Propargylation Of Aldehydes Research Articles

Copper-Catalyzed Umpolung Reactivity of Propargylic Carbonates in the Presence of Diboronates: One Stone Four Birds.

Allylation and propargylation are two powerful synthetic strategies for making new substances that have been of significant importance in chemistry, medicine, and material fields. Conventional tactics employ various preformed allylation and propargylation reagents. In this study, a conceptually novel copper-catalyzed and B2pin2-mediated Umpolung reactivity of propargylic carbonates has been achieved for the first time, realizing both allylation and propargylation of aldehydes and ketones without additional reductants. Three types of allylation products and one type of propargylation product are generated efficiently, and all allylation products are formed with syn-configurations predominantly. The choice of ligands plays a vital role in modulating the Umpolung modes. The synthetic applications have been demonstrated in a myriad of further transformations including natural product synthesis, and systematic mechanistic studies have been conducted to reveal detailed insights into the Umpolung processes.

Combining Polymerization and Templating toward Hyper-Cross-Linked Poly(propargyl aldehyde)s and Poly(propargyl alcohol)s for Reversible H2O and CO2 Capture and Construction of Porous Chiral Networks.

Two series of hyper-cross-linked microporous polyacetylene networks containing either -[CH=C(CH=O)]- or -[CH=C(CH2OH)]- monomeric units are reported. Networks are prepared by chain-growth copolymerization of acetal-protected propargyl aldehyde and acetal-protected propargyl alcohol with a 1,3,5-triethynylbenzene cross-linker followed by hydrolytic deprotection/detemplating. Deprotection not only liberates reactive CH=O and CH2OH groups in the networks but also modifies the texture of the networks towards higher microporosity and higher specific surface area. The final networks with CH=O and CH2OH groups attached directly to the polyene main chains of the networks have a specific surface area from 400 to 800 m2/g and contain functional groups in a high amount, up to 9.6 mmol/g. The CH=O and CH2OH groups in the networks serve as active centres for the reversible capture of CO2 and water vapour. The water vapour capture capacities of the networks (up to 445 mg/g at 297 K) are among the highest values reported for porous polymers, making these materials promising for cyclic water harvesting from the air. Covalent modification of the networks with (R)-(+)-3-aminopyrrolidine and (S)-(+)-2-methylbutyric acid enables the preparation of porous chiral networks and shows networks with CH=O and CH2OH groups as reactive supports suitable for the anchoring of various functional molecules.

Stereoselective Gold(I)-Catalyzed Vinylcyclopropanation via Generation of a Sulfur-Substituted Vinyl Carbene Equivalent.

A stereoselective gold(I)-catalyzed vinylcyclopropanation of alkenes has been developed. A gold-coordinated cationic vinyl carbene species, readily generated via a rearrangement of the ethylenedithioacetal of propargyl aldehyde, reacts with a wide range of alkenes to afford thio-substituted vinylcyclopropanes. The gold-catalyzed vinyl cyclopropanation proceeds under mild conditions at room temperature and is generally selective for the formation of cis-substituted cyclopropanes. The reaction allows the formal introduction of a "naked" vinyl carbene, by subsequent chemoselective hydrodesulfurisation of the ethylenedithio-bridge. The synthetic utility of the new method is demonstrated by a short, racemic formal synthesis of the alkaloid cephalotaxin, hinging on a key vinyl cyclopropane-cyclopentene rearrangement.

Stereoselective Gold(I)‐Catalyzed Vinylcyclopropanation via Generation of a Sulfur‐Substituted Vinyl Carbene Equivalent

AbstractA stereoselective gold(I)‐catalyzed vinylcyclopropanation of alkenes has been developed. A gold‐coordinated cationic vinyl carbene species, readily generated via a rearrangement of the ethylenedithioacetal of propargyl aldehyde, reacts with a wide range of alkenes to afford thio‐substituted vinylcyclopropanes. The gold‐catalyzed vinyl cyclopropanation proceeds under mild conditions at room temperature and is generally selective for the formation of cis‐substituted cyclopropanes. The reaction allows the formal introduction of a “naked” vinyl carbene, by subsequent chemoselective hydrodesulfurisation of the ethylenedithio‐bridge. The synthetic utility of the new method is demonstrated by a short, racemic formal synthesis of the alkaloid cephalotaxin, hinging on a key vinyl cyclopropane‐cyclopentene rearrangement.

