Lactonization Reaction Research Articles

The effect of modulator in the synthesis of UiO-66(Zr) and UiO-67(Zr) and their performances in catalytic transfer hydrogenation reaction of α-angelica lactone to γ-valerolactone

The effect of modulator in the synthesis of UiO-66(Zr) and UiO-67(Zr) and their performances in catalytic transfer hydrogenation reaction of α-angelica lactone to γ-valerolactone

Efficient cascade reactions involving esterification, hydrogen transfer, and lactonization for biomass conversion using MOF/Metal oxide composites as heterogeneous catalysts

Development of heterogeneous catalysts with both Brønsted and Lewis acid properties has proved to be promising and useful because they offer an efficient way to cascade reactions. In this study, we present the synthesis pathway and efficacy evaluation of new composites which combined by sulfonic acid functional group modified TiO2 and MIL-101, analyzing their structure-performance correlation as heterogeneous catalysts in cascade reactions involving esterification, hydrogen transfer, and lactonization. These composites possess an open porous structure (MOF and porous TiO2), as well as active sites including Lewis acid (unsaturated coordination metal), Lewis base (Ti-OH), and Brønsted acid (-SO3H). The role of these active sites and the synergies between them were investigated through the esterification of levulinic acid and the direct synthesis of γ-valerolactone from levulinic acid and furfural under cascade reactions. The composites exhibit a 100% ethyl levulinate (EL) yield at 120°C for 6 hours, with γ-valerolactone yields reaching up to 94.5% (160 °C, 9 h) and 89.5% (160 °C, 16 h) from levulinic acid and furfural, respectively. This synergistic effect of Lewis acid/base and Brønsted acid ensures efficient esterification. The presence of a sulfonic acid group promotes the lactonization reaction, while the Meerwein-Ponndorf-Verley reduction is facilitated by the dual Cr sites located adjacent to each other in the secondary building unit of MIL-101(Cr). Moreover, the double-porous structure of porous TiO2 and MIL-101(Cr) effectively guarantees the efficient mass transfer of reactants and intermediates, leading to enhanced synergistic effects that promote more efficient reaction conversion.

Rh(III)-Catalyzed Regioselective Alkyne Insertion in the Context of C-H Activation and Lactonization Reactions: Synthesis of Fused 1,2-Oxaphospholenes.

Herein, we report an expedient synthesis of fused phosphorus-containing heterocycles via Rh-catalyzed cascade C-H activation, alkyne insertion, and lactonization reactions. The substrate scope and the group tolerance are good, as various substituted benzoic acids, N-methoxybenzamides, and 2-phenylindoles could go through the reactions smoothly to afford the corresponding products in moderate to high yields. Additionally, excellent regioselectivities are shown in the alkyne insertion with the assistance of an electron-withdrawing phosphonate group.

An Overview on the Synthesis of Lamellarins and Related Compounds with Biological Interest.

Lamellarins are natural products with a [3,4]-fused pyrrolocoumarin skeleton possessing interesting biological properties. More than 70 members have been isolated from diverse marine organisms, such as sponges, ascidians, mollusks, and tunicates. There is a continuous interest in the synthesis of these compounds. In this review, the synthetic strategies for the synthesis of the title compounds are presented along with their biological properties. Three routes are followed for the synthesis of lamellarins. Initially, pyrrole derivatives are the starting or intermediate compounds, and then they are fused to isoquinoline or a coumarin moiety. Second, isoquinoline is the starting compound fused to an indole moiety. In the last route, coumarins are the starting compounds, which are fused to a pyrrole moiety and an isoquinoline scaffold. The synthesis of isolamellarins, azacoumestans, isoazacoumestans, and analogues is also described. The above synthesis is achieved via metal-catalyzed cross-coupling, [3 + 2] cycloaddition, substitution, and lactonization reactions. The title compounds exhibit cytotoxic, multidrug resistance (MDR), topoisomerase I-targeted antitumor, anti-HIV, antiproliferative, anti-neurodegenerative disease, and anti-inflammatory activities.

Versatile Copper-Catalyzed γ-C(sp3)-H Lactonization of Aliphatic Acids.

