Terminal Alcohols Research Articles

A Mild and General trans-Diboration of Both Terminal and Internal Propargyl Alcohols.

A practical and efficient trans-diboration of propargyl alcohols was accomplished using sodium hydride (NaH) as a base in N,N-dimethylformamide at room temperature. The mild reaction conditions demonstrate general applicability, facilitating the successful conversion of both terminal and internal propargyl alcohols with diverse structures and functional groups into highly functionalized alkenediboronates [4-borylated 1,2-oxaborol-2(5H)-oles]. The resulting products, which incorporate two boron groups, can be selectively activated and subjected to stepwise transformations, thereby providing an effective platform for synthesizing a wide range of structurally diverse trisubstituted alkenes.

Elucidating the ruthenium-mediated conversion of aryl alkynes to alkoxy(benzyl)carbene and benzyl carbonyl complexes

Metal vinylidenes are key intermediates in the activation of terminal alkynes. Previous studies concerning ruthenium η6-arene complexes showed how the elusive vinylidenes are often transformed into more stable alkoxy(alkyl)carbene complexes upon reaction with alcohols, highlighting their electrophilicity. We reinvestigated the reactivity of terminal alkynes and alcohols with ruthenium(II) η6-arene precursors and we found out new aspects of the formation and the reactivity of the alkoxy(carbene)complexes. First, the reactivity of ruthenium complexes bearing different η6-arene, phosphane, halide co-ligands on the activation process of a series of arylalkynes have been examined. Under optimized conditions, a series of alkoxy(benzyl)carbene complexes of general formula [RuCl{C(OR’)CH2(4-C5H4R)}(PR’’3)(η6-arene)]+ were obtained. Five compounds were isolated in 82–96 % yield and they were characterized by spectroscopic techniques and X-ray diffraction in three cases. Notably, these carbene complexes are the predominant reaction products even in presence of a large molar excess of water in the mixture for short reaction times.In fact, DFT calculations on a model system showed that the vinylidene intermediate, resulting from the Ru/alkyne interaction, is preferentially attacked by MeOH instead of water. The subsequent formation of carbonyl complexes was assessed in various conditions by IR and NMR and four unprecedented and comparatively rare benzyl carbonyl complexes of general formula [Ru{CH2(4-C6H4R)}(CO)(PPh3)(η6-arene)]+ are reported, including the crystal structure of one example. Next, an unprecedented reactivity study on selected alkoxy(benzyl)carbene complexes was carried out. Joint experimental and computational results indicate that these benzyl carbonyl complexes may actually arise from the reaction of the carbene complexes with water, a reactivity pathway that has never been considered in previous studies on the Ru-mediated hydrolytic cleavage of alkynes.

Terminal Cyclopropylsilyl Alcohols as Useful Key Units to Access 2,3,4,6-Tetrasubstituted Tetrahydropyran Scaffolds by Stereocontrolled Prins Cyclization.

In this study, the use of terminal cyclopropylsilyl alcohols in Prins cyclization is reported as a very efficient methodology for the preparation of polysubstituted tetrahydropyrans, in which three new stereogenic centers have been created in a single pot. The reaction is general for a wide variety of aldehydes (alkylic, vinylic, aromatic, or dialdehydes), different types of alcohols, and halogenation agents providing high yields and excellent diastereoselectivity 2,3,4,6-tetrasubstituted tetrahydropyranyl frameworks. Interestingly, diastereomeric alcohols provide the same tetrahydropyranyl derivatives, showing that the reaction mechanism proceeds through common intermediates.

SOCl2-Catalyzed Meyer-Schuster Rearrangement of 3°-Propargylic Alcohols: Synthesis of Densely Arene-Substituted Pyrazolines Bearing Quaternary Centers from α,β-Unsaturated Carbonyl Compounds and Arylhydrazines.

Meyer-Schuster rearrangement of 3°-propargyl alcohol to the corresponding α,β-unsaturated carbonyl compounds under SOCl2 catalysis has been reported. Terminal and internal propargyl alcohols efficiently participated in the reaction. Furthermore, we have demonstrated the synthetic utility of conjugated carbonyl compounds to access densely arene-substituted pyrazolines bearing quaternary centers by reacting with arylhydrazine hydrochloride. Isotopic labeling studies were carried out to gain insights into the reaction mechanism.

LiOtBu-Promoted trans-Stereoselective and β-Regioselective Hydroboration of Propargyl Alcohols.

