Propargylic Alcohols Research Articles

An Electrochemical Route to Novel N‐benzoyl‐1,2,3‐triazoles and Protein Binding Studies of Selected Triazole Derivatives

AbstractAn electrochemical, cost‐efficient and atom‐economic method for the synthesis of novel, structurally unique N‐benzoyl‐1,2,3‐triazole derivatives has been developed via cascade oxidation‐ 1,3‐dipolar cycloaddition reaction of readily available propargyl alcohol and benzoyl azide. The electro‐oxidation of propargyl alcohol and subsequent cycloaddition was performed in an undivided cell using graphite rod and stainless‐steel plate as inexpensive electrode materials. Numerous 4,5‐disubstituted N‐benzoyl‐1,2,3‐triazoles may be synthesized from milli to multi‐gram scale employing this protocol. The biological significance of few selected triazole derivatives were evaluated via protein binding studies.

DMSO/SOCl2‐Mediated Synthesis of Thiomethylnaphthalenes from Propargyl Alcohols

AbstractHerein, we reported the straightforward synthesis of thiomethylnaphthalenes via the reaction of propargyl alcohols with dimethyl sulfoxide/thionyl chloride (DMSO/SOCl2), which also provided easy access to deuterated thiomethyl and other thioalkyl scaffolds when deuterated dimethyl sulfoxide and dialkyl sulfoxides were used, respectively. In addition, the thiomethyl group can be readily derivatized to the corresponding sulfoxide, sulfone, and sulfoximine of interesting photophysical properties.

Hydroxyl-Assisted and Co(III)-Catalyzed Redox-Neutral C-H Activation/Directing Group Migration of 2-Pyridones with Propargyl Alcohols: Synthesis of Tetrasubstituted Alkenes.

This study provides a practical route to synthesize tetrasubstituted alkenes that involves Co(III)-catalyzed C-H bond activation and regioselective insertion of the alkyne, followed by chelation of the substrate hydroxyl to Co and migration of the pyridine group. Density functional theory studies revealed the origin of regioselectivity and elucidated the crucial role of the hydroxyl group for the migration of pyridine. The method can be conducted on a gram scale, is compatible with a wide range of substrates, and has a high functional group tolerance. To demonstrate its significance, the method was used for the late-stage modification of Fasudil. Furthermore, the synthetic significance of the method was demonstrated by the various derivatizations of the products, many of which exhibit intriguing fluorescence characteristics.

Tandem Cyclization of o-Hydroxyphenyl Propargyl Alcohols with Thionucleophiles: A Metal-Free and Modular Access to 3-Fluoroalkylsulfonyl/Thio Benzofurans.

Despite both fluoroalkylsulfonyl groups and benzofurans are important bioactive moieties, the construction of fluoroalkanesulfonylated benzofurans that incorporate these two fragments remains underdeveloped. Here, we report a tandem cyclization protocol to construct a wide range of 3-fluoroalkylsulfonyl benzofurans using readily accessible o-hydroxyphenyl propargyl alcohols and sodium fluoroalkanesulfinates. Furthermore, this synthetic strategy can also be adapted to prepare 3-thio benzofurans by changing the S-nucleophiles to thiols or thiophenols.

Two Sustainable Pathways of MOF-Catalyzed Room Temperature Chemical Fixation of CO2 inside Alkynes under Atmospheric Pressure.

The rising atmospheric CO2 levels necessitate the development of effective materials for its mitigation. Utilization of adsorbent materials for the reversible physisorption of CO2 has a significantly less impact. Recognizing this need, herein, we present a nitrogen-rich, aqua-stable, Ag(0)-nanoparticle-doped metal-organic framework (MOF) designed for the irreversible chemical conversion of CO2 into valuable fine chemicals. We demonstrate two sustainable pathways for CO2 fixation, utilizing the catalyst, 1'@Ag NPs. The designed catalyst facilitates the cyclization of propargylic amines and alcohols under ambient temperature and pressure conditions. Remarkably, this is the first MOF-based catalyst that allows for quantitative conversion of propargylic amines into 2-oxazolidinones at room temperature with atmospheric CO2 pressure. The process successfully transforms various propargylic amines and alcohols into 2-oxazolidinones and α-alkylidene cyclic carbonates under the CO2 atmosphere. Additionally, the catalyst shows excellent recyclability, maintaining its activity and structural integrity across multiple reuse cycles. Control experiments revealed that the catalytic efficiency of 1'@Ag NPs is attributed to the highly exposed alkynophilic Ag(0) sites on its pore walls. Computational studies further elucidate the mechanistic pathway for CO2 fixation. This work highlights the potential of 1'@Ag NPs to enhance environmental sustainability by converting CO2 into valuable bioactive chemicals under mild conditions.

