Acid-catalyzed Addition Research Articles

New approaches for obtaining renewable naphthalenes by acid-catalyzed Diels-Alder additions: The role of furan-aromatic condensations

This study demonstrates the feasibility of producing naphthalenes from renewable sources, specifically furans, olefins, and alcohols. Screening of various zeolites at 500 ºC, 0.2 MPa, with a 1:1 furan ratio and a WHSV of 0.69 h⁻¹ identified MFI (ZSM-5) as the most effective catalyst. Our findings indicate that reactions between furan and alkylated monoaromatics result in lower naphthalene yields with increased aromatic ring alkylation, attributed to steric hindrance and increased electron density from alkyl groups, which interfere with key Diels-Alder reactions. Notably, substituting furan with furfural doubled the naphthalene yield to 20.2 %. Although replacing olefins with alcohols did not significantly alter yields, it improved the process's sustainability by employing bioplatform molecules. We also suggest recycling the large quantity of monoaromatics produced during the reaction, which, after separation, led to a maximum naphthalene yield of 27.4 % and sustained catalytic activity over time.

Lewis Acid-catalyzed Regioselective Addition of Allenoates to Indoles for Synthesis of Bisindolylesters

Lewis Acid-catalyzed Regioselective Addition of Allenoates to Indoles for Synthesis of Bisindolylesters

Lewis acid-catalyzed chemo- and stereoselective addition of pyrroles to skipped diynones: en route to novel pyrrole-based ketocyanine dyes and alkyne-tethered enones

The first chemo- and stereoselective syntheses of hitherto unknown pyrrole-based β,β′-disubstituted ketocyanine dyes and alkyne-tethered enones through Lewis acid-catalyzed addition of pyrroles to skipped diynones (penta-1,4-diyn-3-ones) are described. The protocols feature a good substrate tolerance, mild reaction conditions, and high yields of target products. A wide synthetic utility of synthesized alkyne-tethered enones as novel building blocks is demonstrated by the synthesis of diverse pyrrole-containing compounds. The UV–vis absorption properties for selected representatives of novel adducts are studied to preliminary access their potential as photoinitiators/sensitizers in visible light induced polymerization.

Catalytic Asymmetric Diastereodivergent Synthesis of 2-Alkenylindoles Bearing both Axial and Central Chirality.

The catalytic asymmetric diastereodivergent synthesis of axially chiral 2-alkenylindoles was established via chiral phosphoric acid-catalyzed addition reactions of C3-unsubstituted 2-alkenylindoles with o-hydroxybenzyl alcohols under different reaction conditions. Using this strategy, two series of 2-alkenylindoles bearing both axial and central chirality were synthesized in a diastereodivergent fashion with moderate to high yields and good stereoselectivities (up to 99% yield, 95:5 er, >95:5 dr). Moreover, theoretical calculations were performed on the key transition states leading to different stereoisomers, which provided an in-depth understanding of the origin of the observed stereoselectivity and diastereodivergence of the products under different reaction conditions. More importantly, these 2-alkenylindoles were utilized in asymmetric catalysis as chiral organocatalysts and in medicinal chemistry for evaluation of their cytotoxicity, which demonstrated their potential applications. This study has not only established the catalytic atroposelective synthesis of axially chiral 2-alkenylindoles, but also provided an efficient strategy for catalytic asymmetric diastereodivergent construction of indole-based scaffolds bearing both axial and central chirality.

Accessing Rare α-Heterocyclic Aziridines via Brønsted Acid-catalyzed Michael Addition/Annulation: Scope, Limitations, and Mechanism.

We report an approach to the diastereoselective synthesis of 1,2-disubstituted heterocyclic aziridines. A Brønsted acid-catalyzed conjugate addition of anilines to trisubstituted heterocyclic chloroalkenes provides an intermediate 1,2-chloroamine. Diastereocontrol was found to vary significantly with solvent selection, with computational modelling confirming selective, spontaneous fragmentation in the presence of trace acids, proceeding through a pseudo-cyclic, protonated intermediate and transition state. These chloroamines can then be converted to the aziridine by treatment with LiHMDS with high stereochemical fidelity. This solvent-induced stereochemical enrichment thereby enables an efficient route to rare cis-aziridines with high dr. The scope, limitations, and mechanistic origins of selectivity are also presented.

