recovered by simply pulling it out from the reaction mixture once the reaction is complete, followed by washing and drying. The practical usefulness of the suggested method was further demonstrated by the PVP-AuNP-catalyzed gram-scale synthesis of high-value chemicals like acetophenone. Although the AuNPs are already used for different reactions, their integration into dip-catalysts for oxidation of alcohols and cross-aldol reactions with a wide substrate scope is rare. Overall, these findings demonstrate that developing composite dip-catalyst systems is a realistic strategy for creating high-value chemicals in a sustainable and environmentally friendly way. [ABSTRACT FROM AUTHOR]

Purpose: In our previous study, we constructed a one-pot multi-enzyme system for rare ketoses synthesis based on L-rhamnulose-1-phosphate aldolase (RhaD) from accessible glycerol in vitro. To eliminate tedious purification of enzymes, a facile Escherichia coli whole-cell cascade platform was established in this study. Methods: To enhance the conversion rate, the reaction conditions, substrate concentrations and expressions of related enzymes were extensively optimized. Results: The biosynthetic route for the cascade synthesis of rare ketoses in whole cells was successfully constructed and three rare ketoses including D-allulose, D-sorbose and L-fructose were produced using glycerol and D/L-glyceraldehyde (GA). Under optimized conditions, the conversion rates of rare ketoses were 85.0% and 93.0% using D-GA and L-GA as the receptor, respectively. Furthermore, alditol oxidase (AldO) was introduced to the whole-cell system to generate D-GA from glycerol, and the total production yield of D-sorbose and D-allulose was 8.2 g l−1 only from the sole carbon source glycerol. Conclusion: This study demonstrates a feasible and cost-efficient method for rare sugars synthesis and can also be applied to the green synthesis of other value-added chemicals from glycerol. [ABSTRACT FROM AUTHOR]

This study explores the potential of robust, strongly basic type I ion exchange resins—specifically, Amberlyst® A26 OH and Lewatit® K 6465—as catalysts for the aldol condensation of citral and acetone, yielding pseudoionone. Emphasis is placed on their long-term stability and commendable performance in continuous operational settings. The aldol reaction, which traditionally is carried out using aqueous sodium hydroxide as the catalyst, holds the potential for enhanced sustainability and reduced waste production through the use of basic ion exchange resins in heterogeneous catalysis. Density Functional Theory (DFT) calculations are employed to investigate catalyst deactivation mechanisms. The result of these calculations indicates that the active sites of Amberlyst® A26 OH are cleaved more easily than the active sites of Lewatit® K 6465. However, the experimental data show a gradual decline in catalytic activity for both resins. Batch experiments reveal Amberlyst® A26 OH's active sites diminishing, while Lewatit® K 6465 maintains relative consistency. This points to distinct deactivation processes for each catalyst. The constant count of basic sites in Lewatit® K 6465 during the reaction suggests additional factors due to its unique polymer structure. This intriguing observation also highlights an exceptional temperature stability for Lewatit® K 6465 compared to Amberlyst® A26 OH, effectively surmounting one of the prominent challenges associated with the utilization of ion exchange resins in catalytic applications. [ABSTRACT FROM AUTHOR]

Latrunculins are marine toxins used in cell biology to block actin polymerization. The development of new synthetic strategies and methods for their synthesis is thus important in order to improve, modulate or control this biological value. The total syntheses found in the literature all target similar disconnections, especially an aldol strategy involving a recurrent 4-acetyl-1,3-thiazolidin-2-one ketone partner. Herein, we describe an alternative disconnection and subsequent stereoselective transformations to construct a stereopentade amenable to latrunculin and analogue synthesis, starting from (+)-β-citronellene. Key stereoselective transformations involve an asymmetric Krische allylation, an aldol reaction under 1,5-anti stereocontrol, and a Tishchenko–Evans reduction accompanied by a peculiar ester transposition, allowing to install key stereogenic centers of the natural products.

