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Review
. 2023 Sep 7;28(18):6488.
doi: 10.3390/molecules28186488.

Engaging Isatins and Amino Acids in Multicomponent One-Pot 1,3-Dipolar Cycloaddition Reactions-Easy Access to Structural Diversity

Hua Zhao  1 , Yufen Zhao  1
Affiliations
Review

Engaging Isatins and Amino Acids in Multicomponent One-Pot 1,3-Dipolar Cycloaddition Reactions-Easy Access to Structural Diversity

Hua Zhao et al. Molecules. .

Abstract

Multicomponent reactions (MCRs) have undoubtedly emerged as the most indispensable tool for organic chemists worldwide, finding extensive utility in the synthesis of intricate natural products, heterocyclic molecules with significant bioactivity, and pharmaceutical agents. The multicomponent one-pot 1,3-dipolar cycloaddition reactions, which were initially conceptualized by Rolf Huisgen in 1960, find extensive application in contemporary heterocyclic chemistry. In terms of green synthesis, the multicomponent 1,3-dipolar cycloaddition is highly favored owing to its numerous advantages, including high step- and atom-economies, remarkable product diversity, as well as excellent efficiency and diastereoselectivity. Among the numerous pieces of research, the most fascinating reaction involves the utilization of azomethine ylides generated from isatins and amino acids that can be captured by various dipolarophiles. This approach offers a highly efficient and convenient method for constructing spiro-pyrrolidine oxindole scaffolds, which are crucial building blocks in biologically active molecules. Consequently, this review delves deeper into the dipolarophiles utilized in the 1,3-dipolar cycloaddition of isatins and amino acids over the past six years.

Keywords: 1,3-dipolar cycloadditions; isatin; multicomponent reactions; one-pot reactions; spiro-oxindole.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Representative natural products and bioactive compounds with the spiropyrrolidine oxindole scaffolds.
Figure 2
Figure 2
The various dipolarophiles toward 1,3-dipolar cycloaddition reactions of azomethine ylides derived from isatins and amino acids.
Scheme 1
Scheme 1
Substrate-controlled regioselectivity switch in a three-component 1,3-dipolar cycloaddition reaction.
Scheme 2
Scheme 2
Ag-catalyzed [3 + 2] cycloaddition of substituted isatins and primary α-amino acid esters with chalcones.
Scheme 3
Scheme 3
Three-component one-pot reaction using trans-1,2-dibenzoylethylene 12 as the dipolarophile.
Scheme 4
Scheme 4
Microwave-assisted rapid synthesis of spiro-oxindole–pyrrolizidine analogues and their activity as anti-amyloidogenic agents.
Scheme 5
Scheme 5
The three-component reaction involving α,γ-dialkylallenoate esters, isatin derivatives, and amino acids.
Scheme 6
Scheme 6
Four-component regio- and diastereoselective synthesis of pyrrolizidines incorporating spiro-oxindole/indanedione via 1,3-dipolar cycloaddition reaction.
Scheme 7
Scheme 7
Synthesis of a series of spiro-oxindole pyrrolidine-grafted thiochromene scaffolds as potential anticancer agents.
Scheme 8
Scheme 8
(a) A facile and diverse synthesis of coumarin-substituted spiro-oxindole. (b) Synthesis of novel coumarin substituted dispiro-oxindole compounds.
Scheme 9
Scheme 9
1,3-dipolar cycloaddition with piperine as dipolarophiles.
Scheme 10
Scheme 10
Three-component access to functionalized spiropyrrolidine heterocyclic scaffolds and their cholinesterase inhibitory activity.
Scheme 11
Scheme 11
1,3-dipolar cycloaddition reaction involving (E)-3-arylidene-1-methyl-pyrrolidine-2,5-diones, L-proline, and isatin.
Scheme 12
Scheme 12
Microwave-assisted one-pot [3 + 2] cycloaddition of azomethine ylides and 3-alkenyl oxindoles.
Scheme 13
Scheme 13
Regioselective synthesis of pyrrolizidine bis-spiro-oxindoles as efficient anti-amyloidogenic agents.
Scheme 14
Scheme 14
Diastereospecific entry to pyrrolidinyldispirooxindole skeletons via 1,3-dipolar cycloadditions of methyleneindolinones.
Scheme 15
Scheme 15
Synthesis of highly enantioenriched bis-spiro-oxindole pyrrolizidine/pyrrolidines through asymmetric [3 + 2] cycloaddition reaction.
Scheme 16
Scheme 16
[3 + 2] cycloaddition of azomethine ylides with a thiazolo[3,2-a]indole derivative.
Scheme 17
Scheme 17
Synthesis of dehydrocostus-lactone-inspired hybrid and parthenolide-inspired hybrid via formal oxygen atom insertion.
Scheme 18
Scheme 18
A three-component reaction of α-diketone, amino acid, and maleimide.
Scheme 19
Scheme 19
(a): 1,3-Dipolar cycloaddition of azomethine ylides with heterobicyclic alkenes. (b): Synthesis of oxygen-bridged spirooxindoles via microwave-promoted multicomponent reaction.
Scheme 20
Scheme 20
A reversible [3 + 2] cycloaddition of azomethine ylides with 3-nitro-2-(trifluoromethyl)-2H-chromenes.
Scheme 21
Scheme 21
The construction of chromanone-fused pyrrolidinyl spiro-oxindole collections through a decarboxylative 1,3-dipolar [3 + 2] cycloaddition reaction.
Scheme 22
Scheme 22
The [3 + 2]-cycloaddition of cyclopropenes and azomethine ylides.
Scheme 23
Scheme 23
A diversity-driven three-component 1,3-dipolar cycloaddition of isatins, amino acids, and isatin-derived ketimines.
Scheme 24
Scheme 24
1,3-Dipolar cycloaddition of isatin-derived azomethine ylides with 2H-azirines.
Scheme 25
Scheme 25
Diastereo- and enantioselective construction of spiro-oxindole scaffolds through a catalytic asymmetric [3 + 3] cycloaddition.
Scheme 26
Scheme 26
An asymmetric 1,3-dipolar addition of azomethine ylides to a chiral dehydroalanine Ni(II) complex.
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