Alkynyl Alcohols Research Articles

Regioselective Reversal in One-Pot and Two-Step Reaction of 1-(2-Hydroxyphenyl)-Propargyl Alcohols with Aryl/Alkyl Mercaptan: Construction of 3-(Alkylthio)benzofurans and 2-(Alkylthiomethyl)benzofurans Starting from Identical Materials.

The Cu(MeCN)4PF6-catalyzed reaction of 1-(2-hydroxyphenyl)-propargyl alcohols with aryl/alkyl mercaptan and subsequent treatment with K2CO3 only offered 3-(alkylthio)benzofurans, whereas the stoichiometric-exceeding CuI-mediated reaction and subsequent treatment with DIPEA furnished 2-(alkylthiomethyl)benzofurans with high selectivity. The amount of Cu(I) salts plays a key role in selective formation. This unique protocol for the selective construction of the two series of benzofurans containing alkylthio group proved to be suitable for broad substrates 1 and 2 except for aliphatic alkynyl alcohols.

Synergize Strong and Reactive Metal-Support Interactions to Construct Sub-2 nm Metal Phosphide Cluster for Enhanced Selective Hydrogenation Activities.

Strong metal-support interactions (SMSI) are crucial for stabilizing sub-2 nm metal sites, e.g. single atom (M1) or cluster (Mn). However, further optimizing sub-2 nm sites to break the activity-stability trade-off due to excessive interactions remains significant challenges. Accordingly, for the first time, we propose synergizing SMSI with reactive metal-support interactions (RMSI). Comprehensive characterization confirms that the SMSI stabilizes the metal and regulates the aggregation of Ni1 into Nin site within sub-2 nm. Meanwhile, RMSI modulates Nin through sufficiently activating P in the support and eventually generates sub-2 nm metal phosphide Ni2P cluster (Ni2Pn). The synergetic metal-support interactions triggered the adaptive coordination and electronic structure optimization of Ni2Pn, leading to the desired substrate adsorption-desorption kinetics. Consequently, the activity of Ni2Pn site greatly enhanced towards the selective hydrogenations of p-chloronitrobenzene and alkynyl alcohol. The formation rates of target products are up to 20.2 and 3.0 times greater than that of Ni1 and Nin site, respectively. This work may open a new direction for metal-support interactions and promote innovation and application of active sites below 2 nm.

Ready Access to [5,6,5]-Trioxa-spiro and Fused Ketals via Ag-Catalyzed Cascade Annulation of 4-Pentyn-1-ols and Aldehydes.

In this study, we unveil the versatility of 4-pentyn-1-ols as carbonyl surrogates for the unprecedented synthesis of diverse oxygen heterocycles, including [5,6,5]-bis-spiroketals (trioxadispiroketals) and [5,6,5]-furano-spiroketals related to bioactive natural products. These reactions commence with the π-activation-induced intramolecular hydroalkoxylation of 4-pentyn-1-ols, yielding cyclic enol ethers, which undergo subsequent three-component annulation with aldehydes in a [2+2+1+1] fashion, resulting in the formation of [5,6,5]-bis-spiroketals. Notably, the distinctive steric features of alkynyl alcohols, particularly those with a secondary or tertiary alcohol functionality, dictate divergent reaction pathways, leading to the formation of [5,6,5]-furano-spiroketals.

Palladium-Catalyzed Chain-Walking of Alkynyl Alcohols to α,β-Unsaturated Carbonyls

Palladium-Catalyzed Chain-Walking of Alkynyl Alcohols to α,β-Unsaturated Carbonyls

Remote Functionalization by Pd-Catalyzed Isomerization of Alkynyl Alcohols.

