Abstract
Lawsones and indenopyrazoles are the prevalent structural motifs and building blocks in pharmaceuticals and bioactive molecules, but their synthesis has always remained challenging as no comprehensive protocol has been outlined to date. Herein, a metal-free, ring-expansion reaction of indantrione with diazomethanes, generated in situ from the N-tosylhydrazones, has been developed for the synthesis of lawsone and indenopyrazole derivatives in acetonitrile and alcohol solvents, respectively. It provides these valuable lawsone and pyrazole skeletons in good yields and high levels of diastereoselectivity from simple and readily available starting materials. DFT calculations were used to explore the mechanism in different solutions. The synthetic application example also showed the prospects of this method for the preparation of valuable compounds.
Similar content being viewed by others
Introduction
The generation of privileged natural product scaffolds is a successful strategy for obtaining libraries of bioactive compounds1,2,3,4. Scaffold generation focuses on the application of methodologies capable of generating structures that cover a larger part of the chemical and biological space5,6,7. Since scaffold generation is pivotal during the early stage of drug discovery, issues like chemical efficiency and easy diversification are crucial in chemical reaction development. Using diazo compounds to expand the size of cyclocarbonyl compounds by one carbon unit is a classical homologation method for the generation of structurally complex and diverse scaffolds8,9,10,11. In the last century, the ring expansion of isatins and other cyclic ketones with multiple diazo variants (e.g., diazomethane and α-diazoesters) was reported12,13,14,15. Several catalytic ring-expansion reactions also have been performed by the Kingsbury16, Maruoka17, and Feng groups18. However, the ring-expansion reaction of benzo-fused cyclic dione substrate faces regioselectivity because of 1,2-aryl migration and 1,2-carbonyl migration reaction pathways (Fig. 1a). To the best of our knowledge, the regioselective ring-expansion reaction of indantrione has not been reported. In a continuation of our research with diazo compounds, we report herein the regioselective ring expansion of indantrione with α-aryldiazomethane involving 1,2-carbonyl migration (Fig. 2b).
Lawsones and indenopyrazole derivatives constitute important classes of polycyclic systems embedded in a plethora of natural products and synthetic compounds showing antimalarial (Atovaquone)19, antipneumocystic (Buparvaquone)20 bioactivities, and protease inhibitory activities such as cyclin-dependent kinase (CDK)21,22, hypoxia-inducible factor (HIF)-123,24, and tubulin25,26,27 (Fig. 2). In addition, lawsones are also the essential synthons28 for the synergistic nucleophilicity and electrophilicity to overcome various of synthetic challenges29,30,31. Despite being appealing structural motifs, highly efficient approaches to prepare lawsones and indenopyrazoles are limited32,33,34,35,36,37,38,39,40,41. The reported protocols are generally multi-step reactions, which require high loadings of metal catalysts and properly functionalized substrates that are not readily available. The solvent-controlled ring-expansion reaction of indantrione and α-aryldiazomethane would be a straightforward method for preparing these lawsones and indenopyrazole compounds. Herein, a metal-free, ring-expansion reaction of indantrione with diazomethanes, generated in situ from the N-tosylhydrazones, has been developed for the synthesis of lawsone and indenopyrazole derivatives in acetonitrile and alcohol solvents, respectively.
Results and discussion
Optimization of the reaction conditions
We screened an array of solvents and bases (Table 1) for their reactivity and chemoselectivity in the ring-expansion reaction of indantrione 1a, benzaldehyde 2a, and p-methylbenzenesulfonohydrazide 3. This survey led to the following optimized reaction conditions: (1) 1,2,3-Indantrione 1a (1.0 mmol) and Cs2CO3 (2.0 equiv.) were added to α-aryldiazomethane and stirred at 80 °C in MeCN for 3 h. The desired lawsone 4a product was obtained in 90% yield (Table 1, entry 1); (2) 1,2,3-Indantrione 1a (1.0 mmol) and Cs2CO3 (3.0 equiv.) were added to the α-aryldiazomethane and stirred at 80 °C in EtOH for 10 h. The desired indenopyrazolone 5a product was obtained in 83% yield with a dr value >95:5 (Table 1, entry 5). A small amount of lawson product 4a was generated in a 15% yield. This result shows that solvent-controlled regioselective ring-expansion reaction had a 1,2-carbonyl migratory tendency with two different products.
