title: Development of four-component synthesis of tetra- and pentasubstituted polyfunctional dihydropyrroles: free permutation and combination of aromatic and aliphatic amines.
abstract: We previously reported the novel efficient proton/heat-promoted four-component reactions (4CRs) of but-2-ynedioates, two same/different primary amines, and aldehydes for the synthesis of tetra- and pentasubstituted polyfunctional dihydropyrroles. If aromatic and aliphatic amines were used as reagents, four different series of products should be obtained via the permutation and combination of aromatic and aliphatic primary amines. However, only three/two rather four different series of tetra-/pentasubstisuted dihydropyrroles could be prepared via the proton/heat-promoted 4CRs. Herein, Cu(OAc)2·H2O, a Lewis acid being stable in air and water, was found to be an efficient catalyst for the 4CR synthesis of all the four different series of tetra-/pentasubstisuted dihydropyrroles. The copper-catalyzed 4CR could produce target products at room temperature in good to excellent yields. Interestingly, benzaldehyde, in addition to being used as a useful reactant for the synthesis of pentasubstituted dihydropyrroles, was found to be an excellent additive for preventing the oxidation of aromatic amines with copper(II) and ensuring the sooth conduct of the 4CRs for the synthesis of tetrasubstituted dihydropyrroles with aryl R(3). In addition, salicylic acid was found to be needed to increase the activities and yields of the copper-catalyzed 4CRs for the synthesis of petasubstituted diyhydropyrroles. On the basis of experimental results, the enamination/amidation/intramolecular cyclization mechanism was proposed and amidation is expected to be the rate-limited step in the copper-catalyzed 4CRs.
authors: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, China.
authors: Longyun
authors: L
authors: Lv
authors: Sichao
authors: S
authors: Zheng
authors: Xiaotie
authors: X
authors: Cai
authors: Zhipeng
authors: Z
authors: Chen
authors: Qiuhua
authors: Q
authors: Zhu
authors: Shuwen
authors: S
authors: Liu
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry*; D001547:Benzaldehydes / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003300:Copper / Q000737:chemistry; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis / Q000737:chemistry; D058116:Lewis Acids / Q000737:chemistry; D010084:Oxidation-Reduction; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000588:Amines; D001547:Benzaldehydes; D006841:Hydrocarbons, Aromatic; D058116:Lewis Acids; D011758:Pyrroles; C013231:pyrroline; D003300:Copper; C032175:benzaldehyde