Propargylic Reactions Research Articles

Taming Brønsted Acid Reactivity: Nucleophilic Substitutions of Propargylic Alcohols with N-Nucleophiles Mediated by Phosphorus-Based Brønsted Acid Catalysts.

The activity of diethyl phosphite and diphenyl phosphate in propargylation reactions with N-nucleophiles of varying basicity is presented. A careful choice of the reaction conditions minimized undesired rearrangements and arylation processes, typical side reactions with Brønsted acid catalysis. These systems are compatible with technical solvents and presence of air, and they are also applicable to C-, O-, and S-nucleophiles.

Propargylsilanes as Reagents for Synergistic Gold(I)‐Catalyzed Propargylation of Carbonyl Compounds: Isolation and Characterization of σ‐Gold(I) Allenyl Intermediates

AbstractReported herein is the isolation and characterization, for the first time, of a σ‐gold allenyl complex as an intermediate in gold catalysis. This intermediate was captured during the study of a novel gold(I)‐catalyzed propargylation of carbonyl compounds with propargylsilanes. Notably, the gold‐catalyzed propargylation reaction, which proceeds with aldehydes and ketones, can be driven to the formation of either homopropargyl silyl ethers or the in situ synthesis of corresponding 2‐silyl‐4,5‐dihydrofurans.

Propargylsilanes as Reagents for Synergistic Gold(I)-Catalyzed Propargylation of Carbonyl Compounds: Isolation and Characterization of σ-Gold(I) Allenyl Intermediates.

Reported herein is the isolation and characterization, for the first time, of a σ-gold allenyl complex as an intermediate in gold catalysis. This intermediate was captured during the study of a novel gold(I)-catalyzed propargylation of carbonyl compounds with propargylsilanes. Notably, the gold-catalyzed propargylation reaction, which proceeds with aldehydes and ketones, can be driven to the formation of either homopropargyl silyl ethers or the in situ synthesis of corresponding 2-silyl-4,5-dihydrofurans.

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.

Trialkylborane-Mediated Multicomponent Reaction for the Diastereoselective Synthesis of Anti-δ,δ-Disubstituted Homoallylic Alcohols.

The trialkylborane/O2-mediated reaction of propargyl acetates having a tributylstannyl group at an alkyne terminus with aldehydes in a THF-H2O solvent system gave anti-δ,δ-disubstituted homoallylic alcohols with good to high diastereoselectivity. Intriguingly, two alkyl groups derived from trialkylborane were embedded into the reaction product. The trialkylborane plays a key role not only as a radical initiator but also as a source of alkyl radicals.

CpTiCl2, an Improved Titanocene(III) Catalyst in Organic Synthesis

Preparation, EPR analysis, and advantages in green organic chemistry of CpTiCl2, an improved single‐electron transfer catalyst, are reported. Under mild conditions, this organometallic complex provides excellent yields of homoallylic and homopropargylic alcohols in Barbier‐type allylation and propargylation reactions. Moreover, in the presence of a bidentate BOX ligand, Barbier‐type cyclization reactions catalyzed by CpTiCl2 can be carried out in an enantioselective manner.

Sulfinate‐Organocatalyzed (3+2) Annulation Reaction of Propargyl or Allenyl Sulfones with Activated Imines

An operationally simple methodology for the synthesis of 4‐sulfonyl‐3‐pyrrolines is described using a propargylic sulfone and N‐sulfonyl imines as substrates. This annulation process is initiated by an arenesulfinate organocatalyst, which allows a smooth isomerization of the alkynyl precursor into the corresponding allene, followed by the generation of a highly reactive allyl sulfone anion. An asymmetric version involving an unprecedented enantiopure sulfinate–ammonium cooperative ion pair (PhSO2– R4N+*) was investigated. A proof‐of‐concept, with enantiomeric excesses of up to 41 %, was obtained according to a preliminary screening of commercially available chiral phase‐transfer catalysts.

Solvent incorporated sequential [3 + 2] annulation/substitution reaction of azomethine imines and propargyl sulfur ylide.

A novel solvent incorporated sequential [3 + 2] cycloaddition/substitution reaction of azomethine imines with propargyl sulfur ylide was developed. In the actual three-component reaction, propargyl sulfur ylide acts as a dipole reagent to furnish the annulation with azomethine imines, followed by the protic solvents acting as nucleophiles. The simple, mild, catalyst-free and practical protocol allows for the formation of N,N-bicyclic pyrazolidinones in moderate to excellent yields. Further transformation and gram-scale operations could also be achieved efficiently.