Site-selective C(sp3)-H oxidation is of great importance in organic synthesis and drug discovery. γ-C(sp3)-H lactonization of free carboxylic acids provides the most straightforward means to prepare biologically important lactone scaffolds from abundant and inexpensive carboxylic acids; however, a versatile catalyst for this transformation with a broad substrate scope remains elusive. Herein, we report a simple yet broadly applicable and scalable γ-lactonization reaction of free aliphatic acids enabled by a copper catalyst in combination with inexpensive Selectfluor as the oxidant. This lactonization reaction exhibits compatibility with tertiary, benzylic, allylic, methylene, and primary γ-C-H bonds, affording access to a wide range of structurally diverse lactones such as spiro, fused, and bridged lactones. Notably, exclusive γ-methylene C-H lactonization of cycloalkane carboxylic acids and cycloalkane acetic acids was observed, giving either fused or bridged γ-lactones that are difficult to access by other methods. δ-C-H lactonization was only favored in the presence of tertiary δ-C-H bonds. The synthetic utility of this methodology was demonstrated by the late-stage functionalization of amino acids, drug molecules, and natural products, as well as a two-step total synthesis of (iso)mintlactones (the shortest synthesis reported to date).

Construction of stereogenic center beta to the N-Pyrrolidinyl moiety via diastereoselective reactions of tricyclic lactones and the synthesis of (−)-Indolizidine 195G

The Enolates of hexahydro-3,4-dioxa-8a-aza-as-indacen-2-ones can react with electrophiles in a substrate-controlled fashion to create a new stereogenic center positioned beta to the N-pyrrolidinyl moiety. Preferential diastereoselective reactions predominantly proceeded from the convex face of the enolates, yielding stereospecific alkylated or halo-substituted products with high yields and exceptional diastereoselectivities. Di-substituted compounds were obtained by the alkylation or halogenation of the enolates of the corresponding mono-substituted compounds. Total synthesis of (−)-indolizidine 195G was also accomplished. © 2024 Elsevier Science. All rights reserved.

Adventures in Coumarin Chemistry

AbstractThe cyclization of various nucleophiles, such as 1,3-dicarbonyl compounds, 1,3-bis(silyloxy)-1,3-butadienes, hydrazones, hydroxylamine, amidines, thioglycolic esters, heterocyclic enamines and others, with 4-chlorocoumarins, containing an electron-withdrawing group at position 3, allows for a convenient synthesis of a great variety of benzo[c]coumarins and related fused coumarins. Suzuki–Miyaura reactions of coumarin-derived bis(triflates) result in formation of arylated coumarins with excellent regioselectivity that is controlled by electronic and steric features of the substrate. The combination of Suzuki–Miyaura with lactonization reactions of carba- and heterocyclic substrates allows for the synthesis of benzo[c]coumarins and of other fused coumarins. Domino Michael–retro-Michael–lactonization reactions of 1,3-bis(silyloxy)-1,3-butadienes with chromones provide a convenient access to hydroxylated benzo[c]coumarins. In a related approach, fused coumarins were prepared by domino reactions of heterocyclic enamines with chromone-3-carboxylic acids.1 Introduction2 Reactions of 3-Acceptor-4-chlorocoumarins3 Reactions of Coumarin Triflates4 Synthesis of Fused Coumarins5 Conclusions

Photocatalytic Radical Decarboxylation [4 + 3] Annulation Reactions of Lactones via Dienoic Acid EDA Complexes

Photocatalytic Radical Decarboxylation [4 + 3] Annulation Reactions of Lactones via Dienoic Acid EDA Complexes

Dinuclear NHC-gold(I)-thiolato and -alkynyl complexes: synthesis, anticancer activity, and catalytic activity in lactonization reactions.

A series of novel dinuclear NHC-gold-thiolato and -alkynyl complexes bearing aromatic linkers were successfully synthesized by an efficient and simple synthetic route. The catalytic activity of these complexes was tested in a lactonization reaction. The reaction proceeds in high efficiency, in short reaction time and under mild conditions, and is complementary to existing methods. Furthermore, the digold(I)-thiolato derivatives exhibit remarkable cytotoxicity towards several cancer cell lines.

Solvent-driven isomerization of muconates in DMSO: reaction mechanism and process sustainability

The selective and highly productive formation of trans,trans-muconates from its cis,trans-isomer in a catalyst-free system is reported, revealing the unique role of DMSO/water in suppressing the undesired lactonization reaction.