A convenient and efficient trans-stereoselective and β-regioselective hydroboration of propargyl alcohols was achieved simply with LiOtBu as the base and (Bpin)2 as the boron reagent in dimethyl sulfoxide at room temperature. Both terminal and internal propargyl alcohols with diverse structures and functional groups underwent the transformation smoothly to produce β-Bpin-substituted (E)-allylic alcohols, of which the synthetic potentials were demonstrated by the downstream conversions of boronate, alkenyl, and hydroxyl groups.

Theoretical studies on the mechanisms and origins of substituent effects in CuBr-catalyzed three-component tandem reactions of terminal propargyl alcohols, aldehydes and amines

The CuBr-catalyzed A3-coupling-based tandem reactions of terminal propargyl alcohols, aldehydes and amines to synthesize five-membered dihydrofuran P1, disubstituted furan P2 and six-membered pyrone P3 have been developed. In this work, density functional theory (DFT) calculations have been performed to uncover the detailed reaction mechanisms and the substituent effects on the transformation of dihydrofuran P1 to pyrone P3. Computational results suggest that the catalytic cycle of dihydrofuran P1 is divided into three main processes: A3-coupling, isomerization and intramolecular cyclization. The generation of disubstituted furan P2 from dihydrofuran P1 proceeds via N-methylation and deprotonation steps. The transformation of five-membered dihydrofuran P1 to six-membered pyrone P3 is affected by the substituents R on substrate aldehyde 2. When R = OEt this transformation proceeds smoothly, undergoing the favorable OEt departure pathway. In contrast, the departure pathway is unworkable for Ph- and Me-substituted aldehydes due to the lack of hydrogen-bonding stabilization. They could only follow 1,2-R migration pathways. However, the high activation barriers in the migration pathways for the two aldehydes render the transformation infeasible. The results also reveal that silica gel acts as a significantly important hydrogen bond partner to stabilize the complexes in the transformation process. The theoretical research contributes to deeper insights into the mechanisms and the origins of substituent effects on the transformation between different heterocycles of the title reaction, which would promote the further development and design of the five- and six-membered oxygen-containing heterocycles.

Syn‐Selective Epoxidation of Chiral Terminal Allylic Alcohols with a Titanium Salalen Catalyst and Hydrogen Peroxide

In the Sharpless asymmetric epoxidation of chiral secondary allylic alcohols, one substrate enantiomer is predominantly converted to the anti‐epoxy alcohol. We herein report the first highly syn‐selective epoxidation of terminal allylic alcohols using a titanium salalen complex as catalyst, at room temperature, and aqueous hydrogen peroxide as oxidant. With enantiopure terminal allylic alcohols as substrates, the epoxy alcohols were obtained with up to 98 % yield and up to >99 : 1 dr (syn). Catalyst loadings as low as 1 mol % can be applied without eroding the syn‐diastereoselectivity. Modification of the allylic alcohol to an ether does not affect the diastereoselectivity either [>99 : 1 dr (syn)]. Inverting the catalyst configuration leads to the anti‐product, albeit at lower dr (ca. 20 : 1). The synthetic potential is demonstrated by a short, gram‐scale preparation of a tetrahydrofuran building block with three stereocenters, involving two titanium salalen catalyzed epoxidation steps.

Syn‐Selektive Epoxidierung von chiralen, terminalen Allylalkoholen mit einem Titan‐Salalen‐Katalysator und Wasserstoffperoxid

AbstractIn der asymmetrischen Sharpless‐Epoxidierung von chiralen, sekundären Allylalkoholen wird ein Substratenantiomer bevorzugt zum anti‐Epoxyalkohol umgesetzt. In dieser Arbeit stellen wir die erste hoch syn‐selektive Epoxidierung von terminalen Allylalkoholen vor. Mit einem Titan‐Salalen‐Katalysator und H2O2 als Oxidationsmittel werden enantiomerenreine, terminale Allylalkohole mit bis zu 98 % Ausbeute und >99 : 1 dr (syn) zu Epoxyalkoholen umgesetzt. Diese syn‐Selektivität bleibt auch bei niedrigeren Katalysatorbeladungen (bis zu 1 mol‐%) erhalten. Auch die Modifizierung der Allylalkoholfunktion zu einem Ether beeinflusst die Diastereoselektivität nicht [>99 : 1 dr (syn)]. Wird die Katalysatorkonfiguration invertiert, so wird bevorzugt das anti‐Produkt gebildet, allerdings mit niedrigerem dr (ca. 20 : 1). Das Anwendungspotential wird am Beispiel der Synthese eines THF‐Bausteins mit drei Stereozentren im Grammmaßstab demonstriert, in welcher zwei Ti‐Salalen‐katalysierte Epoxidierungen durchlaufen werden.