Synthesis of multi-substituted allenes from organoalane reagents and propargyl esters by using a nickel catalyst.

A highly efficient and simple route for the synthesis of multi-substituted allenes has been developed by a nickel catalyzed SN2' substitution reaction of propargyl esters with organic aluminium reagents under mild conditions, which gave the corresponding multi-substituted allenes in good to excellent yields (up to 92%) and high selectivities (up to 99%) at 60 °C for 6 h in THF. Aryls bearing electron-donating or electron-withdrawing groups in propargyl esters gave products in good yields. In addition, the multi-substituted allenes bearing a thienyl or a pyridyl group were obtained in 95-97% selectivities with isolated yields of 72-83%. Furthermore, the SN2' substitution reaction worked efficiently with propargyl carbonate compounds as well. On the basis of the experimental results, a possible catalytic cycle has been proposed.

Highly Efficient Synthesis of Multi-Substituted Allenes from Propargyl­ Acetates and Organoaluminum Reagents Mediated by Palladium

A simple and mild catalytic SN2′ substitution reaction of propargyl acetates with organoaluminum reagents is reported. The SN2′ substitution reaction of propargyl acetates with organoaluminum reagents mediated by Pd(PhP3)2Cl2 (1 mol%)/PPh3 (2 mol%)/K2CO3 in tetrahydrofuran at 60 °C for 3–4 hours afforded the corresponding multi-substituted allenes in good yields (up to 94%) with high selectivities (up to 99%). The process was simple and easily performed, which offers an efficient method to synthesize the multi-substituted allene derivatives.

Allenylation and Propargylation Reactions of Ketones, Aldehydes, Imines, and Iminium Ions Using Organoboronates and Related Derivatives

Allenyl- and propargylboronates have emerged as versatile reagents to effect regioselective propargylation or allenylation reactions of aldehydes, ketones, imines, and iminium ions. These boron-­derived reagents have the ability to undergo transmetalation reactions with other metals (Ag, Cu, In, and Zn), often using only catalytic amounts of these metals, leading to more facile and highly regioselective reactions. Enantioselective organocatalyzed reactions have also been developed using, chiral diols, aminophenols, and phosphoric ­acids. This short review highlights recent developments in this area. 1 Introduction 2 Synthesis of Homopropargylic and α-Allenyl Alcohols 2.1 Direct Synthesis of Racemic Homopropargylic and α-Allenyl ­Alcohols 2.2 Metal-Catalyzed Synthesis of Racemic Homopropargylic and α-Allenyl Alcohols 2.3 Enantioselective Synthesis of Homopropargylic Alcohols Using Chiral Allenylboronates 2.4 Enantioselective Synthesis of Homopropargylic Alcohols and α-Allenyl Alcohols Using Chiral Organocatalysts 2.5 Metal-Catalyzed Enantioselective Synthesis of Homopropargylic and α-Allenyl Alcohols 3 Synthesis of Homopropargylic and α-Allenyl Amines 3.1 Direct Synthesis of Homopropargylic Amines from Imines and Iminium Ions 3.2 Metal-Catalyzed Synthesis of Racemic Homopropargylic and α-Allenyl Amines 3.3 Enantioselective Synthesis of α-Allenyl Amines Using Catalytic Amounts of a Chiral Aminophenol 3.4 Metal-Catalyzed Diastereoselective Synthesis of Chiral Homopropargylic and α-Allenyl Amines from Chiral N-tert-Butylsulfinylimines 3.5 Metal-Catalyzed Enantioselective Synthesis of Chiral Homopropargylic and α-Allenyl Amines 4 Applications to Synthesis 5 Conclusions

Synthesis of Multisubstituted Allenes, Furans, and Pyrroles via Tandem Palladium-Catalyzed Substitution and Cycloisomerization.

A palladium-catalyzed propargyl substitution reaction of propargyl acetates with indium organothiolates is developed for the synthesis of multisubstituted allenyl sulfides. This procedure can be applied to the synthesis of multisubstituted furans and pyrroles via tandem palladium-catalyzed propargyl substitution and cycloisomerization reaction in one pot.

Synthesis of Multisubstituted Allenes via Palladium-Catalyzed Cross-Coupling Reaction of Propargyl Acetates with an Organoaluminum Reagent

We describe a convenient method for the synthesis of multisubstituted allenes from cross-coupling of propargyl acetates with ­organoaluminum reagent: The reaction of propargyl acetates with 1.2 equivalents of organoaluminum reagent mediated by Pd(PPh₃)₂Cl₂ (1 mol%)/Ph₃P (2 mol%) and K₂CO₃ in THF may produce tri- or tetrasubstituted allenes in good to excellent yields (83–94%) and high regio­selectivities (up to 99%) at 60 °C in 3–4 hours.

