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

• yield of 88% each step). Since, during the optimization of the reaction conditions, we have noticed a certain instability of the spiro-compounds through chromatography on silica gel, we have initially carried out the purifications using alumina as the stationary phase. However, during the scope studies

• . However, the synthetic protocol presents some limitations: employing non-electron-rich anilines (such as aniline or p-methylaniline) the reaction was unsuccessful, and the desired spiro-compounds were not obtained. To deeply investigate this point, we carried out the synthetic procedure with p

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• -2H-furan-3-one framework at position C-17 [22]. The one-pot procedure involved the condensation of diethyl oxalate with the α-hydroxy ketone moiety of derivatives 28, immediately followed by a cyclization between the 17α-hydroxy group and the carbonyl group of the α-ketoester in 29. Spiro compounds

• et al. reported the synthesis of cycloadducts 47 from reaction of (E)-16-arylidene derivatives 46 and azomethine ylides generated in situ from substituted isatins and sarcosine [27] (Scheme 14). The resulting spiro compounds proved to be potent antiproliferative agents against human cancer cell lines

• decarboxylation of the carboxylic residue when heated at reflux of methanol. After the regioselective cycloadditions, spiro compounds 49a,b were obtained in yields ranging from 75% to 91% (Scheme 15). Related derivatives have similarly been achieved in good to excellent yields [32][33]. Recently, López et al

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• ketimines as suitable three-carbon synthons in [3 + 2] and [3 + 3] annulations [11][12][13][14][15]. However, methods using N-sulfonyl ketimines as dienophiles in [4 + 2] annulation reactions to afford biologically important spiro compounds are still limited to date [16]. 1,2-Diaza-1,3-dienes [17][18][19

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

• yields. The chemical structures of the spiro compounds 7a–n were established by various spectroscopy methods. In addition, the single crystal structure of compound 7a was also determined by X-ray diffraction (Figure 1). As can be seen from Figure 1, both the C–C and C–N double bonds are part of the

• elimination of a proton and the Lewis base. Obviously, the spiro compounds 5 and 7 are formed by a similar reaction mechanism. Additionally, the method was applied to a gram-scale reaction of α-halogenated p-toluenesulfonylhydrazone 6c and MBH nitrile of isatin 2c under the standard conditions (Scheme 6). The

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

• ), in which the in situ-generated adduct of thiophenol and 3-phenacylideneoxindole was believed to be the key intermediate [53][54][55]. Inspired by these elegant synthetic protocols and in continuation of our aim to develop convenient reactions for the synthesis of diverse spiro compounds [56][57][58

• -oxoindolin-3-ylidene)acetate with 5-chloro and 5-fluoro substituent gave the spiro compounds 3a–k in satisfactory yields. However, the dimedone adducts of ethyl 2-(2-oxoindolin-3-ylidene)acetate itself and its derivatives with 5-methyl group gave the products 3l and 3m in moderate yields. The chemical

• is largely general. The 1H NMR spectra of the obtained compounds 4j–p clearly show similar chemical shifts of the characteristic groups as the spiro compounds 4a–i. Therefore, it can be concluded that the spiro compounds 4j–p have the same relative configuration as the spiro compounds 4a–i. In order

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• (Scheme 51B) [94]. Giving only a single diastereomer with good enantioselectivity using a Rh/bicyclo[2.2.2]octane-2,5-diene (bod) complex, a broad variety of spiro compounds were isolated in good to excellent yields. The authors have also shown that this skeleton provides a great opportunity to prepare

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

• chemistry. Recently, we have reported the efficient construction of a series of heterocyclic spiro compounds including tetrahydrospiro[carbazole-3,3’-indolines] by using the Levy three-component reaction of indole-2-acetate, aromatic aldehydes and various cyclic dienophiles such as 3-phenacylideneoxindoles

• examined the scope of aromatic aldehydes (Scheme 5), different substituents on the aromatic ring showed marginal effect on the yields. The spiro compounds 5a–g were successfully produced in moderate to excellent yields with excellent diastereoselectivity (dr > 20:1). Cyclohexane-1,3-dione also reacted

• cycloaddition between the indole-based ortho-quinodimethanes (o-QDMs, A) and dienophiles affords the final spiro compounds 1, 2, 4 and 5 as major isomers through an endo-transition state. Due to the different polarity, 3-phenacylideneoxindole and isatylidene malononitrile resulted in regioisomeric spiro

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• experimentally observed stereoselectivity. Keywords: azomethine ylides; cycloaddition; cyclopropenes; DFT calculations; spiro heterocycles; Introduction Spiro compounds (molecules containing at least two rings with only one common atom) are an important class of both synthetic and naturally occurring

• substances. Many biologically active natural products have a spirocyclic skeleton in their structure [1][2]. In this regard, there is interest in studying heterocyclic spiro compounds for drug discovery. These compounds were found to exhibit a broad range of biological activities, including antioxidant [3

• ], anticancer [4], antidiabetic [5], and antibacterial [6] properties. It is also worth noting that spiro compounds have found application in agriculture as fungicides [7], as well as in materials science as organic semiconductors [8]. The 3-azabicyclo[3.1.0]hexane framework is a valuable structural fragment

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

• find that the diastereoselectivity of this reaction was not very good. Because the polarity of the two diastereoisomers were very similar, it was very difficult to isolate them as pure compounds by column chromatography. For convenience, only the pure major diastereoisomers of the spiro compounds 3a–w