Synthesis and characterization of multinuclear ruthenium clusters assembled by terminal alkyne alcohols and ortho-carborane diselenolate ligands

Two novel half-sandwich trinuclear ruthenium complexes bridged by ortho-carborane-1,2-diselenolato ligands (p-cymene)Ru3(Se2C2B10H10)2(Se2C2B10H9)[HCCH(cyclo-C6H10)OCCH(cyclo-C6H10)] (2) and (p-cymene)Ru3(Se2C2B10H10)2(Se2C2B10H9)[HCCH(CH3)2COCCHC(CH3)2] (3) have been prepared by the reactions of ortho-carborane-1,2-diselenolate ligands and [(p-cymene)RuCl2]2 with CHC(cyclo-C6H10)(OH) and CHCC(OH)(CH3)2, respectively. The complexes have been fully characterized by 1H, 13C, and 11B NMR, mass and IR spectroscopy as well as by element analyzes. The molecular structures of two complexes have been determined by single-crystal X-ray diffraction analyzes.

The Synthesis of α-Keto Acetals from Terminal Alkynes and Alcohols via Synergistic Interaction of Organoselenium Catalysis and Electrochemical Oxidation.

Herein, an unprecedented electrochemical approach for the synthesis of α-keto acetals has been established from readily available terminal alkynes and alcohols. By merging the electrochemical and organoselenium-catalyzed processes, the desired products are obtained at room temperature in the absence of basic or metallic additives, with carbonyl and acetal motifs incorporated simultaneously across the triple bonds in a single operation.

Rare-Earth-Metal-Complex-Catalyzed Hydroalkoxylation and Tandem Hydroalkoxylation/Cyclohydroamination of Isocyanates: Synthesis of Carbamates and Oxazolidinones.

Novel N,N,N-tridentate β-diketiminato rare-earth-metal dialkyl complexes LRE(CH2SiMe3)2 [RE = Y (1a), Gd (1b), Yb (1c), Lu (1d); L = MeC(NDipp)CHC(Me)N(CH2)2NC4H8, where Dipp = 2,6-iPr2C6H3] have been conveniently synthesized by one step from reactions of the rare-earth-metal trialkyl complexes RE(CH2SiMe3)3(THF)2 (THF = tetrahydrofuran) with a pyrrolidine-functionalized β-diketiminate HL, and their catalytic behaviors toward hydroalkoxylation and tandem hydroalkoxylation/cyclohydroamination of isocyanates have been described. These rare-earth-metal catalysts exhibited high efficiency in the hydroalkoxylation of isocyanates, providing a variety of N-alkyl and N-aryl carbamate derivatives under mild reaction conditions with a rather low catalyst loading (0.04 mol %). More significantly, they can promote a tandem hydroalkoxylation/cyclohydroamination reaction between terminal and internal propargylic alcohols with substituted arylisocyanates, leading to the efficient synthesis of methylene and (Z)-selective arylidene oxazolidinones in good-to-high yields via consecutive C-O and C-N bond formation. The stoichiometric reaction of 1a with p-tolylisocyanate generated an unusual dinuclear yttrium complex, {[η2-(4-MePhNCO)(CH2SiMe3)]Y[μ-η2:η1:η1-(4-MePhNCO)CC(Me)(NDipp)C(Me)N(CH2)2NC4H8]}2 (7a), with two different amidate units, which underwent an sp2 C-H bond activation of the β-diketiminato backbone, followed by the insertion of isocyanate.