Organocatalytic Reductive Propargylation: Scope and Applications

An amino acid-catalyzed three-component reductive coupling protocol has been developed for the selective high-yielding synthesis of nearly fifty examples of propargylated cyclic/acyclic systems from the various propargyl aldehydes, cyclic/acyclic CH acids, and Hantzsch ester under ambient conditions. It is an economical, efficient, catalytic, metal-free protocol for the quick gram-scale synthesis of propargylated cyclic/acyclic compounds, and many of these coupling compounds were purified by a simple precipitation-filtration technique instead of column chromatography. Functionally rich propargylated cyclic-1,3-diketones were specifically transformed into dihydropyrans found in natural products and drugs through an annulative etherification reaction by using Lewis-acid (AgOTf) catalysis. Further, we developed the C-methylation reactions on propargylated cyclic-1,3-diketones, which are prolific synthons in natural products and medicinal chemistry.

Stereoselective Oxa‐Michael Addition of Tyrosine to Propargyl Aldehyde/Esters: Formation of Benzofurans and Flavones

AbstractThe steroselective oxa‐Michael addition of the phenol moiety present in tyrosine and 3‐iodotyrosine to different propargyl aldehydes delivered products with predominantly Z stereochemistry, as evidenced by X‐ray crystallography analysis. When ethyl propiolate was used as the propargyl ester source, the products were achieved with exclusively E stereochemistry with yields ranging from 17% to 91%. The oxa‐Michael addition compounds served as substrates in the synthesis of 5‐ and 6‐membered heterocyclic compounds. The atmosphere applied to the reaction medium directly influenced the formation of the products. When an inert atmosphere of nitrogen was applied, a 2‐aryl‐3‐formyl‐5‐alanylbenzofuran core was selectively obtained via a Heck intramolecular reaction, while the reactions carried out under a carbon monoxide atmosphere led exclusively to 6‐alanyl‐2‐arylflavone derivatives via reductive intramolecular acylation.magnified image

Synthesis and characterization of nano−zinc wire using a self designed unit galvanic cell in aqueous medium and its reactivity in propargylation of aldehydes

Electrochemistry is used for propargylation of carbonyls in aqueous ZnCl2 medium. For electrochemical process we designed a unit galvanic cell. ZnCl2 is used as stoichiometric reagent and causes electrochemical deposition of zinc in cathode. Wire shaped nano zinc architecture has been formed in cathode during electrochemical process which is the active reagent. Homopropergylic alcohols are synthesized in good yields. After the organic reaction is over aqueous solution containing zinc salts can be reused up to 5th cycle without significant loss of reactivity.

Active bismuth mediated allylation of carbonyls/N-tosyl aldimines and propargylation of aldehydes in water

Active bismuth is synthesized by the chemical reduction of bismuth trichloride using freshly prepared sodium stannite solution as the reducing agent at room temperature. The as-synthesized active bismuth is applied as a reagent for the synthesis of homoallyl alcohol/homopropargyl alcohol from allyl bromide/propargyl bromide and carbonyl compounds in water at $$50\,{^{\circ }}\hbox {C}$$ . The homoallyl amines are also synthesized from N-tosyl aldimines and allyl bromide using active bismuth reagent in good yields. No assistance of organic co-solvent, co-reagent, phase transfer catalyst or inert atmosphere is required for this reaction. The waste bismuth material obtained after the completion of the organic reaction can be reduced to active bismuth by sodium stannite solution and successfully reused for mediating the allylation of aldehydes. Synopsis Active bismuth mediated allylation/crotylation of aldehydes is developed in water to get homoallyl alcohols. The method is also applied for the allylation of N-tosyl aldimines and propargylation of aldehydes in water to achieve the homoallyl amines and homopropargyl alcohols, respectively. The reactions do not require the assistance of organic co-solvent, co-reagent, phase transfer catalyst or inert atmosphere.

