Four-component condensation reaction

Chucholowski A, Heinrich D, Mathys B, Muller C, Generation of benzodiazepine and benzodiazocine libraries through resin capture of Ugi-four component condensation reaction products, Book of Abstracts, 214th ACS National Meeting, Las Vegas, September 7-11, American Chemical Society, Washington, 1997. 

Chiral homoallylic alcohols and amines were prepared by using a four-component condensation reaction based on a zinc homologation followed by a trapping with an aldehyde or an imine.301 A regio- and stereospecific carbocupration reaction on alkynyl sulfoxide provides the corresponding metallated /3,/3-dialkylated a,/ -ethylenic sufoxide 98. Addition of aldehydes or imines, followed by addition of the bis(iodomethyl)zinc carbenoid, provides adducts 99 in good overall yield and with very high diastereoselectivity (Scheme 36). 

Peptide amide bond cleavage, A-atkylation of the amide bonds, imidoester reaction Carbamylation and thiocarbamylation method, diazotization, the four-component condensation reaction, glutaraldehyde treatment... 

FIGURE 3.16 Schematic representation of (a) carbamylation and thiocarbamylation reactions, (b) four-component condensation reaction, and (c) diazotization activation. 

The Four-Component Condensation Reaction The reaction combines the carboxyl and amino groups to form an amide bond in an aqueous medium at neutral pH (Figure 3.16b) and allow for considerable versatility and high selectivity. This reaction can be used for carboxyl and amine-containing polymers [159]. 

Based on a four component condensation reaction (the Ugi reaction ), Mjalli et developed a solid-phase protocol for the synthesis of tetrasubstituted imidazoles. Because of the limited number of commercially available isocyanides, the selected strategy started with the generation of an isocyanide component tethered to Wang resin. 

Condensation reactions are one of the most frequently used approaches to prepare pyridinones. A novel synthesis of pyridine-2(l//)-thiones has been described using arylmethylenecyanothioacetamides and dimedone <97T 17441, 97JCR(S)200>. A Ugi four-component condensation reaction between cinnamaldehyde, benzoylformic acid, an isocyanide and an amine affords an amide intermediate that upon addition of base cyclizes to the 1,6-... 

One example of a library synthesized via MW-assisted soHd-phase MCRs is that of Hoel and Nielson [13] (Scheme 2.3-9). The authors performed Ugi-4CC (four component condensation) reactions in a monomodal MW reactor between polymer (TentaGel)-bound amines and various aldehydes, carboxylic acids, and isocyanides to yield a mini library of 18a-acylaminoamides in just 15 minutes per compound. The reaction time was reduced by a factor of three. The yields were variable, but the authors reported highly pure products (>95%). 

From the perspective of diversity-oriented synthesis and the rapid constructirai of complex ring systems, the A C pathway may offer the most promising approach. As an example, an Ugi four-component condensation reaction was used as the key step to constmct 146 (Scheme 39). Conversion of 140 to the corresponding diazoimide 146 followed by rhodium(II)-catalyzed intramolecular dipolar cycloaddition then afforded the hexacyclic product 147 in 57% yield (two steps) in a highly stereocontrolled manner. 

The synthesis of 1,4-dihydropyridines (45) by four-component condensation reaction of 1,3-dicarbonyls (43), aldehydes (1), and ammonium carbonate (44) in an aqueous medium was reported at 60°C within 1.5-2.5 h (Scheme 9.11) (Tamaddon and Moradi 2012). ZnO nanoparticles can be used as a heterogeneous catalyst (Yavari and Beheshti 2011) for the one-pot three-component condensation of isatoic anhydride (46), amines (47), and aldehydes (48) to afford the corresponding 2,3-disubstituted quinazolin-4(l//)-ones (49) (Scheme 9.12). A short reaction time (3 h), solvent-free conditions, and an atom-economic nature are the significant advantages of the present method. The catalyst showed good recyclability without much loss of its catalytic activity. 

Cul NPs as efficient catalysts have been used for the preparation of H-pyrazolo[l,2-i]phthalazine-5,10-diones by the four-component condensation reaction of phthalic anhydride, hydrazine monohydrate, aromatic aldehydes, and malo-nonitrile or ethyl cyanoacetate under solvent-free conditions in good-to-excellent yields [39] (Scheme 5.9). The advantages offered by this method include short reaction times, excellent yields, simple procedure, easy workup, and the employment of a cost-effective catalyst. 

The Passerini synthesis is one of the oldest and most important multicomponent reactions (chronologically preceded by the reaction of Biginelli [1] and followed by the equally well-known Ugi four-component condensation reaction [2], currently widely studied for its originality in terms of application and mechanism). Surprisingly, little information is available regarding its discoverer, the Florentine chemist Mario Passerini. The reasons for the lack of a biography of this scientist can be traced, in part, to Passerini s reserved nature, reserved to the point of erroneously being perceived as shadowy. ... 

Ph, CH2Ph) undergo one-pot, four component condensation reactions to give 4-aminoimidazolin-2-ylidene complexes 62. 3 jhe activation parameters and kinetic isotope effect measurements for the reaction of a substituted imidazole with an unsaturated Fischer carbene complex [(OC)5M=C(OEt)CsCPh] clearly show that the reaction proceeds via a two-step process with a... 

The carboline core is of high interest due to its presence in an array of compoimds, some of which are widely distributed in nature, including various plants, foodstuffs, marine creatures, insects, mammalians as well as human tissues and body fluids. Ghahremanzadeh et al. investigated the synthesis of a-carbolines, i.e., pyrido[2,3-b]indoles 169 (Scheme 94) in good yield via a four-component condensation reaction of indolin-2-one, 3-oxo-3-phenylpro-panenitrile, and various hydrazines and aldehydes in the presence of p-toluenesulfonic acid (p-TSA) at 140 °C in IL [BMlM][Br]. The reaction performed well with aromatic aldehydes, however, reaction with aliphatic aldehydes, for example, butanal or pentanal, complications such as incompletion of reaction, by-product formation, and difficulty in purifications arose, and the yield of the expected products were extremely poor. The authors claimed the methodology efficacious in terms of yield and product purity without p-TSA, only a trace of product was obtained even after 12 h. A similar reaction conducted in organic solvents afforded traces of tiie desired products [261]. 

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