Base‐Catalyzed and Solvent‐Dependent Cascade Reaction in the Regioselective Synthesis of Novel Fused Polycycles

Abstract

A novel base-catalyzed cascade reaction induced by Knoevenegal condensation that can regioselectively generate cyanoflavanones and heavily fused polycycles with intensive fluorescence and high quantum yields is reported. The reaction is solvent-dependent, low-polarity solvents promote the formation of polycycles while high-polarity solvents favor the conversion to cyanoflavanones. A possible mechanism for such serial transformations is proposed.Keywords: base-catalyzed reactions; cyanoflavanones; domino reactions; Knoevenegal condensation; polycycles; solvent effects In recent years, there has been great interest in cascade reactions since they involve two or more bondforming transformations from simple starting materials that take place under the same reaction conditions.[1] This results in an increased synthetic efficiency and ecologically and economically favorable synthesis of compounds with complicated or highly functionazlied chemical structures. Among them, the cascade reactions originating from the Knoevenagel condensation are useful approaches to the constructions of fused heterocycles, like Knoevenagel-heteroDiels-Alder reactions, [2] Knoevenagel-hydrogenationRobinson sequences, [3] Knoevenagel-electrocyclization [4] and Knoevenagel-epimerization [5] processes and so on. In order to develop a cascade reaction induced by a Knoevenagel condensation for obtaining some novel fused polycycles, herein we report the triethyl-A C H T U N G T R E N N U N G amine-catalyzed sythesis of 6-amino-2,10-dimethyl-7-substituted-7H-5,13-dioxa-14-azabenzo [a] naphthacen-8-ones which exhibit intensive yellow fluorosence and excellent quatum yields. Although these compounds have highly complicated structures with five fused rings, they can be straightforwardly obtained in reasonable to good yields by the reaction of two easily available starting molecules, that is, a-cyano-ohydroxyacetophenone and aldehydes. Moveover, the chemical outcome of the reaction involving the two substrates can be regioselectively controlled by convenient adjustment of the solvent polarity.For example, when 4-methylbenzaldehyde (1c) and 3-(2-hydroxy-5-methylphenyl)-3-oxopropionitrile (2) are treated with 0.2 equivalents of triethylamine for 3 h in toluene or 10 h in CH 2 Cl 2 at room temperature, polycyclic product 3c is isolated in 78% or 76% yield, respectively (Scheme 1). However, when the same reaction is executed in MeOH or DMF for 4 h at room temperature, a mixture of the cyanoflavanones 4c/4c' is generated in, respectively, 91% or 87% yield as the single product instead (Scheme 1). Apparently, the regioselective products of the reaction are solvent-dependent, the polycycle is favorably formed in low-polarity solvents and the cyanoflavanone is preferentially generated in high-polarity solvents. The cases for other tested aldehydes are analogous to that of 1c when these cascade reactions are performed at room temperature in toluene under the catalysis of 0.2 equivalents of triethylamine (Scheme 1) and the results of the production o...

Synthesis of 2H-Chromeno[2,3-b]tetrahydropyridine Frameworks through Cs2CO3-Promoted Annulation of 2-Amino-4H-chromen-4-ones and 4-Benzylideneoxazol-5(4H)-ones

“…Simultaneously, we also explored 2-aminochromones as a key substrate in the annulation reactions with apt partners for the synthesis of diversely substituted 5 H -chromeno­[2,3- b ]­pyridines . Additionally, a dihydropyridine or tetrahydropyridine scaffold is a privileged structure in drug discovery and development . Many investigations replaced pyridine with a dihydropyridine or tetrahydropyridine scaffold to fuse with chromenone and produce new isomeric derivatives; it was envisioned that the chromeno­[2,3- b ]­dihydropyridine or chromeno­[2,3- b ]­tetrahydropyridine core could be obtained from apt partners.…”