Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• interaction of 2,3,3-trimethylindolenine with 3,5-di(tert-butyl)-1,2-benzoquinone leads to the formation of indolo[1,2-a]indoline derivatives [23], while the presence of a nitro group in 4,6-di(tert-butyl)-3-nitro-1,2-benzoquinone the reaction with 2,3,3-trimethylindolenine leads to an o-quinone ring

• tropolone ring proton, which appears at 6.9 ppm. A characteristic specificity of the 1H NMR spectra of compounds 7 and 8 is the presence of signals of hydroxy group protons forming a strong hydrogen bond with the indoline nitrogen atom, which closes the six-membered chelate cycle. These signals are observed

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• diastereomeric ratios. The relative configurations of the various polycyclic compounds were clearly elucidated by determination of several single crystal structures. Keywords: allylic SN2 reaction; dimerization; isatin; MBH carbonate; 3-methyleneoxindole; Introduction Isatins (indoline-2,3-diones) possessing

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• -glycosides containing the carbohydrate moiety located at the amine-type nitrogen atom (Scheme 18) [25]. For this purpose, we decided to react isatins with N-glycosylated indoxyls which were entirely unknown at that time. The reaction of ʟ-rhamnose α/β-4c with indoline afforded α/β-25a (β:α ≈ 4:1

• -glycosides Sassatelli et al. reported the synthesis of isoindigo-N-glycosides β-57a–c by reaction of benzyl-protected isatin-N-glycosides β-56a–c with oxindole (55) (Scheme 35) [53][54][55]. Deprotection by BBr3 afforded β-58a–c. Isatins 56 were prepared by glycosylation of indoline, benzylation, and

• of rhamnose with indoline (66) afforded β-67a which was transformed to indol-N-rhamnoside β-68a (Scheme 39) [59]. Benzylation and subsequent oxidation gave isatin-N-rhamnoside β-70a, albeit, in low yield. Condensation with 2-coumaranone (63) afforded the benzylated oxoisoindigo-N-rhamnoside β-71a

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• cyclization of the indole derivatives is the most popular (Scheme 1a). For instance, the efficient synthesis of spiro[indoline-3,2′-pyrrolidines] [8][9][10] or spiro-isoxazoles [11] through different dearomatization processes has been reported. Recently, Ramana and Dothe have proposed an elegant gold

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• yield (Scheme 1B). Notably, we are unaware of any reported method to achieve this specific transformation in the literature. Although, Tellitu and co-workers have reported a related preparation of indoline derivatives mediated by bis(trifluoroacetoxy)iodobenzene (PIFA) [17]. Results and Discussion In

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• design of the reported DAs, we designed and synthesized a series of DAs featuring a second-generation DASA switching motif and different chain lengths of the alkyl linker (i.e., DAn) that connects the DASA indoline motif with the hydrophilic part (i.e., the carboxylic acid motif, Scheme 1). The alkyl

• nitrogen atmosphere, followed by reduction of the indole motif in compound 1n to indoline in 2n. The ester group in compound 2n was deprotected under basic conditions to give compound 3n (Scheme 2). DAn with different chain lengths of the alkyl linker were synthesized through an aza-Piancatalli

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• activated by the base dehydrogenates the alcohol to the aldehyde and indoline to indole by acceptorless dehydrogenation. Moreover, C3 alkylation proceeded via BH (Scheme 58). In early 2021, Maji’s group demonstrated an efficient approach for the C-alkylation of methyl N-heteroarenes with primary alcohols

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• synthesis of optically active difluoro-substituted indoline derivatives starting from the corresponding 3H-indoles by chiral phosphoric acid-catalyzed transfer hydrogenation was developed. Using Hantzsch ester as the hydrogen source under mild reaction conditions, the target products can be obtained with

• isostere of polar functional groups [5][6]. Chiral indoline is an important member of the class of nitrogen-containing heterocyclic compounds that often exhibits various pharmaceutical activities and exists in many natural products [7][8]. The enantioselective synthesis of chiral indolines has received

• and practicability of this approach, a 2 mmol scale experiment of the asymmetric transfer hydrogenation of 1a was carried out (Scheme 3). Under the standard reaction conditions, 0.5 gram (98% yield) of chiral difluorinated indoline 2a was obtained with 95% ee. Based on previous studies [31], a

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• . Additionally, the similar reaction with α-halogenated N-tosylhydrazones also afforded N-tosyl-substituted spiro[indoline-3,5'-[1,2]diazepine] in satisfactory yields. This protocol provides a convenient approach for the assembly of diverse highly functionalized spiro[indoline-3,5'-[1,2]diazepines] and also

• efficient synthesis of spiro[azepine-4,3'-indoline] derivatives via the [4 + 3] cycloaddition reaction of bromo-substituted isatin-derived MBH adducts and N-(o-chloromethyl)arylamides. In this efficient protocol, the reactive allylic phosphonium ylides and aza-o-quinone methides were generated in situ and

