Coupling multi-component

Wright DL, Robotham CV, Aboud K (2002) Studies on the sequential multi-component coupling/Diels-Alder cycloaddition reaction. Tetrahedron Lett 43 943-946... 

Using established principles of late-transition metal catalysis, several research groups have engineered multi-component coupling reactions from the basis set of known Group 9 metal vinylidene-mediated reactions. In 2004, Jun and coworkers described a new method for the synthesis of enones via rhodium vinylidene-mediated hydrative dimerization of alkynes (Table 9.12) [24]. 

Two closely related reports of pyrazole generation by condensation of substituted hydrazines with enamino carbonyl compounds have appeared. In situ formation of an enaminoketone, by treatment of a diketone with dimethylformamide dimethyl acetal, was followed by tandem Michael addition-elimination/cyclodehydration under aqueous conditions in sealed microwave vessels (Scheme 3.12)17. Isoxazoles and pyrimidines were also prepared by replacing the substituted hydrazine with hydroxylamine or amidines, respectively (see Chapter 5, Section 5.3.2). The overall process may be regarded as another example of a multi-component coupling. In a similar fashion, enamino propenoates were condensed with substituted hydrazines to afford substituted pyrazoles (see Chapter 5, Section 5.3.2) (Scheme 3.12)18. 

The cross-coupling reactions can be combined with catalytic cyclization of 2-alkynylphenols in a one-pot, multi-component coupling procedure leading to 2,3-disubstituted benzofurans 39 as shown in Scheme 25 . 

Multi-component couplings open up an economic and straightforward route to very different compound libraries. For example, 1,3-dipolar cycloaddition reactions of nitrones with alkenes furnish isoxazolines, which can be transformed reductively to hydroxyketones or )8-amino alcohols. In 1997, two groups reported on the synthesis of isoxazolines by rare earth metal-catalyzed [3 + 2] cycloadditions (Scheme 4) [13,14]. 

Strubing D, Neumann H, Jacobi von Wangelin A et al (2006) An easy and general protocol for multi-component coupling reactions of aldehydes, amides, and dienophiles. Tetrahedron 62 10962-10967... 

Metallacycles have been claimed to play pivotal roles in many transition metal-mediated multi-component coupling reactions [1]. For example, [2 -i- 2 -i- 2] alkyne cyclo-trimerization leading to benzenes - the Reppe reaction - has been considered to proceed via metallacyclopentadiene and elusive metallacycloheptatriene intermediates ("common mechanism ), while metallacyclopentenes have been proposed as intermediates for the [2 -i- 2 -i- 1] cyclo-coupling reactions of an alkyne, an alkene, and CO leading to a cyclopentenone (the Pauson-Khand reaction). A metallacyclic compound - which is defined here as a carbocyclic system with one atom replaced by a transition metal element - can be generally formed by oxidative cyclization of two unsaturated molecules with a low-valent transition metal fragment [2-4]. Alter-... 

Radical carbonylation of an alkyl iodide in the presence of Kim s sulfonyl oxime ethers provides a new type of multi-component coupling reaction, and a typical example is given in Scheme 4-38 [65]. In this method, plural radical Cl synthons are consecutively combined. 

Ni-catalyzed multi-component coupling reactions are an efficient protocol for carbon-carbon bond formation [97]. The Ni-catalyzed asymmetric intermolecular reductive coupling of 1,3-dienes and aldehydes with Et Zn as a reducing reagent was realized... 

According to Blackwell [103] the application of microwave irradiation to expedite solid-phase reactions could be the tool that allows combinatorial chemistry to deliver on its promise - providing rapid access to large collections of diverse small molecules. Several different approaches to microwave-assisted solid-phase reactions and library synthesis are now available. These include the use of solid-supported reagents, multi-component coupling reactions, solvent-free parallel library synthesis, and spatially addressable library synthesis on planar solid support. 

Chaplin, J.H. and n3mn, B.L. (2001) A multi-component coupling approach to benzo[(>]furans and indoles. Chem. Commun., 1594—5. 

Steefel et al. ([23] and references therein) noted that the approach does not account for pH, competitive ion effects or oxidation-reduction reactions. As a consequence, values may vary by orders of magnitude from one set of conditions to another. Chen [25] also highlighted these limitations by comparing numerical modeling results of contaminant transport using a multi-component coupled reactive mass transport model and a based transport model. The conclusion from this work was that values vary with location and time and this variation could not be accounted for in the model. 

A. R. Siamaki, M. Sakalauskas, B. A. Amdtsen, Angew. Chem. Int. Ed 2011, 50, 6552-6556. A palladium-catalyzed multi-component coupling approach to 7t-conjugated oligomers assembling imidazole-based materials from imines and acyl chlorides. 

Nickel-catalyzed highly regioselective multi-component coupling of ynamides, aldehydes and silane a new access to functionalized enamides. Propargyl alcohols (b) H. A. Malik, M. R. Chaulagain, J. Montgomery, Org. Lett. 2009,... 

In this study, the author examined an atom-economical and diversity-oriented synthesis of 2-(aminomethyl)indoles/isoquinolmes by copper-catalyzed domino multi-component coupling-cyclization. One-pot construction of polycyclic in-doles/isoquinolines bearing an aminomethyl moiety was also investigated. 

In contrast to polymer theories, multi-component theories explicitly consider the dynamics of polyions, gegenions and coions and provide a detailed understanding of dynamic coupling phenomena. The theoretical formulation of the multi-component, coupled diffusion problem is quite complex and the mathematical treatment requires gross simplification. Current calculations treat all components as point particles exhibiting different mobilities and charges which obviously represent a rather poor approximation for the polyion structure. 

One-Pot Multi-component Coupling of Bis(alkynyl) silanes, Nitriles and Isocyanides and Synthesis of N-Containing Heterocycles via Intramolecular Cyclization of Iminoacyl-Zr Intermediates... 

The author explored the reaction chemistry of intermediates 2-6 with isocyanides. Isocyanides bearing less-bulky and bulky substituents led to mono- and bis (iminoacyl)-Zr intermediates, respectively. Upon hydrolysis, the isolated mono (iminoacyl)-Zr intermediates underwent intramolecular cyclization to afford tetra-substituted 5-azaindoles, while intramolecular cyclization of bis(iminoacyl)-Zr intermediates led to the formation of dihydropyrrolo[3,2-c]azepines. Based on the above results, the author developed zirconocene-mediated multi-component coupling of bis(alkynyl)silanes, nitriles, and isocyanides. The structure of a bis(imi-noacyl)-Zr intermediate, formed via insertion of two molecules of CyNC into the Zr-C bond, and structures of two dihydropyrrolo[3,2-c]azepines were characterized by single-crystal X-ray structural analysis (Scheme 2.9). 

Scheme 2.9 One-pot synthesis of N-containing heterocycles by multi-component coupling of bis (atkynyl)silanes, nitriles, and isocyanides via intramolecular cyclization of iminoacyl—Zr intermediates...

As introduced in the previous section, reactive organometallic intermediates 2-6 were synthesized in situ in high yields via multi-component coupling of Cp2ZrBu2, bis(alkynyl)silane, and nitriles. Reaction of benzyl azide BnN3 with 2-6a (Ar = Ph,... 

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