Synthesis of Secondary Monoalcohols from Terminal Vicinal Alcohols over Silica-Supported Rhenium-Modified Ruthenium Catalyst

The selective synthesis of secondary alcohols from 1,2-alkanediol by C–O hydrogenolysis, which has been less investigated than the synthesis of primary alcohols, was investigated with Ru-based catalysts and 1,2-propanediol (1,2-PrD) as a model substrate. The modification of Ru/SiO2 with ReOx achieved significant improvement of activity. The hydrogenolysis of 1,2-PrD over Ru–ReOx/SiO2 (Re/Ru = 0.5) initially formed both 2-propanol (2-PrOH) and 1-propanol (1-PrOH) with similar selectivity along with the formation of ≤ C2 compounds, and then 1-PrOH was preferably converted to propane; as a result, only 2-PrOH remained in the liquid phase with 23% yield at longer reaction time. This catalyst was reusable at least twice. The characterization with H2-TPR, XRD, TEM-EDX, XANES, and EXAFS showed that the Ru species in the Ru–ReOx/SiO2 catalysts were completely reduced in the reaction conditions, while a part of Re species were also reduced to partially reduced monomeric species (Reδ+Ox) without Re–Re direct bond located on the surface of Ru metal particles. This ReOx-modified Ru metal surface probably works as the active sites. The excess Re species was reduced to large Re metal particles; however, these Re metal particles are not involved in the catalysis.

Cu nanoparticles-dispersed Mg-Al layered double hydroxides as efficient catalysts for CO2 conversion with propargyl alcohols

Upgrading carbon dioxide (CO2) into valuable products is a highly promising strategy of artificial carbon cycle. In this study, a series of in situ reduced CuMgAl layered double hydroxides (R-CuMgAl-LDHs) composites were synthesized, in which Cu nanoparticles were effectively dispersed and anchored on MgAl-LDHs with formation of Cu+ and Cu0 species. The optimized R-Cu1.5Mg1.5Al1-LDH exhibited excellent catalytic performance for the carboxylative cyclization of 2-methyl-3-butyn-2-ol with CO2 (turnover number of 243) under mild conditions. The layered structure of LDH stabilized the active Cu species with high dispersion, enhancing the catalytic efficiency of this carboxylative cyclization reaction. Simultaneously, the dual-activation of both CO2 and propargylic alcohol by Cu0/Cu+ species generated on the surface of LDH contributed significantly to the catalytic efficiency enhancement. Furthermore, R-Cu1.5Mg1.5Al1-LDH catalyzed the reaction of a wide range of terminal or internal propargyl alcohols with CO2, yielding various functionalized α-alkylene cyclic carbonates. Finally, a reasonable reaction mechanism was put forward according to the comprehensive analysis.

Unlocking the Friedel-Crafts arylation of primary aliphatic alcohols and epoxides driven by hexafluoroisopropanol

Unlocking the Friedel-Crafts arylation of primary aliphatic alcohols and epoxides driven by hexafluoroisopropanol

Radical Silyl‐ and Germylzincation of Propargylic Alcohols

AbstractThe silyl‐ and germylzincation of terminal or internal propargylic alcohols by reaction with (Me3Si)3SiH/Et2Zn, [(Me3Si)3Si]2Zn/Et2Zn or Ph3GeH/Et2Zn is examined. These reactions proceed through the addition of silicon‐ or germanium‐centered radicals across the carbon≡carbon triple bond followed by the trapping by diethylzinc of the produced vinyl radical through homolytic substitution at the zinc atom. The influence of the hydroxy unit on the regio‐ and stereoselectivity of these reactions is discussed and compared to its role played in radical hydrosilylation and hydrogermylation reactions. Protocols developed to achieve the β‐regioselective silylzincation of propargyl alcohol and the α‐regioselective germylzincation of internal propargylic alcohols are particularly important, as they occur with trans stereoselectivity. For both procedures the C(sp2)−Zn bond remains available for subsequent in‐situ electrophilic substitution leading overall to net alkyne trans difunctionalization.

Structural Evolution of MOF-Derived RuCo, A General Catalyst for the Guerbet Reaction.

Guerbet alcohols, a class of β-branched terminal alcohols, find widespread application because of their low melting points and excellent fluidity. Because of the limitations in the activity and selectivity of existing Guerbet catalysts, Guerbet alcohols are not currently produced via the Guerbet reaction but via hydroformylation of oil-derived alkenes followed by aldol condensation. In pursuit of a one-step synthesis of Guerbet alcohols from simple linear alcohol precursors, we show that MOF-derived RuCo alloys achieve over a million turnovers in the Guerbet reaction of 1-propanol, 1-butanol, and 1-pentanol. The active catalyst is formed in situ from ruthenium-impregnated metal-organic framework MFU-1. XPS and XAS studies indicate that the precatalyst is composed of Ru precursor trapped inside the MOF pores with no change in the oxidation state or coordination environment of Ru upon MOF incorporation. The significantly higher reactivity of Ru-impregnated MOF versus a physical mixture of Ru precursor and MOF suggests that the MOF plays an important role in templating the formation of the active catalyst and/or its stabilization. XPS reveals partial reduction of both ruthenium and MOF-derived cobalt under the Guerbet reaction conditions, and TEM/EDX imaging shows that Ru is decorated on the edges of dense nanoparticles, as well as thin nanoplates of CoOx. The use of ethanol rather than higher alcohols as a substrate results in lower turnover frequencies, and RuCo recovered from ethanol upgrading lacks nanostructures with plate-like morphology and does not exhibit Ru-enrichment on the surface and edge sites. Notably, 1H and 31P NMR studies show that through use of K3PO4 as a base promoter in the RuCo-catalyzed alcohol upgrading, the formation of carboxylate salts, a common side product in the Guerbet reaction, was effectively eliminated.

