Three-component reactions reaction

Two- and three-component Hantzsch reactions using C-glycosylated reagents have been reported as an alternate method for conducting asymmetric syntheses of 1,4-dihydropyridines." ° Reaction of 109, 110 and 97 generate 111 with Ri = sugar. Alternatively, 112 and 113 produce 111 with Ri = sugar. While the yields were acceptable (60-90%), the diastereomeric ratio varied from 30-60%. 

Tlie Ca substituent effects have been experimentally studied by synthesizing and investigating the A -(l,2,2,2-tetrachloroethyl)pyridinium chloride (43). Tlie synthesis of 43 follows the standard three-component reaction. Tliionyl chloride, trichloroacetaldehyde, and pyridine were reacted at 0°C in MeCN to give this salt in excellent yield (Scheme 31). 

A short synthesis of ptostaglandm derivatives via a three component coupling reaction reported, in which the enolates are trapped v/ith nitroalkenes. The nitro group is removed v... 

Scheme 5.1-43 Three-component reaction of benzaldehyde, aniline, and diethyl phosphonate in ionic liquids, catalyzed by lanthanide triflates and indium(lll) chloride.

The Maunich reaction of a ketone, an amine, and an aldehyde is one of the few three-component reactions in organic chemistry. Cyclohexanone, for example, reads with dimethylamine and acetaldehyde to yield an amino ketone. The reaction takes place in two steps, both of which are typical carbonyl-group reactions. 

Yamamoto and coworkers developed cycloadditions between activated olefins and vinylaziridines 253 with the aid of a palladium(O) catalyst (Scheme 2.63) [94], based on their three-component aminoallylation reaction. The corresponding 4-vi-nylpyrrolidines 255 were obtained as mixtures of diastereomers (ds trans= 55 45 to 23 77). 

A direct insertion of sulfur dioxide into a C—C bond has been observed under photochemical conditions 3 (equation 72) a related CH insertion followed by an intramolecular sulfinate to carbonyl addition yields the same system 3 (equation 73). A further sulfolene synthesis utilizes a three-component reaction see equation 74 (cf. Section IV below) 35. 

A microwave-assisted three-component reaction has been used to prepare a series of 1,4-disubstituted-1,2,3-triazoles with complete control of regiose-lectivity by click chemistry , a fast and efficient approach to novel functionalized compounds using near perfect reactions [76]. In this user-friendly procedure for the copper(l) catalyzed 1,3-dipolar cycloaddition of azides and alkynes, irradiation of an alkyl halide, sodium azide, an alkyne and the Cu(l) catalyst, produced by the comproportionation of Cu(0) and Cu(ll), at 125 °C for 10-15 min, or at 75 °C for certain substrates, generated the organic azide in situ and gave the 1,4-disubstituted regioisomer 43 in 81-93% yield, with no contamination by the 1,5-regioisomer (Scheme 18). 

The use of microwave-assisted multicomponent cycloaddition reactions allows unique heterocyclic scaffolds to be assembled rapidly from readily accessible starting materials. The three-component reaction of M-alkyl-l,4-DHP... 

Radical-based carbonylation procedures can be advantageously mediated by (TMSlsSiH. Examples of three-component coupling reactions are given in Reactions (74) and (75). The cascade proceeds by the addition of an alkyl or vinyl radical onto carbon monoxide with formation of an acyl radical intermediate, which can further react with electron-deficient olefins to lead to the polyfunctionalized compounds. ... 

In analogy, Ugi et al. reported on a lactam formation by running a one-pot three components reaction the condensation of L-lysine 7, isobutyraldehyde and methyl isocyanide led to the corresponding a-amino-c-caprolactam 9, but the yield was not given. The authors presumed either a nucleophilic substitution of the ester 8 as the primary Ugi product by the amino function of the side chain or, alternatively, the nucleophilic attack of the NH2-group on an intermediately formed 0-acylamide and a subsequent rearrangement (Scheme 1) [4]. 

H)2-D3 is a weak agonist and must be modified by hydroxylation at position Cj for full biologic activity. This is accomplished in mitochondria of the renal proximal convoluted tubule by a three-component monooxygenase reaction that requires NADPFl, Mg, molecular oxygen, and at least three enzymes (1) a flavoprotein, renal ferredoxin reductase (2) an iron sulfur protein, renal ferredoxin and (3) cytochrome P450. This system produces l,25(OH)2-D3, which is the most potent namrally occurring metabolite of vitamin D. 

Scheme 17 Iron-catalyzed three-component coupling reactions of aldehydes, terminal alkynes, and amines...