Synthesis of α,β-diamino acid derivatives by acid-catalyzed Aza-Michael addition of N-phthalyldehydroalanine with different amine

A series of α,β-diamino acid derivatives were synthesized from N-phthalyldehydroalanine with different amines by acetic acid catalytic Aza-Michael additions. This reaction achieves C–N bond formation with good functional group tolerance. Under optimized conditions, the desired products of most aromatic and secondary aliphatic amines were obtained in moderate to good yields under mild conditions. The electronic effect and steric effect play the important roles to the reactivity of amines.

Chiral Phosphoric Acid-Catalyzed Asymmetric Friedel-Crafts Addition of Indolizine to Cyclic N-Sulfonyl Imine.

A highly efficient chiral phosphoric acid-catalyzed enantioselective Friedel-Crafts addition of indolizine to cyclic N-sulfonyl imine has been established. The newly developed protocol, which probably proceeds via a monoactivation reaction pathway, allows the access of enantioenriched sulfonamide functionalized indolizines with excellent yields (up to 99%) and enantioselectivities (up to 99%). Moreover, the synthetic utility of this protocol has been explored with some chemical transformations.

Sequence-Controlled Polymer Synthesis Derived from Alcohols, Cyclic Enol Ethers, and Vinyl Ethers: Selective Generation of 2-Alkoxy Cyclic Ethers Followed by Living Cationic Alternating Copolymerization by the One-Pot Process

Syntheses of sequence-controlled copolymers with controllable molecular weights and chain ends composed of alcohols, cyclic enol ethers, and vinyl ethers (VEs) were demonstrated using an approach consisting of selective monomer generation and subsequent alternating copolymerization. Acid-catalyzed additions of alcohols to 2,3-dihydrofuran or 3,4-dihydro-2H-pyran proceeded quantitatively to yield 2-alkoxy cyclic ethers (2-ACEs). Subsequent cationic alternating copolymerization of the 2-ACE and a VE proceeded successfully via concurrent ring-opening and vinyl-addition mechanisms, yielding copolymers with periodically arranged alcohol-derived side chain-containing cyclic enol ether and VE moieties in the repeating units. Complete degradation of the obtained copolymers into a single compound by alcoholysis confirmed the alternating sequences. The use of 2-propanol, (−)-menthol, and (1R)-endo-(+)-fenchyl alcohol was effective for the syntheses of well-defined polymers, whereas the use of methanol resulted in oligomers. The bulkiness of the alkoxy groups of the 2-ACEs likely contributed to the preference for propagation rather than chain transfer.

Recent advances in aza Friedel–Crafts reaction: strategies for achiral and stereoselective synthesis

The aza-Friedel–Crafts (aza-FC) reaction is a very powerful tool for forming C–C and C–N bonds, based on an acid-catalyzed addition of electron-rich aromatic compounds to imines.

Chiral spirocyclic phosphoric acid-catalyzed enantioselective synthesis of heterotriarylmethanes bearing an amino acid moiety.

We present herein an enantioselective protocol for the chiral phosphoric acid-catalyzed addition of 3-arylisoxazol-5-amines to highly reactive 3-methide-3H-pyrroles to provide a diverse range of heterotriarylmethanes bearing an amino acid moiety in good yields (up to 97%) and high enantioselectivities (up to 93% ee) under mild conditions. The chiral spirocyclic phosphoric acid is crucial in converting the initial 1H-pyrrol-3-yl carbinols into reactive 3-methide-3H-pyrroles and obtaining the good enantiocontrol, thereby facilitating the desired enantioselective transformation.