Substrate scope of indantriones and aldehydes for producing lawsones
We then explored the scope of this reaction with a range of indantriones 1 and aldehydes 2 (Fig. 3) (see Supplementary Notes 1, 2) for producing lawsones. As anticipated, the ring-expansion reaction of indantriones generally tolerated a broad range of substituted aryl aldehydes bearing either electron-donating or electron-withdrawing substituents, such as methyl, fluoro, chloro, bromo, nitro, nitrile, trifluoromethyl, and naphthyl groups. The corresponding hydroxynaphtho-quinones were afforded in high to excellent yield. The electron-donating groups slightly reduced the reaction yield compared with electron-withdrawing groups (e.g., 4b, p-F, 96% and 4j, p-CF3, 93% yields vs. 4e, p-CH3, 90% and 4h, p-OMe, 85% yields). The position of substituents did not significantly affect the reaction yield (e.g., 4b, para-F; 4m, meta-F; 4u, ortho-F; with yields of 96%, 95%, and 90%, respectively). Polysubstituted aryl aldehydes were also suitable for this reaction (e.g., 4aa and 4ab with 85% and 84% yields, respectively). Borate ester-substituted aryl aldehydes (4t, 91% yield), heteroaryl aldehydes (4ad and 4ag, 93% and 81% yields, respectively), and some large sterically hindered aryl aldehydes (4af and 4ah, 85% and 80% yields, respectively) also reacted smoothly. The ring-expansion reaction also produced equally satisfying results using alkyl aldehydes, e.g., prenylaldehyde (4ai, 74% yield), butyraldehyde (4aj, 71% yield), and 2-ethylcaproaldehyde (4ak, 50% yield) as substrates. The corresponding ring-expansion products were also obtained under the standard conditions for substituted indantriones and benzaldehyde (4al 88%, and 4am 85% yields). To verify the relative configurations of the hydroxynaphtho-quinones, 4h, and 4ae were selected as representative compounds and characterized by X-ray crystallography (see Supplementary Data 1, 2, and see Supplementary Note 3, Figs. S1 and S2) (CCDC 2149716 (4h), 2149715 (4ae), 2149717 (5a), 2149718 (5f), 2149719 (5q), 2149720 (5r) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via https://www.ccdc.cam.ac.uk/data_request/cif).
Substrate scope of indantriones and aldehydes for producing indenopyrazoles
Similarly, we investigated the scope of this reaction using a range of indantriones 1 and aldehydes 2 (Fig. 4) (see Supplementary Notes 1, 2) to produce indenopyrazolones. Under the standard reaction conditions, aryl aldehydes with various substituents, such as methyl, fluoro, chloro, bromo, or methoxy groups, smoothly reacted to afford the indenopyrazolone derivatives in high to excellent yields and high stereoselectivities (dr, ≥95:5). Electron-donating groups also slightly reduced the reaction yield compared with electron-withdrawing groups (e.g., 5b, p-CH3, 83% and 5f, p-OCH3, 79% yield vs. 5c, p-F, 91% and 5d, p-Cl, 88% yields). The position and number of substituents did not significantly affect the reaction yield (e.g., 5c, para-F; 5i, meta-F; 5 m ortho-F; with yields of 91%, 90%, and 81%, respectively). The reaction also produced equally satisfying results using heteroaryl aldehydes (e.g., 5q, 85% yield) and sterically bulky aryl aldehydes (e.g., 5t, 81% yield). In different alcohol solutions, the corresponding esterified indenopyrazolone derivatives were obtained, such as 5o–5ab, with medium to excellent yields and high stereoselectivities (dr, ≥95:5). The corresponding products were also obtained under standard conditions for substituted indantriones and benzaldehyde (5ad 85%, and 5ae 87% yields). Unfortunately, alkyl-substituted aldehydes were found to be incompatible with this transformation and did not yield any product. 5a, 5f, 5q, and 5r were characterized by X-ray crystallography (see Supplementary Data 3–6, and see Supplementary Note 3, Figs. S3–S6) (CCDC 2149716 (4h), 2149715 (4ae), 2149717 (5a), 2149718 (5f), 2149719 (5q), 2149720 (5r) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via https://www.ccdc.cam.ac.uk/data_request/cif).
