Molecular Hybridization-Guided One-Pot Multicomponent Synthesis of Turmerone Motif-Fused 3,3′-Pyrrolidinyl-dispirooxindoles via a 1,3-Dipolar Cycloaddition Reaction

Abstract

Described herein is the development of a facile and efficient methodology for the synthesis of novel turmerone motif-fused 3,3′-pyrrolidinyl-dispirooxindoles 3–5 via a multicomponent 1,3-dipolar cycloaddition of dienones 2 with azomethine ylides (thermally generated in situfrom isatins and proline or thioproline or sarcosine). Products bearing four or three consecutive stereocenters consist of two oxindole moieties and a pyrrolidinyl core, including vicinal spiroquaternary stereocenters fused in one ring structure were smoothly obtained in high yields (up to 93% yield) with good diastereoselectivity (up to >20:1). Another valuable application of this method was for the design of new hybrid architectures for biological screening through the adequate fusion of these sub-units of turmerone and 3,3′-pyrrolidinyl-dispirooxindole, generating drug-like molecules.

Dipolarophile-Controlled Regioselective 1,3-Dipolar Cycloaddition: A Switchable Divergent Access to Functionalized N-Fused Pyrrolidinyl Spirooxindoles

“…Isatin-derived azomethine ylides were recognized as typical dipoles and generally generated in situ by decarboxylative condensation of α -amino acids with isatins, which then react with dipolarophiles [ 31 ]. Significantly, diverse dipolarophiles have proven highly fruitful, including electron-deficient alkenes (activated by nitro [ 32 , 33 , 34 , 35 , 36 ], carbonyl [ 37 , 38 , 39 , 40 ], or other electron-withdrawing groups [ 41 , 42 , 43 ]), alkynes [ 44 , 45 , 46 ], arylacetylenes [ 47 ], allenes [ 48 ], N -heteroenes [ 49 , 50 ], and strained cyclopropenes [ 51 ]. However, previously reported methods mainly focused on the traditional ‘single target’ approach, and thus, only one type of spirooxindole skeleton can be prepared via the 1,3-dipolar cycloaddition of isatin-derived azomethine ylides to monogroup-activated dipolarophiles.…”

One-Pot Green Regioselesctive Synthesis of γ-Lactones from Epoxides and Ketene Silyl Acetals Using 1,3-Dimethylimidazolium Fluoride as a Recoverable Metal-Free Catalyst

“…The efficient and high-throughput synthesis of complex organic molecules with lower impact on the environment is one of the most important objectives in modern synthetic organic and green chemistry [ 20 ]. Multicomponent reactions (MCRs) combined with the application of task-specific ionic liquids (TSIL) are valuable tools for the environmentally friendly preparation of structurally diverse chemical libraries of drug-like heterocyclic compounds [ 21 , 22 , 23 , 24 ].…”