Straightforward and Highly Diastereoselective Synthesis of a New Set of Functionalized Dispiropyrrolidines Involving Multicomponent 1,3‐Dipolar Cycloaddition with Azomethine Ylides

Abstract

The diastereoselective synthesis of novel series of dispiropyrrolidines has been achieved by a one‐pot three‐component [3 + 2] cycloaddition reaction of (E)‐2‐arylideneindanones, glycine ethyl ester, and the cyclic diketones 1H‐indole‐2,3‐dione (isatin) or acenaphthenequinone. Moreover, we disclose an unprecedented epimerization of spiroadducts leading to a new family of dispiropyrrolidines with an unusual relative stereochemistry.

Three-Component Access to Functionalized Spiropyrrolidine Heterocyclic Scaffolds and Their Cholinesterase Inhibitory Activity

“…On the basis of our experimental results and previous studies on the reaction mechanism [49][50][51][52][53], we propose in Scheme 4 a plausible mechanism for the regio-and stereoselective dispiropyrrolidine formation. The azomethine ylides d 3 are generated in situ by decarboxylative condensation of cyclic 1,2-diketones 3 with aminoacids 2 or 6.…”

“…Thus, the cycloadducts are formed through an exo-approach between the (Z,E)-dipole and enones 1 as outlined in Scheme 4. The cycloaddition proceeds with high exo-diastereoselectivity affording in each case only one diastereomer.On the basis of our experimental results and previous studies on the reaction mechanism[49][50][51][52][53], we propose in Scheme 4 a plausible mechanism for the regio-and stereoselective dispiropyrrolidine…”

“…The effects of solvents, reaction time, and temperature were examined, and the results are summarized in Table 1. Herein, and in continuation of our interest in azomethine ylide [3+2]-cycloaddition reaction and in the synthesis of novel spiroheterocycles [26,[49][50][51][52][53], we report the synthesis of a novel series of dispiro[pyrrolidine-1-succinimide] derivatives by a one-pot three-component [3+2]-cycloaddition reaction of (E)-3-arylidene-1-phenyl-succinimides 1, α-aminoacids 2 and the cyclic 1,2-diketones isatin 3a-b or acenaphtenequinone 3c. Furthermore, some selected heterocyclic compounds were screened in vitro to evaluate their cholinesterase inhibitory propensity.…”

“…The (Z,E)-dipole d 3 then undergoes a 1,3-dipolar cycloaddition reaction with the dipolarophile 1 in a regio-and stereoselective manner (path A). The formation of the exo-regioisomer 5 via path A is more favorable because of the presence of a secondary orbital interaction (SOI) [49,54,55], which occurs between the oxygen atom of the carbonyl of the diketone and the carbon atom of the carbonyl of the dipolarophile as shown in Scheme 4. Conversely, the formation of the other regioisomers or diastereoisomers is less favorable because of steric or electronic repulsion in their corresponding transition states.…”

Antimicrobial Activity and In Silico Molecular Docking Studies of Pentacyclic Spiro[oxindole-2,3′-pyrrolidines] Tethered with Succinimide Scaffolds

“…Herein, and in continuation of our research in the domain of one-pot MCRs of azomethine ylides [33][34][35][36][37][38][39][40][41], we report on the synthesis of various spiro[oxindole-2,3′-pyrrolidines] tethered with succinimide derivatives. The latter were assembled by a one-pot threecomponent [3+2]-cycloaddition reaction of isatin itself or halogenated isatin derivatives 1, L-valine 2 and (E)-3-arylidene-1-methyl-succinimides 4.…”