ChemInform Abstract: A Simple and Efficient Intramolecular 1,3‐Dipolar Azidoalkyne Cycloaddition: Synthesis of 6‐Perfluoroalkylated Fused exo‐Bicyclic 1,2,3‐Triazolo‐1,4‐oxazines.

Abstract The synthesis of new 6-perfluoroalkylated 1,2,3-triazolo-1,4-oxazine ethers and thioethers as fused exo -heterobicyclic compounds was achieved from terminal perfluoroalkyl oxiranes by azide ion ring opening and propargylation reactions followed by a quick and spontaneous 1,3-dipolar intramolecular cycloaddition reaction.

A simple and efficient intramolecular 1,3-dipolar azidoalkyne cycloaddition: Synthesis of 6-perfluoroalkylated fused exo -bicyclic 1,2,3-triazolo-1,4-oxazines

Abstract The synthesis of new 6-perfluoroalkylated 1,2,3-triazolo-1,4-oxazine ethers and thioethers as fused exo -heterobicyclic compounds was achieved from terminal perfluoroalkyl oxiranes by azide ion ring opening and propargylation reactions followed by a quick and spontaneous 1,3-dipolar intramolecular cycloaddition reaction.

ChemInform Abstract: HBF4‐Catalyzed Nucleophilic Substitutions of Propargylic Alcohols.

AbstractThe catalytic activity of aqueous HBF4 in propargylation reactions is presented.

3′-O- and 5′-O-Propargyl Derivatives of 5-Fluoro-2′-Deoxyuridine: Synthesis, Cytotoxic Evaluation and Conformational Analysis

ABSTRACTA series of new 3′-O- and 5′-O-propargyl derivatives of 5-fluoro-2′-deoxyuridine (1–4) was synthesized by means of propargyl reaction of properly blocked nucleosides (2,4), followed by the deprotection reaction with ammonium fluoride. The synthesized propargylated 5-fluoro-2′-deoxyuridine analogues (1–4) were evaluated for their cytotoxic activity in three human cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7), using the sulforhodamine B (SRB) assay. The highest activity and the best SI coefficient in all of the investigated cancer cells were displayed by 3′-O-propargyl-5-fluoro-2′-deoxyuridine (1), and its activity was higher than that of the parent nucleoside. The other new compounds exhibited moderate activity in all of the used cell lines.

Convenient synthesis of allenylphosphoryl compounds via Cu-catalysed couplings of P(O)H compounds with propargyl acetates.

A novel Cu-catalysed substitution reaction of propargyl acetates with P(O)H compounds is developed to afford allenylphosphoryl compounds via C-P bond coupling in high yields under mild conditions. A plausible mechanism involving the nucleophilic interception of the Cu-allenylidene intermediates is proposed.

HBF4-Catalysed Nucleophilic Substitutions of Propargylic Alcohols.

The activity of HBF4 (aqueous solution) as a catalyst in propargylation reactions is presented. Diverse types of nucleophiles were employed in order to form new C–O, C–N and C–C bonds in technical acetone and in air. Good to excellent yields and good chemoselectivities were obtained using low acid loading (typically 1 mol-%) under simple reaction conditions.

Propargylic substitution reactions with various nucleophilic compounds using efficient and recyclable mesoporous silica spheres embedded with FeCo/graphitic shell nanocrystals.

Phosphomolybdic acid (PMA, H3PMo12O40) functioned as a catalyst for reactions of secondary propargylic alcohols and nucleophiles. Highly stable and magnetically recyclable mesoporous silica spheres (MMS) embedded with FeCo-graphitic carbon shell nanocrystals (FeCo/GC@MSS) were fabricated by a modified Stöber process and chemical vapor deposition (CVD) method. The FeCo/GC@MSS were loaded with phosphomolybdic acid (PMA@FeCo/GC@MSS), and their catalytic activity was investigated. Propargylic reactions of 1,3-diphenyl-2-propyn-1-ol with a wide range of nucleophiles bearing activating substituents were catalyzed under mild conditions. It was found that the MMS possess mesoporosities and have enough inner space to load FeCo and phosphomolybdic acid. The FeCo/GC@MSS were found to be chemically stable against acid etching and oxidation. This suggests that the nanocrystals can be used as a support for an acid catalyst. Moreover, the magnetic property of the nanocrystals enabled the facile separation of catalysts from the products.