Multi component reaction

In this section, a number of interesting reactions in the area of multi-component reactions under microwave conditions are presented. The section is intended as an overview of the subject. 

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The Biginelli reaction involves an one-pot reaction between aldehyde 1, 1,3-dicarbonyl 2, and urea 3a or thiourea 3b in the presence of an acidic catalyst to afford 3,4-dihydropyrimidin-2(l//)-one (DHPM) 4. This reaction is also referred to as the Biginelli condensation and Biginelli dihydropyrimidine synthesis. It belongs to a class of transformations called multi-component reactions (MCRs). 

An alternate approach is to utilize the chromatogram heights as representative of individual concentrations of molecular size. From the kinetic modeling viewpoint, this leads to treating the polymerization as a well-characterized, multi-component reaction system. 

In another report, aspects for automating preparative chemistry are described [130]. A comprehensive description of the Ugi reaction is given in [132] and the vision of a micro multi-component reaction as automated parallel micro-channel synthesis is sketched. An interesting point is to convert aldehydes, chiral primary amines, carboxylic adds and isocyanates into corresponding a-amino acids and peptides (U-4CR). 

Smith and co-workers have employed NHC 81 to catalyse the 0- to C-carboxyl transfer of a range of oxazolyl carbonates 80, forming 82 with the generation of a C-C bond at a quaternary centre with good catalytic efficiency [27], This transformation presumably proceeds via the generation of an intermediate carboxyazolium species, and has been utihsed as a component of domino multi-component reactions [28], as well as the rearrangement of indolyl and benzofuranyl carbonates (Scheme 12.15) [29]. 

Multi-component reactions Most highly atom economical reaction type of all... 

Weber, L., Illgen, K., Almstetter, M. (1999) Discovery of New Multi-Component Reactions with Combinatorial Methods. Synlett, 366-374. 

Domling, A. (2000) The Discovery of New Isocyanide-Based Multi-Component Reactions. Current Opinion in Chemical Biology, 4, 318-323. 

Weber, L. (2002) Multi-Component Reactions and Evolutionary Chemistry. Drug Discovery Today, 7, 143-147. 

Weber, L. (2002) The Application of Multi-Component Reactions in Drug Discovery. Current Medicinal Chemistry, 9, 1241-1253. 

Ugi, L, Werner, B., Domling, A. (2003) The Chemistry of Isocyanides, Their Multi-Component Reactions and Their Libraries. Molecules, 8, 53-66. 

All reactive hazards involve the release of energy in quantities or at rates too high to be absorbed by the immediate environment of the reacting system, and material damage results. The source of the energy may be an exothermic multi-component reaction, or the exothermic decomposition of a single unstable (often endothermic) compound. 

The [l,3]oxazino[4,3- ][l,3]oxazine 387 was obtained as the main product of a combined Asinger and Ugi multi-component reaction from MeOH, NH3, 2,2-dimethyl-3-hydroxypropanal, allyl isocyanate, and C02 in 40% yield. As shown by NMR spectroscopy and X-ray crystallography, 387 is formed as a single diastereomer <1998ACS107>. 

Multi-component Reactions (lmidazo[l,2-a]annulated N-heterocycles -Ugi reaction)... 

The regioselectivity of palladium-catalyzed additions of organoboronic acids to unsymmetrical alkynes is strongly dependent on steric and electronic effects (Scheme 12).62 Multi-component reaction has been reported for the synthesis of tetrasubstituted alkenes.58 The aryl group from an aryl iodide is generally added to the less hindered... 

Dienes such as 90 can be accessed by a multi-component reaction under ruthenium catalysis involving an allene 88 and an enone (methyl vinyl ketone in this case), with cerium(m) chloride as an additive in DMF (Scheme 26).95,96 With an allene concentration of 0.25 M, yields are moderate to good. Different ruthenium catalysts and additives were tested in order to optimize this reaction. CpRu(COD)Cl 89 and CpRu(MeCN)3PF6 appeared to be more versatile ones. The mono-, di-, tri-, and tetrasubstituted allenes have been investigated with methyl vinyl... 

Domino reactions increasingly gain importance in the search for new drugs. Especially appropriate is the use of multi-component reactions in solution combinatorial chemistry. In such a process described by Wessel et al.1231 an alkoxy-nitroenone 48 was treated with different anilines 49 to give ketene-NO-acetals which in the presence of aromatic aldehydes and TfOH are transformed into 50 (scheme 10). The substrate 48 is readily available by oxidation of the nitrosugar 47. 

The Groebke-type multi-component reaction between 3-amino-l,2,4-triazole, aromatic aldehydes and benzylic isonitriles afforded iV-alkylidene-4//-imidazo[l,2-A [l,2,4]triazol-6-amines in moderate to good yields <2006TL6891>. 

Another synthetically very promising area deals with the use of allenes in multi-component reactions. For example, the aryl iodide 365 after oxidative addition and cyclization can insert allene (1) to yield the p-allylpalladium(II) species 366. When this is subsequently captured by a secondary amine the functionalized benzo-fused 5-8-membered ring systems 367 are produced in good yield (Scheme 5.54) [157]. 

Keywords Low melting mixtures, sugars, multi component reactions, green solvent, 1,4 dihydropyridines. 

Rapid Synthesis of Peptoid Macrocycles by Multi Component Reactions. . 163... 

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