Mechanistic studies
To elucidate the reaction mechanism of the regioselective ring-expansion of indantrione and α-aryldiazomethanes, various control experiments were conducted (Fig. 5). The results indicated that: (1) the addition of TEMPO or BHT did not inhibit the reaction under standard conditions, and no radical-TEMPO/BHT coupling products were detected (Fig. 5, eq. 1); (2) isotope-labeling experiments in deuterated methanol showed that the ester group of the indenopyrazolone product was formed by bonding the C1 atom of indantrione with deuterated methyl (Fig. 5, eq. 2); (3) using lawsone 4a and α-aryldiazomethane as the starting material in alcohol solution, indenopyrazolone product 5a was not obtained. This shows that the reaction mechanism of the two products proceeded via different paths (Fig. 5, eq. 3); (4) by using the mixed solvent of acetonitrile and ethanol under standard conditions, the yield of the indenopyrazolone product increased gradually upon increasing the proportion of ethanol. On the contrary, the yield of lawsones increased upon increasing the acetonitrile proportion (Fig. 5, eq. 4). This shows that the solvent had an obvious selectivity for the two different products; (5) Using ninhydrin 1a’ as the starting material, the indenopyrazolone product was also obtained in an alcohol solvent under standard conditions (Fig. 5, eq. 5). The lawsone product was obtained in acetonitrile solvent (Fig. 5, eq. 6).
To better understand the regioselectivity of the ring-expansion process and the cascade reaction mechanism, based on the experimental results, we performed theoretical calculations (see Supplementary Data 8) on the possible reaction pathways of this solvent-controlled regioselective ring-expansion reaction of indantrione and α-aryldiazomethane42,43,44. Initially, aldehyde 2 and p-toluenesulfonyl hydrazide 3 condensed in solution to form aryl alkylenediamine a (Fig. 6). Then, the aryl alkenylamine removed the benzosulfonyl group to obtain α-aryldiazomethane dipoles b and b’. Subsequently, indantriones underwent two different ring-expansion reactions in different solvents. In acetonitrile, the ring-expansion reaction of indantrione proceeded via the competitive pathways A and B. In reaction pathway B, the carboanion of the α-aryldiazomethane dipole b nucleophile attacked the carbonyl C1 atom of indantrione. Then, intermediate INT-4 formed through the cycloaddition of transition state TS-3 (ΔG = 28.2 kcal mol−1). Next, intermediate INT-4 underwent intramolecular ring expansion and denitrogenation. After transition state TS-4 (ΔG = 30.6 kcal mol−1), intermediate INT-5 formed, which underwent enol tautomerism to obtain 4a’ (Fig. 6, pathway B). Similarly, in reaction pathway A, α-aryldiazomethane dipole b attacked carbonyl C2 of indantrione via transition state TS-1 (ΔG = 22.0 kcal mol−1) to form intermediate INT-2. Then, the intermediate underwent intramolecular ring expansion and denitrogenation. After transition state TS-2 (ΔG = 22.1 kcal mol−1), intermediate INT-3 formed, and finally, tautomerism occurred to form stable product 4a. Notably, our calculations showed that the energy barrier of the initial step TS-3 (ΔG = 22.0 kcal mol−1) of pathway B was higher than TS-1 (ΔG = 15.8 kcal mol−1) of pathway A. The energy barrier difference of the two-step transition state was about 6.2 kcal mol−1 (Fig. 6). The results indicated that nucleophilic addition between indantrione and α-aryldiazomethane was more favorable at the C2 site than at the C1 site. The reaction was more likely to produce reaction product 4a. This is consistent with the experimental results. Based on the calculation results, the proposed mechanism is shown in Fig. 7, path a.