The enantioselective addition of difluoroenoxysilanes to aromatic aldehydes, catalyzed by cationic palladium aqua complexes, has been described. The reaction is operationally simple, does not require anhydrous conditions and performs at room temperature. The palladium catalysts, previously discovered and reported by Sodeoka, are easily prepared in two steps from PdCl2(MeCN)2. The aldol compounds were obtained in good yields and with enantiomeric ratios up to 93 : 7, the reaction being more efficient using electron‐rich aldehydes. [ABSTRACT FROM AUTHOR]

The development of regioselective aldol reactions of β‐methyl‐substituted cyclic enone derivatives with isatins to afford the aldol products with the bond formation at the methyl group of the β‐methyl‐substituted cyclic enone derivatives is described. Catalyst systems composed of DBU and pyrrolidine with DMSO were identified that resulted in the aldol reactions with almost perfect regioselectivities. DBU, pyrrolidine, and DMSO were all required to selectively afford the γ‐position‐reacted aldol products. With the use of this method, the scope of the 3‐substituted 3‐hydroxyoxindole derivatives that can be concisely synthesized was expanded. [ABSTRACT FROM AUTHOR]

The tandem hydroformylation‐aldol condensation (tandem HF‐AC) reaction offers an efficient synthetic route to the synthesis of industrially relevant products. The addition of Zn‐MOF‐74 to the cobalt‐catalyzed hydroformylation of 1‐hexene enables tandem HF‐AC under milder pressure and temperature conditions than the aldox process, where zinc salts are added to cobalt‐catalyzed hydroformylation reactions to promote aldol condensation. The yield of the aldol condensation products increases by up to 17 times compared to that of the homogeneous reaction without MOF and up to 5 times compared to the aldox catalytic system. Both Co2(CO)8 and Zn‐MOF‐74 are required to significantly enhance the activity of the catalytic system. Density functional theory simulations and Fourier‐transform infrared experiments show that heptanal, the product of hydroformylation, adsorbs on the open metal site (OMS) of Zn‐MOF‐74, thereby increasing the electrophilic character of the carbonyl carbon atom and facilitating the condensation. [ABSTRACT FROM AUTHOR]

The aldol reaction is one of the most important carbon‐carbon bond‐forming reactions in organic chemistry. Asymmetric direct cross‐aldol reaction of two different aldehydes has been regarded as a difficult reaction because of the side reactions such as self‐aldol reaction and over reaction. We found that trifluoromethyl‐substituted diarylprolinol, α,α‐bis[3,5‐bis(trifluoromethyl)phenyl]‐2‐pyrrolidinemethanol (1), is an effective organocatalyst that promotes several cross‐aldol reactions of aldehydes with excellent diastereo‐ and enantioselectivities. Acetaldehyde can be employed as a suitable nucleophilic aldehyde. Successful electrophilic aldehydes are ethyl glyoxylate, chloroacetaldehyde, dichloroacetaldehyde, chloral, α‐alkyl‐α‐oxo aldehyde, trifluoroacetaldehyde, glyoxal, alkenyl aldehyde, alkynyl aldehyde, and formaldehyde. Some of the aldehydes are commercially available as a polymer solution, an aqueous solution, or in the hydrated form. They can be used directly in the asymmetric aldol reaction as a commercially available form, which is a synthetic advantage. Given that the obtained aldol products possess several functional groups along with a formyl moiety, they are synthetically useful chiral building blocks. [ABSTRACT FROM AUTHOR]

Fluorescent sensors can directly monitor the progression of chemical transformations through increases in fluorescence intensity to allow rapid identification of superior organocatalytic systems. Based on data from more than 4,000 screenings, a combination of pyrrolidine and isophthalic acid was identified as a catalyst template for the quaternary carbon‐containing aldol reaction. Following fine‐tuning of the catalyst template, 5‐hydroxy isophthalic acid was confirmed as an additive with high reactivity. [ABSTRACT FROM AUTHOR]