• satisfactory yields and with good diastereoselectivity (reaction 3, Scheme 1) [57]. Very recently, we found that the base-catalyzed [4 + 3] cycloaddition reaction of isatin-derived MBH carbonates with various α,β-unsaturated N-arylaldimines affords spiro[indoline-3,5'-pyrrolo[3,4-b]azepine] derivatives

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• pyrazole derivatives (including indazole), benzimidazole, 1,2,3-triazole, indole, carbazole, indoline, quinazoline, and isoquinoline. Nevertheless, many heterocyclic motifs still remain beyond the attention of researchers. For example, glutarimides that incorporate tetrazole and 1,2,4-triazole substituents

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• olefinic oxindoles to replace maleimides, the reactions gave spiro[indoline-tetrahydropyrrolothiazole] products 30 in 55–70% with greater than 4:1 dr [76]. The reaction mechanism suggests that the reaction of cysteine with arylaldehydes gives N,S-acetals 27 which convert to AMYs 28 after decarboxlyation

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• dispiro[indoline-3,2'-quinoline-3',3''-indoline] derivatives in good yields and with high diastereoselectivity. On the other hand, a similar reaction of the dimedone adducts of 3-phenacylideneoxindoles afforded unique dispiro[indoline-3,2'-pyrrole-3',3''-indoline] derivatives with a cyclohexanedione

• ][59][60][61][62], we investigated the base-promoted annulation reaction of dimedone adducts of 3-methyleneoxindoles, with isatin and ammonium acetate. It was unexpectedly found that novel dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] were

• the three-component reaction. To our surprise, instead of the above mentioned dispiro[indoline-3,2'-quinoline-3',3''-indolines] 3a–m, the novel dispiro[indoline-3,2'-pyrrole-3',3''-indoline] derivatives 4a–i were obtained in high yields. The results are summarized in Table 3. The structural analysis

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• ]. They disclosed a reaction between acyclic iodonium ylides (e.g., 31/ I-10) and tertiary amines 32, which produced indoline rings 33 by forging two new C–C bonds between the ylidic carbon and unactivated positions on the amine (Scheme 5). In 2020, they disclosed a more complex variant of this reaction

• an example of β-dicarbonyl functionalization. Metal-free cyclopropanations of iodonium ylides, either as intermolecular (a) or intramolecular processes (b, c). Metal-free intramolecular cyclopropanation of iodonium ylides. Reaction of ylide 6 with diphenylketene to form lactone 24 and 25. Indoline

• synthesis from acyclic iodonium ylide 31 and tertiary amines. N-Heterocycle synthesis from acyclic iodonium ylide 31 and secondary amines. Indoline synthesis from acyclic iodonium ylides 39 and tertiary

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• indoline scaffolds (22a,b) via a radical-polar crossover mechanism (Figure 12C) [65], showcasing the power of conPET in dearomatization reactions. Finally, the synthesis of tetraphenylphosphonium chloride (20a) could be scaled up efficiently in an operationally very simple continuous-flow setup with only

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• ) as a product with 59% yield. Similarly, the reaction of cyclic secondary amines also resulted in arylation under the optimal reaction conditions to give products 3s–v with 42–48% yields. The treatment of indoline with iodonium ylide 2b in the presence of 10 mol % of CuSO4·5H2O affords product 3w in

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• reduction with Me2S·BH3 was investigated by Fontaine, and applied to a catalytic variant using HBpin as the turnover reagent (Scheme 7) [70]. Computational analysis showed two plausible, cooperative catalytic cycles: 1) hydroboration of indole 25 with BH3 to give a H2B-N-indoline 26, which then underwent B

• ‒N/B‒H transborylation with HBpin to regenerate BH3 and give the N-Bpin-indoline product 27; 2) two molecules of H2B-N-indoline underwent rearrangement to regenerate BH3 and gave a bisindolinylborane 28. The bis-N-indolinylborane then underwent B‒N/B‒H transborylation with HBpin to regenerate H2B-N

• -indoline and gave the Bpin-N-indoline product 27; this was suggested as the major pathway (Scheme 7). Thomas et al. reported the H-B-9-BBN-catalysed reductive cyanation of enones with HBpin and N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) (Scheme 8) [71]. The reaction was proposed to proceed by 1,4

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• ). The use of the much stronger triflic acid actually paradoxically protects the rather sensitive indoline cycloaddition products such as the dearomatized product 100, derived from skatole (99), by keeping the adduct and all intermediates in their protonated form throughout the progress of the reaction