In alcohol solution, the alcohol oxygen anion first nucleophilically attacked the carbonyl C1 atom of indantriones to form intermediate INT-6 (Fig. 8). Then, the intermediate underwent a 1,2-aryl migration rearrangement to obtain the four-membered-ring intermediate, INT-7 via TS-5 (ΔG = 20.1 kcal mol−1). α-Aryldiazomethane b was then nucleophilically added to the cyclocarbonyl carbon atom of intermediate INT-7 to obtain INT-9 via TS-6 (ΔG = 41.2 kcal mol−1). Next, under the catalysis of Cs2HCO3+, INT-9 underwent transition state TS-7 (ΔG = −52.8 kcal mol−1) and TS-8 (ΔG = −57.49 kcal mol−1) to undergo dehydration to form intermediate INT-11. Subsequently, α-aryldiazomethane dipole b attacked the conjugated double bond of intermediate INT-11 via TS-9 (ΔG = −55.5 kcal mol−1) to obtain INT-13. This process was diastereoselective. Finally, intermediate INT-13 underwent heterocyclic condensation and isomerization to obtain product 5a (Fig. 8). Based on the calculation results, the proposed mechanism is shown in Fig. 7, path b.
Synthetic application
To test the robustness of this solvent-controlled regioselective ring-expansion reaction, a series of multigram-scale experiments were performed (Fig. 9) (see Supplementary Method 1). When 10 mmol of 1a’ and 21 mmol of 2a in EtOH or MeOH solvent were subjected to the standard reaction conditions, product 5a or 5o was isolated in 76% and 81% yield, respectively. Additionally, when 10 mmol of 1a and 12 mmol of 2a in MeCN solvent were subjected to the standard reaction conditions, product 4a was isolated in an 89% yield. The synthetic versatility of lawsones and indenopyrazolones was then explored in an array of derivatizations (see Supplementary Method 2). The carbonyl group of compound 5a was reduced to a hydroxyl group 6a under lithium aluminum hydride reduction, but the ester group was unaffected. Compound 6b was obtained by the selective methoxy stripping of compound 5n under the action of boron tribromide. Lawsone product 4a can be used as a reaction synthon to construct a variety of products with diverse structures that can react with phenylalkynes to construct benzannulated bicyclo[3.3.0]octanes compound 6d with biological activity45. Compound 4a also reacted with diphenylacetylene to obtain alkylidene phthalide 6c, which is a key intermediate for the synthesis of bioactive natural products46. The synthesized bioactive natural product 4a was directly acetylated to obtain hydroxyacetyl product 6e. Notably, compound 4w easily formed carbazoloquinone derivative 6f under metal catalysis, which is of great interest as a privileged structure for anticancer drug molecules47.
Conclusions
In summary, we have described the first solvent-controlled regioselective ring-expansion reaction of indantrione and α-aryldiazomethanes. This reaction preferentially provides the 1,2-carbonyl migration product. In acetonitrile solvent, the reaction products were lawsone derivatives. In alcohol solution, the reaction products were stereoselective indenopyrazolone derivatives. A series of substrates underwent the reaction smoothly, providing highly-functionalized lawsone derivatives and indenopyrazolone derivatives in high yields (up to 95%) and with high levels of diastereoselectivity (up to 95:5 dr). A range of functional groups was also tolerated under the mild reaction conditions. The mechanism control experiment was used to determine the possible reaction mechanism pathways. The synthetic application example also demonstrated the prospect of this method for preparing valuable compounds.
Methods
General procedure for preparing lawsones
A mixture of aldehydes (2, 1.2 mmol) and p-toluenesulfonyl hydrazide (1.2 mmol) in acetonitrile (20 ml) was stirred at room temperature for 0.5 h until complete consumption of starting materials (monitored by TLC). Then, indantrione (1, 1 mmol) and Cs2CO3 (2 equiv) were added to the crude product and stirred at 80 °C for 3 h. After the reaction was finished, the solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate 8:1) to afford the desired product 4. The products were further identified by FTIR spectroscopy, NMR spectroscopy, and HRMS, see Supplementary Data 7.
General procedure for preparing Indenopyrazoles
A mixture of aldehydes (2, 2.1 mmol) and p-toluenesulfonyl hydrazide (2.1 mmol) in alcohol (30 ml) was stirred at room temperature for 0.5–1 h until complete consumption of starting materials (monitored by TLC). Then, indantrione (1, 1 mmol) and Cs2CO3 (3 equiv) were added to the crude product and stirred at 80 °C for 10 h. After the reaction was finished, the solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate 25:1) to afford the desired product 5. The products were further identified by FTIR spectroscopy, NMR spectroscopy, and HRMS (see Supplementary Data 7).
