3-Aryl pyridines, synthesis under

More recently, Shen et al. reported on a green and efficient three-component one-pot synthesis of 2-aryl-pyridines with the same starting materials as the Hanztsch reaction, under solvent-, catalyst-, and heat-free conditions. This methodology does... 

Compound 157 has been used in a short synthesis of (/ )-ibuprofen methyl ester (161) [58] (Scheme 24). Acetalization of optically pure aryl ketone 159 under basic conditions produces hydroxy acetal 160 (74% ee), where the configuration at the asymmetric carbon is inverted. Treatment of 160 with sulfuryl chloride in pyridine at —50 °C causes facile 1,2-aryl migration and affords the target molecule 161 stereospecifically. 

A one-pot, three-component synthesis was reported to give the 2-aryl-pyridines 144 in good to excellent yields under solvent-, catalyst-, and heat-... 

A large number of Brpnsted and Lewis acid catalysts have been employed in the Fischer indole synthesis. Only a few have been found to be sufficiently useful for general use. It is worth noting that some Fischer indolizations are unsuccessful simply due to the sensitivity of the reaction intermediates or products under acidic conditions. In many such cases the thermal indolization process may be of use if the reaction intermediates or products are thermally stable (vide infra). If the products (intermediates) are labile to either thermal or acidic conditions, the use of pyridine chloride in pyridine or biphasic conditions are employed. The general mechanism for the acid catalyzed reaction is believed to be facilitated by the equilibrium between the aryl-hydrazone 13 (R = FF or Lewis acid) and the ene-hydrazine tautomer 14, presumably stabilizing the latter intermediate 14 by either protonation or complex formation (i.e. Lewis acid) at the more basic nitrogen atom (i.e. the 2-nitrogen atom in the arylhydrazone) is important. 

To carry out the similar MCR involving 5-amino-3-methyl-l-phenylpyrazole, aromatic aldehydes, and 3-cyanoacetyl indoles, Zhu et al. [70] used microwave-assisted synthesis in glygol at 150°C. Application of other solvents was less effective and gave either no reaction products (water medium) or led to the sufficient yield decreasing (EtOH, HOAc, DME). Microwave irradiation was also used by Quiroga et al. [71] to synthesize ether 4-aryl-5-cyano-6-phenylpyrazolo[3,4-b]pyridine-3-ones or their dihydroderivatives under argone atmosphere. 

Historically, the first example of such a cyclization was the high-yield synthesis of 2-substituted benzimidazoles 104, on treatment of A -aryl-A -hydroxyamidines 101 with benzenesulfonyl chloride in the presence of a base (usually Et3N or pyridine) under anhydrous conditions (58JCS2086). The reaction most likely proceeds through... 

Ji and co-workers [73] have elaborated a simple and efficient approach for the synthesis of highly functionalized pyridines 24 via a one-pot, three-component reaction under microwave irradiation. This method enables the incorporation of a pyrazolo[3,4-h]pyridine and an indole moiety into the same molecule. The synthesis was achieved by reaction of a suitable aldehyde and 3-cyanoacetyl indole with 5-aminopyrazol. Particularly valuable features of this method include high yields, broad substrate scope, and short reaction times. It has been observed that when there are electron-withdrawing groups on the aryl aldehyde this results in a faster and higher yielding reaction (Scheme 21). 

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