Organocatalytic Asymmetric Cascade Bicyclization of 2‐Indolylmethanols with α‐(2‐Indolyl) Propargylic Alcohols to Access Chiral Fluorescent Hexacyclic Bisindoles

AbstractA cascade regioselective 1,8‐addition/biscyclization of 2‐indolylmethanols with α‐(2‐indolyl) propargylic alcohols has been developed via chiral phosphoric acid (CPA) catalysis. A series of chiral cyclopenta[4,5]pyrrolo biindoles bearing a quaternary stereogenic center were obtained in modest to good yields (72–95%) with high enantioselectivities (82–94%). Additionally, the photophysical properties of these hexacyclic bisindoles are examined, revealing bright fluorescence with high quantum yields.

CuxOy Incorporated COF: A Potential Reusable Catalyst for the Synthesis of α‐Hydroxy Ketones and Oxazolidinones Under Atmospheric CO2 Pressure and Solvent‐Free Conditions

AbstractIn this present work, a newly designed metal‐oxide nanoparticle incorporated Covalent organic framework (COF), CuxOy@TFP‐ODA has been successfully synthesized and used for the effective synthesis of Oxazolidinones and a‐hydroxy ketones under mild conditions utilizing CO2. Initially, imine‐linked 2D COF, TFP‐ODA was synthesized by simple solvothermal method followed by the embedment of copper oxide nanoparticles (NPs) into the skeleton of the as‐synthesized COF. Different characterization techniques were employed to establish the physical and chemical characteristics of both CuxOy@TFP‐ODA and TFP‐ODA COF materials. To study the catalytic efficiency of the highly porous CuxOy@TFP‐ODA, three components coupling reaction involving primary amine, propargyl alcohol and CO2 to synthesize a series of 2‐Oxazolidinone and synthesis of α‐hydroxy ketones using CO2 as a Co‐catalyst were carried out over the as‐prepared catalyst under green and sustainable conditions which illustrated excellent yields and selectivity of the corresponding products. The synthesized catalyst was proved to be completely heterogeneous and especially, the catalyst material demonstrated significant potential for reuse across several catalytic cycles.

Mechanochemical cyclization of push-pull enamines with propargyl alcohols

We developed an efficient mechanochemical method for the synthesis of 1,2-dihydropyridine derivatives from push-pull enamines and tert-propargyl alcohols under ball milling with p-TsOH/HFIP. The reaction proceeds smoothly under metal-free conditions with fast, efficient, and high-yielding synthesis of 1,2-dihydropyridines. The reaction shows excellent atom economy, with a broad substrate generality.

Organocatalytic Asymmetric [3 + 2] Cyclization: Enantioselective Synthesis of α-Indolyl Pyrrolo[1,2-a]indole Scaffolds.

A novel asymmetric [3 + 2] cyclization of α-indolyl propargylic alcohols with 3-alkyl-1H-indoles via chiral phosphoric acid catalysis has been established. This strategy allowed the synthesis of chiral α-indolyl pyrrolo[1,2-a]indole derivatives with high yields (up to 91%) and excellent enantioselectivities (up to 99% ee), facilitating both the reaction activity and enantioselectivity by using the solvent of CH3CFCl2. Significantly, this protocol will provide an effective synthetic approach for constructing enantioenriched α-indolyl pyrrolo[1,2-a]indole cores of antimalarial natural product isoborreverine analogues.

Enamine Synthesis via Regiocontrolled 6‐endo‐dig and 5‐exo‐dig Tethered Carboamination of Propargylic Alcohols

AbstractEnamines are versatile building blocks for the synthesis of biologically active compounds. Nevertheless, only a limited number of strategies have been reported for preparing trisubstituted enamines in a regio‐ and stereoselective manner. Herein, we report a regiocontrolled 6‐endo and 5‐exo tethered carboamination of propargylic alcohols for the synthesis of trisubstituted enamines. High regioselectivity was achieved through fine‐tuning of the amine protecting group during the Pd‐catalyzed carboamination. The introduced trifluoromethylated tether enables further stereoselective functionalizations, such as hydrogenation and fluorination.

Nickel-Catalyzed Asymmetric (3 + 2) Annulations of Propargylic Carbonates and Vinylogous Donors via an Alkenylation Pathway.

The transition-metal-catalyzed alkenylation strategy of propargylic alcohol derivatives provides an efficient protocol to access multifunctional products in a double-nucleophilic attack pattern. While limited relevant asymmetric examples have been reported via palladium catalysis, here we first demonstrate that a nonprecious Ni(0)-based chiral complex can efficiently promote the tandem substitution process between propargylic carbonates and N-trifluoroethyl ketimines via consecutive aza-vinylogous activations, finally accomplishing a (3 + 2) annulation reaction to afford products embedding a 4-methylene-3,4-dihydro-2H-pyrrole framework with high regio-, diastereo-, and enantiocontrol. Their assemblies with a few all-carbon-based vinylogous precursors are also successful, and enantioenriched adducts containing a 3-methylenecyclopentene scaffold are furnished effectively. The substitution patterns for both types of substrates are substantial, and an array of synthetic elaborations is conducted to deliver more versatile architectures with high application potential. In addition, density functional theory calculations and control experiments have been conducted to rationalize the catalytic pathways and regio- and enantioselectivity control.