Jones, R. M. Selenski, C. Pettus, T. R. R. Rapid syntheses of benzopyrans from o-OBOC salicylaldehydes and salicyl alcohols a three-component reaction. J. Org. Chem. 2002,67, 6911-6915. 

Recently, a Pd/Cu-catalyzed three-component coupling reaction of aryl halides, norbomadiene, and alkynols was reported to generate 2,3-disubstituted norbomenes in high yields in the presence of aqueous NaOH and a phase-transfer catalyst in toluene at 100°C (Eq. 3.39).151... 

Recently, on the basis of the Markovnikov addition of water to alkynes, Trost et al. developed a three-component addition reaction of terminal alkynes, water, and methyl vinyl ketone, affording 1,5-diketones in DMF/water in the presence of ruthenium and indium catalysts (Eq. 4.38). 

A tin(II)-catalyzed asymmetric aldol reaction and lanthanide-catalyzed aqueous three-component reaction have been used as the key steps for the synthesis of febrifugine and isofebrifugine (Scheme 8.31).293... 

Scheme 2.95. Results of the three-component reaction leading to compounds 2-402.

Scheme 2.117. Three-component domino reaction leading to aza-analogs of podophyllotoxin (2-508).

In 1987, Vaultier and coworkers [27] developed a combination of a [4+2] cycloaddition of a bora-1,3-diene to provide an allylborane, which then reacts with an aldehyde to give a highly functionalized alcohol. The Lallemand group, as well as Hall and colleagues, has recently used this procedure. In an approach for the synthesis of the antifeedant natural product clerodin (4-83), Lallemand and coworkers performed a three-component domino reaction of 4-80, 4-81 and methyl acrylate to give 4-82 (Scheme 4.18) [28]. 

The Hall group [52] has developed a new three-component domino reaction of 1-aza-4-borono-1,3-butadiene 4-152, a dienophile and an aldehyde to give a-hydroxy-methylpiperidine derivatives. In the first step, a hetero-Diels-Alder reaction takes place, which is followed by allylboration. As an example, reaction of 4-152 with the maleimide 4-153 in the presence of benzaldehyde furnished 4-154 in yields of up to 80% using the three substrates in a 1 2 1 ratio (Scheme 4.32). 

As main product, 4-219 (56%) was obtained together with 9% of a stereoisomer. The reaction can also be performed as a three-component reaction using 4-216, 4-217 and 4-218, which gave a mixture of 4-219, 4-220 and 4-221. The latter transformation indicates that intermediates such as 4-222 or 4-223 might play a role in this domino process. 

A domino process based on the twofold addition of alkenyl anions to a squarate ester was used by Paquette and coworkers [96] for the total synthesis of the triqui-nane sesquiterpene hypnophilin (4-284). The three-component reaction of 4-281,4-282 and vinyl lithium gave primarily the trans- and cis-adducts A and B, which furnished D either by an electrocyclic ring opening/ring closure via C or a dianionic oxy-Cope rearrangement (Scheme 4.60). Further transformations led to E and F, which resulted in the formation of 4-283 on treatment with acid. 

Recently, Larock and coworkers used a domino Heck/Suzuki process for the synthesis of a multitude of tamoxifen analogues [48] (Scheme 6/1.20). In their approach, these authors used a three-component coupling reaction of readily available aryl iodides, internal alkynes and aryl boronic acids to give the expected tetrasubsti-tuted olefins in good yields. As an example, treatment of a mixture of phenyliodide, the alkyne 6/1-78 and phenylboronic acid with catalytic amounts of PdCl2(PhCN)2 gave 6/1-79 in 90% yield. In this process, substituted aryl iodides and heteroaromatic boronic acids may also be employed. It can be assumed that, after Pd°-cata-lyzed oxidative addition of the aryl iodide, a ds-carbopalladation of the internal alkyne takes place to form a vinylic palladium intermediate. This then reacts with the ate complex of the aryl boronic acid in a transmetalation, followed by a reductive elimination. 

Based on a transformation described by Catellani and coworkers [61], the Lautens group [62] developed a three-component domino reaction catalyzed by palladium for the synthesis of benzo annulated oxacycles 6/1-114 (Scheme 6/1.30). As substrates, these authors used a m-iodoaryl iodoalkyl ether 6/1-113, an alkene substi-... 

N-Acyl-a-amino acids are important compounds in both chemistry and biology. They are easily obtained in a transition metal-catalyzed, three-component domino reaction of an aldehyde, an amide, and CO. Whereas cobalt was mainly used for this process, Beller and coworkers [159] have recently shown that palladium has a... 

Scheme 6/2.7. Three-component reaction of a a-diazoester, an imine and an alkene.

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