Sultines as o-Quinodimethane Precursors in an Oxa-Diels–Alder Reaction: Synthesis of Functionalized Isochromans

Aurapat Ngamnithiporn; Padon Chuentragool; Poramate Songthammawat; Supakarn Punnita; Kittithuch Photong; Poonsakdi Ploypradith; Somsak Ruchirawat

doi:10.1055/a-2236-9589

Synlett, Table of Contents

Synlett 2024; 35(10): 1180-1184
DOI: 10.1055/a-2236-9589

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Thieme Chemistry Journals Awardees 2023

Sultines as o-Quinodimethane Precursors in an Oxa-Diels–Alder Reaction: Synthesis of Functionalized Isochromans

Aurapat Ngamnithiporn ∗

^aLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6 Road, Bangkok 10210, Thailand

,

Padon Chuentragool

^aLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6 Road, Bangkok 10210, Thailand

,

Poramate Songthammawat

^aLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6 Road, Bangkok 10210, Thailand

,

Supakarn Punnita

^aLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6 Road, Bangkok 10210, Thailand

,

Kittithuch Photong

^aLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6 Road, Bangkok 10210, Thailand

,

Poonsakdi Ploypradith

^aLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6 Road, Bangkok 10210, Thailand

^bProgram in Chemical Sciences, Chulabhorn Graduate Institute, 54 Kamphaeng Phet 6 Road, Bangkok 10210, Thailand

^cCenter of Excellence on Environmental Health and Toxicology, Office of the Permanent Secretary (OPS), Ministry of Higher Education, Research, and Innovation (MHESI), Bangkok 10400,, Thailand

,

Somsak Ruchirawat

^aLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6 Road, Bangkok 10210, Thailand

^bProgram in Chemical Sciences, Chulabhorn Graduate Institute, 54 Kamphaeng Phet 6 Road, Bangkok 10210, Thailand

^cCenter of Excellence on Environmental Health and Toxicology, Office of the Permanent Secretary (OPS), Ministry of Higher Education, Research, and Innovation (MHESI), Bangkok 10400,, Thailand

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Abstract

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Abstract

The development of an oxa-Diels–Alder reaction between sultines and carbonyl compounds is reported. o-Quinodimethanes, generated from sultines, undergo a [4+2]-cycloaddition with activated aldehydes or ketones in the presence of Cu(OTf)₂ to provide a variety of functionalized isochromans, including spiroisochromans, in up to 99% yield. The developed protocol demonstrates broad functional-group compatibility and tolerates unprotected isatins bearing free NH-functionalities.

Key words

quinodimethanes - oxa-Diels–Alder reaction - cycloaddition - sultines - isochromans

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References

References and Notes
1 Zhao Z, Kang K, Yue J, Ji X, Qiao H, Fan P, Zheng X. Eur. J. Med. Chem. 2021; 210: 113073
2 Cheng M, Li P, Jiang Y, Tang X, Zhang W, Wang Q, Li G. J. Nat. Prod. 2021; 84: 1345
3 Lakshminarayana N, Rajendra Prasad Y, Gharat L, Thomas A, Ravikumar P, Narayanan S, Srinivasan CV, Gopalan B. Eur. J. Med. Chem. 2009; 44: 3147
4 Larghi EL, Kaufman TS. Eur. J. Org. Chem. 2011; 2011: 5195
5 Muller C, Horký F, Vayer M, Golushko A, Lebœuf D, Moran J. Chem. Sci. 2023; 14: 2983

For reviews, see

6a Tamanna, Kumar M, Joshi K, Chauhan P. Adv. Synth. Catal. 2020; 362: 1907
6b Albano G, Aronica LA. Eur. J. Org. Chem. 2017; 2017: 7204

For some selected recent reports, see

7a Pandey G, Pal S, Laha R. Angew. Chem. Int. Ed. 2013; 52: 5146
7b Maity S, Parhi B, Ghorai P. Angew. Chem. Int. Ed. 2016; 55: 7723
7c Nickerson LA, Bergstrom BD, Gao M, Shiue Y.-S, Laconsay CJ, Culberson MR, Knauss WA, Fettinger JC, Tantillo DJ, Shaw JT. Chem. Sci. 2020; 11: 494
7d Jongcharoenkamol J, Jancharoen K, Batsomboon P, Ruchirawat S, Ploypradith P. Synthesis 2023; 55: 2757

8a Ngamnithiporn A, Chuentragool P, Ploypradith P, Ruchirawat S. Org. Lett. 2022; 24: 4192
8b Ngamnithiporn A, Chuentragool P, Ploypradith P, Ruchirawat S. Asian J. Org. Chem. 2023; 12: e202300366

For reviews on chemistry using sultines as masked; o-QDMs, see

9a Segura JL, Martín N. Chem. Rev. 1999; 99: 3199
9b Yang B, Gao S. Chem. Soc. Rev. 2018; 47: 7926
9c Kotha S, Khedkar P, Dommaraju Y. Tetrahedron Lett. 2019; 60: 631

