Five-component reaction

More recently, a catalyst-free aqueous version of this strategy was proposed with simple acyclic 1,3-dicarbonyls, formaldehyde, and styrene or anilines derivatives (Scheme 40) [131], In the first case (Scheme 40), the very reactive 2-methylene-1,3-dicarbonyl intermediate reacts smoothly at 80°C with a variety of substituted styrenes to give the corresponding dihydropyrans in moderate to good yields. Remarkably, when styrenes were replaced by A-ethylaniline, a novel five-component reaction involving twofold excess of both formaldehyde and 1,3-dicarbonyl selectively occurred (Scheme 41). The result is the formation of complex fused pyranoquinolines following a Friedel-Craft alkylation - dehydration sequence to furnish the quinoline nucleus, which suffers the Hetero-Diels-Alder cyclization in synthetically useful yields. 

Scheme 5.15 Possible reaction sequence of the five-component reaction.

By using a multicomponent cascade reaction. Parsons et al. [88] achieved one-pot sequential [1+4] and [3+2] cycloadditions to synthesize highly substituted iso-xazolines via nitrile oxides (Scheme 11.28). These five-component reactions proceed by initial formation of isonitriles 109 that react with nitroalkenes 110 to form unstable N-(isoxazolylidene)alkylamines, which in turn fragment to generate the nitrile oxides 111. Cycloaddition then occurs with methyl acrylate, chosen for its expected reactivity with nitrile oxide dipoles, to generate the isoxazolines 112. Reactions using standard thermal conditions and microwave irradiation were com-... 

Alternatively, halide-free 1,3-dialkylimidazolium ILs can be prepared from the five-component reaction (glyoxal, formaldehyde, two different amines and acids. Scheme 2), and those containing alkyl sulfate or trifluoromethane sulfonate anions by simple alkylation of 1-alkylimidazole with the corresponding dialkylsulfate or alkyltrifluoro-methane sulfonate ester, respectively. " ... 

Lashkari M, Maghsoodlou MT, Hazeri N, Habibi-Khraassani SM, Sajadikhah SS, Doostmohamadi R. Synthesis of highly functionalized piperidines via one-pot, five-component reactions in the presence of acetic acid solvent. Synthetic Comm 2013 43(5) 635. ... 

A one-pot five-component reaction of salicylaldehydes, malononi-trile, hydrazine hydrate, aryl isothiocyanates, and water in a mixture of... 

By applying thiophene-2,5-dicarbonyl dichloride (4a) and 2,5-diethy-nylthiophene (5f) in the sense of a pseudo five-component reaction under slightly adjusted reaction conditions, symmetrically substituted and regioisomeric terthiophenes 46 and quinquethiophenes 47 can be synthesized in a straightforward fashion (Scheme 28) (2013OBC(l 1)3541). 

Similarly, terephthaloyl dichloride (4b) and 1,4-diethynylbenzene (5g) can be appbed in a pseudo five-component reaction to synthesize the corresponding p-phenylene-bridged derivatives 48 and 49 in moderate to good yields (Scheme 29). 

By combing the three-component synthesis of oxazole with the above two bimolecular domino processes, a five-component reaction was subsequently developed [37]. The optimized conditions consisted of performing the reaction in toluene in the presence of a catalytic amount of camphorsulfonic acid (CSA, O.lequiv). 

Shaabani, A., Ghadari, R., Ghasemi, S., Pedarpour, M., Rezayan, A.H., Sarvary, A., Ng, S.W. 2009. Novel one-pot three- and pseudo-five-component reactions Synthesis of functionalized benzo[g]- and dihydropyrano[2,3-g]chromene derivatives. Journal of Combinatorial Chemistry ll(6) 956-959. 

Although less explored, five-component reactions represent an interesting manner to obtain highly functionalized scaffolds, but only few examples have appeared after the pioneering work reported by Armstrong in 1998 [54]. The... 

M. Baraijanian, S. Balalaie, B. Movassagh, H. R. Bijanzadeh, Tetrahedron Lett. 2010, 51, 3277-3279. Efficient synthesis of 1,4-disnbstituted polyfunctional piperazines via a seqnential one-pot Ugi/nucleophilic addition five-component reaction. 

Khan et al. [131] reported a simple and convenient one-pot multicomponent reaction (MCR) for the synthesis of highly functionalized piperidines 87,88, and 89 using molecular iodine as a catalyst. This strategy demonstrated the five-component reaction of 1,3-dicaiboityl compounds, amines, and aromatic aldehydes in... 

Khan AT, Khan MM, Bannuru KKR (2010) Iodine catalyzed one-pot five-component reactions for direct synthesis of densely functionalized piperidines. Tetrahedron 66 7762-7772... 

Shaabani, A., Ghadari, R., Sarvary, A., and Rezayan, A. H. (2009). Synthesis of highly functionalized bis(477-chromene) and 477-benzo[g]chromene derivatives via an isocyanide-based pseudo-five-component reaction. J. Org. Chem., 69, 4372-4374. 

An elegant approach to the diastereoselective synthesis of densely functionalized 1,2,5,6-tetrahydropyridines 31 based on the a,Y-difunctionalization of 1,3-dicarbonyl compounds was pioneered in 2007 by Clarke [23], and then followed up by other groups [24-26], It generates five new eovalent bonds and proceeds via a domino pseudo five-component reaction from anilines, aromatic aldehydes (2 equiv. of each). 

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