Base-catalyzed Reaction Research Articles

A Fully Saturated Covalent Organic Framework.

We report the design and synthesis of the first aliphatic covalent organic framework (COF), NUS-119, and its subsequent conversion to NUS-120, marking the first fully saturated COF. NUS-119 is built by imine-linkages exhibiting high crystallinity and porosity, achieved by using a Lewis acid as a reaction modulator to circumvent compatibility issues between the Brønsted acid and the strong basic monomer. The structure was successfully solved using 3D microelectron diffraction (microED) techniques. NUS-119 and NUS-120 demonstrated remarkable catalytic performance in base-catalyzed Knoevenagel condensation reactions, exhibiting high conversion rates, excellent size selectivity, and good recyclability. This work advances the understanding of COF materials and paves the way for future research and applications.

Investigating base-catalyzed aldol condensation reactions on alkali-free hydrotalcites and the role of thermal decomposition

Aldolization is a crucial carbon–carbon coupling reaction used in the conversion of biomass-derived platform molecules into valuable chemicals and fuels. In this work, we combine experiment and theory to explore the role thermal decomposition has in controlling the structure of alkali-free Mg-Al layered double hydroxides (LDHs) and their subsequent performance in the base-catalyzed aldol condensation of acetone, focusing on the constituent aldolization and dehydration steps. LDHs were synthesized via co-precipitation and subjected to calcination at temperatures up to 600 °C to produce mixed metal oxides of the form Mg3AlOz which were further examined by SEM, N2 physisorption, XRD, and CO2-TPD. Aldolization and dehydration behaviors were examined in a batch reactor and fit with kinetic models to capture the sensitivities of both reactions to calcination temperature. Additional experiments involving the selective blocking of base sites by CO2 poisoning and reversal at varying temperatures showed that both aldolization and dehydration are likely driven by the strongest base sites, yielding a site density (0.19 μmol m−2) in agreement with separate propionic acid titration studies. Density functional theory (DFT) simulations of Mg5Al2O8 surfaces were employed to gain microscopic insights into these materials, revealing the importance of Al substitution in creating cation vacancies which can drive aldol condensation through enolate intermediates stabilized in the oxyanion resonance form. High-coverage simulations of the surface show participation of the vacancy in both aldolization and dehydration, rationalizing the coupling of rate trends observed experimentally. Ultimately, this study provides new insights and approaches useful in the design of heterogeneous aldolization catalysts.

Reducing Stoichiometric Excess of Base to Catalytic Amount: Revisiting Staudinger Reaction for -lactam Synthesis

Background: -lactams have been primarily utilized as a leading class of effective antibiotics. They have been found to show activity against various diseases, prompting the scientific community to prioritise innovative protocols for their synthesis. The general and well-known synthetic strategy involves the classical Staudinger reaction exhibiting [2+2] cycloaddition reaction. However, the protocol utilizes stoichiometric excess of base for efficient product formation. Objective: A smarter and more acceptable approach for the synthesis of -lactams would be to reduce the excess base to a catalytic amount, furnishing a catalytic version of the Staudinger reaction. The modified version can eliminate the hazards arising out of excess use of the base, ultimately promoting the environmentally benign approach. Methods: With this hypothesis, a base-catalyzed approach in dimethyl formamide (DMF) towards the synthesis of -lactam via Staudinger reaction has been endorsed under moderate reaction conditions. Results: The scope of the substrates was explored with both electron-withdrawing and electronreleasing substitutions in the formation of -lactam. The reduction of the base amount from stoichiometric to catalytic amount was justified by the involvement of DMF in generating the basic condition for the reaction. Conclusion: It was hypothesized that the decomposition of DMF under the base-catalysed reaction condition can generate dimethylamine, which produces the required basic environment. conclusion: A base-catalysed approach in dimethyl formamide (DMF) towards the synthesis of β-lactam via Staudinger reaction has been endorsed under moderate reaction conditions. The substrates scope was explored with both electron withdrawing and electron releasing substitutions in the formation of β-lactam. The reduction of base amount from stoichiometric to catalytic was justified by the involvement of DMF in generating the basic condition for the reaction. It was hypothesized that the decomposition of DMF under the base catalysed reaction condition can generate dimethylamine which produces the required basic environment.