For reviews on methods to prepare sultines, see

10a Zhu Z, Deng Z, Ouyang X, Shu C. Synlett 2023; 34: 1943
10b Zhang Y, Li H, Yang X, Zhou P, Shu C. Chem. Commun. 2023; 59: 6272
10c Bondarenko OB, Saginova LG, Zyk NV. Russ. Chem. Rev. 1996; 65: 147

11 Janssen-Müller D, Singha S, Olyschläger T, Daniliuc CG, Glorius F. Org. Lett. 2016; 18: 4444
12 Wang H, Chen X, Li Y, Wang J, Wu S, Xue W, Yang S, Chi YR. Org. Lett. 2018; 20: 333
13 Hu Y, Pan D, Cong L, Yao Y, Yu C, Li T, Yao C. ChemistrySelect 2018; 3: 1708
14 Mavroskoufis A, Rajes K, Golz P, Agrawal A, Ruß V, Götze JP, Hopkinson MN. Angew. Chem. Int. Ed. 2020; 59: 3190
15 Wurm T, Turnbull BW. H, Ambler BR, Krische MJ. J. Org. Chem. 2017; 82: 13751

16a Hentemann MF, Allen JG, Danishefsky SJ. Angew. Chem. Int. Ed. 2000; 39: 1937
16b Ueno S, Ohtsubo M, Kuwano R. Org. Lett. 2010; 12: 4332
16c Gao M, Ruiz JM, Jimenez E, Lo A, Laconsay CJ, Fettinger JC, Tantillo DJ, Shaw JT. Chem. Sci. 2023; 14: 6443

17 Attardo GG. Doctoral Dissertation. McGill University; Canada: 1990
18 See the Supporting Information for full results and analysis.
19 Jung F, Molin M, Van der Elzen R, Durst T. J. Am. Chem. Soc. 1974; 96: 935
20 See the Supporting Information for additional optimization results.
21 For the determination of isomeric ratios and analyses of the major and minor isomers, see the Supporting Information.
22 Attempts to perform the reaction in the absence of Cu(OTf)₂ resulted in no detectable amount of product, with methyl dimethoxyacetate remaining unreacted.
23 For a list of unsuccessful substrates, see the Supporting Information.
24 Yamazaki S. Org. Lett. 1999; 1: 2129
25 Isochromans 5aa–5am; General Procedure A flame-dried 25-mL round-bottomed flask equipped with a magnetic stirrer bar was charged with the appropriate sultine (0.4 mmol, 2 equiv) and Cu(OTf)₂ (0.01 mmol, 5 mol %). The flask was sealed with a septum then evacuated and backfilled with argon for three cycles. The appropriate aldehyde or ketone (0.2 mmol, 1 equiv) and DCE (2 mL) were added, and the septum was replaced with a Findenser equipped with an Ar balloon at the top. The mixture was stirred at 90 °C (preheated oil bath) for 18 h, then cooled to r.t., and filtered through a silica plug that was subsequently rinsed with EtOAc. The organic phase was then concentrated in vacuo, and the crude product was purified by column chromatography (silica gel; EtOAc–hexanes). Ethyl Isochroman-3-carboxylate (5aa) Prepared from sultine 3a (67.3 mg, 0.4 mmol) and a 47% solution of ethyl glyoxylate (polymer form) in toluene (42 μL, 0.2 mmol) by the general procedure, and purified by column chromatography (silica gel, 10% EtOAc/hexanes) as a pale-yellow oil; yield: 37.9 mg (92%). ¹H NMR (400 MHz, CDCl₃): δ = 7.22–7.17 (m, 2 H), 7.16–7.12 (m, 1 H), 7.04–6.98 (m, 1 H), 5.01 (d, J = 15.0 Hz, 1 H), 4.87 (d, J = 15.1 Hz, 1 H), 4.37 (dd, J = 8.8, 5.7 Hz, 1 H), 4.29 (q, J = 7.1 Hz, 2 H), 3.16–2.99 (m, 2 H), 1.33 (t, J = 7.1 Hz, 3 H). Ethyl 6,7-Dimethylisochroman-3-carboxylate (5ab) Prepared from sultine 3b and a 47% solution of ethyl glyoxylate (polymer form) in toluene (42 μL, 0.2 mmol) by the general procedure, and purified by column chromatography (silica gel, 10% EtOAc/hexanes) as a yellow oil; yield: 43.7 mg (93%). IR (UATR): 2924, 1734, 1451, 1186, 1117 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 6.91 (s, 1 H), 6.78 (s, 1 H), 4.95 (d, J = 14.8 Hz, 1 H), 4.81 (d, J = 14.8 Hz, 1 H), 4.36–4.31 (m, 1 H), 4.28 (q, J = 7.6 Hz, 2 H), 3.05–2.93 (m, 2 H), 2.22 (s, 3 H), 2.22 (s, 3 H), 1.32 (t, J = 7.1 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 171.4, 135.2, 135.0, 131.1, 129.9, 129.0, 125.3, 73.7, 67.9, 61.4, 30.6, 19.6, 14.5. HRMS (ESI-TOF); m/z [M + H]⁺ calcd for C₁₄H₁₉O₃: 235.1329; found: 235.1329.

Supplementary Material

Supporting Information