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.     

Nickel‐catalyzed three‐component coupling reaction of terminal alkynes,dihalomethane and amines to propargylamines

Direct C―H and C―halogen activation is an important and practical task in C―C, C―N bond formation reactions using alkynes. Propargylic amines are synthetically versatile intermediates for the preparation of many nitrogen‐containing biologically active motifs. Herein, a 15 mol% Ni(py)₄Cl₂/bipyridine‐catalyzed three‐component coupling reaction of alkynes, halomethane and amines through C―H and C―halogen activation was developed for the facile synthesis of propargylic amines. Tetramethylguanidine shows excellent basicity in acetonitrile and works under mild conditions. The reaction has very good functional group tolerance to aliphatic and aromatic alkynes. Copyright © 2013 John Wiley & Sons, Ltd.     

An unprecedented highly efficient solvent-free oxidation of alkynes to α,β-acetylenic ketones with tert-butyl hydroperoxide catalyzed by water-soluble copper complex

The catalytic system composed of CuCl₂ and 2,2′-biquinoline-4,4′-dicarboxylic acid dipotassium salt (BQC) was found to be highly efficient for the selective α-oxidation of internal alkynes to the corresponding α,β-acetylenic ketones, with aqueous tert-butyl hydroperoxide under mild conditions. For the first time, full conversions of alkynes were reached with excellent selectivities, and propargylic tert-butylperoxy ethers were observed and suggested as the reaction intermediates. In the case of terminal alkynes, the oxidations are sluggish and low yields ranging from 32% to 40% were obtained.     

Enantioselective addition of terminal alkynes to N-(diphenylphosphinoyl)imines catalyzed by Zn–BINOL complexes

Chiral nonracemic N-(diphenylphosphinoyl)-protected propargylic amines have been prepared by addition of terminal alkynes to N-(diphenylphosphinoyl)aldimines in the presence of dimethylzinc and 3,3′-dibromo-BINOL as catalyst. The reaction works with a variety of aromatic and heteroaromatic aldimines and with different alkynes, providing the expected products in generally good yields and enantiomeric excesses (up to 96%).     

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.     

Highly efficient transition metal-free coupling of acid chlorides with terminal alkynes in [bmim]Br: A rapid route to access ynones using MgCl2

A simple, mild, highly efficient and transition metal-free protocol for synthesis of ynones in an ionic liquid is described. In this approach, the coupling reaction of different acid chlorides with terminal alkynes was efficiently carried out using 0.05 mol% MgCl₂ in the presence of triethylamine in [bmim]Br at room temperature to afford the corresponding ynones in good to excellent yields. This method is highly efficient for various acid chlorides and alkynes including aliphatic, aromatic, and heteroaromatic substrates bearing different functional groups. The influence of some parameters in this reaction including type of ionic liquid, base and catalyst has been discussed.     

Ligand-free Ag(I)-catalyzed carboxylative coupling of terminal alkynes,chloride compounds,and CO2

Simple silver(I) slats were found to be highly efficient and selective catalyst for carboxylative coupling of aryl- or alkyl-substituted terminal alkynes, CO₂, and various allylic, propargylic or benzylic chlorides to exclusively yield functionalized 2-alkynoates. The activity is about 300 times that of the previously reported N-heterocyclic carbene copper(I) catalytic system. The ligand-free silver(I) catalytic system showed the wide generality of substrates involving both functionalized terminal alkynes and chloride compounds.     

Palladium-catalyzed deacetonative coupling of aryl propargylic alcohols with aryl chlorides in water

A highly efficient and green process for palladium-catalyzed deacetonative coupling of aryl propargylic alcohols with aryl chlorides has been developed. The reaction occurs smoothly in neat water with 2?mol% PdCl₂ as catalyst, and various synthetically useful functional groups, including ether, aldehyde, ketone, and heterocyclics, are well tolerated. Moreover, the reaction could proceed through a consecutive Sonogashira/deacetonative process using 2-methyl-3-butyn-2-ol and aryl chlorides as coupling partners, affording the symmetric alkynes in good yields.     

Palladium-Catalyzed Carbo-Oxygenation of Propargylic Amines using in Situ Tether Formation

1,2-Amino alcohols and α-aminocarbonyls are frequently found in natural products, drugs, chiral auxiliaries, and catalysts. This work reports a new method for the palladium-catalyzed oxyalkynylation and oxyarylation of propargylic amines. The reaction is perfectly regioselective based on the in situ introduction of a hemiacetal tether derived from trifluoroacetaldehyde. cis-Selective carbo-oxygenation was achieved for terminal alkynes, whereas internal alkynes gave trans-carbo-oxygenation products. The obtained enol ethers could be easily transformed into 1,2-amino alcohols or α-amino ketones using hydrogenation or hydrolysis, respectively.     

3‐(Diphenylphosphino)propanoic acid: an efficient ligand for the Pd/Cu‐catalyzed homo‐coupling of terminal alkynes in the presence of oxygen at room temperature

A simple, yet efficient system for PdCl₂/CuI to catalyze the homo‐coupling reactions of various terminal alkynes has been developed using 3‐(diphenylphosphino)propanoic acid as ligand in the presence of oxygen. The alkynes, including aromatic, heteroaromatic and aliphatic alkynes, were transformed at room temperature into the corresponding 1,3‐diynes in moderate to excellent yields. The turnover number was up to 1.04 × 10³. Copyright © 2015 John Wiley & Sons, Ltd.     