Synthesis, spectroscopic characterization, DFT analysis, antibacterial, antifungal, antioxidant, molecular docking, and ADME study of 3,4-dihydro-2H-napthalen-1-one tagged chalcone derivatives

Chalcone derivatives were synthesized from 3,4-dihydro-2H-naphthalen-1-one using a base-catalyzed Claisen-Schmidt reaction and characterized by FT-IR, ¹H NMR, and ¹³C NMR spectroscopy. Density functional theory (DFT) with the B3LYP/6-311G(d,p) basis set was employed to explore the structural, electronic, and quantum properties of the compounds. Simulated electronic absorption spectra for compounds 3c and 3e in gas phase, DMSO, and DCM were generated using time-dependent DFT (TD-DFT). Compound 3c's first singlet excited state shifted from 376.10 nm in the gas phase to 390.08 nm in DMSO, while compound 3e shifted from 381.58 nm to 383.54 nm in DMSO. Experimental absorption values matched the theoretical predictions, with higher oscillator strengths in DMSO and DCM indicating solvent-enhanced transition probabilities. The antimicrobial activity of the chalcones was evaluated against four bacterial strains (E. coli, B. subtilis, S. aureus, and Streptococcus spp.) and four fungal strains (R. oryzae, P. chrysogenum, A. niger, and C. albicans). Compounds 3d and 3f showed strong antibacterial activity with MIC values of 3.9 µg/mL and moderate antifungal activity. Antioxidant properties were assessed using DPPH and hydroxyl radical assays, with compound 3d demonstrating 75.8 % and 76.4 % scavenging activity for OH and DPPH radicals, respectively. ADME studies were conducted to evaluate pharmacokinetics, and molecular docking studies revealed strong binding affinities. Compounds 3a and 3e had docking scores of -8.7 kcal/mol with the E. coli protein (PDB ID: 1KZN), while 3d and 3f performed best against B. subtilis (PDB ID: 1BAG) and S. aureus gyrase (PDB ID: 2XCT), with scores of -9.1 and -8.3 kcal/mol, respectively. Molecular dynamics simulation of compound 3d with 1BAG over 100 ns confirmed stable binding. These findings suggest chalcone derivatives have strong potential for pharmaceutical development.

Base-Catalyzed Reaction of Isatins and (3-Hydroxyprop-1-yn-1-yl)phosphonates as a Tool for the Synthesis of Spiro-1,3-dioxolane Oxindoles with Anticancer and Anti-Platelet Properties

An approach to the synthesis of phosphoryl substituted spiro-1,3-dioxolane oxindoles was developed from the base-catalyzed reaction of various isatins with (3-hydroxyprop-1-yn-1-yl)phosphonates. It was found that various aryl-substituted and N-functionalized isatins with the formation of appropriate products with high yields and stereoselectivity when using t-BuOLi are able to react. Cytotoxic activity evaluation suggests that the most significant results in relation to the HuTu 80 cell line were shown by N-benzylated spirodioxolanes. 5-Cloro-N-unsubstituted spirooxindoles exhibit antiaggregational activity exceeding the values of acetylsalicylic acid.

Merging Organocatalysis with 1,2-Boronate Rearrangement: A Lewis Base-Catalyzed Asymmetric Multicomponent Reaction.

Catalytic asymmetric multicomponent 1,2-boronate rearrangements provide a practical approach for synthesizing highly valuable enantioenriched boronic esters. When applied to alkenyl or heteroaryl boronates, these reactions have relied mainly on transition-metal catalysis. Herein, we present an organocatalytic, Lewis base-catalyzed asymmetric multicomponent 1,2-boronate rearrangement, involving indoles, boronic esters, and Morita-Baylis-Hillman carbonates, leading to enantioenriched, highly substituted indole and indoline derivatives. Using cinchona alkaloid-based catalysts, high selectivity has been achieved, enabling expansion of the chemical space around pharmaceutically relevant indole and indoline derivatives.

Calcium single atoms stabilized by nitrogen coordination in metal–organic frameworks as efficient solid base catalysts

Considerable attention has been paid to the preparation of single-atom solid base catalysts (SASBCs) owing to their high activity and maximized utilization of basic sites. At present, the reported fabrication methods of SASBCs, such as two-step reduction strategy and sublimation capture strategy, require high temperature. Such a high activation temperature is easy to cause the sublimation loss of alkali or alkaline earth metal atoms and destructive to the support structure. Herein, a new SASBC, Ca1/UiO-67-BPY, is fabricated, in which the alkaline earth metal Ca sites are immobilized onto N-rich metal–organic framework UiO-67-BPY at room temperature. The results show that the atomic configuration of Ca single atoms is coordinated by two N atoms in the framework. The obtained Ca SASBC possesses ordered structure and exhibits high product yield of 87.2% in the Knoevenagel reaction between benzaldehyde and malononitrile. Furthermore, thanks to the Ca single atoms sites anchored on UiO-67-BPY, the Ca1/UiO-67-BPY catalyst also shows good stability during cycles. This work might offer new insight in designing SASBCs for different base-catalyzed reactions.

