BigineUi reaction

Dong F, Jun L, Xinli Z, et al. One-pot green procedure for bigineUi reaction catalyzed by novel task-specific room-temperature ionic liquids. /. Mol. Catal. A-Chem. 2007. 274, 208-211. 

BigineUi reaction (Scheme 95) [359] A sample of the resin-bound (3-ketoester (459) (238 mg, 0.5 mmol) was suspended in dry dioxane (4 mL) at r.t. Then, the corresponding aldehydes (1.5 mmol), urea (90 mg, 1.5 mmol) and diox-ane/HClconc 2 1 (v/v) (10 mL) were added. The reaction mixture was gently stirred at 70 °C for 18 h. After the mixture was cooled to r.t, dioxane/HClconc 1 1 (v/v) (2 mL) was added and the mixture was stirred for an additional 5 min at r. t in order to dissolve the precipitated bisureide. The suspension was filtered, and the resulting resin-bound dihydropyrimiclines were washed as follows ... 

Peng J, Deng Y (2001) Ionic liquids catalyzed BigineUi reaction under solvent-free conditions. Tetrahedron Lett 42 5917-5919... 

Kappe et al. reported a microwave-assisted automated screening of conditions for the BigineUi reaction which was then used to synthesize a library of dihydropyrimidines (DHPMs Scheme... 

Ranu, B. C., Hajra, A. and Jana, U. 2000. Indium (HI) 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 BigineUi reaction. J. Org. Ghent. 65(19) 6270-6272. 

Although the original BigineUi reaction is an add-catalyzed process, more recently, base-catalyzed approaches have also gained interest because of their moderate to good results compared to that of the original procedure [39]. 

SCHEME 9.19 Invoked mechanism for one-pot oxidative multicomponent BigineUi reaction. 

SCHEME 9.20 SnCl -catalyzed BigineUi reaction using P-oxodithioesters as dicarbonyl compound. 

M.-I. Lannou, F. HeUon, J.-L. Namy, Synlett 2008, 105-107. Applications of lanthanide trichloride hydrates, prepared from mischmetaU, in the BigineUi reaction. 

R. Gonzalez-Olvera, P. Demare, 1. Regia, E. Juaristi, Arkivoc 2008, (vi), 61-72. Application of (15,4S )-2,5-diazabicy-clo[2.2.1]heptane derivatives in asymmetric organocatalysis the BigineUi reaction. 

J. Xin, L. Chang, Z. Hon, D. Shang, X. Liu, X. Feng, Chem.-Eur. J. 2008, 14, 3177-3181. An enantioselective BigineUi reaction catalyzed by a simple chiral secondary amine and achiral Brpnsted acid by a dual-activation route. 

J.-H. Sohn, H.-M. Choi, S. Lee, S. Joung, H.-Y. Lee, Eur. J. Org. Chem. 2009, 3858-3862. Probing the mode of asymmetric induction of BigineUi reaction using proline ester salts. 

S. Saha, J. N. Moorthy, J. Org. Chem. 2011, 76, 396-402. Enantioselective oiganocatalytic BigineUi reaction dependence of the catalyst on sterics, hydrogen bonding, and reinforced chirality. 

Garima, V. P. Srivastava, L. D. S. Yadav, Tetrahedron Lett. 2010,51, 6436-6438. BigineUi reaction starting directly fiom alcohols. 

For selected examples, see (a) M. Matloobi, C. O. Kappe, Comb. Chem. 2007, 9, 275-284. Microwave-assisted solution- and solid-phase synthesis of 2-amino -arylpyrimi-dinederivatives, (b) L. Pisani, H. Prokopcova, J. M. Kremsner, C. O. Kappe, J. Comb. Chem. 2007, 9, 415-421. 5-Aroyl-3, 4-dihydropyriniidin-2-one Ubrary generation via automated sequential and paraUel microwave-assisted synthesis techniques. (c) L. D. S. Yadav, A. Rai, V. K. Rai, C. Awasthi, Synlett 2007, 1905-1908. Biorenewable resources in the BigineUi reaction cerium(III)-catalyzed synthesis of novel iminosugar-annulatedperhydropyrimidines. 

Huang, Y. J., Yang, F. Y, Zhu, C. J. (2005). Highly enantioselective BigineUi reaction using a new chiral ytterbium catalyst asymmetric synthesis of dihydropyrimidines. Journal of the American Chemical Society, 127, 16386-16387. 

Scheme 199 The BigineUi reaction with abnormal regioselectivity...

Timoshenko VM, MarkitanovYM, ShermolovichYG (2011) 2-Oxo-2-polyfluoroalkylethane-1-sulfones and -sulfamides in the Biginelli and retro-BigineUi reactions. Tetrahedron Lett... 

FIGURE 7 Three possible key steps involved in the transfer of chirality in the BigineUi reaction catalyzed by L-proline and its derivatives. A Activation of acyHrnine by the chiral Bronsted acid B Stereoselectivy attack of chiral enamine to the acylimine C Involvement of both (A and B) activation properties on the asymmetric induction to provide chiral BigineUi adducts. 

FIGURE 8 Catalysts evaluated by Sohn and coUaborators for the BigineUi reaction. The values presented in parenthesis correspond to the... 

Thorat and co-workers [33] demonstrated that N-(4-F-phenyl)-l-tosylpyrrolidine-2-carboxamide (CAT-23) is an efficient catalyst for the BigineUi reaction (Table 4) [33]. An example of an organic salt that catalyzes the BiginelU reaction was reported by Ganem and coUaborators in 2006. This me odology uses L-proline methyl ester hydrochloride (CAT-24, Table 4) as a catalyst and provides the BigineUi adducts in reasonable yields (>77%) however, the adducts obtained from aliphatic aldehydes are obtained in more modest yields (<66%) [34]. 

L. IsmailH, A. Nadaradjane, L. Nicod, Synthesis and antioxidant activity evaluation of new hexahydropyrimido[5,4-c]quinolone-2,5-diones and 2-thioxohexahydropyrimido[5,4-c]quinolone-5-ones obtained by BigineUi reaction in two steps, Eur. J. Med. Chem. (2008) 1270-1275. 

To furnish a convenient reaction platform, polymer chemists have explored the utility of non-isocyanide-based MCRs in order to avoid the use of isocyanides. For example, Tao and coworkers focused intensively on the employment of non-isocyanide MCRs such as the BigineUi reaction [70] and the three-compmient reaction between aldehydes, amines, and mercaptoacetic acid [71]. In additimi, the utility of the Kabachnik-Fields reaction was demonstrated independently by the groups of Theato [72] and Tao [73]. To be precise, Kakuchi and Theato showed that the Kabachnik-Fields post-polymerization modification reaction on poly(4-vinyl benzaldehyde) with amines and phosphites proceeded very efficiently to afford polymers featuring a-amino phosphonate pendant groups (Scheme 3) [72]. Furthermore, the group of Tao succeeded in synthesizing polymeric a-amino phosphonates via concurrent Kabachnik-Fields reactions of vinyl compounds and RAFT polymerization of the vinyl monomers in a one-pot process [73]. 

Recently, scientists have been looking for a better modification motif to improve the functionality of polymer. Modem efficient reactions, such as click reactions, have been chosen and applied to achieve efficient PPM [118]. Because the BigineUi reaction has proved to be a powerful tool for easily achieving complex DHPM stmctures with high yield, this efficient reaction can also be a potential tool for polymer modification. 

SCHEME 1.7 Carbohydrate-derived primary amine-thiourea-catalyzed BigineUi reaction. 

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