Multi-component coupling reactions

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]. 

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. 

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

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]. 

Although multi-component domino reactions under NHC-catalysis are still scarce in the literature, an elegant three-component example allowing the access to highly functionalized dx-e-ketoesters (130) has been documented. " This three-component domino method involves coupling of an enal, a chalcone and propargyl alcohol using... 

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. 

In this book we considered mass transfer and elemental migration between the atmosphere, hydrosphere, soils, rocks, biosphere and humans in earth s surface environment on the basis of earth system sciences. In Chaps. 2, 3, and 4, fundamental theories (thermodynamics, kinetics, coupling model such as dissolution kinetics-fluid flow modeling, etc.) of mass transfer mechanisms (dissolution, precipitation, diffusion, fluid flow) in water-rock interaction of elements in chemical weathering, formation of hydrothermal ore deposits, hydrothermal alteration, formation of ground water quality, seawater chemistry. However, more complicated geochemical models (multi-components, multi-phases coupled reaction-fluid flow-diffusion model) and phenomenon (autocatalysis, chemical oscillation, etc.) are not considered. 

Microwave irradiation has been proven useful in accelerating chemical reactions. A unique approach to multi-component reactions - the combination of microwave irradiation and microreactors - was developed by Organ and Bremner [37]. The three-component coupling reaction of amino pyrazole with aldehyde and diketone in a glass capillary tube microflow system (1180 p,m i.d.) under microwave irradiation (170 W) proceeded smoothly to give the desired quinolinone in high yield (Scheme 5.26). Without microwave irradiation, the reaction efficiency was very low. 

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). 

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,... 

Here va and va are the stoichiometric coefficients for the reaction. The formulation is easily extended to treat a set of coupled chemical reactions. Reactive MPC dynamics again consists of free streaming and collisions, which take place at discrete times x. We partition the system into cells in order to carry out the reactive multiparticle collisions. The partition of the multicomponent system into collision cells is shown schematically in Fig. 7. In each cell, independently of the other cells, reactive and nonreactive collisions occur at times x. The nonreactive collisions can be carried out as described earlier for multi-component systems. The reactive collisions occur by birth-death stochastic rules. Such rules can be constructed to conserve mass, momentum, and energy. This is especially useful for coupling reactions to fluid flow. The reactive collision model can also be applied to far-from-equilibrium situations, where certain species are held fixed by constraints. In this case conservation laws... 

Abstract Recent advances in the metal-catalyzed one-electron reduction reactions are described in this chapter. One-electron reduction induced by redox of early transition metals including titanium, vanadium, and lanthanide metals provides a variety of synthetic methods for carbon-carbon bond formation via radical species, as observed in the pinacol coupling, dehalogenation, and related radical-like reactions. The reversible catalytic cycle is achieved by a multi-component catalytic system in combination with a co-reductant and additives, which serve for the recycling, activation, and liberation of the real catalyst and the facilitation of the reaction steps. In the catalytic reductive transformations, the high stereoselectivity is attained by the design of the multi-component catalytic system. This article focuses mostly on the pinacol coupling reaction. 

It is important to select stoichiometric co-reductants or co-oxidants for the reversible cycle of a catalyst. A metallic co-reductant is ultimately converted to the corresponding metal salt in a higher oxidation state, which may work as a Lewis acid. Taking these interactions into account, the requisite catalytic system can be attained through multi-component interactions. Stereoselectivity should also be controlled, from synthetic points of view. The stereoselective and/or stereospecific transformations depend on the intermediary structure. The potential interaction and structural control permit efficient and selective methods in synthetic radical reactions. This chapter describes the construction of the catalytic system for one-electron reduction reactions represented by the pinacol coupling reaction. 

The above-mentioned multi-component catalytic systems are of synthetic potential in radical reactions. The generated ketyl radicals are able to undergo the inter- and intra-molecular coupling with a variety of radical acceptors. 

A combination of cat. Ybt and A1 is effective for the photo-induced catalytic hydrogenative debromination of alkyl bromide (Scheme 28) [69]. The ytterbium catalyst forms a reversible redox cycle in the presence of Al. In both vanadium- and ytterbium-catalyzed reactions, the multi-component redox systems are achieved by an appropriate combination of a catalyst and a co-reductant as described in the pinacol coupling, which is mostly dependent on their redox potentials. 

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