Multicomponent reactions three-component couplings

As the intermolecular multicomponent reactions, three-component cycloaddition reactions (21.2 [2+2-1-2] cycloaddition and 21.3 [3+2+1] cycloaddition) and two-component cycloaddition reactions (21.4 [4+2] cycloaddition) are described. As the intramolecnlar single-component reactions, cycloaromatization reactions (21.5 intramolecular hydroarylation of alkynes and cychzation via transition metal vinybdenes) are described. Aromatic ring constrnction reactions involving aryne reactions (Chapter 12), rearrangement reactions (Chapters 16 and 18), metathesis reactions (Chapter 17), and coupling reactions (Chapters 19 and 20) are described in these different chapters. 

Carbon monoxide is able to participate in allyltin-mediated multicomponent reactions. In Scheme 6.19, two examples of three-component coupling reactions giving unsaturated ketones are shown [33], Because of the slow reaction of acyl... 

Microwave irradiation has been proven useful in accelerating chemical reactions. A unique approach to multicomponent reactions - the combination of microwave irradiation and microreactors - was developed by Organ and Bremner [25]. The three-component coupling reaction of amino pyrazole with an aldehyde and diketone in a glass capillary tube microflow system (1180 pm i.d.) under microwave irradiation (170 W) proceeded smoothly to give the desired quinolinone in high yield (Scheme 4.16). Without microwave irradiation, the reaction efficiency was very low. 

A four-component coupling between benzyl halides and alkynyl stannanes has been developed for the preparation of functionalized enynes. Activated olefins participate in a regioselec-tive Pd(dba)2-catalyzed three-component coupling with allylic acetates and BusSnH. Allylic amines have been prepared via reaction of vinyl halides, alkenes, and amines in the presence of Pd(dba)2 and BU4NCI. Organogermanes and silanes have been constructed via multicomponent carbogermanylation and carbosilylation sequences. 

The first multicomponent reaction was the Strecker reaction reported in 1850 by Adolf Strecker [241aj. It is a three-component coupling between carbonyl derivatives, amines, and cyanide source, such as hydrogen cyanide, to provide a-aminonitriles which constitute potent starting materials to achieve important a-amino acids by simple hydrolysis. The mechanism of the Strecker reaction involves the initial formation of an imine from condensation of the amine component to the carbonyl component, after which addition of the cyanide component to this imine intermediate follows. Although the first enantioselective, metal-catalyzed Strecker... 

A three component coupling reaction involving carbopallada-tion of the aryne followed by a Fleck coupling with tert-butyl acrylate affords oFtAo-substituted cinnamic acids in good yields (eq 11). An ene reaction between the aryne, generated in THF at room temperature, and an alkyne creates allenylbenzenes in moderate yields. The reaction of jr-allylpalladium species with the benzyne created from 2-(trimethylsilyl)phenyl triflate provides access to several types of products in multicomponent... 

A novel three-component coupling reaction for the synthesis of 2-(aminomethyl) indoles and polycyclic indole derivatives from readily available N-protected ethynylanilines, amines, and aldehydes was reported by Ohno, Fujii, and coworkers. This is the first copper catalytic multicomponent construction of an indole ring that produces water as the only by-product. Two C-N bonds and one C-C bond are formed, whereas C(sp)-H bonds of alkynes and C(sp )-H bonds of aldehydes were activated in this reaction [45-48] (Scheme 8.19). 

The first multicomponent coupling was a three-component coupling of vinylketones with alkynes and water resulting in the formation of the 1,5-diketones 196 (Scheme 86). The reaction was catalyzed by the ruthenium complex 78 and the successful course of the reaction required the presence of a Lewis acid (indium(III)triflate). Some typical examples are given Table 40 [124]. 

