Organocatalytic Enantioselective Synthesis of 1,4‐Dihydropyridines

Abstract

This review aims to bring light upon a very interesting group of compounds, the 1,4-dihydropyridines (1,4-DHPs). These structures are well-known pharmacophores, used for many years to treat cardiovascular diseases because of their activity as calcium channel blockers. In addition, their potential as drugs to treat other affections has been recently exposed. The racemic synthesis of 1,4-DHPs has been well studied, while the asymmetric approaches are mainly based on the use of chiral auxiliaries or chiral resolutions. However, there are scarce examples regarding enantioselective organocatalytic methods. Herein, we will summarize the existing examples in this field of research. 1 Introduction 2 BINOL-derived phosphoric acid mediated organocatalysis 3 (Thio)urea mediated organocatalysis 4 Aminocatalysis 5 Dual catalysis 6 Summary and outlook

Practical and Scalable Organic Reactions with Flow Microwave Apparatus

“…[24] Therefore, various methods have been developed for the synthesis of dihydropyridine derivatives. [25] Among them, the Hantzsch dihydropyridine synthesis is recognized to be a conventional and reliable method [26] and thus has been applied to flow microwave conditions. [27] We also examined the Hantzsch dihydropyridine synthesis under our flow microwave conditions.…”

“…The reaction between 4-hydroxy-cinnamic acid (25) and 5-bromo-1-pentene (26) was selected for the application of the SAIDA flow microwave system due to the utility of product 27 as a component of liquid crystal materials. [48] According to the literature, the reaction was carried out for 24 h at 90 8C using oil bath heating in order to check the property of the reaction mixture, and the desired compound 27 was obtained in 96% yield ( Table 6, entry 1).…”

Sulfonated Caspian Sea Sand: A Promising Heterogeneous Solid Acid Catalyst in Comparison with –SO3H Functionalized NiFe2O4@SiO2@KIT‐6

“…Although the classical Hantszch method is a straightforward route for preparation of 1,4‐dihydropyridines from β‐ketoesters, an aldehyde and ammonia, there are several modifications for this method to facilitate the synthesis of other substituted 1,4‐dihydropyridines. These include the use of enamines in presence of either aldehydes or ketones, reduction of pyridine and pyridinium salts in presence of metal‐hydrides, condensation of α,β‐unsaturated carbonyl compounds with active‐methylene compounds and amines, and multi component condensation of 1,3‐dicarbonyl compounds with aldehydes and NH 4 OAc, in presence of a wide range of homogeneous and heterogeneous catalysts . Also, 3,4‐dihydropyrimidin‐2( 1H )‐ones as analogs of 1,4‐dihydropyridines, play significant biological roles such as antibacterial, antioxidant, anti HIV and anticancer.…”

“…These include the use of enamines in presence of either aldehydes or ketones, [11] reduction of pyridine and pyridinium salts in presence of metal-hydrides, [12] condensation of α,β-unsaturated carbonyl compounds with active-methylene compounds and amines, [13] and multi component condensation of 1,3-dicarbonyl compounds with aldehydes and NH 4 OAc, in presence of a wide range of homogeneous and heterogeneous catalysts. [14][15][16][17][18][19][20][21][22][23][24] Also, 3,4-dihydropyrimidin-2(1H)-ones as analogs of 1,4-dihydropyridines, play significant biological roles such as antibacterial, antioxidant, anti HIV and anticancer. 3,4-dihydropyrimidin-2(1H)-ones can be prepared via Biginelli multicomponent reaction of an aldehyde, a β-ketoester and urea under catalysis of a vast number of Brønsted and Lewis acids.…”

Synthesis of Benzofuran‐fused 1,4‐Dihydropyridines via Bifunctional Squaramide‐catalyzed Formal [4+2] Cycloaddition of Azadienes with Malononitrile

“…[7] In spite of great progress, there are only few examples of organocatalytic enantioselective syntheses of 1,4-dihydropyridines. [8] Hence, the asymmetric catalytic construction of chiral 1,4-dihydropyridines is still an active challenging task and highly desirable. In the last few years, azadienes have been regarded as an effective four-atom synthon in the construction of benzofuranfused heterocyclic compounds owing to the driving force of aromatization.…”