Propargylic Alcohols Research Articles

Comprehensive Strategies for the Synthesis of 1,3-Enyne Derivatives

AbstractThe synthesis of 1,3-enyne has widespread appeal in organic synthesis due to their proven adaptability as intermediates in routes to compounds of significant biological and material interest. A variety of methods have been designed to formulate 1,3-enynes from diverse substrates, such as alkynes, 1,3-diynes, alkynyl-substituted cyclopropanes, and propargyl alcohols. This review covers the synthesis of 1,3-enynes utilizing the homo- and cross-coupling of alkynes, nucleophilic metal/acid-induced cyclopropane ring opening, and rearrangement/dehydration of propargyl alcohols. A key concern in procedures starting from alkynes and 1,3-diynes is the management of regio-, stereo-, and, where fitting, chemoselectivity. In contrast, in cyclopropyl ring opening nucleophile orientation determines the 1,3-enynes formed. Efficient methods for the broad and selective synthesis of 1,3-enynes are highlighted and specific examples are given to demonstrate the efficacy of these processes.1 Introduction and Scope2 Synthesis2.1 Synthesis of 1,3-Enynes from Alkynes2.1.1 Metal-Catalyzed Cross-Coupling/Additions of Alkynes with Alkenes or Vinyl or Aryl Halides2.1.1.1 Palladium Catalysis2.1.1.2 Rhodium Catalysis2.1.1.3 Copper Catalysis2.1.1.4 I ron Catalysis2.1.1.5 Nickel Catalysis2.1.1.6 Miscellaneous2.2 Synthesis of Enynes from Propargyl Alcohols2.3 Metal/Acid-Catalyzed Ring Opening of Cyclopropanes3 Conclusion

Gold-Catalyzed Oxidative Rearrangement Strategy to Yield 2-Hydroxycyclohepta-1,3-diene-1-carbonyl Compounds.

A gold-catalyzed oxidative rearrangement of propargyl alcohols, derived from commercially available cyclohex-2-en-1-ones and alkynes, was successfully developed for the efficient synthesis of seven-membered rings. Thorough investigations were conducted to optimize the reaction conditions and evaluate its compatibility with various functional groups. Additionally, this methodology was applied to the formal total synthesis of guanacastepene A, demonstrating its practical utility in complex natural product synthesis. This versatile and efficient approach opens up new possibilities for the construction of diverse seven-membered ring systems, providing valuable building blocks for further exploration in drug discovery and the synthesis of intricate molecules.

Enantioselective Synthesis of α-Quaternary Isochromanes by Oxidative Aminocatalysis and Gold Catalysis.

A novel strategy that combines oxidative aminocatalysis and gold catalysis allows the preparation of chiral α-quaternary isochromanes, a motif that is prevalent in natural products and synthetic bioactive compounds. In the first step, α-branched aldehydes and propargylic alcohols are transformed into α-quaternary ethers with excellent optical purities (>90 % ee) via oxidative umpolung with DDQ and an amino acid-derived primary amine catalyst. Subsequent gold(I)-catalyzed intramolecular hydroarylation affords the isochromane products with retention of the quaternary stereocenter. A second approach explores the use of allylic alcohols as reaction partners for the oxidative coupling to furnish α-quaternary ethers with generally lower enantiopurities. Stereoretentive cyclization to isochromane products is achieved via intramolecular Friedel-Crafts type alkylation with allylic acetates as a reactive handle. A number of synthetic elaborations and a biological study on these α-quaternary isochromanes highlight the potential applicability of the presented method.

Photoinduced Regioselective Fluorination and Vinylation of Remote C(sp3)-H Bonds Using Thianthrenium Salts.

Herein, a photoredox-driven practical protocol for fluorinated alkene synthesis using easily accessible and modular thianthrenium salts with electron-withdrawing alkynes or propargyl alcohols is reported. Vinyl radical intermediates, formed by the reaction between the alkyl or trifluoromethyl thianthrenium salts and electronically diverse alkynes, can mediate the key 1,5-HAT process of regioselective C(sp3)-H fluorination and vinylation. This protocol provides straightforward access to structurally diverse trifluoromethyl- or distally fluoro-functionalized alkene products in 21-79% yields with a broad substrate range under mild photocatalytic conditions.

