Application of the Intramolecular Didehydro-Diels–Alder (IMDDA) Reaction for the Synthesis of Thieno[2,3-f]isoindole-4(8)-carboxylic Acids

Evgeniya R. Shelukho; Elizaveta D. Yakovleva; Nikita A. Logvinenko; Victor N. Khrustalev; Roman A. Novikov; Fedor I. Zubkov; Vladimir P. Zaytsev

doi:10.1055/s-0043-1773527

Synlett, Table of Contents

Synlett 2025; 36(10): 1358-1362
DOI: 10.1055/s-0043-1773527

letter

Application of the Intramolecular Didehydro-Diels–Alder (IMDDA) Reaction for the Synthesis of Thieno[2,3-f]isoindole-4(8)-carboxylic Acids

Evgeniya R. Shelukho

^aRUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation

,

Elizaveta D. Yakovleva

^aRUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation

,

Nikita A. Logvinenko

^aRUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation

,

Victor N. Khrustalev

^aRUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation

^bZelinsky Institute of Organic Chemistry of RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation

,

Roman A. Novikov

^сV. A. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov St., Moscow, 119991, Russian Federation

,

Fedor I. Zubkov

^aRUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation

,

Vladimir P. Zaytsev ∗

^aRUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation

› Author Affiliations

Abstract

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Abstract

The reaction of 3-(thienyl)propargylamines with maleic anhydride, followed by a domino sequence involving successive acylation/[4+2] cycloaddition steps, leads to the formation of the thieno[2,3-f]isoindole core. The key step, the intramolecular didehydro-Diels–Alder (IMDDA) reaction, proceeds with a high level of selectivity, yielding the target products – 7-oxo-5,6,7,8-tetrahydro-4H-thieno[2,3-f]isoindole-4(8)-carboxylic acids – in good yields. X-ray analysis and DFT calculations have revealed that the key step, the IMDDA reaction, proceeds via an exo transition allene state, resulting in the exclusive formation of a single isomer of the target heterocycle.

Key words

intramolecular didehydro-Diels–Alder reaction - propargylamine - IMDDA reaction - thieno[2,3-f]isoindole - thiophene - thienylacetylene

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References

References and Notes

1a Wessig P, Mueller G. Chem. Rev. 2008; 108: 2051
1b Johnson RP. J. Phys. Org. Chem. 2010; 23: 283
1c Li W, Zhou L, Zhang J. Chem. Eur. J. 2016; 22: 1558
1d Ajaz A, Bradley AZ, Burrell RC, Li WH. H, Daoust KJ, Bovee LB, DiRico KJ, Johnson RP. J. Org. Chem. 2011; 76: 9320

2a Krishna G, Grudinin DG, Nikitina EV, Zubkov FI. Synthesis 2022; 54: 797
2b Bober AE, Proto JT. Brummond K. M. Org. Lett. 2017; 19: 1500
2c Rana A, Paul I, Schmittel M. J. Phys. Org. Chem. 2017; 30: e3732
2d Wang T, Niu D, Hoye TR. J. Am. Chem. Soc. 2016; 138: 7832
2e Brummond KM. Kocsis L. S. Acc. Chem. Res. 2015; 48: 2320
2f Kocsis LS, Kagalwala HN, Mutto S, Godugu B, Bernhard S, Tantillo DJ, Brummond KM. J. Org. Chem. 2015; 80: 11686
2g Hoye TR, Baire B, Niu D, Willoughby PH, Woods BP. Nature 2012; 490: 208
2h Lima HM, Sivappa R, Yousufuddin M, Lovely CJ. Org. Lett. 2012; 14: 2274
2i Rodríguez D, Navarro A, Castedo L, Domínguez D, Saá C. Org. Lett. 2000; 2: 1497

3a Michael A, Bucher JE. Ber. Dtsch. Chem. Ges. 1895; 28: 2511
3b Bucher JE. J. Am. Chem. Soc. 1908; 30: 1244
3c Butz LW, Gaddis AM, Butz EW. J, Davis RE. J. Org. Chem. 1940; 5: 379

4a Chen X, Fontaine-Vive F, Poulain-Martini S, Michelet V. Catal. Commun. 2020; 147: 106117
4b Wang Z, Yamazaki S, Morimoto T, Takashima H, Nakaoku A, Shimizu M, Ogawa A. Org. Biomol. Chem. 2023; 21: 2172
4c Eghbali N, Eddy J, Anastas PT. J. Org. Chem. 2008; 73: 6932
4d Liu B, Wang H, Xie H, Zeng B, Chen J, Tao J, Wen TB, Cao Z, Xia H. Angew. Chem. Int. Ed. 2009; 48: 5430
4e Nieto-Oberhuber C, Perez-Galan P, Herrero-Gomez E, Lauterbach T, Rodriguez C, Lopez S, Bour C, Rosellon A, Cardenas DJ, Echavarren AM. J. Am. Chem. Soc. 2008; 130: 269
4f Martinez-Esperon MF, Rodriguez D, Castedo L, Saa C. Tetrahedron 2008; 64: 3674
4g Barluenga J, Fernandez-Rodriguez Manuel A, Garcia-Garcia P, Aguilar E. J. Am. Chem. Soc. 2008; 130: 2764
4h Wessig P, Mueller G, Pick C, Matthes A. Synthesis 2007; 464
4i Sato K, Menggenbateer, Kubota T, Asao N. Tetrahedron 2008; 64: 787
4j Dai M, Sarlah D, Yu M, Danishefsky SJ, Jones GO, Houk KN. J. Am. Chem. Soc. 2007; 129: 645
4k Gonzalez-Cantalapiedra E, de Frutos O, Atienza C, Mateo C, Echavarren AM. Eur. J. Org. Chem. 2006; 1430
4l Nieto-Oberhuber C, Lopez S, Echavarren AM. J. Am. Chem. Soc. 2005; 127: 6178
4m Martinez-Esperon MF, Rodriguez D, Castedo L, Saa C. Org. Lett. 2005; 7: 2213
4n Hayes ME, Shinokubo H, Danheiser RL. Org. Lett. 2005; 7: 3917
4o Rodriguez D, Martinez-Esperon Maria F, Navarro-Vazquez A, Castedo L, Dominguez D, Saa C. J. Org. Chem. 2004; 69: 3842