The total synthesis of lucidumone (1), a Ganoderma meroterpenoid, was accomplished in racemic form from easily prepared 6 and 7 in 10 steps as the longest linear sequence. The synthesis was completed through one‐pot preparation of the tetracyclic core skeleton by Claisen rearrangement followed by an intramolecular aldol reaction. The intramolecular aldol reaction allowed for the stereocontrolled construction of the bicyclo [2.2.2] octane skeleton fused to an indanone structure. The enantioselective total synthesis of 1 was also described via a chiral transfer strategy in the Claisen rearrangement. [ABSTRACT FROM AUTHOR]

Aromatic donor modified prolinamide and aromatic acceptor modified thiourea were synthesized. They self‐assembled into a cooperative organocatalytic system through the aromatic donor‐acceptor interaction and catalyzed aldol reactions in high yields and stereoselectivity on water. The aromatic donor‐acceptor interaction was confirmed by mass spectrum, UV‐vis titraition and 1H‐NMR titration experiments. [ABSTRACT FROM AUTHOR]

Multi‐enzymatic cascades exploiting engineered enzymes are a powerful tool for the tailor‐made synthesis of complex molecules from simple inexpensive building blocks. In this work, we engineered the promiscuous enzyme 4‐oxalocrotonate tautomerase (4‐OT) into an effective aldolase with 160‐fold increased activity compared to 4‐OT wild type. Subsequently, we applied the evolved 4‐OT variant to perform an aldol condensation, followed by an epoxidation reaction catalyzed by a previously engineered 4‐OT mutant, in a one‐pot two‐step cascade for the synthesis of enantioenriched epoxides (up to 98 % ee) from biomass‐derived starting materials. For three chosen substrates, the reaction was performed at milligram scale with product yields up to 68 % and remarkably high enantioselectivity. Furthermore, we developed a three‐step enzymatic cascade involving an epoxide hydrolase for the production of chiral aromatic 1,2,3‐prim,sec,sec‐triols with high enantiopurity and good isolated yields. The reported one‐pot, three‐step cascade, with no intermediate isolation and being completely cofactor‐less, provides an attractive route for the synthesis of chiral aromatic triols from biomass‐based synthons. [ABSTRACT FROM AUTHOR]

A novel NHC-catalyzed regiodivergent reaction of ynones with trifluoromethyl ketones consisting of Aldol reactions and intermolecular [3 + 2] annulations has been developed. Employing two different NHC catalysts, various tertiary alcohols and dihyrofuranones containing trifluoromethyl can be obtained in moderate to good yields (35 examples, up to 91% yield). This protocol features mild reaction conditions, high efficiency and broad substrates scope, promoting the development of NHC catalysis and transformations of ynones.

This method offers several advantages over traditional methods for the asymmetric synthesis of β‐azido esters. First, the use of N‐acetyl camphorsultam allows for excellent stereoselectivity in the aldol reaction, which is crucial for the subsequent Mitsunobu reaction. Second, the use of trimethylsilyl azide (TMSN3) instead of hydrazoic acid (HN3) eliminates the need for handling a highly toxic and explosive reagent, making the process safer and easier to carry out. Third, the use of basic conditions for the Mitsunobu reaction allows for the reaction to proceed efficiently without the formation of the undesired silyl ethers. [ABSTRACT FROM AUTHOR]

In this study, the research hotspot of polycyclic aromatic hydrocarbons was introduced into undergraduate experimental teaching, and a synthesis experiment based on the aldol and Diels-Alder reactions was developed for benzene ring formation. Using 9,10-phenanthrenequinone and dibenzyl ketone as raw materials, the cyclopentadienone derivative 1 was obtained by the aldol reaction, and 1 was further reacted with diethyl acetylene dicarboxylate to obtain triphenylene derivative 2 by the Diels-Alder reaction. The reagents in this study are easily accessible, the reaction conditions are mild, the phenomenon is clear, the purification is simple, and the reliability is high. Students can master the principle and operation of the aldol and Diels-Alder reactions and gain an understanding of the important strategy for forming benzene rings. [ABSTRACT FROM AUTHOR]