CO2-Based Stable Porous Metal-Organic Frameworks for CO2 Utilization.

The transformation of carbon dioxide (CO2) into functional materials has garnered considerable worldwide interest. Metal-organic frameworks (MOFs), as a distinctive class of materials, have made great contributions to CO2 capture and conversion. However, facile conversion of CO2 to stable porous MOFs for CO2 utilization remains unexplored. Herein, we present a facile methodology of using CO2 to synthesize stable zirconium-based MOFs. Two zirconium-based MOFs CO2-Zr-DEP and CO2-Zr-DEDP with face-centered cubic topology were obtained via a sequential desilylation-carboxylation-coordination reaction. The MOFs exhibit excellent crystallinity, as verified through powder X-ray diffraction and high-resolution transmission electron microscopy analyses. They also have notable porosity with high surface area (SBET up to 3688 m2 g-1) and good CO2 adsorption capacity (up to 12.5 wt %). The resulting MOFs have abundant alkyne functional moieties, confirmed through 13C cross-polarization/magic angle spinning nuclear magnetic resonance and Fourier transform infrared spectra. Leveraging the catalytic prowess of Ag(I) in diverse CO2-involved reactions, we incorporated Ag(I) into zirconium-based MOFs, capitalizing on their interactions with carbon-carbon π-bonds of alkynes, thereby forming a heterogeneous catalyst. This catalyst demonstrates outstanding efficiency in catalyzing the conversion of CO2 and propargylic alcohols into cyclic carbonates, achieving >99% yield at room temperature and atmospheric pressure conditions. Thus, this work provides a dual CO2 utilization strategy, encompassing the synthesis of CO2-based MOFs (20-24 wt % from CO2) and their subsequent application in CO2 capture and conversion processes. This approach significantly enhances overall CO2 utilization.

Ga(OTf)3 catalysed rapid nucleophilic substitution of propargyl alcohols with enoxysilanes

Ga(OTf)3 efficiently catalyses the nucleophilic substitution of the hydroxyl group of propargyl alcohols with enoxysilanes to aid in CC bond formation. The reactions can be performed in an undried solvent under air to obtain the desired products quickly in good yields. Other nucleophiles, such as indole, phenol, and furan are also suitable for this transformation. The use of inexpensive and readily available catalysts makes this method simple, convenient, and practical.

Study on the molecular interactions of some binary mixtures through thermodynamic properties and FT-IR spectra and correlation with the Jouyban–Acree model

ABSTRACT Densities (ρ), speeds of sound (u) and viscosities (η) were measured for three binary mixtures of propargyl alcohol with tetra chloromethane, trichloromethane, and dichloromethane from 303.15 K to 313.15 K at atmospheric pressure across the composition range. Excess molar volume, excess isentropic compressibility, deviation in viscosity, and excess Gibbs free energy of activation of viscous flow were calculated. Partial molar properties and infinite dilution molar partial properties were also determined for each system. Results suggest heteroassociates forming cross complexes and chemical forces with specific interactions. PFP theory was used to identify the predominant molecular interactions. The Jouyban–Acree model findings were discussed, considering mean relative deviation (MRDs) and individual relative deviation (IRD) between calculated and experimental data. FTIR studies were included to corroborate the experimental findings.