Synthesis of α-Alkylated Ketones via Selective Epoxide Opening/Alkylation Reactions with Primary Alcohols.

A new method for converting terminal epoxides and primary alcohols into α-alkylated ketones under borrowing hydrogen conditions is reported. The procedure involves a one-pot epoxide ring opening and alkylation via primary alcohols in the presence of an N-heterocyclic carbene iridium(I) catalyst, under aerobic conditions, with water as the side product.

Trans(Cl)-2,2′-bipyridinedicarbonyldichlororuthenium(II) complex catalyzed oxidation of olefins, aryl hydrocarbons and alcohols in homogeneous phase

Catalytic oxidation of organic substrates has wide applications in chemical industries due to which huge extensive research work is continuously going on throughout the world. Present study reports efficacious use of Trans (Cl)-2,2′-bipyridinedicarbonyldichlororuthenium(II) complex catalyzed oxidation of internal and terminal olefins, aryl hydrocarbons and alcohols. CH2Cl2–C2H5OH (6:4) was suitable solvent system for these oxidation reactions. The normal pressure oxidation reaction has been carried out at 1 ​atm. Pressure of oxygen and at 300C. The high pressure oxidation reaction was done at 4.48 ​× ​103 KNm3 pressure of oxygen and at 600C. No diminished catalytic activity was observed while checking the recyclability of catalyst up to 6–8 catalytic runs. Catalytic activity was also investigated using tert-butyl hydroperoxide as oxidant inspite of di-oxygen. Effect of different parameters on the rate of oxidation was also studied i.e. extra ligand, temperature, solvents, acids and bases. Kinetic studies have been done and on the basis of kinetics, the mechanism is proposed.

A bifunctional ligand enables efficient gold-catalyzed hydroarylation of terminal unactivated propargylic alcohols with heteroareneboronic acids

Abstract Terminal allylic alcohols are important motifs in natural products, and also key intermediates/precursors in numerous novel reaction transformations. In this study, enabled by a bifunctional ligand featuring a basic amino group, a gold-catalyzed hydroarylation of terminal unactivated propargylic alcohols with heteroareneboronic acids has been first established, and efficiently affords various terminal aryl-substituted allylic alcohols with moderate to high yields under mild conditions.

Catalytic Selective Oxidation of Primary and Secondary Alcohols Using Nonheme [Iron(III)(Pyridine‐Containing Ligand)] Complexes

The selective oxidation of different primary and secondary alcohols to carbonyl compounds by hydrogen peroxide was found to be catalyzed in conversion ranging from good to excellent by an iron(III) complex of a pyridine‐containing macrocyclic ligand (Pc‐L), without the need of any additive. The choice of the counteranion (Cl, Br, OTf) appeared to be of fundamental importance and the best results in terms of selectivity (up to 99 %) and conversion (up to 98 %) were obtained using the well‐characterized [Fe(III)(Br)2(Pc‐L)]Br complex, 4c. Magnetic moments in solid‐state, also confirmed in solution ([D6]DMSO) by Evans NMR method, were calculated and point out to an iron metal center in the high spin state of 5/2. The crystal structure shows that the iron(III) center is coordinated by the four nitrogen atoms of the macrocycle and two bromide anions to form a distorted octahedral coordination environment. The catalytic oxidation of benzyl alcohol in acetonitrile was found occurring with better conversions and selectivities than in other solvents. The reaction proved to be quite general, tolerating aromatic and aliphatic alcohols, although very low yields were obtained for terminal aliphatic alcohols. Preliminary mechanistic studies are in agreement with a catalytic cycle promoted by a high‐spin iron complex.