Unveiling the potency of a phenalenyl-based photocatalyst for intramolecular dehydrogenative lactonization

Here, an intramolecular dehydrogenative lactonization reaction has been accomplished using a phenalenyl-based organic photocatalyst.

HFIP promoted carbo-lactonisation as a new route to functionalised lactones.

We have been able to induce a series of lactonisation reactions of unsaturated acids using a carbocationic intermediate formed in situ. The transformation generates five and six membered lactone rings AND forms a new exocyclic C-C bond at the same time, thus removing the need for further derivatisation of typical lactonisation products (such as from iodo lactonisation). The reaction is operationally straightforward, does not employ any metals and utilises readily accessible alcohol and unsaturated acid substrates.

The role of decarboxylation reactions during the initiation of the methanol-to-olefins process

The mechanism for direct CC bond formation during the initiation of the methanol-to-olefins (MTO) process is still under discussion. Carbon dioxide formation is often observed during initiation, but there are only few investigations into the role of decarboxylation. We investigate decarboxylation pathways in the H-SSZ-13 zeolite from methanol to olefins via direct carbon–carbon coupling. Additionally, the rate-determining steps were recomputed in the H-ZSM-5 and H-SAPO-34 zeolite. Gibbs free energy barriers were calculated using periodic density functional theory in combination with CCSD(T) calculations on cluster models. For H-SSZ-13, kinetic batch reactor simulations were performed. We found for H-SSZ-13 that pathways via decarboxylation reactions are equally likely as previously computed pathways including decarbonylation mechanisms (also known as ketene or CO pathway). Lactones formed from ketenes and formaldehyde were identified as the main intermediates. The decarboxylation mechanism has similar barriers in H-SSZ-13, H-ZSM-5, and H-SAPO-34, while the barriers for methylation and decarbonylation reactions are significantly lower in H-ZSM-5 and higher in H-SAPO-34. Decarboxylation reactions of lactones could explain experimentally detected carbon dioxide during the initial phase of the MTO process.

Trichloromethylative Olefin Lactonization by Photoredox Catalysis

AbstractA trichloromethylative olefin lactonization reaction using an iridium photoredox catalyst was developed. The reactions proceeded at room temperature for olefins with various substituents and substitution patterns, and a variety of lactones with a tetrasubstituted carbon and trichloromethyl group were obtained regio‐ and stereoselectively. The reaction mechanism was elucidated through isotope labeling experiments. The chemical properties of the lactones containing the trichloromethyl groups were investigated, and synthetic transformations of the product were realized.

Stereoelectronic Effect in the Reaction of α-Methylene Lactones with Tertiary Phosphines and Its Application in Organocatalysis.

The kinetic data indicate that the addition of tertiary phosphines to α-methylene lactones in acetic acid is strongly accelerated in comparison to the reactions of related open-chain esters. Six-membered α-methylene-δ-valerolactone exhibited a more pronounced rate increase than five-membered α-methylene-γ-butyrolactone. The use of α-methylene-γ-butyrolactam as a nitrogen analogue of α-methylene-γ-butyrolactone resulted in a total loss of the reaction acceleration. The observed reactivities were rationalized by DFT calculations at the RwB97XD/6-31+G(d,p) level of theory, showing that the intramolecular interaction between phosphonium and enolate oxygen centers provided by the locked s-cis-geometry of the heterocycles plays an important role in the stabilization of intermediate zwitterions. The reactivity is also controlled by the conformational flexibility of the heterocycle. The geometries of five-membered and, especially, six-membered lactone cycles are slightly changed upon the nucleophilic attack of phosphine, leading to the stabilizing stereoelectronic effect by the Ρ···Ο interaction. The addition of phosphine to α-methylene-γ-butyrolactam significantly distorts the initial geometry of the heterocycle, making the nucleophilic attack unfavorable. The application of the stereoelectronic effect to enhance the efficiency of the phosphine-catalyzed Michael and Pudovik reactions of α-methylene lactones was demonstrated.