Construction of Polymers with Highly Dispersed Reactive Phases and Open Pores for Catalyzing the Efficient Synthesis of CO2 to α‐Methylene Cyclic Carbonates

AbstractSelective capture of carbon dioxide as a C1 feedstock for the preparation of high‐value chemicals has been recognised as an important way to mitigate the crisis. In this work, a new heterogeneous catalyst, Cu@CP‐PII, was developed through the rational construction of an open‐pore organic skeleton, which is easy to synthesise and highly efficient. With the synergistic effect between the high CO2 affinity of the porous skeleton and the highly dispersed Cu(I) sites of the activated alkynes, it can be used for the efficient preparation of α‐methylene cyclic carbonates at ambient temperature and pressure. The structure and morphology were exhaustively characterised by Solid State 13C‐NMR, FT‐IR, XPS, TEM and N2 adsorption‐desorption tests, and this catalyst possessed a high surface area of 273.7 m2 ⋅ g−1 and uniformly dispersion of CuI. To test its catalytic activity, Cu@CP‐PII in an amount of only 0.4 mol% was used as a catalyst for the carboxylative cyclization reaction of propargylic alcohols with CO2, which resulted in substrate conversions up to 100 % and yields greater than 99 %. In addition, controlled experiments and mechanistic elucidation confirmed that anhydrous and low temperatures are necessary to achieve high selective control of the target product α‐methylene cyclic carbonates.

Recent Advances in Radical Transformations of Propargylic Alcohols

AbstractPropargylic alcohols are regarded as a class of readily available and versatile synthons in organic synthesis. Due to their unique bifunctional character, the transformation of propargylic alcohols has been widely utilized as a powerful strategy for the construction of various functionalized frameworks over the past few decades. Recently, the radical transformation of propargylic alcohols has attracted considerable attention in synthetic chemistry. This review summarizes recent progress in the radical transformation of propargylic alcohols. Based on the different mechanisms of radical formation underlying these transformations, this review has been divided into four parts: (1) transition‐metal catalyzed radical transformation; (2) photo‐induced radical transformation; (3) electro‐induced radical transformation; and (4) metal‐free or oxidant‐mediated radical transformation of propargylic alcohols.

Access to 4‐Membered Heterocycles via Visible‐Light Triggered Intramolecular Cyclization from Alkynes: Bypassing Unfavorable 4‐endo‐dig Cyclization

AbstractWe describe a catalyst, oxidant, and coupling‐reagent free strategy to access 4‐membered heterocycles, representing a unique example of visible‐light triggered intramolecular cyclization of propargylic alcohols and amines to access oxetanones and azetidinones respectively. Despite the direct 4‐endo‐dig cyclization from these starting materials has proven to be unfavorable, the formation of key p‐quinone methide intermediacy allows an efficient bypass for regioselective 4‐exo‐trig cyclization, resulting in the formation of the desired 4‐membered heterocycles. This mild and operationally simple protocol facilitates the synthesis of products with distinct substitution patterns such as quaternary α‐carbons, and enables late‐stage functionalization.

TFA-Promoted Cascade Sulfonylation/Rearrangement/Cyclization of 1,5-Diynols and Sodium Sulfinates to Construct Sulfonylated Benzo[b]fluorenes.

A novel conversion of 1,5-diynols into sulfonylated benzo[b]fluorenes is reported by a TFA-promoted cascade cyclization with sodium sulfinates under mild conditions. This strategy provides an efficient and practical approach for accessing various sulfonated benzo[b]fluorenes in moderate to excellent yields under metal-free conditions. On the basis of the control experimental results and density functional theory calculations, a possible cascade transformation mechanism consisting of the dehydration of propargylic alcohols, sulfonylation, allenylation, and Schmittel-type cyclization is proposed. It is worth noting that TFA played an important role in this cascade cyclization, which promoted C-SO2R bond cleavage in a propargylic sulfone intermediate to form allenyl sulfones, followed by Schmittel-type cyclization to give the target product.

Substrate Controlled [3+3] Relay Catalytic Cyclization of α‐(3‐Isoindolinonyl) Propargylic Alcohols with 5‐Aminoisoxazoles

AbstractTwo different skeletons have been constructed by cyclization of α‐(3‐isoindolinonyl) propargylic alcohols with 5‐aminoisoxazoles bearing different N‐substituents under the relay catalysis of Brønsted acid and Lewis acid. This method provided spiro‐isoindolinone‐dihydropyridines with moderate to high yields (up to 99 %) as well as isoxazolo[4,5‐b]pyridines in moderate to good yields (up to 86 %). The structures of two products were determined by X‐ray crystal structural analyses. Moreover, fluorescence testing proved that one of the isoxazolo[4,5‐b]pyridines exhibited aggregation induced emission (AIE) effect. Finally, the control experiments revealed the possible reaction mechanism.