5a Klemm LH, Gopinath KW. J. Heterocycl. Chem. 1965; 2: 225
5b Klemm LH, Gopinath KW, Hsu Lee D, Kelly FW, Trod E, McGuire TM. Tetrahedron 1966; 22: 1797
5c Lu K, Luo T, Xiang Z, You Z, Fathi R, Chen J, Yang Z. J. Comb. Chem. 2005; 7: 958
5d Huang J, Du X, Hecke KV, Eycken EV. V, Pereshivko OP, Peshkov VA. Eur. J. Org. Chem. 2017; 4379
5e Cadby PA, Hearn MT. W, Ward AD. Aust. J. Chem. 1973; 26: 557
5f Herz H.-G, Schatz J, Maas G. J. Org. Chem. 2001; 66: 3176
5g Zhang L, Jin T, Guo Y, Martin AC, Sun K, Dudley GB, Yang J. J. Org. Chem. 2021; 86: 16716
5h Wang X, Yin J, Mao W, Wang Z, Wu S, You Y. Org. Lett. 2024; 26: 7757

6a Horak YI, Lytvyn RZ, Laba Y.-OV, Homza YV, Zaytsev VP, Nadirova MA, Nikanorova TV, Zubkov FI, Varlamov AV, Obushak MD. Tetrahedron Lett. 2017; 58: 4103
6b Nadirova MA, Laba Y.-OV, Zaytsev VP, Sokolova JS, Pokazeev KM, Anokhina VA, Khrustalev VN, Horak YI, Lytvyn RZ, Siczek M, Kinzhybalo V, Zubavichuse YV, Kuznetsov ML, Obushak MD, Zubkov FI. Synthesis 2020; 52: 2196
6c Yakovleva ED, Shelukho ER, Nadirova MA, Erokhin PP, Simakova DN, Khrustalev VN, Grigoriev MS, Novikov AP, Romanycheva AA, Shetnev AA, Bychkova OP, Trenin AS, Zubkov FI. Zaytsev V. P. Org. Biomol. Chem. 2024; 22: 2643

7 Jaroskova L, Linders J, Theodorus M, van der Veken L, Jozef E, Willemsens GH. M. Patent WO2006/24628, 2006
8 Xu Y, Wang Q, Wu Y, Zeng Z, Rudolph M, Hashmi AS. K. Adv. Synth. Catal. 2019; 361: 2309
9 Neese F. WIREs Comput. Mol. Sci. 2012; 2: 73
10 General Procedure for the Synthesis of Products 10a–l and Characterization Data Maleic anhydride (1 equiv) was added to the corresponding propargylamine 12 diluted in PhCH₃ (3 mL). The resulting mixture was heated at reflux for 5 h and then cooled to room temperature. The resulting precipitate was filtered off, washed with PhCH₃ (3 mL), Et₂O (2 × 3 mL), and air dried to give the title acids 10a–n as colorful solid powders. 5-Oxo-6-phenyl-5,6,7,8-tetrahydro-4H-thieno[3,2-f]isoindole-4-carboxylic acid (10a) For the reaction 48 mg (0.225 mmol) of thienylpropargylamine 12a and 22 mg (0.225 mmol) of maleic anhydride were taken. Yield 31.5 mg (45%); colorful powder; mp 213–214 °C. ¹H NMR (700.2 MHz, DMSO-d ₆, 25 °C): δ = 12.77 (br s, 1 H, CO₂H), 7.79 (d, J = 7.8 Hz, 2 H, H-2,6 Ph), 7.52 (d, J = 4.7 Hz, 1 H, H-Thien), 7.40 (d, J = 7.3 Hz, 2 H, H-3,5 Ph), 7.10 (m, 2 H, H-4Ph, H-Thien), 4.70 (d, J = 18.6 Hz, 1 H, NHCH₂), 4.62 (d, J = 18.6 Hz, 1 H, NHCH₂), 4.48 (br s, 1 H, CH), 3.91 (m, 2 H, CH₂) ppm. ¹³C NMR (176.1 MHz, DMSO-d ₆, 25 °C): δ = 171.9, 168.7, 150.0, 139.9, 132.9, 130.6, 129.5 (2 C), 129.2, 126.5, 125.3, 123.8, 118.4 (2 C), 53.0, 41.0, 25.9 ppm. IR (KBr): ν_max = 1737 (СО₂), 1650 (N–C = O) сm^–1. MS (ESI): m/z 312 [M + H]⁺. Anal. Calcd for C₁₇H₁₃NO₃S: C, 65.58; H, 4.21; N, 4.50; S, 10.30. Found: C, 65.27; H, 4.69; N, 4.81; S, 10.04.

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