Synlett 2020; 31(14): 1423-1429
DOI: 10.1055/s-0039-1690891
letter
© Georg Thieme Verlag Stuttgart · New York

An Efficient Two-Step Protocol for the Isoprenylation of Xanthone at the C2 Position Starting from 1-Fluoroxanthone Derivative

,
Chisato Furukawa
,
Kanae Takahashi
,
Miho Mochizuki
,
,
This work was financially supported by the Japan Society for the Promotion of Science (JSPS KAKENHI Grant Number JP17K15425) and the MEXT-Supported Program for the Private University Research Branding Project.
Further Information

Publication History

Received: 04 March 2020

Accepted: 24 March 2020

Publication Date:
14 May 2020 (online)


Abstract

The SNAr reaction of 1-fluoroxanthone derivatives with alkoxide of 1,1-dimethylallyl alcohol cleanly afforded the corresponding ethers, which have thus far been unavailable. The obtained ethers underwent the Claisen rearrangement at room temperature by treatment with silica gel in toluene. This two-step protocol provides expeditious and high-yield access to xanthones possessing isoprenyl or the related allylic side chain at the C2 position.

Supporting Information

 
  • References and Notes


    • For reviews on natural xanthones, see:
    • 1a Klein-Júnior LC, Campos A, Niero R, Corrêa R, Heyden YV, Filho VC. Chemistry & Biodiversity 2020; 17: e1900499
    • 1b El-Seedi HR, El-Barbary MA, El-Ghorab DM, Bohlin L, Borg-Karlson AK, Göransson U, Verpoorte R. Curr. Med. Chem. 2010; 17: 854
    • 1c Pinto MM. M, Sousa ME, Nascimento MS. J. Curr. Med. Chem. 2005; 12: 2517

      For reviews on the synthesis of xanthones, see:
    • 2a Masters K.-S, Bräse S. Chem. Rev. 2012; 112: 3717
    • 2b Azevedo CM. G, Afonso CM. M, Pinto MM. M. Curr. Org. Chem. 2012; 16: 2818
    • 2c Sousa ME, Pinto MM. M. Curr. Med. Chem. 2005; 12: 2447

      For recent examples of biological study of prenylated xanthones, see:
    • 3a Natrsanga P, Jongaramruong J, Rassamee K, Siripong P, Tip-Pyang S. J. Nat. Med. 2020; 74: 467
    • 3b Li P, Yang Z, Tang B, Zhang Q, Chen Z, Zhang J, Wei J, Sun L, Yan J. ACS Omega 2020; 5: 334
    • 3c Jin S, Shi K, Liu L, Chen Y, Yang G. Int. J. Mol. Sci. 2019; 20: 4803

    • For a review, see:
    • 3d Pinto MM. M, Castanheiro RA. P. In Natural Products: Chemistry, Biochemistry and Pharmacology, Brahmachari G. Alpha Science; Oxford: 2009: 520

      For examples of the SNAr reaction of xanthone derivative, see:
    • 5a Sharghi H, Tamaddon F. J. Heterocycl. Chem. 2001; 38: 617
    • 5b Gobbi S, Rampa A, Bisi A, Belluti F, Valenti P, Caputo A, Zampiron A, Carrara M. J. Med. Chem. 2002; 45: 4931
    • 5c Piazzi L, Belluti F, Bisi A, Gobbi S, Rizzo S, Bartolini M, Andrisano V, Recanatini M, Rampa A. Bioorg. Med. Chem. 2007; 15: 575
    • 5d Waszkielewicz AM, Słoczysńka K, Pękala E, Żmudzki P, Siwek A, Gryboś A, Marona H. Chem. Biol. Drug Des. 2017; 89: 339
    • 5e Kubacka M, Szkaradek N, Mogilski S, Pańczyk K, Siwek A, Gryboś A, Filipek B, Żmudzki P, Marona H, Waszkielewicz AM. Bioorg. Med. Chem. 2018; 26: 3773 . See also ref. 4a

      For reviews on the aromatic Claisen rearrangement, see:
    • 6a Ito H, Taguchi T. In The Claisen Rearrangement. Hiersemann M, Nubbemeyer U. Wiley-VCH; Weinheim: 2007: 86
    • 6b Castro AM. M. Chem. Rev. 2004; 104: 2939

