Umpolung Strategy for the Synthesis of Chiral Dispiro[2-amino-4,5-dihydrofuran-3-carbonitrile]bisoxindoles

Abstract

Based on a novel umpolung strategy, an efficient and highly enantioselective cascade aldol/cyclization/tautomerization of the 2-(2-oxoindolin-3-yl)malononitrile to active carbonyl compounds with excellent diastereo-and enantioselectivity has been developed. Also, various enantio-enriched multifunctional dispiro[2-amino-4,5dihydrofuran-3-carbonitrile]bisoxindoles with adjacent spiro-stereocenters were conveniently obtained by this novel methodology. Also, the dispiro[2-amino-4,5-dihydrofuran-3-carbonitrile]bisoxindoles were easily transformed into structurally complex molecules without any effect on the diastereo-and enantioselectivity.

Diastereoselective Preparation of Spiro[2,3‐dihydrofuran‐3,3’‐oxindole] Derivatives by an Atom‐Economic Tandem Reaction in Water

“…3). [27] In this work, the starting material 2-(2-oxoindolin-3-yl) malononitriles [28] and carbonyl compounds were used as highly active nucleophiles and electrophiles, a cinchona alkaloids-derived www.eurjoc.org thioureas promoted the cascade reaction smoothly as efficient organocatalysts at À 40 °C. As a continuation of our previous research, we sought to design a green and milder approach to synthesizing a series of substituted spiro[2,3-dihydrofuran-3,3'oxindole] derivatives from 2-(2-oxoindolin-3-yl)malononitriles and aldehydes.…”

“…More recently, we have successfully synthesized various enantio‐enriched multifunctional dispiro[2‐amino‐4,5‐dihydrofuran‐3‐carbonitrile]bisoxindoles with adjacent spiro‐stereocenters through a cascade aldol/cyclization/tautomerization strategy (Scheme 1, eq. 3) [27] …”

Microwave-assisted catalyst-free multicomponent one-pot green synthesis of highly functionalized aminocyanopyridines and (4-hydroxy)quinolines in aqueous medium and its in silico studies

“…1 compound III ) which is a building block of various carbazolespirooxindoles or quaternary carbon stereocenters which are interesting targets for medicinal research and many other synthetic applications. 32,51–60…”

“…1 compound III) which is a building block of various carbazolespirooxindoles or quaternary carbon stereocenters which are interesting targets for medicinal research and many other synthetic applications. 32,[51][52][53][54][55][56][57][58][59][60] Moreover, in order to determine the binding mechanism and fate of synthesized compounds, we have employed molecular modelling studies with mitogen-activated protein kinaseactivated protein kinase 2 which is effective in the treatment of diseases like rheumatoid and psoriatic arthritis. 24 Molecular docking analyses are widely used to illustrate the binding mechanism of drugs with their specific protein target for different diseases.…”

Chemodivergent Photocatalytic Synthesis of Dihydrofurans and β,γ‐Unsaturated Ketones

“…Among the traditional methods we can mention the "interrupted" Feist-Bénary reaction, [7] the oxidative coupling reaction between 1,3-dicarbonyl compounds and olefins mediated by stoichiometric manganese(III), [8] cerium (IV), [8d,9a-b] or copper(II), [9c] the 1,3-dipolar reaction involving diazocarbonyl compounds and alkenes cata- lyzed by rhodium(II), [10] ruthenium(II), [11] or copper (II). [12] More recently, some innovative examples of [3 + 2] annulations have been proposed: i) the reaction between ketones and alkenes mediated by copper, [13] palladium, [14] or potassium persulfate, [15] by cooperative systems indium(III)/silver(I) [16] or I 2 /oxidant, [17] or electrochemically promoted; [18] ii) several base-promoted additions to functionalized olefins, [19] alkynyl systems, [20] or carbonyls; [21] iii) Morita-Baylis-Hillman-type annulations; [22] iv) some copper-catalyzed formal cycloadditions involving active methylene compounds and unusual acceptors; [23] v) gold(I)-catalyzed syntheses of silyl-2,3-dihydrofurans. [24] Some approaches different from [3 + 2] annulation have also been described for 2,3-dihydrofurans construction, as for example the cyclization of olefinic dicarbonyl compounds, [25] catalytic [4 + 1] cycloadditions, [26] the ring opening of cyclopropanes [27] or cyclopropenes, [28] the arylation of 2,5dihydrofurans.…”