Facile construction of densely functionalized 4H-chromenes via three-component reactions catalyzed by l-proline

Abstract

Three-component reactions of salicylaldehydes, 1,3-cyclohexanediones and a sulfur, carbon, or nitrogenbased nucleophile were developed, for the first time, by using L-proline as a catalyst, which generated various substituted 4H-chromene derivatives in good to excellent yields. The reactions were performed in ethanol under mild and metal-free conditions. In these reactions, the use of L-proline as a catalyst was proven to be key for rendering the reactions possible because replacing L-proline with other acids or bases resulted in the generation of many side products. Many nucleophiles, such as thiophenols, mercaptans, indoles, sulfinic acid, benzotriazole, 2-naphthol, 5-methyl-2-phenyl-1,2-dihydropyrazol-3-one, 6-aminouracil, 6-amino-1,3-dimethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione and some commonly used C-H acids including 4-hydroxycoumarin, 2-hydroxy-1,4-naphthoquinone and barbituric acid could be successively used to assemble with dimedone and salicylaldehyde. Particularly, the product generated from the reaction of benzotriazole, 3-methoxysalicylaldehyde and dimedone can also be used as a starting material, in which the fragment of benzotriazole acts as a leaving group, for the synthesis of some important compounds by reacting with many carbon-based nucleophiles, such as dibenzoylmethane, ethyl benzoylacetate, 1,3-cyclohexanedione, N,N-dimethylaniline, 2-methylfuran and sesamol in acidic conditions. This offers a complementary route to access some 4H-chromenes that cannot be attained with the above-mentioned three-component reactions. † Electronic supplementary information (ESI) available. See

Non-catalytic multicomponent rapid and efficient approach to 10-(2,4,6-trioxohexahydropyrimidin-5-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-ones from salicylaldehydes, dimedone, and barbituric acids

“…In the case of L-prolin as catalyst only one example of this multicomponent reaction is known. From salicylaldehyde, dimedone, and barbituric acid (80°C, 6 h) 2,4,6-trioxohexahydropyrimidine substituted tetrahydro-1H-xanthen-1-one 1 was obtained in 87 % yield [15]. The similar reaction with TH amino acid catalyst resulted in only 56 % yield of 1 after 24 h heating at 80°C [16] (Scheme 1).…”

“…The similar reaction with TH amino acid catalyst resulted in only 56 % yield of 1 after 24 h heating at 80°C [16] (Scheme 1). Both these catalytic methods are characterized by heating at 80°C during long reaction time (6-24 h), and resulted in moderate yields of tetrahydro-1H-xanthen-1-one 1 [15,16]. Moreover, from the position of 'green chemistry' one could formulate that 'the best catalyst is no catalyst' [17,18].…”

“…Recently two catalytic methods were suggested for 10-(2,4,6-trioxohexahydropyrimidin-5-yl)-2,3,4,9-tetrahydro-1H-xanthen-1-one synthesis from salicylaldehydes, dimedone, and barbituric acid under different catalytic conditions. Among these catalysts are known L-prolin (10 mol%) [15] and TH amino acid catalyst [16] (20 % by weight of salicylaldehyde), which was specially obtained by tedious hydrolysis of bovine tendon [16]. In the case of L-prolin as catalyst only one example of this multicomponent reaction is known.…”

Multicomponent reaction in deep eutectic solvent for synthesis of substituted 1-aminoalkyl-2-naphthols

“…Furthermore, there is growing interest in Betti bases as chiral inductors or chiral precursors for asymmetric synthesis of a-aminophosphonic acids [15]. Owing to the wide variety of applications of Betti bases in chiral drug synthesis, various modifications have been made to prepare Betti base derivatives under operationally straightforward and green conditions [16][17][18][19][20][21][22][23][24]. Furthermore, several asymmetric procedures for these multicomponent reactions have also been successfully developed [25][26][27][28].…”

A metal-free tandem C–C/C–O bond formation approach to densely functionalized indolyl $$4H$$ 4 H -chromenes catalyzed by polystyrene-supported $$p$$ p -toluenesulfonic acid under solvent-free conditions

“…Therefore, considerable effort has been invested in the synthesis of indolyl 4H -chromene derivatives using L-proline and an aqueous micellar system for the reaction between salicylic aldehyde, dimedone, and indole [10]; tetrahydrothiophenecatalyzed ylide annulation reaction (E)-ethyl 4-(2-(bromome thyl)phenyl) but-2-enoate gave 4H -chromene [11]; DBUcatalyzed reaction between salicylic aldehydes and ethyl 2-methylbuta-2,3-dienoate [12]; tandem benzylation and cyclization catalyzed by FeCl 3 [13]; Cu(I)-catalyzed domino reactions [14]; and triazine-functionalized ordered mesoporous organosilica as an organocatalyst [15]. A survey of the literature shows that the majority of the strategies for the synthesis of 4H -chromene derivatives involve multistep reaction sequences [11,16], prolonged reaction times, harsh reaction conditions [13,17,18], tedious work-up procedure [19], and some procedures failed to recover and reuse the catalyst [20][21][22][23][24].…”