Data availability
The authors declare that the data supporting the findings of this study are available within the article and the Supplementary Information as well as from the authors upon reasonable request. The X-ray crystallographic coordinates for structures 4h, 4ae, 5a, 5f, 5q, and 5r, reported in this study have been deposited at the Cambridge Crystallographic Data Centre (CCDC), under CCDC 2149716 (4h, Supplementary Data 1), 2149715 (4ae, Supplementary Data 2), 2149717 (5a, Supplementary Data 3), 2149718 (5f, Supplementary Data 4), 2149719 (5q, Supplementary Data 5) and 2149720 (5r, Supplementary Data 6), respectively. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. The compound characterizations are available in Supplementary Data 7. DFT calculations are available in Supplementary Data 8. The computed output file is in the open database (https://zenodo.org/) link (DOI:10.5281/zenodo.7296393).
References
Rizzo, S. & Waldmann, H. Development of a natural-product-derived chemical toolbox for modulation of protein function. Chem. Rev. 114, 4621 (2014).
Nandy, J. P. et al. Advances in solution-and solid-phase synthesis toward the generation of natural product-like libraries. Chem. Rev. 109, 1999–2060 (2009).
Andrei, S. A. et al. Rationally designed semisynthetic natural product analogues for stabilization of 14-3-3 protein–protein interactions. Angew. Chem. Int. Ed. 57, 13470–13474 (2018).
Itoh, H. et al. Development of a high-throughput strategy for discovery of potent analogues of antibiotic lysocin E. Nat. Commun. 10, 1–11 (2019).
Rodrigues, T., Reker, D., Schneider, P. & Schneider, G. Counting on natural products for drug design. Nat. Chem. 8, 531–541 (2016).
Grigalunas, M., Brakmann, S. & Waldmann, H. Chemical evolution of natural product structure. J. Am. Chem. Soc. 144, 3314–3329 (2022).
Bon, R. S. & Waldmann, H. Bioactivity-guided navigation of chemical space. Acc. Chem. Res. 43, 1103 (2010).
Ford, A. et al. Modern organic synthesis with α-diazocarbonyl compounds. Chem. Rev. 115, 9981–10080 (2015).
Ye, T. & McKervey, M. A. Organic synthesis with. alpha.-diazo carbonyl compounds. Chem. Rev. 94, 1091–1160 (1994).
Candeias, N. R., Paterna, R. & Gois, P. M. Homologation reaction of ketones with diazo compounds. Chem. Rev. 116, 2937–2981 (2016).
Tan, F. et al. Catalytic Asymmetric Homologation of Ketones with α-Alkyl α-Diazo Esters. J. Am. Chem. Soc. 143, 2394–2402 (2021).
Mosettig, E. & Burger, A. Ring enlargement with diazomethane in the hydroaromatic series1. J. Am. Chem. Soc. 52, 3456–3463 (1930).
Gutsche, C. D. The reaction of diazomethane and its derivatives with aldehydes and ketones. Org. React. 8, 364–430 (2004).
Tangella, Y. et al. Regioselective ring expansion of isatins with in situ generated α-aryldiazomethanes: direct access to viridicatin alkaloids. Org. lett. 20, 3639–3642 (2018).
Skubi, K. L. et al. Enantioselective excited-state photoreactions controlled by a chiral hydrogen-bonding iridium sensitizer. J. Am. Chem. Soc. 139, 17186–17192 (2017).
Rendina, V. L., Moebius, D. C. & Kingsbury, J. S. An enantioselective synthesis of 2-aryl cycloalkanones by Sc-catalyzed carbon insertion. Org. lett. 13, 2004–2007 (2011).
Hashimoto, T., Naganawa, Y. & Maruoka, K. Desymmetrizing asymmetric ring expansion of cyclohexanones with α-diazoacetates catalyzed by chiral aluminum Lewis acid. J. Am. Chem. Soc. 133, 8834–8837 (2017).
Li, W. et al. A catalytic asymmetric ring-expansion reaction of isatins and α-alkyl-α-diazoesters: highly efficient synthesis of functionalized 2‐quinolone derivatives. Angew. Chem. Int. Ed. 124, 8772–8775 (2012).
