Identifying a Highly Active Copper Catalyst for KA2 Reaction of Aromatic Ketones

The well‐established A³ coupling reaction of terminal alkynes, aldehydes, and amines provides the most straightforward approach to propargylic amines. However, the related reaction of ketones, especially aromatic ketones, is still a significant challenge. A highly efficient catalytic protocol has been developed for the coupling of aromatic ketones with amines and terminal alkynes, in which Cu^I, generated in situ from the reduction of CuBr₂ with sodium ascorbate, has been identified as the highly efficient catalyst. Since propargylic amines are versatile synthetic intermediates and important units in pharmaceutical products, such an advance will greatly stimulate research interest involving the previously unavailable propargylic amines.     

Propargylic amines constructed via copper-catalyzed three-component coupling of terminal alkynes, benzal halides and amines

A method for the synthesis of propargylic amines has been developed via an efficient copper(I)-catalyzed three-component coupling reaction of alkynes, benzal halides and amines through C-H and C-halogen activation. This reaction is conducted under mild conditions and provides an alternative method for the synthesis of propargylic amines.     

Synthesis of allenes via palladium-catalyzed hydrogen-transfer reactions: propargylic amines as an allenyl anion equivalent

Synthesis of allenes has been achieved by using palladium-catalyzed hydrogen-transfer reactions. Various propargylic amines, which were readily prepapred from iodobenzenes and propargylic amines by Sonogashira coupling reaction, underwent the hydrogen-transfer reaction in the presence of Pd2dba3.CHCl3/(C6F5)3P catalyst at 100 degrees C in dioxane for 24 h, giving the corresponding allenes in 43-99% yields. Various propargylic alcohols containing a propargylic aminomethyl group, synthesized by the addition of lithium acetylides of N,N-diisopropylprop-2-ynylamine to aldehydes and a ketone, also underwent the hydrogen-transfer reaction in the presence of Pd2dba3.CHCl3 catalyst and (C6F5)3P at 80 degrees C in dioxane, giving the corresponding allenes in 56-92% yields. In the current transformation, propargylic amines can be handled as an allenyl anion equivalent and introduced into various electrophiles to be transformed into allenes under palladium-catalyzed conditions.     

PdCl2-catalyzed efficient transformation of propargylic amines to (E)-alpha-chloroalkylidene-beta-lactams

[reaction: see text] The PdCl2-catalyzed cyclocarbonylation reaction of propargylic amines with CuCl2 and benzoquinone afforded (E)-alpha-chloroalkylidene-beta-lactams in moderate to good yields. The formation of the corresponding Z-isomers or five-membered products was not observed. The reaction of the readily available optically active propargylic amines provides a convenient synthesis of the corresponding (E)-alpha-chloroalkylidene-beta-lactams with high ee values. The structure and the stereochemistry of the products were established by the X-ray single-crystal diffraction study of (E)-6d and (E)-6e, which indicates that the stereoselectivity in this reaction is different from what was observed with propargylic alcohols. A rationale for this reaction was proposed.     

Cobalt-catalyzed hydrohydrazination of dienes and enynes: access to allylic and propargylic hydrazides

[reaction: see text] The cobalt-catalyzed hydrohydrazination reaction of dienes and enynes is presented. Allylic and propargylic hydrazines were obtained in synthetically useful yields (allylic amines, 60-90%; propargylic amines, 47-83%) and good chemo- and regioselectivity.     

Dimethylzinc-mediated alkynylation of imines

The treatment of various aromatic and aliphatic aldimines with a mixture of a terminal alkyne and a commercially available dimethylzinc solution in toluene yields the corresponding protected propargylic amines in moderate to excellent yields. The reaction proceeds in the absence of any activator. These observations led to the development of a three-component synthesis of propargylic amines in which the product was obtained upon mixing an aldehyde with ortho-methoxyaniline and phenylacetylene in the presence of dimethylzinc, through in situ formation of the corresponding imine.     

Zinc(II)-catalyzed redox cross-dehydrogenative coupling of propargylic amines and terminal alkynes for synthesis of N-tethered 1,6-enynes

The zinc(II)-catalyzed redox cross-dehydrogenative coupling (CDC) of propargylic amines and terminal alkynes proceeds to afford N-tethered 1,6-enynes. In the current CDC reaction, a C(sp)-C(sp(3)) bond is formed between the carbon adjacent to the nitrogen atom in the propargylic amine and the terminal carbon of the alkyne with reduction of the C-C triple bond of the propargylic amine, which acts as an internal oxidant.     

The first silver-catalyzed three-component coupling of aldehyde, alkyne, and amine

[reaction: see text] Silver iodide catalyzed the three-component coupling of aldehyde, alkyne, and amines to generate propargylic amines with high efficiency in water. The silver-catalyzed reaction is especially effective for reactions involving aliphatic aldehyde. No additional cocatalyst or activator is required.     