In recent years, progress has been made in the development of catalytic methods that allow remote functionalizations based on alkene isomerization. In contrast, protocols based on alkyne isomerization are comparatively rare. Herein, we report a general Pd-catalyzed long-range isomerization of alkynyl alcohols. Starting from aryl-, heteroaryl-, or alkyl-substituted precursors, the optimized system provides access preferentially to the thermodynamically more stable α,β-unsaturated aldehydes and is compatible with potentially sensitive functional groups. We showed that the migration of both π-components of the carbon-carbon triple bond can be sustained over several methylene units. Computational investigations served to shed light on the key elementary steps responsible for the reactivity and selectivity. These include an unorthodox phosphine-assisted deprotonation rather than a more conventional β-hydride elimination in the final tautomerization event.

Regioselective [3+2]‐Spiroannulation and [4+n]‐Annulation Approaches through Activation of C−H Bond Facilitated by Ru(II) as Catalyst: Role of Solvent Selectivity

AbstractRu(II)‐catalyzed and solvent‐switched [3+2]‐spiroannulation and [4+n] (n=1, 2, 3) annulations of 2‐aryl quinazolinone or 2‐aryl‐2,3‐dihydrophthalazine‐1,4‐diones with ynones or alkynyl alcohol or 1,3‐diynes under mild reaction conditions have been analyzed. These reactions take place in the presence of the appropriate solvent and features a redox‐neutral pathway. Ynone serves as an ‘atypical one‐carbon unit’ in [4+1] annulation and generates a tetrasubstituted carbon center bearing diverse heterocycles through [3+2] and [4+1] annulation strategies. Post transformations of the synthesized spiro‐products augments the potential of the developed methodology.

Synthesis of alkynyl alcohol derivatives and its corrosion inhibition on N80 steel in 5 M HCl

AbstractAlkynyl alcohol derivatives (N‐14) were synthesized by 2‐chloromethyl pyridine, propargyl alcohol and bromotetradecane and the structure was confirmed by 1H NMR, 13C NMR, MS and FTIR. The corrosion inhibition performance was evaluated by weight loss, Tafel polarization, EIS measurements and DFT quantum calculations. The results proved that N‐14 effectively inhibited the acid corrosion of N80 steel. The corrosion inhibition of N‐14 increased with its concentration and decreased with increasing temperature. A maximum of 99.56% inhibition efficiency was achieved using 5 × 10−5 mol/l of N‐14 at 60°C. Thermodynamic parameters showed that the adsorption of N‐14 on N80 steel is spontaneous and exothermic, conforming to Langmuir's adsorption. Electrochemical results showed that N‐14 behaved as a mixed‐type inhibitor. In addition, corrosion products produced on N80 steel surface were researched by SEM, XRD, UV and contact angle. At the same time, the corrosion inhibition mechanism was discussed.

Divergent access to polycyclic spiro- and fused-N,O-ketals through Bi(OTf)3-catalyzed [4+2]-annulation of cyclic N-sulfonyl ketimines and alkynols.

Bismuth(III) triflate-catalyzed [4+2]-annulation of cyclic N-sulfonyl ketimines (derived from saccharin) and alkynyl alcohols (4-pentyn-1-ols and 5-hexyn-1-ols) has been reported. This cascade annulation provides a diverse array of polycyclic spiro-and-fused N,O-ketals with excellent substrate scope, good isolated yields, and diastereoselectivities under mild reaction conditions.

Cyclisation of Alkynyl Alcohols and Carboxylic Acids Mediated by N‐Heterocyclic Carbene Copper(I) Complexes

AbstractThe cyclisation of alkynyl alcohols and carboxylic acids in the presence of a [Cu(NHC)2]X complex is reported. The reactions were carried out in technical grade toluene in the presence of air with a catalyst that is readily accessible. N‐Heterocyclic carbenes are recognised for stabilising metal centres in a range of oxidation states, and this work further supports that NHCs can also be used as activation sites in air and moisture stable yet active catalysts.

B(C6F5)3-Catalyzed Intramolecular Hydroalkoxylation Deuteration Reactions of Unactivated Alkynyl Alcohols.