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• from the indoline to B(C6F5)3. The resultant iminium ion is deprotonated by a second indoline molecule with the formation of an ammonium ion and the final indole. The ammonium ion reacts with a HB(C6F5)3 anion with the release of a H2 molecule and the regeneration of B(C6F5)3 for the next catalytic

From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• outstanding results were achieved in the N-formylation of indoline (Scheme 1, formamide 10). The present methodology could also be effectively applied to the synthesis of N-formylmorpholine (Scheme 1, product 11). Aliphatic primary amines can be more challenging substrates [22]. In fact, when the reaction was

Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

• Shao-Cong Zhan,
• Ren-Jie Fang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80

• [carbazole-3,3'-indoline] 1 and spiro[carbazole-2,3'-indoline] 2 as the final products. It can be seen that the two aryl groups at 1,3-positions actually exist on the e-bonds in the newly formed cyclohexyl ring in the spiro compounds 4 and 5. This also means that the major isomers 4 and 5 are the

• '-indoline]-3,3(1H)-dicarbonitrile (2a): White solid, 51%, mp 201–204 °C; 1H NMR (400 MHz, CDCl3) δ 8.27 (s, 1H, NH), 7.52–7.46 (m, 3H, ArH), 7.43–7.38 (m, 4H, ArH), 7.35–7.28 (m, 5H, ArH), 7.20 (t, J = 7.6 Hz, 1H, CH), 6.95–6.90 (m, 4H, ArH), 6.54 (d, J = 8.0 Hz, 1H, CH), 5.14 (d, J = 15.6 Hz, 1H, CH), 4.96

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• . Additionally, the tri(n-butyl)phosphine-promoted domino annulation reaction of isatins and ethyl isatylidene cyanoacetates produced spiro[indoline-3,2'-furan-3',3''-indolines] in satisfactory yields. Keywords: isatin; spiro[cyclohexane-1,3'-indoline]; spiro[indoline-3,2'-furan-3',3''-indoline]; spirooxindole

• [cyclohexane-1,3'-indoline] 3a albeit with low yields (entries 4–6 in Table 1). The spiro[cyclohexane-1,3'-indoline] 3a was clearly produced by a tri(n-butyl)phosphine-catalyzed formal [4 + 2] cycloaddition reaction. This result showed that tri(n-butyl)phosphine has a higher nucleophilic catalytic ability than

• employed in the reaction. However, the reaction did not proceed to give the expected spiro[cyclohexane-1,3'-indoline], while a new spiro[indoline-3,2'-furan-3',3''-indoline] was obtained, which was clearly constructed from the annulation reaction of isatin with ethyl isatylidene cyanoacetate. Therefore, we

New synthesis of a late-stage tetracyclic key intermediate of lumateperone

• Mátyás Milen,
• Bálint Nyulasi,
• Tamás Nagy,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2022, 18, 653–659, doi:10.3762/bjoc.18.66

• to the hydrazine derivative 4, followed by a Fischer indole synthesis with ethyl 4-oxopiperidine-1-carboxylate (5) provided tetracyclic compound 6. Its reduction with sodium cyanoborohydride in trifluoroacetic acid (TFA) to cis-indoline derivative (±)-7, followed by N-methylation [(±)-8] and

• in various ways (we only show here the path that seems the most advantageous). According to this, compound 17 was N-alkylated at the indoline nitrogen atom with N-methylchloroacetamide to give 18, then cyclized in one pot to derivative 8. Alternate methods for the 17→8 transformation require more

• reduced with sodium cyanoborohydride in acetic acid to cis-indoline derivative (±)-35. Removal of the trifluoroacetyl group to (±)-36 followed by N-methylation with formaldehyde and sodium cyanoborohydride gave target compound (±)-9a. It has to be mentioned that the preparation of compound 31 has been

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• . Again, in 2018, Yang et al. [26] synthesized functionalized dispiro[indoline-3,1-cyclopentane-3,3-indolines] via cyclodimerization of 3-phenacylideneoxindolines with benzoyl hydrazides and arylhydrazines. Encouraged by these synthetic methodologies and in continuation to our efforts towards the

• substitutions on the indoline ring could be unambiguously converted into the corresponding products (Scheme 2, Scheme 3). Halo-substituted indolines (5-Cl, 5-Br) were found to furnish the desired products in good yields (70–80%) which provided possibilities of further functionalization. In addition, the

• indoline ring was also investigated. Varieties of N-protected (Me, Et, propyl, benzyl and allyl) 3-phenacylideneoxindoles were used and provide good to excellent yield of the dimerized products (Scheme 2, Scheme 3). During the detailed study of the reaction, we conducted the reaction with 2-(2-oxindole-3

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• of functional groups with neither EDGs nor EWGs altering the reactivity of the acrylamide. Once synthesized, the authors demonstrated the oxindoles could be transformed into fused indoline–heterocycle frameworks in good yield, an attractive scaffold found in many biologically active compounds [119