• (thiophen-2-yl)penta-1,4-dien-3-one was also successfully employed in the reaction. The major isomers of the corresponding spiro compounds 3x and 3y were predominately produced in moderate yields. In order to determine the relative configuration of the spiro compounds, the single crystal structures of the

• should be pointed out that the exocyclic benzylidene group exists on the C3-position in the newly formed cyclohexyl ring, while it exists on the C6-position in the above obtained spiro compounds 3a–z. This result clearly indicated that these two reactions have the opposite regioselectivity. Another kind

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• /indandione-fused spirocyclopentanes 104 bearing four contiguous stereogenic centers, was described by Chen et al. [68]. This transformation was catalyzed by a cinchona-thiourea derivative 105 furnishing the spiro compounds with good to high yield and enantioselectivity (Scheme 33). In this method two

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• in Fe(III)-promoted hydroalkylation/cyclization cascades (Scheme 26A) [93]. Here, the carbocyclization occurred via a SN2 mechanism between the enolate intermediate and the tethered halide (Scheme 26B). Using arylidene diones 67 as radical acceptors, spiro compounds 69 were obtained in moderate to

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• tautomeric mixture containing condensed oxazolidine 15E as the main component. Additional minor components included the other condensed oxazolidine (15D), spiro compounds 15B and 15C as well as the Schiff’ base 15A existing in a ratio of 15A/15B/15C/15D/15E = 4:<1:4:12:79 (Scheme 4) [39][40]. The structures

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• that the reaction is broad in scope. Remarkably, C–S bonds and spiro compounds have been constructed simultaneously in this approach, which are promising for drug synthesis. Substrate 46 comprises both indole and alkynone groups, leading to light-promoted intramolecular electron transfer in order to

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• reagent was also used for the synthesis of organic spiro compounds, containing selectively fluorinated cyclopropanes 38a,b [45], for the preparation of 6,6-difluoro-3-azabicyclo[3.1.0]hexane (39) (on a 10 g scale) [46], and of the epothilone B analog 40 [47] (Table 2). The reagents (chlorodifluoromethyl

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• approach. The polyfunctional molecular scaffolds were tested on the cyclopentenone reactivity to further expand the skeletal diversity, demonstrating the utility of this combined approach in generating novel spiro compounds as starting material for the generation of chemical libraries. The chemoinformatics

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• individual spiro compounds, not to a mixture of substances. However, condensations with the use of N-unsubstituted isatins are accompanied by the resinification of the reaction mixture, which may be caused by competing reactions of heterocyclization of the mentioned Knoevenagel adducts. In similar reactions

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• %). Finally, the spiro compound 30 was subjected to the SM coupling using two different boronic acids to produce the aryl substituted spiro compounds such as 31 (96%) and 32 (79%) (Scheme 4). Along similar lines, we have also demonstrated the synthesis of bis-spirocycles such as 37 by adopting a double RCM

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• oxidation of the chiral C2-symmetric iodoarene 85 that was playing the key role for the oxidative spirocyclization of phenols. In addition, N-methyl-N-(2-naphthyl)-2-naphthamides 87 were also cyclized to corresponding spiro compounds 88 in high yields and with upto 84% enantiomeric excess (Scheme 31

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• ; spiro compounds; synthetic methods; Introduction Molecular structures based on partially or exhaustively hydrogenated indole and benzofuran cores are omnipresent in nature. Both types of ring systems are found in a variety of important biologically active natural products [1][2][3][4][5][6][7][8][9][10

Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

• Manjunatha Narayanarao,
• Lokesh Koodlur,
• Vijayakumar G. Revanasiddappa,
• Subramanya Gopal and
• Susmita Kamila

Beilstein J. Org. Chem. 2016, 12, 2893–2897, doi:10.3762/bjoc.12.288

• of biological importance [1][2]. The regio- and stereoselective construction of spiro compounds by utilizing the 1,3-dipolar cycloaddition reaction of azomethine ylides has been reported [3][4][5][6]. However, unlike the previous reports, the present method is concise and facilitates the one-pot

• in the construction of functionalized spiro compounds. We report herein the facile synthesis of novel spiropyrrolidine compounds through a one-pot three-component reaction involving N-substituted vinylindole/indazole, ninhydrin and sarcosine/L-proline. The present multicomponent reaction (MCR) leads

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• be linked to the inhibition of the protein–protein p53-MDM2 interaction. Docking measurements support the biological data. Keywords: antitumor agents; DFT studies; 1,3-dipolar cycloaddition; docking studies; spiro-compounds; Introduction The p53 tumor suppressor protein is a transcriptional factor

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• ; nitrogen heterocycles; spiro compounds; Introduction A global trend in modern organic chemistry is the design of molecular systems with various degrees of complexity to maximize the incorporation of useful properties while optimizing cost and efficiency [1]. A very extended and powerful approach for

• interest to synthesize the other types of spiro compounds such as the 2,3’-spiropyrrolidinyloxindole structure which is isosteric with the 3,3’-spiropyrrolidinyloxindole and to study the diastereoselectivity of its formation. It could be expected that the cycloaddition of more bulky azomethine ylides

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation

• Jochen Kraft,
• Martin Golkowski and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 166–171, doi:10.3762/bjoc.12.18

• ; carbohydrates; oxazolines; palladium; spiro compounds; Introduction The design of new chiral ligands for stereo-differentiating metal catalysts that enable asymmetric syntheses is still a highly active field of research in organic chemistry, for there is a continuously growing demand for enantiomeric pure