Two fields are better than one – A multifunctional (semi)automated setup for quantitative measurements of parahydrogen-induced signal enhancement at low and high fields

The rapid advancement of parahydrogen-induced hyperpolarization (PHIP) and its diverse array of applications highlights the critical need for enhanced signals in both 1H NMR and heteronuclear NMR spectroscopy. Simultaneously, there is an increasing interest in utilizing benchtop NMR analysis across various laboratory settings. However, due to their lower magnetic fields, benchtop NMR spectrometers inherently produce weaker signal intensities. Here, PHIP is a well-established solution to this challenge. Consequently, we are expanding our cost-effective PHIP setup from a high-field NMR spectrometer (11.7 T) to include an additional benchtop NMR spectrometer (1.4 T), thereby enabling concurrent execution of PHIP experiments and measurements. Through the implementation of automated experimental protocols, we aim to minimize experiment time while increasing reproducibility. In this work, a non-isotope labelled propargyl alcohol sample is used at low concentrations to demonstrate our setup’s capabilities. It could be shown that single-scan PASADENA experiments can be run with comparable signal enhancements at the benchtop as well as the high-field spectrometer. At 1.4 T, fully automated PHIP pseudo-2D measurements will also be demonstrated. Additionally, two different field profiles for the spin-order transfer of p-H2 to 13C at zero- to ultralow fields are elaborated upon. The setup facilitates the measurement of carbon signal enhancement of more than 2000 on the benchtop NMR spectrometer, employing a straightforward one-pulse, one-scan experiment.

Thermo physical properties and IR spectral studies of some binary liquid mixtures and correlation with the Jouyban–Acree model

ABSTRACT Excess molar volume, excess isentropic compressibility, deviation in viscosity and excess Gibbs free energy for activation of viscous flow for binary mixtures of propargyl alcohol (J) with benzyl aldehyde (J1), benzylamine (J2) and benzyl alcohol (J3) components with selected compositions were determined from the measured values of densities (ρ), viscosities (η), and speeds of sound (u) of pure components and their mixtures from 303.15 K to 313.15 K. The effect of various functional groups on the excess properties has been discussed in terms of attractive forces between the components. The results of the Jouyban-Acree model are discussed in terms of the mean relative deviation and individual relative between the calculated and experimental densities, speed of sound, and viscosities as an accuracy criterion.FTIR studies have also been added to confirm the experimental findings of the investigated mixtures

Regiocontrolled Ruthenium-Catalyzed Isomerization of Propargyl Alcohols

AbstractA diaminocyclopentadienone ruthenium complex allows control of regioselectivity in the ruthenium-catalyzed isomerization of propargyl alcohols through the choice of additive. Thereby, both products of the Meyer–Schuster rearrangement and redox isomerization products are selectively accessible. In the presence of hydroxylamine-O-sulfonic acid, unsaturated nitriles are formed instead. The ruthenium catalyst is readily available and stable to moisture, air, and acidic conditions.

Synthesis of Alkenylgold(I) Complexes Relevant to Catalytic Carboxylative Cyclization of Unsaturated Amines and Alcohols.

The carboxylation of unsaturated amine and alcohol compounds, including 4-benzylamino-1-phenyl-1-butyne (homopropargylamine), 2-butyne-1-ol (propargylic alcohol), and 2,3-butadiene-1-ol (allenylmethyl alcohol), using the hydroxidogold(I) complex, AuOH(IPr) [IPr = 1,3-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene], produces corresponding alkenylgold(I) complexes with a cyclic urethane or carbonate framework in high yields. The reaction takes place in aprotic THF at room temperature under the atmospheric pressure of CO2 in the absence of base additives. The products were characterized by NMR spectroscopy, elemental analysis, and X-ray crystallography. The functionalized alkenyl complexes prepared from the alkynes can be protonated by treatment with an equimolar amount of acetic acid to afford five- or six-membered carboxylation products, whereas the related alkenyl complex derived from allenylmethyl alcohol decomposed to recover the starting allene via ring-opening decarboxylation.