Deciphering iopamidol transformation during the joint disinfection of monochloramine and peroxymonosulfate: A base-catalyzed mutual activation

The joint disinfection of monochloramine (MCA) and peroxymonosulfate (PMS) can combine the advantages of both sides; and the iodine-containing micropollutants are widely present in drinking water. For the first time, the conversion of iopamidol (IPM) was investigated in the MCA/PMS system. For IPM degradation, the observed pseudo-first-order rate constant (kobs) was 0.0076 min−1, and the apparent rate constant (kapp) was 6.14 × 10−7 μM−2.16 min−1. The reaction orders for MCA (m) and PMS (n) were fitted to be 1.14 and 1.02, respectively. The mutual activation of MCA and PMS was a base-catalyzed reaction, which was highly exothermic and thermodynamically favored with a free energy of − 78.74 kcal/mol. It is believed that Cl• and 1O2 contributed to IPM degradation. The kobs value was increased by an alkaline pH and the presence of Cl−, while reduced by the existence of NOM, HCO3− and NH4+. The N in MCA was converted to NH4+-N, NO2−-N and NO3−-N, and 47.0 % of I in IPM was converted to IO3−. In the MCA/PMS system, IPM transformation was mainly via amide hydrolysis, deiodination and substitution reaction by reactive species. The study provides an insight into the fate of iodine-containing micropollutants during the joint disinfection of MCA and PMS.

Crystallization kinetics as a tool to fine-tune the catalytic activity of Na-LTA zeolite precursors in the transesterification of glycerol to glycerol carbonate

Glycerol carbonate is a versatile molecule used as a fuel additive and a chemical building block. It is a prominent route for glycerol valorization, improving the biodiesel production chain. This base-catalyzed reaction can be carried out using sodium-type zeolites if accessibility to the basic sites is ensured. Herein, we report a facile strategy to fine-tune the number and access to basic sites of Na-LTA zeolite precursors via monitoring the crystallization kinetics of the microporous material. It is demonstrated that an optimal glycerol to glycerol carbonate conversion is obtained when using the solid obtained at the beginning of the crystallization (90 min at 100 °C of hydrothermal step). Textural and spectroscopy characterization reveals that semicrystalline material presents many basic aluminate anions in a very open structure, allowing facile access to glycerol and propylene carbonate. Moreover, it is shown that this catalyst is stable in four successive reaction cycles and active in different reactions conditions

Design, synthesis, and study of 2-pyridone-based pharmaceutical analogues

2-pyridones are an important class of compounds among the N-heterocycles due to the abundant presence of their structural derivatives in many biologically active compounds. The synthesis of 2-pyridone derivatives (compounds 3A-3C) involves the condensation of aldehyde, malononitrile, and ethyl acetoacetate by a base-catalyzed reaction. Heterocyclic ring rearrangements were carried out using the simplest acid as a catalyst to produce hydroaromatic compounds, followed by dehydrogenation to yield the corresponding aromatic analogues. A sample of the crystals obtained from the synthesized compounds 3A-3C were studied to explore the types of hydrogen bonding and other intermolecular interactions involved in the supramolecular assemblies. Hirsheld surface analyses were also conducted to support the weak interactions and investigate their contributions within the supramolecular assemblies. In silico studies were also performed on the molecular recognition and ADMET properties of the compounds to reveal the most promising compounds for drug development.

Synthesis of 3-methyl-3-buten-1-ol by supercritical CO2 in coordination with HZSM-5-catalyzed formaldehyde-isobutene Prins reaction.