Enantioselective Zinc/BINOL‐Catalysed Alkynylation of Aldimines Generated in Situ from α‐Amido Sulfones

Chiral nonracemic N‐Cbz‐protected propargylic amines have been prepared by the addition of terminal alkynes to imines generated in situ from α‐amido sulfones in the presence of diethylzinc and BINOL‐type ligands as catalysts. The reactions give good yields and high enantioselectivities (ee values up to 95 %) for a good number of aromatic and heteroaromatic α‐amido sulfones and alkynes.     

Syntheses of N-sulfonyl-N,N-disubstituted amidines via a three-component free-radical coupling reaction of tertiary amines and arenesulfonyl azides with terminal alkynes

A facile and efficient synthesis of N-sulfonyl-N,N-disubstituted amidines has been achieved via a CuI-catalyzed three-component free-radical coupling reaction of tertiary amines and arenesulfonyl azides with terminal alkynes in the presence of azodiisobutyronitrile(AIBN).The reaction mechanism of this reaction has also been studied.     

CuPy2Cl2: A Novel and Efficient Catalyst for Synthesis of Propargylamines Under the Conventional Method and Microwave Irradiation

CuPy₂Cl₂ is an efficient catalyst for the preparation of propargylamines via three-component coupling reaction of aromatic aldehydes, amines, and aromatic alkynes stirred at 95 °C without using any solvent to afford the corresponding products in good yields. The reaction mixture was irradiated at 450 W in a microwave oven to furnish the expected products in excellent yields.     

A microwave-enhanced, solventless Mannich condensation of terminal alkynes and secondary amines with para-formaldehyde on cuprous iodide doped alumina

A microwave-enhanced, solventless Mannich condensation of terminal alkynes and secondary amines with para-formaldehyde on cuprous iodide doped alumina has been developed. β-Aminoalkynes are generated in good yields. The reaction can be extended to include a cyclization, which affords 2-substituted benzo[b]furans. The chemoselectivity of the reaction indicates that terminal alkynes are much more reactive than enolizable ketones under the reaction conditions.     

An efficient and facile one-pot synthesis of propargylamines by three-component coupling of aldehydes, amines, and alkynes via C-H activation catalyzed by NiCl2

NiCl₂ was found to be a highly efficient and effective catalyst for the one-pot three-component (A³) coupling of aldehydes, amines, and alkynes to produce propargylamines in nearly quantitative yields. Structurally divergent aldehydes, amines, and alkynes were converted into the corresponding propargylamines. No co-catalyst or activator is needed and water is the only byproduct of this novel protocol.     

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.     

Selective Benzylic and Allylic Alkylation of Protic Nucleophiles with Sulfonamides through Double Lewis Acid Catalyzed Cleavage of sp3 Carbon–Nitrogen Bonds

The acid‐catalyzed benzylic and allylic alkylation of protic nucleophiles is fundamentally important for the formation of carbon? carbon and carbon? heteroatom bonds, and it is a formidable challenge for benzylic and allylic amine derivatives to be used as the alkylating agents. Herein we report a highly efficient benzylic and allylic alkylation of protic carbon and sulfur nucleophiles with sulfonamides through double Lewis acid catalyzed cleavage of sp³ carbon–nitrogen bonds at room temperature. In the presence of a catalytic amount of inexpensive ZnCl₂‐TMSCl (TMSCl: chlorotrimethylsilane), 1,3‐diketones, β‐keto esters, β‐keto amides, malononitrile, aromatic compounds, thiols, and thioacetic acid can couple with a broad range of tosyl‐activated benzylic and allylic amines to give diversely functionalized products in good to excellent yields and with high regioselectivity. Furthermore, the cross‐coupling reaction of 1,3‐dicarbonyl compounds with benzylic propargylic amine derivatives has been successfully applied to the one‐step synthesis of polysubstituted furans and benzofurans.     

Silver(I)-catalyzed tandem 1,3-acyloxy migration/Mannich-type addition/elimination of the sulfonyl group of N-sulfonylhydrazone-propargylic esters to 5,6-dihydropyridazin-4-one derivatives

The addition of nucleophiles to C=N bonds offers a highly efficient synthetic strategy for accessing nitrogen-containing molecules.1 Among the well-developed addition reactions, such as the highly efficient Mannich reaction, various C-H bond-activated compounds including carboxylic acid derivatives, nitroalkanes, and terminal alkynes have been applied as nucleophiles to achieve different classes of amines.2 However, employing new nucleophiles without activated C-H bonds, such as internal alkynes and allenic esters are limited when using metal catalysts.3 Herein, we wish to report a new addition of allenic esters to C=N bonds initiated by a silver-catalyzed 1,3-migration of propargylic esters.     

Recent advances in organic synthesis with CO2 as C1 synthon

Carbon dioxide as a green, nontoxic and low-cost C1 synthon holds great potential in organic synthesis. In this paper, the recent studies of conversion of CO₂ with organic compounds (including alkenes, alkynes, amines, allylamines, propenyl ketones, propargylic alcohols/amines, arenes, and heteroarenes as well as their derivatives) to value-added chemicals are briefly reviewed.     

A Highly Efficient Gold‐Catalyzed Photoredox α‐C(sp3)H Alkynylation of Tertiary Aliphatic Amines with Sunlight

A new α‐C(sp³)? H alkynylation of unactivated tertiary aliphatic amines with 1‐iodoalkynes as radical alkynylating reagents in the presence of [Au₂(μ‐dppm)₂]²⁺ in sunlight provides propargylic amines. Based on mechanistic studies, a C? C coupling of an α‐aminoalkyl radical and an alkynyl radical is proposed for the C(sp³)? C(sp) bond formation. The mild, convenient, efficient, and highly selective C(sp³)? H alkynylation reaction shows excellent regioselectivity and good functional‐group compatibility. A scale‐up to gram quantities is possible with sunlight used as a clean and sustainable energy source.