Pyridines multicomponent approach

Pyridine and its partially or totally unsaturated derivatives such as tetrahydropy-ridines, DHPs, and piperidines are ubiquitous cores found in numerous natural product skeletons and in synthetic compounds of primary interest for synthetic chemistry, agrochemistry, or pharmacology. Among the various methodologies available for the synthesis of these compounds, multicomponent approaches have attracted much attention in the last few years. Most of these sequences are initiated by a Michael addition. 

MUller reports a four component, one-pot synthesis of pyridines <02TL6907>. For example, aryl halide 15 and propargylic alcohol 16 were combined in the presence of copper and palladium to afford enone 17. The addition of cyclic enamine 18 led to Michael addition and the subsequent cyclocondensation was achieved by adding ammonium chloride and acetic acid (19—>20). Other multicomponent approaches to substituted pyridines have been reports by Litvinov <02RCBIE362>, Elkholy <02SC3493> and Veronese <02T9709>. 

Dediu OG, Yehia NAM, Oeser T, Polbom K, Muller TJJ (2005) Coupling-isomerization-enamine-addition-cyclocondensation sequences - a multicomponent approach to substituted and annealed pyridines. Eur J Org Chem 1834-1858... 

Scheme 5 An iron-catalyzed multicomponent approach to pyridines.

As CH-acids in the MCRs with aldehydes and aminoazoles, other classes of organic compounds were used as well. Cyanoacetic acid derivatives, acetoyl(aroyl) acetonitriles, ketosulfones, acetophenones, and other reagents were successfully introduced into these three-component heterocyclizations. For example, synthesis of pyrazolo[3,4-b]pyridine-5-carbonitriles 40 was carried out as the multicomponent treatment of 5-aminopyrazole, aldehyde, and benzoylacetonitriles solvent-free by fusion either in ammonium acetate at 120°C or in boiling ethanol with EtsN (Scheme 17) [69]. The second approach gave the worst results from the viewpoint of yields and purity of the target compounds. 

H.-R. Pan, Y.-J. Li, C.-X. Yan, J. Xing, Y. Cheng, J. Org. Chem. 2010, 75, 6644—6652. Multicomponent reaction of imidazo[l,5-a]pyridine carhenes with aldehydes and dimethyl acetylenedicarhoxylate or aUenoates a straightforward approach to fiiUy substituted finans. 

O. de Paohs, J. Baffoe, S. M. Landge, B. Torok, Synthesis 2008, 3423-3428. Multicomponent domino cyclization-oxidative aromatization on a bifunctional Pd/C/K-10 catalyst an environmentally benign approach toward the synthesis of pyridines. 

A series of azomethine yUdes have been generated through a rhodium-catalyzed reaction between sulfonyl triazoles and functionalized pyridines (Schane 3.141) [150]. Using this approach, an array of sterically and electronically diverse azomethine ylides were generated by systematic modification of the precursors. In addition to the isolation of these intriguing species, they were also used as intermediates in the preparation of 1,4-diazepines through a one-pot multicomponent reaction involving an internal activated alkyne such as dimethyl acetylenedicarboxylate. 

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