The reaction solvent and catalyst play essential roles in the Prins reaction for the synthesis of 3-methyl-3-buten-1-ol (MBO) from formaldehyde and isobutene. The reactivity of the solid base-catalyzed Prins condensation reaction by formaldehyde and isobutene in supercritical CO2 was investigated using CsH2PO4-modified HZSM-5. We found that the alkaline sites of the alkali-loaded catalyst could extract the α-H on isobutene to generate olefin carbon-negative ions, while the supercritical CO2 with weak Lewis acidity could activate formaldehyde to carbon-positive ions, which can combine more easily with carbon-negative isobutene to react, thus improving the reactivity of the reaction system.

Chiral Brønsted Acid-Catalyzed Asymmetric Reaction via Vinylidene Ortho-Quinone Methides.

Vinylidene ortho-quinone methides (VQMs) have been proven to be versatile and crucial intermediates in the catalytic asymmetric reaction in last decade, and thus have drawn considerable concentrations on account of the practical application in the construction of enantiomerically pure functional organic molecules. However, in comparison to the well established chiral Brønsted base-catalyzed asymmetric reaction via VQMs, chiral Brønsted acid-catalyzed reaction is rarely studied and there is no systematic summary to date. In this review, we summarize the recent advances in the chiral Brønsted acid-catalyzed asymmetric reaction via VQMs according to three types of reactions: a) intermolecular asymmetric nucleophilic addition to VQMs; b) intermolecular asymmetric cycloaddition of VQMs; c) intramolecular asymmetric cyclization of VQMs. Finally, we put forward the remained challenges and opportunities for potential breakthroughs in this area.

Investigating the synergetic effect of tungsten oxide doping into the 1,3-dicarbonyl moiety grafted chitosan and phytic acid impregnated sodium alginate for efficient U(VI) adsorption

In this work, chemical modification of the chitosan with ethyl acetoacetate was performed through a base-catalyzed reaction in which epichlorohydrin facilitated the insertion as well as nucleophilic substitution reaction to graft the 1,3-dioxo moiety across the linear chains of the base biopolymer to establish specificity and selectivity for U(VI) removal. The modified chitosan (EAA-CS) was intercalated into phosphate rich alginate matrix (PASA). Later on, the WO3-doped composites with different WO3 to PASA mass ratio were prepared and characterized using FTIR, XPS, SEM-EDS, XRD, and elemental mapping analysis. WO3 significantly contributed to chemically stable inorganic-organic composites with improved porous texture. Among the prepared composites, MCPS-3 microspherical beads, having mass ratio of 30.0 % w/w, exhibited excellent sorption capacity for U(VI) at an optimal pH 4.5. The successful U(VI) sorption was validated by the existence of two U4f peaks at 392.25 and 381.36 eV due to U4f5/2 and U4f7/2 sub-peaks with an intensity ratio of 3:4, respectively. Batch mode sorption kinetics followed pseudo-second-order rate equation (R2 ≈ 0.99, qe,th ≈ 116.88 mg/g, k2 = 0.86 × 10−4 g/mg.min−1) and equilibrium sorption data aligns with Langmuir (R2 = 0.99, qm = 343.85 mg/g at 310 K and pH = 4.5, KL = 2.00 × 10−2 L/mg) and Temkin models (R2 ≈ 0.99). Thermodynamic parameters ΔHo (30.51 kJ/mol), ΔSo (0.19 kJ/mol.K) and ΔGo (−25.64, −26.89, and − 27.91 kJ/mol) at 298, 305, and 310 K, respectively, suggested that the uptake process is feasible, endothermic and spontaneous. Based on these findings, it is reasonable to conclude that MCPS-3 could be a better hydrogel-based biomaterial for appreciable uranium recovery.

Modulating dielectric properties of polyimide composite membranes with hydrophobic mesoporous silica via ball milling processing