Lewis-Acid-Catalyzed (3+2) Annulation of 2-Indolylmethanols with Propargylic Alcohols to Access Cyclopenta[b]indoles.

Herein, a Sc(OTf)3-catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols is reported. The reaction proceeds via a Friedel-Crafts-type allenylation/5-exo-annulation cascade. In the reaction, 2-indolylmethanol is used as a three-carbon synthon, and propargyl alcohol is used as a two-carbon synthon. This method provides a direct and high-yield pathway for synthetically useful cyclopenta[b]indoles. In general, the method features easily accessible substrates with broad scope and generality, the formation of multiple bonds with high efficiency, and easy scale-up.

A theoretical investigation to understand the difference in reactivities of secondary and tertiary propargylic alcohols with 1,3,5‐trimethoxybenzene in presence of Brnøsted acid

AbstractThe work presented here establishes the experimental findings of the reaction between secondary/tertiary propargylic alcohol (PA) and 1,3,5‐trimethoxybenzene (TMB) in the presence of acetonitrile solvent (MeCN) based on theoretical calculations. When secondary PA reacts, the reaction goes via SN2 pathway, where the reaction barrier is about 14.32 kcal/mol. On the other hand, tertiary PA reacts with TMB via SN2′ and SN1′ pathway, and the corresponding reaction barriers are 17.59 and 17.86 kcal/mol. Other possible pathways, namely, SN1, SN1′, etc. for secondary PA, and SN2, SN1 pathways for tertiary PA are also investigated and the associated barrier heights are found higher. Rates of those reactions are also calculated considering the rate‐determining steps only. Reaction of secondary PA with TMB is found to be much faster than the reaction of tertiary PA and the results are in accordance with the experimental findings.

Catalytic Enantioselective Alkyne Addition to Nitrones Enabled by Tunable Axially Chiral Imidazole-Based P,N-Ligands.

Although catalytic enantioselective alkyne addition is an established method for the synthesis of chiral propargylic alcohols and amines, addition to nitrones presents unique challenges, and no general chiral catalyst system has been developed. In this manuscript, we report the first Cu-catalyzed enantioselective alkyne addition to nitrones utilizing tunable axially chiral imidazole-based P,N-ligands. Our approach effectively overcomes difficulties in both reactivity and selectivity, resulting in a simple Cu-catalyzed protocol. The reaction accommodates a wide range of nitrones and alkynes, enabling the streamlined synthesis of chiral propargyl N-hydroxylamines via the enantioselective C-C bond formation. A diverse array of optically active nitrogen-containing compounds, including chiral hydroxylamines, can be accessed directly through facile transformations of the reaction products.

Regioselective Synthesis of Isoxazoles from Propargylic Alcohols via In‐situ‐formed α‐Iodo Enones/Enals

AbstractA regioselective synthesis of isoxazoles with propargyl alcohols, N‐iodosuccinimide (NIS), and N‐tert‐butyl hydroxylamine hydrochloride (t‐BuNHOH•HCl) as the reaction substrates is reported. Reaction scope investigations indicated that primary and secondary propargyl alcohols underwent this transformation smoothly to afford 5‐, 3‐, and 3,5‐substituted isoxazoles in moderate to good yields. The reaction most likely involves an electrophilic‐intercepted Meyer‐Schuster rearrangement of the propargyl alcohol, followed by intermolecular cyclocondensation of N‐tert‐butyl hydroxylamine and in‐situ‐formed α‐iodo enones/enals. This one‐pot method is regioselective and easy to perform, making it a valuable method for the construction of isoxazoles. Finally, its application was explored through the synthesis of valdecoxib.