Review

. 2022 Sep 14;27(18):5976.

doi: 10.3390/molecules27185976.

Indane-1,3-Dione: From Synthetic Strategies to Applications

Corentin Pigot¹, Damien Brunel¹, Frédéric Dumur¹

Affiliations

PMID: 36144711
PMCID: PMC9501146
DOI: 10.3390/molecules27185976

Review

Indane-1,3-Dione: From Synthetic Strategies to Applications

Corentin Pigot et al. Molecules. 2022.

. 2022 Sep 14;27(18):5976.

doi: 10.3390/molecules27185976.

Authors

Corentin Pigot¹, Damien Brunel¹, Frédéric Dumur¹

Affiliation

¹ Aix Marseille Univ, CNRS, ICR, UMR 7273, F-13397 Marseille, France.

PMID: 36144711
PMCID: PMC9501146
DOI: 10.3390/molecules27185976

Abstract

Indane-1,3-dione is a versatile building block used in numerous applications ranging from biosensing, bioactivity, bioimaging to electronics or photopolymerization. In this review, an overview of the different chemical reactions enabling access to this scaffold but also to the most common derivatives of indane-1,3-dione are presented. Parallel to this, the different applications in which indane-1,3-dione-based structures have been used are also presented, evidencing the versatility of this structure.

Keywords: MCR; chemical modification; domino reaction; indanedione; spiro compounds.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Scheme 1**
Synthetic routes to indane-1,3-dione 4.

**Scheme 2**
Synthetic routes to substituted indane-1,3-diones **19–21** and **25, 26**.

**Scheme 3**
Synthetic routes to 28, 31, **31′**, 33, **33′**, 35, **35′**.

**Scheme 4**
Synthetic routes to **37a–37d, 39, 41, 43, 45, 47** and 49.

**Scheme 6**
Synthetic route to *bis*-thiazoles and *bis*-thiazolidinone starting from 4.

**Scheme 7**
Synthetic routes to 68, 72 and 75.

**Scheme 8**
Examples of halogenated indane-1,3-diones **76–82**, 84 reported in the literature.

**Scheme 9**
Synthesis of nitro-substituted indane-1,3-diones 19 and 21.

**Scheme 10**
Ethoxy-carbonyl compound 32.

**Scheme 11**
Synthesis of push–pull dyes **95–114**.

**Scheme 12**
Mechanism resulting in the synthesis of 3-(dialkylamino)-1,2-dihydro-9-oxo-9H-indeno [2,1-c]pyridine-4-carbonitrile derivatives **115**.

**Scheme 13**
Mechanism supporting the formation of **117** starting from **116**.

**Figure 1**
Crystal structure of **117**. Reproduced with permission from Ref. [57].

**Scheme 14**
Synthetic routes to **119** starting from 29.

**Scheme 15**
Knoevenagel reactions performed in classical ethanol/piperidine conditions.

**Scheme 16**
Synthetic route to push–pull dye **127**.

**Scheme 17**
Synthetic route to ninhydrin **138**.

**Scheme 18**
Different routes for halogenation of indane-1,3-dione 4 at the methylene position.

**Scheme 19**
Fluorination reactions of indane-1,3-dione 4.

**Scheme 20**
Mechanism involved in the fluorination of 4.

**Scheme 21**
Mechanism supporting the coexistence of a radical and an electrophilic bromination pathway for the bromination of 4.