The palladium-catalyzed multicomponent coupling reactions have attracted considerable interest.12,12a 12e A reaction using allylstannane 39 and allyl chloride 40 was applied to the three-component diallylation of benzylidenema-lonitrile and its congeners by Yamamoto et al 2 Analogous diallylation of isocyanate 41 was studied by Szabo et al. (Scheme 7).12a The reaction mechanism can be explained by formation of an amphoteric bis-allylpalladium intermediate 43 which undergoes an initial electrophilic attack on one of the allyl moieties followed by a nucleophilic attack on the other. 

This chapter contains a survey of free-radical-mediated multicomponent reactions (MCRs), which permit the coupling of three or more components. Even though they are not technically classified as MCRs, remarkable intramolecular radical cascade processes have been developed. Some examples, such as those shown in Scheme 6.3, use an isonitrile or acrylonitrile as the intermolecular component for each reaction [6]. These examples demonstrate the tremendous power of the combination of inter- and intramolecular radical cascade processes in organic synthesis. Readers are advised to be aware of remarkable intramolecular aspects of modem radical chemistry through excellent review articles published elsewhere [1, 7]. It should also be noted that there has also been remarkable progress in the area of living radical polymerizations, but this will not be covered here. 

The combination of carbon monoxide with sulfonyl oxime ethers allow for a set of multicomponent coupling reactions involving consecutive Cl/Cl-type coupling, a rare class of radical multicomponent reactions. In Scheme 6.27, examples of three-, four-, and five-component coupling reactions are shown [46], In these reactions, allyltin is not incorporated into the product, but serves as an acceptor of the phenylsulfonyl radical and a source of the tributyltin radical, which delivers the radical chain. 

Andreana and co-workers [188] developed a one-pot method for generating molecular diversity via a multicomponent coupling reaction under microwave irradiation. The initially formed Ugi four-component coupling products gave rise to three structurally distinct scaffolds depending on the solvent effects and sterics the 2,5-diketopiperazines 137, the 2-azaspiro[4.5]deca-6,9-diene-3,8-diones 138, and the thiophene-derived Diels-Alder tricyclic lactams 139 (Scheme 107). 

Dihydropyridines can be prepared via the three-eomponent coupling of cinnamaldehyde, aniline and p-keto esters under solvent-free conditions by means again of L-Pro as catalyst in the transformation. The three-component reaction of 1,3-indanedione, isatins and enamines as the nucleophiles is also possible in the presence of L-Pro for the one-pot synthesis of highly functionalised spirooxindoles derivatives. While only some examples are highlighted here, ° ° the possibilities of L-Pro in multicomponent reactions are tremendous. It has also shown good catalytie activity in classic multicomponent reactions such as Biginelli reactions and Hantzsch dihydropyridine synthesis. 

Considering the practical importance of isocyanide-free MCRs, metal-catalyzed multicomponent reactions (MC-MCRs) are ideal candidates for polymer synthesis. Among the growing number of MC-MCRs, the three-component reaction between amines, aldehydes, and acetylenes (A -coupling) should be addressed. A -coupling... 

Multicomponent reactions (MCRs) have attracted much attention in the past decade because of advantages such as high atom economy, simple procedure, and high efficiency. [1] Because of their ability to generate complex structures economically and efficiently [2], numerous MCRs have been developed and widely studied, such as the Cu-catalyzed three-component reactions [3-6], Mannich reactions [7, 8], Passerini reactions [9, 10], and A3-coupling reactions [11]. Of these, multicomponent alkyne reactions have become quite popular recently and abundant literature has been published regarding the various MCRs of alkynes with all sorts of reactants [12, 13]. 

Abstract The Biginelli reaction, a three-component cyclocondensation reaction, is an important member of the multicomponent reaction (MCR) family. The Biginelli reaction is so efficient and shares many similar properties as the recent click reactions. In this chapter, we summarised the current applications of the Biginelli reaction in polymer chemistry including polymer coupling, post polymer modification, and new functional polymer synthesis. We expect this old reaction (>120 years) can draw attention from polymer chemists and play new roles in the polymer science. 

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