Resolving the Mechanistic Complexity in Triarylborane-Induced Conjugate Additions

Previous studies have shown that the catalytically active species in the Lewis acid-catalyzed addition reactions of allyl silanes or silyl enol ethers to carbonyl compounds or Michael acceptors are often silylium-carbonyl adducts rather than the adducts of the carbonyl group with the Lewis acid used for the induction of the reaction. Indirect evidence for such catalyst variations has so far been derived from double-label crossover experiments and comparisons of absolute reaction rates. We have now performed a detailed investigation on the kinetics and mechanism of the triarylborane-initiated conjugate addition reactions of allylsilanes and silyl enol ethers to α,β-unsaturated carbonyl compounds. NMR spectroscopic monitoring of such reactions gave rise to sigmoidal kinetic profiles, allowing us to directly follow the change of the catalytically active Lewis acid from triarylboranes in the induction period to silylium ions during the main part of the reaction. Crossover experiments and the isolation of four- and five-membered cyclic intramolecular trapping products provided further insight into the mechanism. DFT calculations of various mechanistic variants and kinetic modeling elucidated the operation of a complex reaction network, which rationalizes the experimental observations.

Brønsted acid-catalyzed enantioselective addition of 1,3-diones to in situ generated N-acyl ketimines.

A Brønsted acid-catalyzed asymmetric Mannich-type addition of 1,3-diones to cyclic N-acyl ketimines is reported for the synthesis of enantioenriched isoindolinones. Various dicarbonyl-substituted isoindolinones bearing a quaternary carbon stereocenter were synthesized with excellent yields (up to 98%) and moderate to high enantioselectivities (up to 95% ee), and most of them possess a fluorine atom at the reactive center. Furthermore, the synthetic utility of the protocol has been demonstrated by the debenzoylation of the product.

A Brønsted acid-catalyzed thioacid addition to in situ-generated aldimine for the synthesis of isoindolinones with the N,S-acetal framework.

A facile methodology was demonstrated for the synthesis of isoindolinones containing the N,S-acetal framework by employing a Brønsted acid catalyst with a three-component reaction. The reaction proceeded via the addition of thioacid to in situ-generated aldimine followed by lactamization, which involved the formation of one C-S bond and two C-N bonds under easily controlled and ambient reaction conditions. A variety of substituted isoindolinones were synthesized with up to 99% yields. Furthermore, the importance of this methodology was also justified by a gram-scale synthesis and demonstration of some interesting synthetic transformations.

Asymmetric synthesis of planar-chiral macrocycles via organocatalyzed enantioselective macrocyclization.

A novel enantioselective macrocyclization method has been developed for the asymmetric synthesis of planar-chiral macrocycles through chiral phosphoric acid-catalyzed intramolecular addition of the hydroxy group with the allenamide moiety. A series of planar-chiral macrocycles bearing various ring sizes (18-member to 22-member) and various functional groups were generated with good to high enantioselectivities.

Mechanism of degradation of propargyl alcohol by acid-catalysed hydrolysis and corrosion inhibition efficiency of propargyl alcohol intermediates for carbon steel in hydrochloric acid

Acetylenic alcohols are one of the most important groups of film-forming corrosion inhibitors for carbon steel in hydrochloric acid (HCl). The inhibition mechanism of acetylenic alcohols has been widely discussed for more than 50 years, however, it is not well-understood, particularly with regard to the chemical degradation reactions of acetylenic alcohols in HCl solution. In the present paper, proton nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR) techniques were used to investigate the mechanism and the rate of degradation of propargyl alcohol in 3.6–10.8 M HCl at 20–95 °C. Several water-soluble products, such as 1-hydroxypropan-2-one, 2-chloroprop-2-en-1-ol, 2,2-dichloropropan-1-ol and 2-chloropropane-1,2-diol were formed via the electrophilic acid-catalysed addition of HCl and water to the alkyne. Some intermediates further polymerize to form water-insoluble polymers, such as poly (propargyl alcohol), poly (allyl alcohol) and poly (acrolein). The hydrolysis half-life constants of propargyl alcohol decreased with increasing HCl concentration and temperature. The inhibition efficiency (η) of propargyl alcohol and its precursors for carbon steel in 3.6 M and 7.83 M HCl was studied. The critical role of acrolein intermediates on the corrosion performance of propargyl alcohol in hydrochloric acid was identified. Products of propargyl alcohol hydrolysis, 1-hydroxypropan-2-one and 2-chloroprop-2-en-1-ol are poor corrosion inhibitors. However, acrolein and its reactive intermediates are good corrosion inhibitors with inhibitor efficiency, η in the range from 97.69 ± 0.4 % for fresh acrolein to η = 97.94 ± 0.8 % for aged acrolein.