Copper-catalyzed enantioselective propargylic amination of nonaromatic propargylic esters with amines

The enantioselective propargylic amination of propargylic pentafluorobenzoates bearing an alkyl group at the propargylic position with amines in the presence of catalytic amounts of a copper complex and an optically active diphosphine such as BINAP has been found to give the corresponding propargylic amines in good yields with high enantioselectivity.     

Quaternary ammonium salt-catalyzed carboxylative cyclization of propargylic amines with CO2

By employing quaternary ammonium salts as catalysts, the carboxylative cyclization of the propargylic amines with CO₂ proceeded to afford the corresponding 2-oxazolidinones. In particular, tetra-n-butylammonium fluoride was the most effective catalyst for the reaction, providing a 2-oxazolidinone derivative in a maximum chemical yield of 99%. From a screening of the structure of a catalyst, it was found that both a quaternary ammonium cation and a basicity of the counter anion were essential to catalyze the carboxylative cyclization of the propargylic amines with CO₂.     

Dimethylzinc-mediated, enantioselective synthesis of propargylic amines

A one-pot, enantioselective synthesis of N-aryl propargylic amines, using alkynylation reagents obtained from dimethylzinc and terminal acetylenes in combination with various aldehydes and o-methoxyaniline as starting materials, has been developed. Enantiopure beta-amino alcohols derived from norephedrine were used as non-covalent chiral auxiliaries, both in stoichiometric or substoichiometric amount. After optimization, propargylic amines were obtained in good to high yields (up to 93%) and with moderate to high enantiomeric excesses (up to 97% ee). The possibility to recover the chiral auxiliary after the reaction was demonstrated.     

A mild and efficient AgSbF6-catalyzed synthesis of fully substituted pyrroles through a sequential propargylation/amination/cycloisomerization reaction

Development of an efficient synthesis of fully substituted pyrroles via a sequential propargylation/amination/cycloisomerization was accomplished using AgSbF₆ as a catalyst. The one-pot three-component reaction of propargylic alcohols, 1,3-dicarbonyl compounds, and primary amines proceeds at a mild temperature, which prevents the formation of furan by-product. The reaction was also successfully applied to the more basic aliphatic amines with the addition of 1.1 equiv of acetic acid.     

Highly Efficient Conversion of Propargylic Amines and CO2 Catalyzed by Noble-Metal-Free [Zn116] Nanocages

The reaction of propargylic amines and CO₂ can provide high-value-added chemical products. However, most of catalysts in such reactions employ noble metals to obtain high yield, and it is important to seek eco-friendly noble-metal-free MOFs catalysts. Here, a giant and lantern-like [Zn₁₁₆] nanocage in zinc-tetrazole 3D framework [Zn₂₂(Trz)₈(OH)₁₂(H₂O)₉⋅8 H₂O]_n Trz=(C₄N₁₂O)⁴⁻ ( 1 ) was obtained and structurally characterized. It consists of six [Zn₁₄O₂₁] clusters and eight [Zn₄O₄] clusters. To our knowledge, this is the highest-nuclearity nanocages constructed by Zn-clusters as building blocks to date. Importantly, catalytic investigations reveal that 1 can efficiently catalyze the cycloaddition of propargylic amines with CO₂, exclusively affording various 2-oxazolidinones under mild conditions. It is the first eco-friendly noble-metal-free MOFs catalyst for the cyclization of propargylic amines with CO₂. DFT calculations uncover that Zn^II ions can efficiently activate both C≡C bonds of propargylic amines and CO₂ by coordination interaction. NMR and FTIR spectroscopy further prove that Zn-clusters play an important role in activating C≡C bonds of propargylic amines. Furthermore, the electronic properties of related reactants, intermediates and products can help to understand the basic reaction mechanism and crucial role of catalyst 1 .     

Zn-alkynylide additions to acyl iminiums

[reaction: see text] A new addition reaction of zinc-alkynylides to N-acyl and N-phosphinoyl iminiums is reported. These can be prepared in situ from imines with acid halides in the presence of a Zn-acetylide. The reaction is general with regard to imine, alkyne, and acid halides, allowing access to a large number of differentially protected propargylic amines.     

Ruthenium-catalyzed propargylic substitution reactions of propargylic alcohols with oxygen-, nitrogen-, and phosphorus-centered nucleophiles