Paton, D. G. et al. Exposing Anopheles mosquitoes to antimalarials blocks Plasmodium parasite transmission. Nature 567, 239–243 (2019).
Mäntylä, A. et al. Synthesis, in vitro evaluation, and antileishmanial activity of water-soluble prodrugs of buparvaquone. J. Med. Chem. 47, 188–195 (2004).
Nugiel, D. A. et al. Synthesis and evaluation of indenopyrazoles as cyclin-dependent kinase inhibitors. 2. Probing the indeno ring substituent pattern. J. Med. Chem. 45, 5224–5232 (2002).
Yue, E. W. et al. Synthesis and evaluation of indenopyrazoles as cyclin-dependent kinase inhibitors. 3. Structure–activity relationships at C3. J. Med. Chem. 45, 5233–5248 (2002).
Fuse, S. et al. Design, synthesis, and evaluation of indeno[2,1-c]pyrazolones for use as inhibitors against hypoxia-inducible factor (HIF)-1 transcriptional activity. Bioorg. Med. Chem. 28, 115207 (2020).
Minegishi, H., Fukashiro, S., Ban, H. S. & Nakamura, H. Discovery of Indenopyrazoles as a New Class of Hypoxia Inducible Factor (HIF)-1 Inhibitors. ACS Med. Chem. Lett. 4, 297–301 (2013).
Khan, I. et al. Design, synthesis and biological evaluation of 1, 4-dihydro indeno[1,2-c] pyrazole linked oxindole analogues as potential anticancer agents targeting tubulin and inducing p53 dependent apoptosis. Eur. J. Med. Chem. 144, 104–115 (2018).
Liu, Y.-N. et al. Design, synthesis, and biological evaluation of 1-methyl-1,4-dihydroindeno[1,2-c]pyrazole analogues as potential anticancer agents targeting tubulin colchicine binding site. J. Med. Chem. 59, 5341–5355 (2016).
Minegishi, H. et al. Methyl 3-((6-Methoxy-1,4-dihydroindeno[1,2-c]pyrazol-3-yl)amino)benzoate (GN39482) as a tubulin polymerization inhibitor identified by MorphoBase and ChemProteoBase profiling methods. J. Med. Chem. 58, 4230–4241 (2015).
Sadeghpour, M., Olyaei, A. & Adl, A. Recent progress on the synthesis of henna-based dibenzoxanthenes. N. J. Chem. 45, 13669–13691 (2021).
Rueping, M., Sugiono, E. & Merino, E. Asymmetric iminium ion catalysis: an efficient enantioselective synthesis of pyranonaphthoquinones and β-lapachones. Angew. Chem. Int. Ed. 47, 3046–3049 (2008).
Ramachary, D. B., Anif Pasha, M. & Thirupathi, G. Organocatalytic asymmetric formal [3+2] cycloaddition as a versatile platform to access methanobenzo [7] annulenes. Angew. Chem. Int. Ed. 56, 12930–12934 (2017).
Kaya, U. et al. Enantioselective synthesis of 4 H-pyranonaphthoquinones via sequential squaramide and silver catalysis. Chem. Commun. 52, 1669–1672 (2016).
Louvis, A. D. R. et al. Synthesis, characterization and biological activities of 3-aryl-1, 4-naphthoquinones–green palladium-catalysed Suzuki cross coupling. N. J. Chem. 40, 7643–7656 (2016).
Yu, D., Chen, X. L., Ai, B. R., Zhang, X. M. & Wang, J. Y. Tetrabutylammonium iodide catalyzed hydroxylation of naphthoquinone derivatives with tert-butyl hydroperoxide as an oxidant. Tetrahedron Lett. 59, 3620–3623 (2018).
Allan, K. M., Hong, B. D. & Stoltz, B. M. Expedient synthesis of 3-hydroxyisoquinolines and 2-hydroxy-1, 4-naphthoquinones via one-pot aryne acyl-alkylation/condensation. Org. Biomol. Chem. 7, 4960–4964 (2009).
Schank, K., La Vecchia, L. & Lick, C. Chemie freier, cyclischer vicinaler Tricarbonyl-Verbindungen (1, 2, 3-Trione’), Teil 1, Reaktionsweise von Diazomethan und seinen Derivaten mit 5, 5-Dimethylcyclohexan-1, 2, 3-trion (=Oxo-dimedon’) und verwandten Cyclohexan-1, 2, 3-trionen. Helv. Chim. Acta 84, 2071–2088 (2001).