Enantioselective Protonation of Cyclic Carbonyl Ylides by Chiral Lewis Acid Assisted Alcohols.

Chiral Lewis acid-catalyzed asymmetric alcohol addition reactions to cyclic carbonyl ylides generated from N-(α-diazocarbonyl)-2-oxazolidinones featuring a dual catalytic system are reported. Construction of a chiral quaternary heteroatom-substituted carbon center was accomplished in which the unique heterobicycles were obtained in good yields with high stereoselection. The alcohol adducts were successfully converted to optically active oxazolidine-2,4-diones by hydrolysis. Mechanistic studies by DFT calculations revealed that alcohols could be activated by Lewis acids, enabling enantioselective protonation of the carbonyl ylides.

Radical addition reaction between chromenols and toluene derivatives initiated by Brønsted acid catalyst under light irradiation

A Brønsted acid-catalyzed radical addition reaction between chromenols and toluene derivatives was accomplished under light irradiation, affording benzylated chromene derivatives through benzylic C(sp3)–H functionalization of toluene derivatives.

Acid-catalyzed three-component addition of carbonyl compounds with 1,2,3-triazoles and indoles.

A facile and efficient acid-catalyzed three-component reaction of indoles, 1-tosyl-1,2,3-triazoles and carbonyl compounds has been developed. The use of TsOH with a small amount of water significantly promoted the reaction yield. This method provided a general and one-pot approach for the synthesis of structurally diverse C3-alkylated indole derivatives. The alkylation exclusively occurred at the N2 position of triazoles. Various functional groups were tolerated under the optimized simple reaction conditions.

Development of α,α-Disubstituted Crotylboronate Reagents and Stereoselective Crotylation via Brønsted or Lewis Acid Catalysis.

The development of α,α-disubstituted crotylboronate reagents is reported. Chiral Brønsted acid-catalyzed asymmetric aldehyde addition with the developed E-crotylboron reagent gave (E)-anti-1,2-oxaborinan-3-enes with excellent enantioselectivities and E-selectivities. With BF3·OEt2 catalysis, the stereoselectivity is reversed, and (Z)-δ-boryl-anti-homoallylic alcohols are obtained with excellent Z-selectivities from the same E-crotylboron reagent. The Z-crotylboron reagent also participates in BF3·OEt2-catalyzed crotylation to furnish (Z)-δ-boryl-syn-homoallylic alcohols with good Z-selectivities. DFT computations establish the origins of observed enantio- and stereoselectivities of chiral Brønsted acid-catalyzed asymmetric allylation. Stereochemical models for BF3·OEt2-catalyzed reactions are proposed to rationalize the Z-selective allyl additions. These reactions generate highly valuable homoallylic alcohol products with a stereodefined trisubstituted alkene unit. The synthetic utility is further demonstrated by the total syntheses of salinipyrones A and B.

Inter- and Intramolecular [2+2+2] Cycloaddition of Alkyne Triple Bonds to the Carbonyl Function of Aldehydes and Ketones Enabled by η5-Cyclopentadienylcobalt(L)(L′)

Abstract1,7-Octadiyne underwent [2+2+2] cycloaddition to acetone in the presence of η5-cyclopentadienylcobalt(L)(L′) complexes to give (η5-cyclopentadienyl)[(1,4,4a,8a-η4)-5,6,7,8-tetrahydro-3,3-dimethyl-3H-2-benzopyran]cobalt, in which the two triple bonds and the carbonyl moiety have combined to engender a 2H-pyran ring complexed to CpCo. The scope of this reaction was explored, including cocyclizations of ynals and ynones with bis(trimethylsilyl)acetylene, as well as all-intramolecular reorganizations of α,ω-diynals and -diynones. Two major trajectories were observed in the case of aldehydes, the (often minor) [2+2+2] pathway and a competing trail featuring a formal 1,5-hydride shift that results in CpCo–dienones. The latter is obviated for ketone substrates. Preliminary chemistry of selected complexes uncovered unprecedented reactions, such as acid-catalyzed ring openings and additions of amines, the latter providing access to novel carbon frames.