A Brønsted acid catalysed enantioselective Biginelli reaction

Abstract

A chiral derivative of 1,2-benzenedisulfonimide, namely (-)-4,5-dimethyl-3,6-bis(o-tolyl)-1,2-benzenedisulfonimide is herein proven to be an efficient chiral catalyst in a one pot three-component Biginelli reaction. In fact the yields of the target dihydropyrimidines were very high (25 examples; average 91%) and enantiomeric excesses were always excellent (14 examples; average 97%). Ultimately, we herein propose a sustainable procedure that ensures that the principles of Green Chemistry are met. The reaction displays a number of green benefits and advantages including the total absence of solvents, mild reaction conditions, relatively short reaction times and the stoichiometric reagent ratio. Target dihydropyrimidines are obtained in adequate purity, making further cromatographic purification unnecessary. Moreover, the chiral catalyst was easily recovered from the reaction mixture and reused, without the loss of catalytic activity.

Immobilized Gelatin–λ–Carrageenan on Magnetite Nanoparticles as an Efficient Organocatalyst for Enantioselective Biginelli Reaction

“…The specific rotations of these products were obtained from the literature. [20,[61][62][63][64][65][66][67] The absolute configuration of all these products (4 a-g) with dextrorotatory (+) was determined to be (S)-configuration. Based on the obtained values of the above table, Dimedone gave better yield than ethyl acetoacetate and among various aldehydes, mehtoxysubstituted benzaldehyde derivatives gave higher yields of the product.…”

Chiral Spirocyclic Phosphoric Acid‐Catalyzed Synthesis of 4‐Alkyl‐3,4‐dihydropyrimidin‐2(1H)‐one Derivatives by Asymmetric Biginelli Reactions

“…The seminal research of Juaristi in 2003 made clear that asymmetric three‐component Biginelli reaction can provide a rapid approach to highly enantioenriched DHMPs . In recent years, some novel catalytic methods have been developed for asymmetric Biginelli reaction, including chiral Lewis acid catalyst, chiral phosphoric acids, chiral amines, chiral thiourea, chiral sulfonimide, and cooperative catalysis . In spite of these meaningful work with good yields and enantioselectivities, the effective coupling partner has been mainly limited to the use of classical aromatic aldehyde substrates …”

Untitled

“…3,4-Dihydropyrimidin-2 (1H)-one derivatives have various pharmaceutical and biological activities, and have been used as antihypertensive [29], antibacterial [30], antitumor [31], antiviral [32], calcium channel blockers [33], neuropeptide antagonist [34], α1a-adrenergic antagonists [35], and anti-inflammatory [36] agents. The general method which has been utilized for production of this class of compounds consists of the condensation reaction of arylaldehydes with βketoesters (or compounds containing active methylene) and urea in the presence of a catalyst; for example Mg-Al-CO3 and Ca-Al-CO3 hydrotalcite [37] nano-γ-Fe2O3@SiO2 [38], 1butyl-1,3-thiazolidine-2-thione ptoluenesulfate [39], H4SiMO12O40 [40], 3D printed α-Al2O3 [41], silica-supported imidazolium salt [42], TiCl3OTf-1-butyl-3methylimidazolium chloride [43], [Co (BPO)2 (H2O)4] (BS)2 (H2O)2 [44], chitosan/graphene oxide [45], (-)-4, 5-dimethyl-3, 6-bis(o-tolyl)-1,2-benzenedisulfonimide [46], and Fe3O4@mesoporous SBA-15 [47]. Although some catalysts for the synthesis of 3,4dihydropyrimidin-2 (1H)-ones are known, newer catalysts continue to attract attention for solving the drawbacks accompanied with the reported ones, such as harsh conditions, long reaction times, moderate yields, the use of expensive, non-available or toxic catalysts, difficulty in catalyst preparation, and performing the reaction in volatile and toxic organic solvents.…”