This research work investigated the impact of the ball-milling (BM) process on the dielectric properties of polyimide (PI) composite membranes incorporating hydrophobic mesoporous silica (HMS) particles. Initially, HMS particles were synthesized through base-catalyzed sol-gel reactions among APTES, MTMS, and TEOS, utilizing D-(−)-Fructose as a template. Following synthesis, the HMS particles underwent ball-milling to fine-tune corresponding specific surface area and average particle size. Three distinctive ball-milled HMS variants (referred to as BMS) were thoroughly characterized using FTIR, 13C NMR, 29Si-NMR spectra, DLS, BET, CA, TGA, SEM, and TEM techniques. Subsequently, a series of PI composite membranes were fabricated and subjected to characterization via FTIR, EDS, CA, and TGA analyses. It should be noted that the three distinctive BM treated HMS was found to exhibit higher specific surface area and hydrophobicity as compared to non-BM treated HMS based on the data of BET and CA, respectively. Moreover, the surface area and hydrophobicity of ball-milled HMS exhibited the upward trend of BMS1 < BMS2 < BMS3. Subsequently, the dielectric constant (Dk) and dielectric loss (Df) of PI and its composite membranes containing HMS particles measured at frequency of 10 GHz was found to show the downward trend. For example, the Dk of PI composite membranes: PI/BMS3 (3.34) < PI/BMS2 (3.41) < PI/BMS1 (3.55) < PI/HMS (3.58) < PI (3.66). On the other hand, the Df of PI composite membranes: PI-BMS3 (0.0113) < PI/BMS2 (0.0114) < PI/BMS1(0.0115) < PI/HMS (0.0121) < PI (0.0123). This resulting decreasing trend of dielectric constant of as-prepared composite membranes may be attributed to the incorporated of HMS particles in PI membrane exhibiting lower moisture absorption (Dk of water = 80) and higher surface area (Dk of air = 1) based on the TGA and CA, respectively.

Facile Access to Organostibines via Selective Organic Superbase Catalyzed Antimony-Carbon Protonolysis.

The selective formation of antimony-carbon bonds via organic superbase catalysis under metal- and salt-free conditions is reported. This novel approach utilizes electron-deficient stibine, Sb(C6F5)3, to give upon base-catalyzed reactions with weakly acidic aromatic and heteroaromatic hydrocarbons access to a range of new aromatic and heteroaromatic stibines, respectively, with loss of C6HF5. Also, the significantly less electron-deficient stibines, Ph2SbC6F5 and PhSb(C6F5)2 smoothly underwent base-catalyzed exchange reactions with a range of terminal alkynes to generate the stibines of formulae PhSb(C≡CPh)2, and Ph2SbC≡CR [R=C6H5, C6H4-NO2, COOEt, CH2Cl, CH2NEt2, CH2OSiMe3, Sb(C6H5)2], respectively. These formal substitution reactions proceed with high selectivity as only the C6F5 groups serve as a leaving group to be liberated as C6HF5 upon formal proton transfer from the alkyne. Kinetic studies of the base-catalyzed reaction of Ph2SbC6F5 with phenyl acetylene to form Ph2SbC≡CPh and C6HF5 suggested the empirical rate law to exhibit a first-order dependence with respect to the base catalyst, alkyne and stibine. DFT calculations support a pathway proceeding via a concerted σ-bond metathesis transition state, where the base catalyst activates the Sb-C6F5 bond sequence through secondary bond interactions.

Influence of biodegradable plastics on the generation of disinfection byproducts in the chlorination process

Biodegradable plastics (BPs) have seen a continuous increase in annual production and application due to their environmentally sustainable characteristics. However, research on the formation of disinfection byproducts (DBPs) from biodegradable microplastics (BMPs) during chlorination is limited, and the effects of aqueous solution chemistry on this process have yet to be explored. Therefore, two biodegradable microplastics, polylactic acid (PLA) and polybutylene adipate terephthalate (PBAT), were investigated in this study to examine the changes in their physicochemical properties before and after chlorination, and the formation of DBPs under different environmental conditions. The results showed that PLA was more chlorine-responsive, and generated more DBPs. The pH converted some of the intermediates into more stable DBPs by affecting the concentration of HClO and base-catalyzed reactions, whereas ionic strength slightly reduced DBP concentration by ion adsorption and promoting the aggregation of BMPs. Finally, since PLA has a slightly greater volume of mesopores and micropores compared to PBAT, it may more effectively adsorb DBP precursors beyond natural organic matter (NOM), such as some anthropogenic pollutants, thus potentially decreasing the formation of chlorinated DBPs in surface water. This research explored the potentiality for DBP formation by BMPs under different water quality conditions during the disinfection process, which is useful for assessing the environmental hazards of BMPs.

Leaf on a Film: Mesoporous Silica-Based Epoxy Composites with Superhydrophobic Biomimetic Surface Structure as Anti-Corrosion and Anti-Biofilm Coatings.

