Biginelli reaction three component coupling

Ranu, B. C., Hajra, A., Jana, U. Indium(lll) chloride-catalyzed one-pot synthesis of dihydropyrimidinones by a three-component coupling of 1,3-dicarbonyl compounds, aldehydes, and urea an improved procedure for the Biginelli reaction. J. Org. Cbem. 2000, 65, 6270-6272. 

Scheme 3.6 Enantioselective Biginelli reaction via three component coupling...

This catalyst also promoted a three-component coupling reaction under improved protocol conditions for the Biginelli reaction. The recovered catalyst, which is washed with acetonitrile and dried at 150°C/0.5 Torr for 1.5 h, can be reused four successive times (Scheme 5.22) [123]. 

Other examples of scale-up involved a triphenylphosphine-free one-pot Wittig olefination, a one-step three-component synthesis of imidazo annulated pyridine and a metal-catalyzed Suzuki coupling. Kappe and co-workers also recently transferred conditions for reactions originally performed on a small scale with a mono-modal system, to scale-up by parallel synthesis in a multimodal batch reactor [13]. Typically, the scale-up was 100-fold, from 1 mmol examples included Biginelli condensations, Heck and Negishi couplings, and Diels-Alder cycloadditions with gaseous reactants. 

Dihydropyridines can be prepared via the three-eomponent coupling of cinnamaldehyde, aniline and p-keto esters under solvent-free conditions by means again of L-Pro as catalyst in the transformation. The three-component reaction of 1,3-indanedione, isatins and enamines as the nucleophiles is also possible in the presence of L-Pro for the one-pot synthesis of highly functionalised spirooxindoles derivatives. While only some examples are highlighted here, ° ° the possibilities of L-Pro in multicomponent reactions are tremendous. It has also shown good catalytie activity in classic multicomponent reactions such as Biginelli reactions and Hantzsch dihydropyridine synthesis. 

Biginelli reaction beyond three-component limit synthesis of functionalized pyrimidinones via a one-pot Biginelli-Pd mediated C-C coupling strategy. 

Abstract The Biginelli reaction, a three-component cyclocondensation reaction, is an important member of the multicomponent reaction (MCR) family. The Biginelli reaction is so efficient and shares many similar properties as the recent click reactions. In this chapter, we summarised the current applications of the Biginelli reaction in polymer chemistry including polymer coupling, post polymer modification, and new functional polymer synthesis. We expect this old reaction (>120 years) can draw attention from polymer chemists and play new roles in the polymer science. 

Urea and its derivatives can form imines when treated with aldehydes. In the presence of [3-ketoesters, these imines are subject to nucleophilic attack followed by intramolecular imine formation. This three-component transformation is known as the Biginelli reaction [94]. The resulting products are dihydropyrimidi-nones, which are compounds of high importance in medicinal chemistry [95]. In 2006, Gong and coworkers reported the first organocatalytic Biginelli reactions. Several different aromatic aldehydes 186, ]3-ketoesters 188, and (thio)urea (187) were successfully coupled in the presence of chiral phosphoric acid catalyst 99a (Scheme 42.43). Whereas aromatic aldehydes delivered the desired Biginelli... 

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