TMSCl-Promoted Sulfonylation of Propargylic Alcohols with Sodium Sulfinates for the Construction of (E)-1,3-Disulfonylpropenes and (E)-1-Sulfonylpropenols.

A direct and novel transformation of propargylic alcohols with sodium sulfinates for the regio- and stereoselective synthesis of (E)-1,3-disulfonylpropenes and (E)-1-sulfonylpropenols was successfully developed in the presence of TMSCl under mild conditions. The preliminary mechanistic experiments demonstrated that the reaction underwent an unprecedented dual nucleophilic substitution/radical addition process, in which sodium sulfinates were used not only as nucleophiles but also as a sulfonyl radical source.

β,β‐Disubstituted Alkan‐2‐ones from Propargylic Alcohols Combining a Meyer‐Schuster Rearrangement and Asymmetric Alkene Bioreduction

AbstractThe combination of a gold(I) N‐heterocyclic carbene complex and an ene‐reductase (ERED) has made possible the synthesis of enantiopure β,β‐disubstituted ketones in a one‐pot concurrent approach. The protocol consists of the Meyer‐Schuster rearrangement of racemic propargylic tertiary alcohols using [1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene]‐[bis(trifluoromethanesulfonyl)‐imide]gold(I) (IPrAuNTf2), followed by an asymmetric alkene reduction of the α,β‐unsaturated ketone intermediate using the Zymomonas mobilis ERED (NCR‐ERED). The chemoenzymatic cascade was optimised with a model substrate, where E/Z‐isomers both generated the (R)‐ketone, which was rationalised using in silico molecular docking experiments. The cascade was then applied towards the production of a series of (R)‐4‐substituted‐alkan‐2‐ones in enantiopure form in a straightforward manner.

Non-Noble Metal Anchored 2D Covalent Organic Framework for Ambient CO2 Fixation to High-Value Compounds.

The catalytic functionalization of CO2 into high-value compounds comprises a promising approach to mitigate its atmospheric content and sustainable generation of fine chemicals. Herein, we report application of a crystalline, nano-porous 2D COF (ET-BP-COF) for utilization of CO2. The ET-BP-COF features a unique 2D kagome (kgm) topology composed of hexagonal and triangular 1D channels decorated with bipyridine sites, which were exploited for covalent anchoring of eco-friendly Cu(I) by post-synthetic method. The Cu(I) engrafted COF was applied as a recyclable catalyst for coupling CO2 with alkynes to generate two high-value compounds, α-alkylidene cyclic carbonates (α-ACCs) and 2-oxazolidinones. Notably, Cu(I)@ET-BP-COF demonstrated excellent catalytic performance for transforming propargylic amine and CO2 to 2-oxazolidinone, an essential building block for antibiotics. Besides, an efficient transformation of propargylic alcohols to generate α-ACCs, valuable commodity chemicals, has been achieved by utilizing carbon dioxide. Further, detailed theoretical simulations disclosed the insight mechanistic path of Cu(I) catalyzed coupling of CO2 with alkynes to produce 2-oxazolidinones and α-ACCs. Significantly, Cu(I)@COF was reusable for multiple cycles without losing framework rigidity and catalytic performance. This study showcases the potential application of ET-BP-COF for stable anchoring of eco-friendly metals as catalytic sites for effective utilization of CO2 to produce two high-value products.

Gold(I)‐Catalyzed Desymmetrization of Homopropargylic Alcohols via Cycloisomerization: Enantioselective Synthesis of Cyclopentenes Featuring a Quaternary Chiral Center

AbstractCyclopentene rings possessing a chiral quaternary center are important structural motifs found in various natural products. In this work, we disclose expedient and efficient access to this class of synthetically valuable structures via highly enantioselective desymmetrization of prochiral propargylic alcohols. The efficient chirality induction in this asymmetric gold catalysis is achieved via two‐point bindings between a gold catalyst featuring a bifunctional phosphine ligand and the substrate homopropargylic alcohol moiety—an H‐bonding interaction between the substrate HO group and a ligand phosphine oxide moiety and the gold‐alkyne complexation. The propargylic alcohol substrates can be prepared readily via propargylation of enoate and ketone precursors. In addition to monocyclic cyclopentenes, spirocyclic and bicyclic ones are formed with additional neighboring chiral centers of flexible stereochemistry in addition to the quaternary center. This work represents rare gold‐catalyzed highly enantioselective cycloisomerization of 1,5‐enynes. Density functional theory (DFT) calculations support the chirality induction model and suggest that the rate acceleration enabled by the bifunctional ligand can be attributed to a facilitated protodeauration step at the end of the catalysis.