A mechanistic study on homo- and copolymerization of L-Lactide and ε-caprolactone catalyzed by an aluminum complex bearing a Bis(phenoxy)amine ligand: A DFT study

Polymerization of biodegradable lactide and lactone has been the subject of intense research during the past decade. We used density functional theory (DFT) calculations to investigate the initiation and first propagation for ring-opening polymerization (ROP) mechanisms of L-lactide (LA) and ε-caprolactone (CL) on aluminum complexes bearing the bis(phenoxy)-amine ligand with pyridine (Catalyst I) and diethylamine (Catalyst II) sidearm. Here, the ROP mechanisms of LA and CL on both catalysts were classified into 3 parts: (1) LA homopolymerization, (2) CL homopolymerization, and (3) LA and CL copolymerization. For homopolymerization, Catalyst I shows a greater performance than Catalyst II on both LA and CL due to its less bulky sidearm. However, CL homopolymerization on Catalyst I is more favorable than that of LA, which is caused by the stronger CL coordination on the catalyst. For LA and CL copolymerization, the amine sidearm variation and the vdW interactions of monomers on Catalysts I and II provide different copolymer products, the tapered and random copolymers, respectively. These calculated results are in good agreement with our previous experimental reports. The understanding gained in the current study might be helpful in the development of high-performance catalysts for the ROP reaction of biodegradable lactide and lactone.

Visible-Light-Driven C-H Imidation of Arenes and Heteroarenes by a Phosphonium Ylide Organophotoredox Catalyst: Application to C-H Functionalization of Alkenes.

Phosphonium ylide catalysis through an oxidative quenching cycle has been developed for visible-light-driven C-H imidation of arenes and heteroarenes. The present protocol could be applied not only to trihalomethylative lactonization reactions involving trifluoromethyl, trichloromethyl, and tribromomethyl radicals but also to the first example of an organophotoredox-catalyzed imidative lactonization reaction involving a nitrogen-centered electrophilic radical species.

Controlled Lactonization of o-Coumaric Esters Mediated by Supramolecular Gels

Fragrances are volatile organic compounds widely used in our daily life. Unfortunately, the high volatility required to reach human receptors reduces their persistency in the air. To contrast this effect, several strategies may be used. Among them, we present here the combination of two techniques: the microencapsulation in supramolecular gels and the use of profragrances. We report a study on the controlled lactonization of four esters derived from o-coumaric acid. The ester lactonization spontaneously occurs after exposure to solar light, releasing coumarin and the corresponding alcohol. To determine the rate of fragrance release, we compared the reaction in solution and in a supramolecular gel and we demonstrated that the lactonization reaction always occurs slower in the gel. We also studied the more suitable gel for this aim, by comparing the properties of two supramolecular gels obtained with the gelator Boc-L-DOPA(Bn)2-OH in a 1:1 ethanol/water mixture in different gelator concentration (0.2% and 1% w/v). The gel prepared with 1% w/v gelator concentration is stronger and less transparent than the other and was used for the profragrances encapsulation. In any case, we obtained a significative reduction of lactonization reaction in gel, compared with the same reaction in solution.

A Catalytic Asymmetric Hydrolactonization.

Despite recent advancements in the development of catalytic asymmetric electrophile induced lactonization reactions of olefinic carboxylic acids, the archetypical hydrolactonization has long remained an unsolved and well-recognized challenge. Here, we report the realization of a catalytic asymmetric hydrolactonization using a confined imidodiphosphorimidate (IDPi) Brønsted acid catalyst. The method is operationally simple, scalable, and compatible with a wide variety of substrates. Its potential is showcased with concise syntheses of the sesquiterpenes (-)-boivinianin A and (+)-gossonorol. Through in-depth physicochemical and DFT analyses, we derive a nuanced picture of the mechanism and enantioselectivity of this reaction.

Chemo‐ and Regioselective Construction of Functionalized Isocoumarin, Flavone, and Isoquinolinedione via a One‐pot Reaction of o‐Quinol Acetate and Soft Nucleophiles

AbstractA one‐pot strategy for the synthesis of substituted isocoumarin, flavone, and isoquinolinedione derivatives through a switchable C‐arylation/lactonization or SNAr reaction from a wide range of soft nucleophiles and o‐quinol acetates has been developed. This base‐mediated protocol proceeds under transition‐metal‐free conditions and selectively affords various heteroarenes in 13–98% yields from readily prepared or commercially available 1,3‐dicarbonyl and α‐EWG‐substituted carbonyl compounds. The synthetic utility is further demonstrated in the synthesis of potential anti‐HIV and anti‐coronavirus derivatives and COX‐2 inhibitors. In addition, detailed experimental and computational studies are performed to provide an intensive understanding and strong support of the reaction mechanism.