**Scheme 22**
Synthesis of **150** using NBS as the bromination agent.

**Scheme 23**
Synthetic route to **153**.

**Scheme 24**
Synthetic route to **154**.

**Scheme 25**
Synthetic routes to cyclophanes **158a** and **158b**.

**Scheme 26**
Synthetic routes to the crown ether derivative of 1,3-indandione **159**.

**Scheme 27**
Synthetic route to **162**.

**Scheme 28**
Synthetic routes to tetracycline heterocyclic analogues.

**Scheme 29**
Synthetic routes to **172**.

**Scheme 30**
Synthetic Routes to **177**, **179**, **181** and **182**.

**Scheme 31**
Synthetic routes to **185–192**.

**Scheme 32**
Synthetic route to **196**.

**Scheme 33**
Synthetic routes to porphyrins **199** and **200**.

**Scheme 34**
Synthetic routes to various (metallo)porphyrins.

**Scheme 35**
Synthetic route to **208**.

**Scheme 36**
Mechanism involved in the synthesis of **212**.

**Scheme 37**
Synthetic routes to **212** and **213**.

**Scheme 38**
Chemical structures of the indeno-fused structures **216–224** treated below.

**Scheme 39**
Synthetic route to **217b**.

**Scheme 40**
Mechanism involved in the synthesis of indeno-fused structures **218**.

**Scheme 41**
General mechanism of indeno-fused structures synthetized by MCR.

**Scheme 42**
The different synthetic routes to spiroindanediones discussed in this part.

**Scheme 43**
Synthesis of the ferrocenecarbocyaldehyde adduct **230**.

**Scheme 44**
Synthetic route to **235**.

**Scheme 45**
Synthetic routes to **236**, **238**, **240** and **242**.

**Scheme 46**
Synthetic route to azomethine ylide **245**.

**Scheme 47**
Synthetic routes to dihydro-spiro[indene-2,3′-pyrrolidines] **247**.

**Scheme 48**
Mechanism supporting the formation of a unique diastereoisomer.

**Scheme 49**
Synthetic route to **250**.

**Scheme 50**
Synthesis of azomethine imine.

**Scheme 52**
Mechanism supporting the synthesis of **256**. Reproduced with permission from Ref. [254].

**Scheme 53**
Synthetic route to chromeno [3,4-b]pyrrolidine **259**.

**Scheme 54**
Synthesis of chromeno [3,4-c]pyrrolidine **262** while using TMG as the base.

**Scheme 57**
Synthetic route to a fluorinated dipolarophile **264** further used for cycloaddition reactions.

**Scheme 58**
Cycloaddition reaction using TEBAB **266** as the catalyst.

**Scheme 62**
Mechanism of formation of the coumarin-indanedione cycloadducts. Reproduced with permission from Ref. [258].

**Scheme 64**
Mechanism involved in the cycloaddition reaction with Morita–Baylis–Hillman carbonates **275**. Reproduced with permission from Ref. [259].

**Scheme 66**
Mechanism supporting the formation of only one diastereoisomer during the Pd-catalyzed reaction.

**Scheme 68**
Synthetic route to spirovinylcyclopropaneindanedione (VCP) **287**.

**Scheme 69**
Synthetic route to a five-membered spiroindanedione **289**.

**Scheme 70**
Cycloaddition reaction with VCP **287** and cinnamaldehyde **292**.

**Scheme 71**
Cycloaddition reactions with aryl and naphthyl derivatives **295** and **296**.

**Scheme 72**
Mechanism of cyclization determined for cycloaddition reactions occurring with nitroalkenes. Reproduced with permission from Ref. [262].

**Scheme 75**
Mechanism involved in the synthesis of the oxindole-fused spiropyrazolidine. Reproduced with permission from Ref. [265].

**Scheme 76**
Annulation reaction between *para*-quinone methide **307** and 2-vinylspiro[cyclopropane-1,2′-indene]-1′,3′-dione **289**.

**Scheme 79**
Mechanism proposed to support the formation of 2-arylideneindane-1,3-diones. Reproduced with permission from Ref. [268].

**Scheme 81**
Mechanism supporting the formation of a unique diastereoisomer during the cycloaddition of azomethine ylides **314** and arylidene-indane-1,3-diones **255**. Reproduced with permission from Ref. [269].

**Scheme 83**
The two plausible mechanisms supporting the cycloaddition reaction or the epoxidation reaction. Reproduced with permission from Ref. [270].

**Scheme 85**
Synthetic route to **320**.

**Scheme 86**
Cyclotrimerization reaction of **319** and **320**.

**Scheme 88**
Synthetic route to **327**.

**Scheme 89**
Synthetic route to **329** and **331**.

**Scheme 90**
Synthetic route to **329** and **334**.

**Scheme 92**
Synthesis of compounds **338** and **339**.

**Scheme 93**
Cobalt-catalyzed cycloaddition reactions.

**Scheme 94**
Rhodium-catalyzed cycloaddition reactions.

**Scheme 95**
Mechanism involved in the Co and Rh-catalyzed cyclization reaction.

**Scheme 96**
Synthetic route to **346**.

**Scheme 98**
Ni-catalyzed cycloaddition reaction furnishing **352**.

**Scheme 99**
Base-catalyzed [4+1] cycloaddition.

**Scheme 100**
Rh-catalyzed cycloaddition reactions.

**Scheme 101**
[4+4] Cycloaddition of indanone containing benzo[c]oxepines providing dibenzocycloooctadiene derivatives **359**, **360**, **363** and **364**.

**Scheme 102**
Examples of asymmetric cross [10+2] cycloadditions producing **367** starting from **365** and **249**.

**Scheme 104**
Mechanism of domino Knoevenagel/Diels–Alder/Epimerization sequence providing **370**.

**Figure 2**
Crystal structure of a product used to determine the reaction mechanism. Reproduced with permission of Duan et al. [287].

**Scheme 109**
Domino reactions carried out with (benzo)thiazoles **382** and **383**.

**Scheme 110**
Domino reactions involving a Michael addition followed by a 1,3 dipolar cycloaddition of 2-arylidene-1,3-indanediones **255** and 5-aryl-1,3,4-oxathiazol-2-ones **388**.