Ramu, G., Kodiripaka, B. G., Chaitanya, K. R. & Babu, B. N. A facile and metal-free domino reaction of TsDAM and 2-alkenylarylaldehyde: An easy access to 8-hydroxy-2, 8-dihydro indeno [2, 1-c] pyrazoles. Org. Biomol. Chem. 19, 4118–4125 (2021).
Chaturvedi, A. K., Kant, R. & Rastogi, N. Access to the phosphorylindenopyrazole scaffold via a metal-free domino reaction of diazoalkylphosphonates with 3-bromophthalides. J. Org. Chem. 81, 11291–11296 (2016).
Davies, D. L., Ellul, C. E., Macgregor, S. A., McMullin, C. L. & Singh, K. Experimental and DFT studies explain solvent control of C–H activation and product selectivity in the Rh (III)-catalyzed formation of neutral and cationic heterocycles. J. Am. Chem. Soc. 137, 9659–9669 (2015).
Deng, Y. et al. Solvent tunes the selectivity of hydrogenation reaction over α-MoC catalyst. J. Am. Chem. Soc. 140, 14481–14489 (2018).
Wang, H. et al. Solvent-enabled radical selectivities: controlled syntheses of sulfoxides and sulfides. Angew. Chem. Int. Ed. 55, 1094–1097 (2017).
Liu, C., Zhu, C., Cai, Y. & Jiang, H. Solvent-switched oxidation selectivities with O2: controlled synthesis of α-difluoro (thio) methylated alcohols and ketones. Angew. Chem. Int. Ed. 60, 12038–12045 (2021).
Deng, S., Qu, C. X., Jiao, Y. C., Liu, W. Q. & Shi, F. Insights into 2-indoly lmethanol-involved cycloadditions: origins of regioselectivity and enantioselectivity. J. Org. Chem. 85, 11641–11653 (2020).
Li, T.-Z. et al. Regio- and enantioselective (3+3) cycloaddition of nitrones with 2-indolylmethanols enabled by cooperative organocatalysis. Angew. Chem. Int. Ed. 60, 2355–2363 (2021).
Wu, P. et al. Design and synthesis of axially chiral aryl-pyrroloindoles via the strategy of organocatalytic asymmetric (2 + 3) cyclization. Fund. Res. https://doi.org/10.1016/j.fmre.2022.01.002 (2022).
Kumar, A. S., Thirupathi, G., Reddy, G. S. & Ramachary, D. B. Stereoselective insertion of benzynes into lawsones: synthesis of biologically important benzannulated bicyclo [3.3. 0] octanes. Chemistry 25, 1177–1183 (2019).
Borthakur, S., Baruah, S., Sarma, B. & Gogoi, S. Pd (II)-catalyzed synthesis of alkylidene phthalides via a decarbonylative annulation reaction. Org. Lett. 21, 2768–2771 (2019).
Barcia, J. C. et al. A new approach to the synthesis of benzo [b] naphtho [2, 3-b] furan-6, 11-diones and 2-benzyl-3-hydroxynaphthalene-1, 4-diones. SynOpen 1, 0156–0165 (2017).
Acknowledgements
The authors gratefully acknowledge for financial support of the Program for the NSFC (Nos. 22267021, 22067020), Yunnan Fundamental Research Projects (202101AS070034, 202001BB050009), and the Program for Excellent Young Talents, Yunnan University.
Author information
Authors and Affiliations
Contributions
Y.J. conceived and directed the project. BW.H., PY.J., L.J., and X.Y. performed the experiments. WX.Y. performed the theoretical calculations. J.L., YC.J., and Y.J. analyzed the results, and Y.J. wrote the manuscript.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Peer review
Peer review information
Communications Chemistry thanks Fernando da Silva and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Hu, B., Yan, W., Jiang, P. et al. Switchable synthesis of natural-product-like lawsones and indenopyrazoles through regioselective ring-expansion of indantrione. Commun Chem 6, 17 (2023). https://doi.org/10.1038/s42004-022-00807-z
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s42004-022-00807-z
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.