An Environmentally Benign Cascade Reaction of 1,1-Enediamines (EDAMs) for Site-Selective Synthesis of Highly Functionalized 2,10-Dihydro-1H-imidazo[1',2':1,6]pyrido[2,3-b]indoles and Pyrroles.

A novel protocol for the synthesis of pyrido[2,3-b]indoles (α-carbolines, 3) from (E)-3-(2-oxo-2-phenylethylidene) indolin-2-one derivatives 1 and 1,1-enediamine (EDAM) 2a via an unexpected cascade reaction in ethanol was developed. Pyrido[2,3-b]indole derivatives 4 were obtained by the same reaction, albeit by stirring the mixture for a longer period of time (about 48 h). As a result, two kinds of functionalized α-carbolines 3 and 4 were synthesized by the facile reaction of the (E)-3-(2-oxo-2-phenylethylidene)indolin-2-one derivatives and 2-(nitromethylene)imidazolidine under basic conditions (Cs2CO3) in ethanol. In addition, a diverse array of EDAM substrates (2b-2k) were tested in this reaction to afford the expected target compounds 5. This protocol is suitable for the combinatorial and parallel syntheses of natural-like products, including highly functionalized α-carbolines and pyrroles, especially 2-oxoindolin-3-yl pyrroles. This approach features several advantages, such as being a simple and practical operation (requiring only filtration and washing without column chromatography), furnishing excellent yields (72-98%), and producing diverse libraries of target compounds with potential biological activities.

Cascade reaction of isatins with nitro-substituted enamines: highly selective synthesis of functionalized (Z)-3-(1-(arylamino)-2-oxoarylidene)indolin-2-ones.

A novel protocol for the construction of functionalized (Z)-3-(1(-arylamino)-2-oxoarylidene)indolin-2-ones (AOIDOs) from isatins 1 with nitro-substituted enamines 2via an unprecedented cascade reaction catalyzed by sulfamic acid is developed. The AOIDOs are prepared by simply refluxing a mixture of isatins with a wide variety of nitro-substituted enamines. Interestingly, the AOIDOs 3 were formed through the novel cascade reaction involving a unique cleavage of two C-N bonds of the nitro-substituted enamines. Overall, the novel reaction is accomplished by the formation of three new bonds and the cleavage of two C-N bonds in a single step. This protocol can be used in the synthesis of a wide variety of AOIDOs and is suitable for combinatorial and parallel syntheses of natural-like AOIDO products.

Three-Component Site-Selective Synthesis of Highly Substituted 5 H-Chromeno-[4,3- b]pyridines.

An efficient and concise one-pot procedure was developed based on a cascade reaction of 3-formylchromones 1 and different types of 1,1-enediamines (EDAMs) 2 with different alcohols or amines 3 by a site-selective synthesis of 5 H-chromeno[4,3- b]pyridines in an environmentally friendly solvent. This protocol is especially suitable for the efficient and rapid parallel synthesis of 5 H-chromeno[4,3- b]pyridine compounds. It also has some advantages, such as convenience of operation, short reaction times, use of a green solvent, and ease of purification by washing the crude products with ethanol.

Cascade Reaction of Isatins with 1,1-Enediamines: Synthesis of Multisubstituted Quinoline-4-carboxamides.

A one-step methodology for the synthesis of multisubstituted quinoline-4-carboxamides was developed by simply refluxing a mixture of isatins 1 and various kinds of 1,1-enediamines 2-4 in a reaction catalyzed by NH2SO3H. As a result, a series of quinolone-4-carboxamides were produced through a novel cascade reaction mechanism. This reaction involved the formation of the quinoline ring accompanied by the formation of an amide bond in one step. Accordingly, this protocol is suitable for combinatorial and parallel syntheses of quinolone-4-carboxamide drugs or natural products.