Using D2O as a deuterium source, a method for the deuteration of intra- and extra-cyclic methylene has been developed for cyclic ethers with moderate yield and excellent deuterium incorporation. This transformation features superb functional group tolerance in a wide range of alkynols. Notably, the critical factor to achieve high deuterium incorporation is determined by the hydrogen isotope exchange reaction of an unstable oxonium ion. This novel methodology provides an efficient and concise synthetic route to a number of valuable deuterated cyclic ethers that are often difficult to prepare with other methods.

Cu/SaBox-Catalyzed Photoinduced Coupling of Acylsilanes with Alkynes.

The transition metal-catalyzed cross-coupling reaction with Fischer metal carbene intermediates bearing an electron-rich alkoxyl or siloxyl group remains a big challenge due to the lack of readily available corresponding carbene precursors. Herein, we report the coupling of alkynes with the Fischer-type copper carbene species bearing a α-siloxyl group, which could be in situ generated from acylsilanes catalytically under photoirradiation and redox-neutral conditions. The side-arm modified bisoxazoline (SaBox) ligands prove to be crucial for this coupling reaction, which provides the corresponding alkynyl alcohol in high yields with remarkable heterocycle tolerance and broad substrate scope.

Cu/SaBox‐Catalyzed Photoinduced Coupling of Acylsilanes with Alkynes

AbstractThe transition metal‐catalyzed cross‐coupling reaction with Fischer metal carbene intermediates bearing an electron‐rich alkoxyl or siloxyl group remains a big challenge due to the lack of readily available corresponding carbene precursors. Herein, we report the coupling of alkynes with the Fischer‐type copper carbene species bearing aα‐siloxyl group, which could be in situ generated from acylsilanes catalytically under photoirradiation and redox‐neutral conditions. The side‐arm modified bisoxazoline (SaBox) ligands prove to be crucial for this coupling reaction, which provides the corresponding alkynyl alcohol in high yields with remarkable heterocycle tolerance and broad substrate scope.

Bismuth(III)-catalyzed cascade condensation of alkynyl alcohols with terminal alkynes: A facile construction of propargyl cyclic ethers

Herein, we report a Bi(OTf)3-catalyzed cascade condensation between alkynols (particularly pent-4-yn-1-ols and hex-5-yn-1-ols) and terminal alkynes (aryl alkynes) to facile access to diverse propargyl cyclic ethers (2‑alkynyl tetrahydrofurans and 2‑alkynyl tetrahydropyrans). This simple and efficient cascade transformation proceeds through initial intramolecular hydroalkoxylation of alkynols to give corresponding cyclic enol ethers (via exo-dig or endo-dig mode of ring-closure) followed by hydroalkynylation. Cost-effective, naturally abundant, green Lewis acid catalysis, ambient reaction conditions, short reaction times, good substrate scope, and high yields are salient features of this strategy.

Theoretical study on mechanism of cycloaddition reaction between o-alkynylbenzaldoximes and hexynol catalyzed by silver(I)

• A detailed description of the reaction mechanism of AgOTf-catalyzed synthesis of 2-(3-cyclopropylisoquinolin-1-yl)-1,1-diphenylhexen-3-one using DFT calculations. • Parr function analysis showed that the generation of Ag-π complexes could influence the electrophilicity of reaction species. • During intramolecular dehydration, AgOTf acts as a dehydration medium. Lewis acid metal-catalyzed cyclizations to construct quinoline ring compounds have made breakthroughs in the more recent years. Understanding the specific mechanism of this kind of reactions remains a challenging issue in this field. In this work, the mechanism of the silver(I)-catalyzed cyclization of o-alkynylbenzaldoxime with propargyl alcohol to construct 2-(3-cyclopropylisoquinolin-1-yl)-1,1-diphenylhex-1-en-3-one was investigated using density functional theory (DFT). The calculated results indicated that the 1,3-dipole cycloaddition process is the rate-determined step of the whole reaction process. The Ag-π complex formed by AgOTf with o-alkynylbenzaldehyde oxime increased the electrophilicity of the γ-C of the alkyne group prompting the intramolecular 6-endo cyclization. In addition, the Ag-π complex formed by AgOTf with alkynyl alcohol enhances the nucleophilicity of α-C atom and the electrophilicity of β-C atom of o-alkynylbenzaldehyde oxime, thus promoting the 1,3-dipole cycloaddition reaction with isoquinoline-N-oxide. The revealed mechanism will provide valuable a clue for the design of the Ag-based novel catalyst. Abstract