On the interaction of propynal with HNO, HF, HCl, H2O, CH3OH, and NH3: Red- and blue-shifting hydrogen bonds and tetrel bonds

The potential energy surfaces of the complexes of propynal, (propiolaldehyde, propargyl aldehyde, HCCCOH), with a series of small molecules (HNO, HF, HCl, H2O, CH3OH, and NH3) have been investigated theoretically at the MP2 and CCSD(T) levels using several extended basis sets. Thirty low-lying minima have been detected, eight for HCCCOH-HNO, four for each of the dimers HCCCOH-HF, HCCCOH-HCl, and HCCCOH-H2O, seven for the HCCCOH-CH3OH complex, and three for HCCCOH-NH3. The most stable HCCCOH-HNO complex has a non-planar, orthogonal structure with a tetrel bond and a hydrogen bond. In most cases the calculated intramolecular bond length changes as induced by complex formation are allegeable on the basis of the intramolecular harmonic force fields of propynal and the partner molecules. The vibrational frequency shifts, typical for formyl groups engaged in hydrogen bonding, red shifts of CO stretches and blue shifts of CH stretches, occur in most of the dimers, whereas the acetylenic CH and CC stretches are red-shifted when this CH bond is involved in hydrogen bonding. In almost all HCCCOH-HNO complexes, the NH stretching frequency is also blue-shifted. However, in case of the most stable HCCCOH-HNO complex a red-shift of the harmonic NH stretch is calculated. Inclusion of anharmonic contributions reduces this red shift substantially and even converts it to a blue shift. Conventional red shifts of X-H (X = F, Cl, O) stretching frequencies and blue shifts for formyl CH stretches are calculated for most of the complexes with HF, HCl, H2O, CH3OH, and NH3.

Synthesis, characterization of active Sn(0), and its application in selective propargylation of aldehyde at room temperature in water

Active Sn(0) particles are synthesized in high yields by the chemical reduction of the blue–black stannous oxide using freshly prepared sodium stannite solution as reducing agent at 40 °C and 60 °C. The Sn(0) particles are characterized using powder XRD, SEM, and DSC. The as-synthesized Sn(0) particles are applied as reagent for the regioselective synthesis of homopropargyl alcohols from propargyl bromide and aldehydes in distilled water at room temperature (in 50%–84% yields). No assistance of heat, microwave, ultrasound, organic co-solvent, co-reagent, or inert atmosphere is required for this reaction. The propargylation reaction is highly chemoselective towards aldehyde over other less electrophilic carbonyl functional groups such as ketone, amide, and carboxylic acid. Our in-house synthesized homopropargyl alcohols can be used to synthesize conjugated 1,3-diynes.

Chiral Supramolecular U-Shaped Catalysts Induce the Multiselective Diels-Alder Reaction of Propargyl Aldehyde.

The Diels-Alder reaction, which is a traditional [4 + 2] cycloaddition with two carbon-carbon bond formations, is one of the most powerful tools to synthesize versatile and unique six-membered rings. We show that chiral supramolecular U-shaped boron Lewis acid catalysts promote the unprecedented multiselective Diels-Alder reaction of propargyl aldehyde with cyclic dienes. Independent from the substrate control, enantio-, endo/exo-, π-facial-, regio-, site-, and substrate-selectivities could be controlled by the present U-shaped catalysts. The obtained reaction products could access the concise synthesis of chiral diene ligands and a key intermediate of (+)-sarkomycin. The results presented here might partially contribute to the development of artificial enzyme-like supramolecular catalysts for multiselective reactions, which will be able to target organic compounds that have thus far eluded synthesis.

Synthesis and Some Transformations of Cyclic Acetals of Propargyl Aldehyde

Dehydrobromination of 2-(1,2-dibromoethyl)-1,3-dioxocyclanes with sodium amide in liquid ammonia provided cyclic acetals of propargyl aldehyde. Reactions of the resulting compounds with nitrile oxides and diazomethane afforded the corresponding isoxazole and pyrazole derivatives.

Dramatic Enantioselectivity Reversal in the Propargylation of Aldehyde with Alkynyllithium Catalyzed by Dilithium Binaphtholate Derivatives

Dramatic Enantioselectivity Reversal in the Propargylation of Aldehyde with Alkynyllithium Catalyzed by Dilithium Binaphtholate Derivatives

NMR and experimental reinvestigation of the condensation reaction between γ-methylene-α,β-unsaturated aldehydes and propargyl aldehydes.