The scope and limitations of the ruthenium-catalyzed propargylic substitution reaction of propargylic alcohols with heteroatom-centered nucleophiles are presented. Oxygen-, nitrogen-, and phosphorus-centered nucleophiles such as alcohols, amines, amides, and phosphine oxide are available for this catalytic reaction. Only the thiolate-bridged diruthenium complexes can work as catalysts for this reaction. Results of some stoichiometric and catalytic reactions indicate that the catalytic propargylic substitution reaction proceeds via an allenylidene complex formed in situ, whereby the attack of nucleophiles to the allenylidene C(gamma) atom is a key step. Investigation of the relative rate constants for the reaction of propargylic alcohols with several para-substituted anilines reveals that the attack of anilines on the allenylidene C(gamma) atom is not involved in the rate-determining step and rather the acidity of conjugated anilines of an alkynyl complex, which is formed after the attack of aniline on the C(gamma) atom, is considered to be the most important factor to determine the rate of this catalytic reaction. The key point to promote this catalytic reaction by using the thiolate-bridged diruthenium complexes is considered to be the ease of the ligand exchange step between a vinylidene ligand on the diruthenium complexes and another propargylic alcohol in the catalytic cycle. The reason why only the thiolate-bridged diruthenium complexes promote the ligand exchange step more easily with respect to other monoruthenium complexes in this catalytic reaction should be that one Ru moiety, which is not involved in the allenylidene formation, works as an electron pool or a mobile ligand to another Ru site. The catalytic procedure presented here provides a versatile, direct, and one-step method for propargylic substitution of propargylic alcohols in contrast to the so far well-known stoichiometric and stepwise Nicholas reaction.     

Three-component one-pot process to propargylic amines and related amide and sulfonamide compounds: application to the construction of 2-(aminomethyl)benzofurans and indoles

An efficient palladium-copper-catalyzed three-component assembling of propargyl halides, aryl or heteroaryl halides, and secondary amines is described. A wide variety of tertiary propargylic amines were synthesized in good to excellent yields from easily accessible starting materials. This three-component assembling was also effective when using potassium phthalimide or di-tert-butyliminodicarbonate instead of secondary amines. Consequently, it provides a quick entry to N-protected propargylic amines suitable intermediates for the synthesis of primary and secondary propargylic amines. In a similar way, related compounds including propargylic amide, carbamate and sulfonamide derivatives were efficiently obtained. This catalytic domino three-component process has been applied successfully to the construction of functionalized 2-(aminomethyl)benzo[b]furan or indole derivatives of biological interest.     

Highly Efficient Conversion of Propargylic Amines and CO2 Catalyzed by Noble‐Metal‐Free [Zn116] Nanocages

The reaction of propargylic amines and CO₂ can provide high‐value‐added chemical products. However, most of catalysts in such reactions employ noble metals to obtain high yield, and it is important to seek eco‐friendly noble‐metal‐free MOFs catalysts. Here, a giant and lantern‐like [Zn₁₁₆] nanocage in zinc‐tetrazole 3D framework [Zn₂₂(Trz)₈(OH)₁₂(H₂O)₉?8 H₂O]_n Trz=(C₄N₁₂O)^4? ( 1 ) was obtained and structurally characterized. It consists of six [Zn₁₄O₂₁] clusters and eight [Zn₄O₄] clusters. To our knowledge, this is the highest‐nuclearity nanocages constructed by Zn‐clusters as building blocks to date. Importantly, catalytic investigations reveal that 1 can efficiently catalyze the cycloaddition of propargylic amines with CO₂, exclusively affording various 2‐oxazolidinones under mild conditions. It is the first eco‐friendly noble‐metal‐free MOFs catalyst for the cyclization of propargylic amines with CO₂. DFT calculations uncover that Zn^II ions can efficiently activate both C≡C bonds of propargylic amines and CO₂ by coordination interaction. NMR and FTIR spectroscopy further prove that Zn‐clusters play an important role in activating C≡C bonds of propargylic amines. Furthermore, the electronic properties of related reactants, intermediates and products can help to understand the basic reaction mechanism and crucial role of catalyst 1 .     

Pathways of the reaction between N,N-disubstituted propargylic amines and cationic zirconium complexes

Russian Chemical Bulletin - The reaction of N-tert-alkyl-substituted propargylic amines with trialkylalanes in the presence of 20 mol.% Cp2ZrCl2 was studied. The pattern of the products depended on...     

Palladium-catalyzed cross-coupling of 2-haloselenophene with terminal alkynes in the absence of additive

We present herein our results of the Sonogashira coupling reaction of 2-haloselenophenes with terminal alkynes catalyzed by PdCl₂(PPh₃)₂, under co-catalyst free conditions and establish a new procedure to prepare (2-alkynyl)-selenophenes in good yields. The reaction proceeded cleanly under mild reaction conditions and was performed with propargylic alcohols, protected propargylic alcohols, propargylic amines, as well as alkyl, and aryl alkynes, in the presence of PdCl₂(PPh₃)₂, Et₃N, DMF, and in the absence of any supplementary additives. In addition, by this protocol (2,5-bis-alkynyl)-selenophenes were also obtained, in a one pot procedure, using 2,5-bis-iodoselenofene with an excess of terminal alkynes.     

Gold/Acid‐Co‐catalyzed Direct Microwave‐Assisted Synthesis of Fused Azaheterocycles from Propargylic Hydroperoxides

The gold–acid‐co‐catalyzed synthesis of nine series of fused azaheterocycles with structural diversity starting from the same synthons as readily available propargylic hydroperoxides and aromatic amines has been achieved. The overall tandem process consists in a gold‐catalyzed hydroperoxide rearrangement/Michael reaction followed by a final acid‐catalyzed cyclization.