A silver-catalyzed [3 + 3]-annulation cascade of alkynyl alcohols and α,β-unsaturated ketones for the regioselective assembly of chromanes

An unprecedented Ag(i)-catalyzed [3 + 3]-annulation of alkynyl alcohols (5-hexyn-1-ols) and α,β-unsaturated ketones is reported to construct simple to complex chromanes.

Use of NAD-Seq to Profile NAD+-Capped RNAs in Plants.

A 7-methylguanosine (m7G) cap in the 5′ end of eukaryotic mRNA transcript to protect mRNAs from degradation and regulate gene expression has been well characterized. Recently, some RNAs were found to contain a NAD+ cap, which is a different type of 5′ cap structure in eukaryotic organisms, including bacteria, yeast, mammalian cells, and Arabidopsis thaliana (arabidopsis) plant. NAD captureSeq was the first method to label NAD+-capped RNAs (NAD-RNAs) and uses ADP ribose cyclase (ADPRC)-catalyzed replacement of the nicotinamide of NAD+ with an alkynyl alcohol followed by copper-catalyzed azide-alkyne cycloaddition (CuAAC) to biotinylate NAD-RNA. In the next step, the eluted RNAs are subjected to library preparation and sequencing, followed by determination of NAD+-capped RNA in the transcriptome. Improved methods are emerging to determine NAD-RNAs, such as NAD tagSeq and strain-promoted azide–alkyne cycloaddition reaction (SPAAC)-NAD-Seq. Commonly, those methods use an enzymatic reaction followed by a click chemistry reaction to label NAD-RNAs with biotin or synthetic RNA tag (TagRNA).

Zinc-Catalyzed Hydroalkoxylation/Cyclization of Alkynyl Alcohols.

Despite the great interest in zinc catalysis for hydroelementation reactions, the use of zinc complexes as catalysts for the hydroalkoxylation of alkynyl alcohols has not been reported to date. Scorpionate zinc complexes have been successfully designed as precatalysts for the hydroalkoxylation reaction of alkynyl alcohols under mild reaction conditions. Zinc amide complex 8 has been shown to be an excellent precatalyst for the highly selective intramolecular hydroalkoxylation process to yield the corresponding exocyclic enol ethers. Kinetic studies have been performed and confirmed that reactions are first-order in [catalyst] and zero-order in [alkynyl alcohol]. NMR spectroscopy and X-ray diffraction analysis provided evidence for the formation of an alkynyl zinc compound which has been shown to be a key intermediate in the hydroalkoxylation process. On the basis of the experimental results, a catalytic cycle is proposed.

Gold-catalyzed domino reactions of alkynol and p-quinone methides: divergent synthesis of fused- and spiro-ketals

A gold-catalyzed domino reaction of alkynyl alcohols and p-quinone methides to obtain divergent fused- and spiro-ketals has been developed.

One-Pot Synthesis of 9-Spirofluorenes via Tandem Copper-Catalyzed Arylative Cyclization and Spirocyclization of Biaryl-Substituted Alkynyl Alcohols

One-Pot Synthesis of 9-Spirofluorenes via Tandem Copper-Catalyzed Arylative Cyclization and Spirocyclization of Biaryl-Substituted Alkynyl Alcohols

Diastereoselective Synthesis of Polysubstituted Spirocyclopenta[ c]furans by Gold-Catalyzed Cascade Reaction.

With the synergistic activation of alkynyl alcohols and alkynyl enones by a single gold catalyst, diverse multisubstituted spirocyclopenta[ c]furans were synthesized in good to excellent yields under mild conditions. Three rings were constructed efficiently in one pot from easily available acyclic starting materials.