In this study, a series of amine-modified mesoporous silica (AMS)-based epoxy composites with superhydrophobic biomimetic structure surface of Xanthosoma sagittifolium leaves (XSLs) were prepared and applied as anti-corrosion and anti-biofilm coatings. Initially, the AMS was synthesized by the base-catalyzed sol-gel reaction of tetraethoxysilane (TEOS) and triethoxysilane (APTES) through a non-surfactant templating route. Subsequently, a series of AMS-based epoxy composites were prepared by performing the ring-opening polymerization of DGEBA with T-403 in the presence of AMS spheres, followed by characterization through FTIR, TEM, and CA. Furthermore, a nano-casting technique with polydimethylsiloxane (PDMS) as the soft template was utilized to transfer the surface pattern of natural XSLs to AMS-based epoxy composites, leading to the formation of AMS-based epoxy composites with biomimetic structure. From a hydrophilic CA of 69°, the surface of non-biomimetic epoxy significantly increased to 152° upon introducing XSL surface structure to the AMS-based epoxy composites. Based on the standard electrochemical anti-corrosion and anti-biofilm measurements, the superhydrophobic BEAMS3 composite was found to exhibit a remarkable anti-corrosion efficiency of ~99% and antimicrobial efficacy of 82% as compared to that of hydrophilic epoxy coatings.

Transition Metal-Free Catalytic C-H Zincation and Alumination.

C-H metalation is the most efficient method to prepare aryl-zinc and -aluminium complexes that are ubiquitous nucleophiles. Virtually all C-H metalation routes to form Al/Zn organometallics require stoichiometric, strong Brønsted bases with no base-catalyzed reactions reported. Herein we present a catalytic in amine/ammonium salt (Et3N/[(Et3N)H]+) C-H metalation process to form aryl-zinc and aryl-aluminium complexes. Key to this approach is coupling an endergonic C-H metalation step with a sufficiently exergonic dehydrocoupling step between the ammonium salt by-product of C-H metalation ([(Et3N)H]+) and a Zn-H or Al-Me containing complex. This step, forming H2/MeH, makes the overall cycle exergonic while generating more of the reactive metal electrophile. Mechanistic studies supported by DFT calculations revealed metal-specific dehydrocoupling pathways, with the divergent reactivity due to the different metal valency (which impacts the accessibility of amine-free cationic metal complexes) and steric environment. Notably, dehydrocoupling in the zinc system proceeds through a ligand-mediated pathway involving protonation of the β-diketiminate Cγ position. Given this process is applicable to two disparate metals (Zn and Al), other main group metals and ligand sets are expected to be amenable to this transition metal-free, catalytic C-H metalation.

Water effect on CO2 absorption mechanism and phase change behavior in [N1111][Gly]/EtOH anhydrous biphasic absorbent: In density functional theory and molecular dynamics view

Ionic liquids-based anhydrous biphasic absorbents have the potential to lower the energy consumption for CO2 capture. Recent experimental studies have revealed that the presence of water in [N1111][Gly]/EtOH system leads to generation of a new CO2-product – bicarbonate and affects the phase change behavior. However, the reaction pathway for bicarbonate formation remains unclear. In this work, the reaction pathways were investigated in depth through quantum chemical calculations employing density functional theory, with reaction rate constants determined via transition state theory. Among the three possible reaction pathways, the base-catalyzed CO2 hydration reaction prevailed, i.e. a one-step reaction involving [Gly]-, H2O, and CO2. An H atom in H2O was transferred to [Gly]-’s amino group, forming protonated [Gly]-, and hydroxide combined with CO2 to generate bicarbonate. Additionally, molecular dynamics simulations were conducted to understand the phase change behaviors with varying water content. When water content exceeded 5 wt%, an increased water content led to reduced hydrogen bonding among products and enhanced hydrogen bonding of products-solvent with the solvent, diminishing product self-aggregation. No phase change behavior were observed at water contents up to 80 wt%. This study could well explain the experimental phenomena of water effect on CO2 absorption in [N1111][Gly]/EtOH, providing theoretical references for application of ILs-based anhydrous biphasic absorbent.

Total Synthesis of Keramaphidin B and Ingenamine by Base-Catalyzed Diels-Alder Reaction Using Dynamic Regioselective Crystallization.

The control of the selectivity is a central issue in the total synthesis of complex natural products. In this paper, we report the total synthesis of (±)-keramaphidin B and (±)-ingenamine. The key reaction is a DMAP-catalyzed Diels-Alder reaction in which the regioselectivity is completely controlled by dynamic crystallization. Our synthesis successfully demonstrates that dynamic crystallization can be an alternative when the selectivity is not controlled by either kinetic or thermodynamic approaches in solution.