The Efficient One‐Pot Reaction of up to Eight Components by the Union of Multicomponent Reactions

Elders, Niels; Born, Dion van der; Hendrickx, Loes J. D.; Timmer, Brian J. J.; Krause, Alrik; Janssen, Elwin; Kanter, Frans J. J. de; Ruijter, Eelco; Orru, Romano V. A.

doi:10.1002/anie.200902683

Cited by 132 publications

(63 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To test the feasibility of using alkynols in the A 3 -coupling reaction, we screened a range of solvents, temperatures, and potential metal catalysts in the reaction of butyraldehyde (1a), 4-piperidone hydrochloride hydrate (2), and homopropargyl alcohol (3a) using 4 Å molecular sieves as a dehydrating agent ( Table 1).…”

Section: Resultsmentioning

confidence: 99%

A general A³: coupling reaction based on functionalized alkynes

Wendler¹,

Santos²

2013

Quím. Nova

View full text Add to dashboard Cite

Recebido em 15/1/13; aceito em 16/4/13; publicado na web em 17/7/13 A range of hydroxypropargylpiperidones were efficiently obtained by a one-pot three-component coupling reaction of aldehydes, alkynols, and a primary amine equivalent (4-piperidone hydrochloride hydrate) in ethyl acetate using copper(I) chloride as a catalyst. The developed protocol proved to be equally efficient using a range of aliphatic aldehydes, including paraformaldehyde, and using protected and unprotected alkynols.Keywords: hydroxypropargylamine; multicomponent reaction; A 3 -coupling. INTRODUCTIONConnecting organic fragments that have desired functionalities by short and inexpensive synthetic routes is one of the most exciting and challenging tasks for organic chemists, and it requires a high level of creativity and elegance.Recently, multicomponent reactions have been receiving significant attention, because multiple carbon-carbon and carbonheteroatom bonds can be generated in a single step, allowing for the straightforward construction of intricate organic compounds. Recent developments in this area have been very impressive, and procedures involving seven 1 and even eight 2 components have been reported.The three-component coupling of aldehydes, amines, and alkynes (A 3 -coupling) is a very efficient method for forming propargylamines by C-H activation.3 A 3 -coupling is more practical than the other methods available for preparing this class of compounds, because no moisture-sensitive stoichiometric organometallics, such as Grignard or organolithium reagents, are involved. It is also applicable to various substrates. This transformation can be catalyzed by a large number of transition-metal salts, including copper, 4 19 It is interesting to note that, although the use of various amines and aldehydes in this method has been described, the number of alkynes used has been limited. Non-functionalized alkynes, such as phenylacetylene and trimethylsilylacetylene, have been used most frequently, but the A 3 -coupling of alkynols, to prepare functionalized allenols, has recently been described. 20In 2006, Gommermann and Knochel described the use of an A 3 -coupling silylated adduct in the asymmetric synthesis of (S)-(+)-coniine. 21 We know of only a few examples of unprotected alkynols being used in the A 3 -coupling reaction, and all of them, except for ones we have previously reported, 22 have been limited to aromatic aldehydes. 23,24 A general procedure for the preparation of hydroxypropargylamines would be very desirable because these chemicals are direct precursors for alkaloids. The desired carbon skeleton could be achieved in a one-pot process using an A 3 -coupling-type protocol and using the correct functionalities for cyclization to form five-and six-(and higher) ring alkaloid systems.In 2006, Carreira reported using 4-piperidone hydrochloride hydrate as a secondary amine source in an A 3 -coupling reaction. 25The authors demonstrated that using this amine source allowed the A 3 -coupling adducts (tertiary amines) to be easily con...

show abstract

Section: Resultsmentioning

confidence: 99%

A general A³: coupling reaction based on functionalized alkynes

Wendler¹,

Santos²

2013

Quím. Nova

View full text Add to dashboard Cite

show abstract

“…Ugi synthesis of α-acylamino amides may now be carried out with isonitriles prepared in situ from bromides with AgCN/KCN and a phase transfer catalyst 38 . Multicomponent reactions have now been extended to reactions involving five, six or even eight components by the introduction of orthogonal functional groups 39 . Some random highlights deserving a mention include: a site-selective glycosylation of hydroxyketones at the ketone or the alcohol via hydrosilylation 40 ; a transition metal-free reductive C−C coupling of tosylhydrazones and aromatic or aliphatic boronic acids 41 ; N-heterocyclic carbene-catalyzed 1,4-addition-α-hydroxyalkylation of α,β-ethylenecarbonyl compounds with bis(pinacolato)diborane 42 ; a catalytic Wittig synthesis starting from bromides and aldehydes with regeneration of the [cyclic] phosphine using diphenylsilane 43 ; a biocatalytic equivalent of Friedel-Crafts allyl-, benzyl-or propargyl-ation using S-adenosyl-L-methionine and methyltransferases 44 ; and a synthesis of 2-functionalized pyrimidines/quinazolines from cyanic acid derivatives and enacylamines/anilides, providing a route to C2-and C4-substituted compounds 45 .…”

Section: Further Trends and Developments In Synthetic Organic Chemistmentioning

confidence: 99%

Title Pages

2010

Theilheimer's Synthetic Methods of Organic Chemistry

View full text Add to dashboard Cite

show abstract

“…The multicomponent process (MCPs) provides a powerful method for the construction of a variety of chemicals including pharmaceuticals, complex organic molecules, and biological active compounds in a time and cost effective approach. Significant consideration has been focused on MCPs because of their valuable features such as high efficiency, mild conditions, simplistic completion, lower costs, shorter reaction times, higher atom-economy, energy saving, and environment friendliness [5][6][7][8][9][10][11][12] . An important source with various applications in biology, pharmacology and diseases therapy is 4H-Pyran nucleus.…”

mentioning

confidence: 99%

Insights into the Reaction Mechanism of the Tetrahydrobenzo [b] pyran by means of Kinetic Studies in the Presence of Fructose as a Green Catalyst

Ghalandarzehi¹,

Habibi‐Khorassani²,

Shahraki³

2016

Orient. J. Chem

View full text Add to dashboard Cite

Extensive kinetic studies were performed to investigate the mechanism of the reaction between 4-methoxybenzaldehyde 1, malononitrile 2, and dimedone 3 in the presence of fructose as a catalyst in a mixture of water and ethanol. The synthesis reaction of tetrahydrobenzo[b]pyran followed second-order kinetics. The partial orders with respect to 1, 2 were one and one, respectively. Temperature effect has been investigated on the reaction rate, and relevant parameters have been determined with two linearized forms of Eyring equation. The proposed mechanism theoretical rate law were compatible with the experimental data. From the temperature, concentration and solvent studies, the activation energy (E a = 70.05 ± 1.39 kJmol

show abstract

The Efficient One‐Pot Reaction of up to Eight Components by the Union of Multicomponent Reactions

Cited by 132 publications

References 34 publications

A general A³: coupling reaction based on functionalized alkynes

A general A³: coupling reaction based on functionalized alkynes

Title Pages

Insights into the Reaction Mechanism of the Tetrahydrobenzo [b] pyran by means of Kinetic Studies in the Presence of Fructose as a Green Catalyst

Contact Info

Product

Resources

About