Gold(I)-Catalyzed Desymmetrization of Homopropargylic Alcohols via Cycloisomerization: Enantioselective Synthesis of Cyclopentenes Featuring a Quaternary Chiral Center.

Cyclopentene rings possessing a chiral quaternary center are important structural motifs found in various natural products. In this work, we disclose expedient and efficient access to this class of synthetically valuable structures via highly enantioselective desymmetrization of prochiral propargylic alcohols. The efficient chirality induction in this asymmetric gold catalysis is achieved via two-point bindings between a gold catalyst featuring a bifunctional phosphine ligand and the substrate homopropargylic alcohol moiety-an H-bonding interaction between the substrate HO group and a ligand phosphine oxide moiety and the gold-alkyne complexation. The propargylic alcohol substrates can be prepared readily via propargylation of enoate and ketone precursors. In addition to monocyclic cyclopentenes, spirocyclic and bicyclic ones are formed with additional neighboring chiral centers of flexible stereochemistry in addition to the quaternary center. This work represents rare gold-catalyzed highly enantioselective cycloisomerization of 1,5-enynes. Density functional theory (DFT) calculations support the chirality induction model and suggest that the rate acceleration enabled by the bifunctional ligand can be attributed to a facilitated protodeauration step at the end of the catalysis.

Effect of Allyl and Propargyl Alcohols on the Equilibrium Conditions of Methane Hydrate Formation

Effect of Allyl and Propargyl Alcohols on the Equilibrium Conditions of Methane Hydrate Formation

Novel and reusable magnetic MOF nanocomposite coupled ionic liquid- promoted efficient chemical fixation of CO2 into α-alkylidene cyclic carbonates

Carbon dioxide as a C1 building block to synthesize α-alkylidene cyclic carbonates is an environmental and sustainable approach. In this work, we designed and synthesized a type of multifunctional magnetic MOF nanocomposite catalysts, which could realize the carboxylic cyclization of CO2 and propargylic alcohols into α-alkylidene cyclic carbonates under solvent-free conditions. Among all the prepared nanocomposites, the MnFe2O4@SiO2@Cu-MOF nanocomposite is the best in catalytic activity combined with the tetrabutylphosphonium acetate ([Bu4P]OAc) ionic liquid cocatalyst. The catalytic system MnFe2O4@SiO2@Cu-MOF/[Bu4P]OAc displayed excellent performance in catalyzing the carboxylic cyclization of CO2 and different propargylic alcohols, and a series of α-alkylidene cyclic carbonates were obtained in high to excellent yields (88 ∼ 98 %) under mild reaction conditions (0.2 MPa, 35 °C). In addition, the two-component catalytic system had high stability and reusability, and can be easily separated and reused up to six consecutive cycles without considerable decrease in catalytic activity. Moreover, using the ionic liquid [Bu4P]OAc as the cocatalyst, the nanocomposite had good substrate adaptability for the catalytic carboxylic cyclization, which opens interesting prospects for the development of new magnetic MOF nanocomposites as efficient heterogeneous catalysts for the chemical transformation of CO2 into value-added chemicals.

Ruthenium Catalyzed Formation of Fused Pyridine Derivatives or Substituted Indoles from Hydrazine‐Derived Enamines and Propargyl Alcohols

New ruthenium‐catalyzed transformations of secondary propargyl alcohols with hydrazine‐derived enamines are presented, affording fused pyridines or substituted indoles depending on the hydrazine derivative used. The cascade reactions are catalyzed by an air‐ and moisture‐stable bifunctional ruthenium complex and proceed via redox‐isomerization of the propargyl alcohol, subsequent Michael addition and cyclocondensation. In case of phenylhydrazine a Fischer‐indole synthesis also takes place, prior to the final release of the products. The produced heterocyclic motifs are important scaffolds in medicinal and agricultural chemistry.

Allenyl Thianthrenium Salt: A Bench-Stable C3 Synthon for Annulation and Cross-Coupling Reactions.

Herein, we report the first bench-stable and nonhygroscopic monosubstituted allenyl sulfonium salt (ATT) synthesized from thianthrene and propargyl alcohol. We demonstrate its use in annulation chemistry to synthesize heterocycles, such as 2-hydroxy morpholine, 2-methyl quinoxalines, and benzodioxepinone derivatives, with an exocyclic double bond. The reagent is the first allenyl sulfonium salt that can undergo palladium-catalyzed cross-coupling reactions to form a C(sp2)-C(sp2) bond via Suzuki coupling and a C(sp3)-C(sp2) bond formation via reductive coupling.