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.

Nano Fe3O4 as a magnetically recyclable, powerful, and stable catalyst for the multi-component synthesis of highly functionalized dihydro-2-oxopyrroles

“…On the basis of above experimental results together with the related reports [24,25], a plausible mechanism for this four-component domino reaction is proposed as shown in Scheme 2. The first two steps involve the reaction of amine 1 with dialkyl acetylenedicarboxylate 2 to form dialkyl 2-(aryl or alkylamino) fumarate 7, and the …”

Access of Diverse 2-Pyrrolidinone, 3,4,5-Substituted Furanone and 2-Oxo-dihydropyrroles Applying Graphene Oxide Nanosheet: Unraveling of Solvent Selectivity

“…Furthermore, dihydropyrroles, an important class of five‐membered aza‐heterocycles with outstanding biological activities present as a core of several natural products like bilirubins and indolocarbazolealkaloids as well as the inhibitors of bacterial peptidedeformylase, human mitotic kinesin, cardiac cAMPphosphodiesterase, human immune deficiency virus (HIV) integrase, vascular endothelial growth factor receptors (VEGFR) and antitumor agents . In the quest for the synthesis of this significant target, substantial synthetic advances are adapted such as UiO‐66‐SO 3 H metal–organic framework, I 2 , p ‐toluenesulfonicacid, Cu(OAc) 2 .2H 2 O/salicylic acid, and BF 3 /nano‐sawdust . In spite of enough achievement, the previous methods are allied with several shortcomings of long completion time, application of expensive and toxic metal, use of strong acidic condition and tiresome work up procedure.…”

Vitamin B12: An efficient type catalyst for the one-pot synthesis of 3,4,5-trisubstituted furan-2(5 H )-ones and N -aryl-3-aminodihydropyrrol-2-one-4-carboxylates

“…On the other hand, dihydropyrrol-2-ones have been successfully used as peptidomimetic [38], HIV integrase [39], herbicidals [40], DNA polymerase inhibitors [41], caspase-3 inhibitors [42] cytotoxic and antitumor agents [43], antibiotics [44], and also inhibitors of the annexin A2-S100A10 protein interaction [45]. Recently, a few methods have been reported for the synthesis of highly substituted dihydropyrrol-2-ones using one-pot, four-component reactions in the presence of catalyst, such as AcOH, I 2 , benzoic acid, TiO 2 nanopowder or Cu(OAc) 2 _ H 2 O [46][47][48][49][50][51]. However, some of these methods have drawbacks, such as high temperature and utilize a…”