**Scheme 111**
Mechanism supporting the formation of the previous compound **395**. Reproduced with permission from Ref. [290].

**Scheme 113**
Synthetic route to **395**.

**Scheme 114**
Mechanism of the domino reaction between ynones **397** and 2-arylidene-indane-1,3-diones **255**. Reproduced with permission from Ref. [291].

**Scheme 115**
Synthesis of spiro-compounds **403** by domino reaction involving a silver-based catalyst.

**Scheme 116**
Mechanism of the domino reaction involving a silver-based catalyst. Reproduced with permission from Ref. [292].

**Scheme 117**
Synthetic access to **404**.

**Scheme 118**
Synthesis of 5′-hydroxy-6′-methyl-1′,3′-dihydro-2,2′-spirobi[indene]-1,3-dione **406**.

**Scheme 120**
Mechanism of the cascade Michael addition/cycloaddition reaction between 2-arylidene-indane-1,3-diones **255** and allenoates **407**. Reproduced with permission from Ref. [293].

**Scheme 122**
Mechanism of the domino reaction between 2-arylidene-indane-1,3-diones **255** and N-alkoxyacrylamides **410** in the presence of a base. Reproduced with permission from Ref. [294].

**Scheme 124**
Mechanism involved in the cascade double Michael addition/acetalization reactions. Reproduced with permission from Ref. [295].

**Scheme 125**
Product **423** obtained in a quadruple cascade reaction.

**Scheme 126**
Mechanism involved in the quadruple cascade reaction.

**Scheme 127**
Mechanism involved in the synthesis of spiro-indane-1,3-diones **428**.

**Scheme 129**
Examples of compounds **437** and **438** obtained during the MRC of indane-1,3-dione 4, dimethyl but-2-ynedioate **434** and various substituted benzothiazoles **435** or **436**.

**Scheme 130**
Mechanism of MRC between the MRC between indane-1,3-dione 4, dimethyl but-2-ynedioate **434** and benzothiazoles **437** or **438**.

**Scheme 131**
Synthesis of spiro-N-fused indane-1,3-diones **441** and **442**.

**Scheme 132**
Synthesis of **441** and **442**.

**Scheme 134**
Synthesis of **448** and **450**.

**Scheme 136**
Mechanism involved in the MRC reaction using Fe-particles as catalysts. Reproduced with permission from Ref. [301].

**Scheme 137**
Example of pH-switchable compound **454**.

**Scheme 138**
Various products obtained by reacting indane-1,3-dione 4 in the presence of base.

**Scheme 139**
Synthetic routes to 50 and **458**.

**Scheme 140**
Synthetic route to **455**.

**Scheme 141**
Synthetic route to **457**.

**Scheme 143**
Mechanism occurring during alkene hydrofunctionnalizations of 2-arylidene-indane-1,3-diones **255** providing **463**. Reproduced with permission from Ref. [304].

**Scheme 145**
Mechanism involved in the copper-catalyzed synthesis of spiro compounds. Reproduced with permission from Ref. [305].

**Scheme 147**
Mechanism occurring in the copper catalyzed cycloaddition reaction of 2-arylene-indane-1,3-dione **255** with various oximes **466**. Reproduced with permission from Ref. [306].

**Scheme 148**
The different products obtained during the reaction of 2-arylidene-indane-1,3-diones **255** and the Seyferth–Gilbert reagent **468**.

**Scheme 150**
Chemical structures of indane-1,3-dione-based push–pull dyes **470–497**.

**Scheme 151**
Chemical structures of dyes **498–506**.

**Scheme 152**
Reaction occurring with cyanide anions.

**Scheme 153**
Reaction occurring with cyanide anions.

**Figure 3**
Cyanide ion detection with **509**: (a) optically with the naked eye; (b) by fluorescence changes. Reproduced with permission from Wang et al. [359].

**Scheme 154**
Chemical structures of **510–518**.

**Scheme 155**
Synthesis of 4-hydroxyindan-1,3-diones **521** studied in the 1930s by Robinson et al. and Walker et al., first indanediones known for their antiseptic activities [388].

**Scheme 156**
Examples of hydroxyindanediones **522–524** with important antibacterial activities against *Bacterium typhosum*.

**Scheme 157**
The two families of indeno [1,2-c]pyrazoles examined for their antimicrobial activities.

**Scheme 158**
Synthetic routes to 3-aryl-1-heteroarylindeno [1,2-c]pyrazol-4(1H)-ones **532**.

**Scheme 159**
Synthesis of ethyl 4-(9-ethyl-9H-carbazol-3-yl)-2-methyl-5-oxo-4,5-dihydro-1H-indeno [1,2-b]pyridine-3-carboxylate (ECPC) **536**.