The condensation reaction between a γ-methylene-α,β-unsaturated aldehyde and phenylpropargyl aldehyde was revisited and, guided by extensive DFT calculations of NMR shifts, was found to afford a deconjugative aldol condensation product. In this manner, a simple protocol for the preparation of valuable cross-conjugated oxatrienes was uncovered.

ChemInform Abstract: Copper‐Catalyzed A3‐Coupling: Synthesis of 3‐Amino‐1,4‐diynes.

Cu-catalyzed A3 (amine, aldehyde, and alkyne) coupling reactions were investigated for the synthesis of 3-amino-1,4-diynes. Although metal-catalyzed A3-coupling reactions have been extensively used to synthesize various propargylamines, the A3-coupling for the synthesis of 3-amino-1,4-diynes has been rarely reported. In this study, various symmetrical 3-amino-1,4-diynes were synthesized by the sequential Cu-catalyzed dealkynylation of propargyl aldehydes followed by A3-coupling. Unsymmetrical 3-amino-1,4-diynes were also synthesized in 49–85 % yields by Cu-catalyzed A3-coupling.

Copper‐Catalyzed A3‐Coupling: Synthesis of 3‐Amino‐1,4‐diynes

Cu‐catalyzed A3 (amine, aldehyde, and alkyne) coupling reactions were investigated for the synthesis of 3‐amino‐1,4‐diynes. Although metal‐catalyzed A3‐coupling reactions have been extensively used to synthesize various propargylamines, the A3‐coupling for the synthesis of 3‐amino‐1,4‐diynes has been rarely reported. In this study, various symmetrical 3‐amino‐1,4‐diynes were synthesized by the sequential Cu‐catalyzed dealkynylation of propargyl aldehydes followed by A3‐coupling. Unsymmetrical 3‐amino‐1,4‐diynes were also synthesized in 49–85 % yields by Cu‐catalyzed A3‐coupling.

ChemInform Abstract: Regioselective Propargylation of Aldehydes Using Potassium Allenyltrifluoroborate Promoted by Tonsil.

Abstract The propargylation of aldehydes using potassium allenyltrifluoroborate promoted by tonsil, an inexpensive and readily available clay, in a chemo- and regioselective way is described. The method is simple and avoids the use of air and moisture sensitive organometallics and products were obtained in good to moderate yields.

ChemInform Abstract: Tunable and Diastereoselective Broensted Acid Catalyzed Synthesis of β‐Enaminones.

AbstractDepending on the Broensted acid, the electronic effect of the propargyl aldehyde substrate and the steric effect of the amine substrate used the β‐enaminone products may be obtained as single (E)‐ or (Z)‐isomers.

Tunable and Diastereoselective Brønsted Acid Catalyzed Synthesis of β-Enaminones.

The Brønsted acid catalyzed Meyer-Schuster reaction of hemiaminals was studied for the stereoselective synthesis of β-enaminones. Hemiaminals were formed from propargyl aldehydes (or the oxidation of propargyl alcohols) and amines in the presence of Brønsted acids. A critical step to control the stereochemistry of the products is the protonation of the corresponding allenol intermediate, which is dictated by the Brønsted acid used, the steric effect of the amine, and the electronic effect of the propargyl aldehyde.

Stereoselective Iterative Convergent Synthesis of Z-Oligodiacetylenes from Propargylic Dithioacetals.

A series of (t)Bu-substituted Z-oligodiacetylenes (Z-ODAs) are synthesized from the reactions of allenyl/propargylic zinc reagents, obtained from the corresponding propargylic dithiolanes and BuLi, with dithiolane-substituted propargylic aldehydes followed by stereospecific elimination of β-thioalkoxy alcohols under Mitsunobu conditions. The stereochemical assignments are based on NOE experiments. The X-ray structure of the hexamer further supports the Z configuration for each of the double bonds in these ODAs. The photophysical properties of these Z-ODAs have been examined and are compared with known related E- and Z-ODAs with different substituents.