Multi-component reactions Biginelli reaction

The same catalyst (93) was applied with success to the first organocatalytic multi component asymmetric Biginelli reaction providing medicinally relevant chiral 3,4-dihydropyrimidini-2-(l//)-ones (94) (Scheme 29)7 Chiral acid-catalyzed inverse electron-demanding aza Diels-Alder reaction of aldimines (95) with electron-rich alkenes (Scheme 30). A new catalyst salt (96) that consist of an achiral ammonium ion and chiral phosphate anion has been developed that catalyzes highly... 

While the early examples of this cyclocondensation process typically involved a / -ketoester, aromatic aldehyde and urea, the scope of this heterocycle synthesis has now been extended considerably by variation of all three building blocks, allowing access to a large number of multifunctionalized pyrimidine derivatives. For this particular heterocyclic scaffold the acronym DHPM has been adopted in the literature and is also used throughout this chapter. Owing to the importance of multi-component reactions in combinatorial chemistry there has been renewed interest in the Biginelli reaction, and the number of publications and patents describing... 

A comprehensive study has investigated multidirectional cyclative cleavage transformations leading to bicyclic dihydropyrimidinones [61]. This approach required synthesis of 4-chloroacetoacetate resin as the key starting material this was prepared by microwave-assisted acetoacetylation of commercial available hydroxymethyl polystyrene resin under open-vessel conditions. This resin precursor was subsequently treated with urea and a variety of aldehydes in a Biginelli-type multi-component reaction, leading to the corresponding resin-bound dihydropyrimidinones (Scheme 16.40). The desired furo[3,4-d]pyrimidine-2,5-dione scaffold was obtained by a novel procedure for cyclative release under the action of micro-wave irradiation in sealed vials at 150 °C for 10 min. 

Several of the parallel-type Milestone microwave reactor systans have been used for scale-up of reactions, including the pharmaceutically valuable Biginelli and Hantzsch multi-component reactions. The work showed reproducibility throughout a set of small reaction vessels run in parallel, and also the applicability of one set of conditions across a range of substrates. 

The Passerini reaction followed the reaction of Pietro Biginelli (1860-1937) who, in 1891, proposed the revolutionary idea of a multi-component reaction [5-8]. 

The Biginelli reaction involves an one-pot reaction between aldehyde 1, 1,3-dicarbonyl 2, and urea 3a or thiourea 3b in the presence of an acidic catalyst to afford 3,4-dihydropyrimidin-2(l//)-one (DHPM) 4. This reaction is also referred to as the Biginelli condensation and Biginelli dihydropyrimidine synthesis. It belongs to a class of transformations called multi-component reactions (MCRs). 

Heterocyclic chemistry has been a major beneficiary of MW-expedited solvent-lfee chemistry utilizing mineral supported reagents. It has been exploited for parallel synthesis, a strategy that is adaptable for multicomponent reactions, such as Ugi " and Biginelli reactions " , for rapid assembly of a library of compoimds. A representative multi-component condensation reaction to create a small-molecule library of imidazo[l,2-a]pyridines, imidazo[l,2-a] pyrazines, and imidazo[l,2-a]pyrimidines is depicted in Scheme 3. 

S. R. Jetti, D. Verma, S. Jain, J. Chem. Pharm. Res. 2012,4, 2373-2379. NBS/AIBN promoted one-pot multi component regioselective synthesis of spiro heterobicyclic rings via Biginelli-like condensation reaction. 

The Biginelli multi-component synthesis of 5-acyl dihydropyrimidin(thi)ones (117, X = S or O) from a (thio)urea, [H2N-C(=X)-NH2], an aldehyde (R -CHO) and a )5-ketoester (R -CO-CH2-CO-R ) has provided a wide range of anti-tumour candidates. " Using an ion-tagged iron catalyst - an imidazolium with FeC " or Fe2Cl7 as counterion - the reaction can be carried out under ionic liquid conditions. 

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