**Scheme 160**
Synthesis of pyrimidine-2-thiones **538** starting from indane-1,3-dione 4 along with their corresponding antibacterial and antifungal activities.

**Scheme 161**
Strategy used for the synthesis of spiro[indolo-3,10′-indeno[1,2-b]quinolin]-2,4,11′-triones **540-**(IVa-IVv) along with their graphical representations of the diameter of growth of inhibition (mm) against bacteria strains. Reproduced with permission from Ref. [397].

**Scheme 162**
MCR leading to two different structures of indeno-heterocycles **541**. Apoptosis properties were evaluated at 25 µM.

**Scheme 163**
Camptothecin-inspired pentacycle-based indeno-heterocycles **544** and **545**.

**Scheme 164**
Synthetic routes to indenopyridine derivatives **549** examined in Ghorab’s study.

**Scheme 165**
Synthetic routes to indenopyrazoles and the best candidate **553-k**.

**Scheme 166**
“Push–pull” effect in IND-TPA with TICT schematisation used in this study.

**Figure 4**
(A) Generation of ROS in PBS buffer. (B) Cell viability of HeLa living cells, stained with MPAT, upon irradiation with a green light for 10 min. Reproduced with permission from Ref. [419].

**Scheme 167**
Chemical structure of **557** and the different advantages of this AIE dye.

**Figure 5**
CLSM images of HCC827 (A–E) and A549 (F–J) cells after incubation with **557** (5 mM) and BODIPY493/503 (100 nM) at 37 °C for 15 min. (A,F) Bright-field images. (B,G) Fluorescence image from **557** and from BODIPY493/503. (D,I) The merged images. (E,J) The intensity profile of ROI lines. Scale bar = 20 mm. Reproduced with permission of Gao M, Su H, Lin Y, Ling X, Li S, Qin A, and Zhong Tang B. Photoactivatable aggregation-induced emission probes for lipid droplets-specific live cell imaging. Reproduced with permission from Ref. [421].

**Figure 6**
I/I₀ (%) of fluorescence intensity of HCC827 cells colored with **557** (5 µM) with increasing time of irradiation at 514 nm with 7% laser power. Inset: Fluorescence images of HCC827 cells with increasing time of irradiation. Reproduced with permission from Gao M, Su H, Lin Y, Ling X, Li S, Qin A, Zhong Tang B. Photoactivatable aggregation-induced emission probes for lipid droplets-specific live cell imaging. Reproduced with permission from Ref. [421].

**Scheme 168**
Series of molecules **561–564** synthetized by MWAMCR.

**Scheme 169**
Plausible mechanism of the above molecules in the presence of Zn²⁺ cations.

**Scheme 170**
Synthetic route to arylindenopyrimidines **565**.

**Scheme 171**
Summary of the synthetic strategy developed to access compounds **577** and **584** substituted at the 8- and 9-positions.

**Scheme 172**
Comparisons between six compounds substituted at the 8- and the 9-positions for their in vitro and in vivo activities. In vitro activity for A2a and A1 functional assays and in vivo results for mouse catalepsy at 10 mg/kg, po.

**Scheme 173**
Chemical structure of JNJ-40255293 (**585**).

**Scheme 174**
Strategy employed for the synthesis of arylindenopyridines **589** and **593** in the patents.

**Scheme 175**
Synthesis of tricyclic 3,4-dihydropyrimidine derivatives **595** via Biginelli reaction along with the most promising compounds. ^a human TRPA1 antagonism ^b rat TRPA1 antagonism.

**Scheme 176**
MCR for the synthesis of **222** with three examples having decent anticonvulsant activity. ^a, Values represent means SEM (n = 3). ^b, Rotarod toxicity (number of animals exhibiting toxicity/number of animals tested).

**Scheme 177**
Synthetic route to dihydropyrimidine.

**Figure 7**
Close-up depiction of the lowest-energy three-dimensional (3-D) docking poses of 600 into the binding site of Torpedo californica acetylcholinesterase TcAChE. Reproduced with permission from Ref. [445].

**Scheme 178**
Chemical structures of indane-2-arylhydrazinylmethylene-1,3-diones **605a–f** and indol-2-aryldiazenylmethylene-3-ones **608a–m**.

**Scheme 179**
Chemical structures of various indane-1,3-dione derivatives **609–611** with anticoagulant properties.

**Scheme 180**
The different synthetic routes to acylindane-1,3-diones **613**.

**Scheme 181**
New synthetic route developed by Larsen et al. to access to acylindanediones **616**.

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Indane-1,3-Dione: From Synthetic Strategies to Applications

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Indane-1,3-Dione: From Synthetic Strategies to Applications

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