Reactions three-component

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). 

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. 

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... 

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]. 

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. 

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.

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. 

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

Staudinger reduction/aza-Wittig/Ugi three component reaction... 

A one pot samarium-catalyzed three-component reaction of aldehydes, amines, and nitroal-kanes leads to pyrroles. The reaction proceeds via imines, generated from the amine and carbonyl compound, followed by the Michael addition of the nitro compound (Eq. 10.10).12a In... 

Ugi five-center three-component reaction of pipecolinic acid and glycol aldehyde dimer with isocyanides gave a 1 1.7-2.1 diastereomeric mixture of l-oxoperhydropyrido[2,Tc][l,4]oxazine-9-carboxamides 397 (Scheme 35) <20010L4149>. Using CF3CH2OH as solvent is critical for the reaction. When 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid was employed, 1,3,4,6,11,11 a-hexahydro-[ l,4]oxazino[4,3+]isoquinoline-4-carboxarnide was formed. 

Pyrazole iminophosphorane 620 reacts with phenyl isocyanate and several ArTADs in a three-component reaction to provide low yields of the corresponding heteroannulated pyrazoles 621 as the final products (Equation 93) <1994JOC3985>. 

The three-component reaction between isatin 432a, a-aminoacids 433 (proline and thioproline) and dipolarophiles in methanol/water medium was carried out by heating at 90 °C to afford the pyrrolidine-2-spiro-3 -(2-oxindoles) 51. The first step of the reaction is the formation of oxazlidinones 448. Loss of carbon dioxide from oxazolidinone proceeds via a stereospecific 1,3-cycloreversion to produce the formation of oxazolidinones almost exclusively with /razw-stereoselectivity. This /f-azomethine ylide undergo 1,3-dipolar cycloaddition with dipolarophiles to yield the pyrrohdinc-2-r/ V -3-(2-oxindolcs) 51. (Scheme 101) <2004EJ0413>. 

Oxidation of the tetrahydroindolizine 338 with sodium chlorite gives the lactam 339, which rapidly lactonizes to give the pyranoindolizine 340 (Equation 122) <2001T8647>, and the one-pot , three-component reaction between the keto ester 235, acrolein, and o-aminophenol (formally analogous to that of Equation 63) gives the benzoxazolo-naphthyridine 341 (Equation 123) <20010L2145>. 

Three-component reaction of thiazolium salt, ketene precursor, and dimethyl acetylenedicarboxylate using Pr2Net as base gave rise to 1,4-thiazepine-fused furans in high yields, as can be seen in the following scheme <06AG(I)7793>. 

A recent total synthesis of tubulysin U and V makes use of a one-pot, three-component reaction to form 2-acyloxymethylthiazoles <06AG(E)7235>. Treatment of isonitrile 25, Boc-protected Z-homovaline aldehyde 26, and thioacetic acid with boron trifluoride etherate gives a 3 1 mixture of two diastereomers 30. The reaction pathway involves transacylation of the initial adduct 27 to give thioamide 28. This amide is in equilibrium with its mercaptoimine tautomer 29, which undergoes intramolecular Michael addition followed by elimination of dimethylamine to afford thiazole 30. The major diastereomer serves as an intermediate in the synthesis of tubulysin U and V. 

Nitroisoxazolines were prepared from ALalkoxy-3,3-dinitroisoxazolidines by thermally induced P-elimination. For example, isoxazolidines 42 synthesized by a three-component reaction of tetranitromethane with two equivalents of alkenes 41, were converted into isoxazolines 43 by heating in boiling chlorobenzene <06S706>. 

Novel three-component reactions of thiazole Schiff bases, ammonium acetate and aromatic aldehydes under solvent-free microwave irradiation conditions yielded diastereoselectively thiazolo-s-triazines <06GC455>. 

---