      For examples of isoprenylation of xanthone core by the Claisen rearrangement, see:
    • 7a Burling ED, Jefferson A, Scheinmann F. Tetrahedron 1965; 21: 2653
    • 7b Locksley HD, Quillinan AJ, Scheinmann F. J. Chem. Soc. C 1971; 3804
    • 7c Quillinan AJ, Scheinmann F. J. Chem. Soc., Perkin Trans. 1 1972; 1382
    • 7d Quillinan AJ, Scheinmann F. J. Chem. Soc., Perkin Trans. 1 1975; 241
    • 7e Ohira S, Fukamichi N, Nakagawa O, Yamada M, Nozaki H, Iinuma M. Chem. Lett. 2000; 464
    • 7f Ito S, Kitamura T, Arulmozhiraja S, Manabe K, Tokiwa H, Suzuki Y. Org. Lett. 2019; 21: 2777. See also ref. 9a-d, 10a,b
  • 8 So far, the selective 1,1-dimethylallylation, but not the 3,3-dimethylallylation, of hydroxy groups of xanthones had been achieved by utilizing the 1,1-dimethylpropargylation/half-reduction sequence9 or the Tsuji–Trost allylation with 1,1-dimethylallyl carbonate derivatives.10 However, these methods are not effective for the reaction of the C1-hydroxy group.7 , 11 , 12

    • For examples of 1,1-dimethylallylation of hydroxy groups of xanthones by utilizing the 1,1-dimethylpropargylation/half-reduction sequence, see:
    • 9a Fellows IM, Schwaebe M, Dexheimer TS, Vankayalapati H, Gleason-Guzman M, Whitten JP, Hurley LH. Mol. Cancer Ther. 2005; 4: 1729
    • 9b Nicolaou KC, Xu H, Wartmann M. Angew. Chem. Int. Ed. 2005; 44: 756
    • 9c Tisdale EJ, Vong BG, Li H, Kim SH, Chowdhury C, Theodorakis EA. Tetrahedron 2003; 59: 6873
    • 9d Tisdale EJ, Slobodov I, Theodrakis EA. Org. Biomol. Chem. 2003; 1: 4418

      For examples of 1,1-dimethylallylation of hydroxy groups of xanthones by utilizing the Tsuji–Trost allylation, see:
    • 10a Chantarasriwong O, Cho WC, Batova A, Chavasiri W, Moore C, Rheingold AL, Theodorakis EA. Org. Biomol. Chem. 2009; 7: 4886
    • 10b Elbel KM, Guizzunti G, Theodoraki MA, Xu J, Batova A, Dakanali M, Theodorakis EA. Org. Biomol. Chem. 2013; 11: 3341

    • For the Tsuji–Trost allylation, see:
    • 10c Tsuji J, Takahshi H, Morikawa M. Tetrahedron Lett. 1965; 49: 4387
    • 10d Trost BM, Vranken DL. V. Chem. Rev. 1996; 96: 395
    • 10e Tsuji J. Palladium Reagents and Catalysts, New Perspectives for the 21st Century. John Wiley & Sons; Chichester: 2004

    • See also:
    • 10f Kaiho T, Miyamoto M, Nobori T, Katakami T. J. Synth. Org. Chem., Jpn. 2004; 62: 27
  • 11 Wang et al. pointed out the propargylation/half-reduction sequence was not capable of 1,1-dimethylallylation of C1-hydroxy group of xanthone derivative, see: Xu D, Nie Y, Liang X, Ji L, Hu S, You Q, Wang F, Ye H, Wang J. Nat. Prod. Commun. 2013; 8: 1101
  • 12 In fact, our attempts to apply the Tsuji–Trost allylation to 1-hydroxyxanthone (4a) under various conditions with tert-butyl 1,1-dimethylallyl carbonate resulted in failure, as exemplified by Scheme 6.

    • For examples of solid-acid catalysis in aromatic Claisen rearrangement, see:
    • 13a Dauben WG, Cogen JM, Behar V. Tetrahedron Lett. 1990; 31: 3241
    • 13b Cruz-Almanza R, Pérez-Flores F, Breña L. J. Heterocycl. Chem. 1995; 32: 219
    • 13c Sucholeiki I, Pavia MR, Kresge CT, McCullen SB, Malek A, Schramm S. Mol. Diversity 1998; 3: 161
    • 13d Yadav GD, Lande SV. Synth. Commun. 2007; 37: 941
    • 13e Liu Y, Guo Y, Ji F, Gao D, Song C, Chang J. J. Org. Chem. 2016; 81: 4310
    • 13f Shiozawa M, Iida K, Odagi M, Yamanaka M, Nagasawa K. J. Org. Chem. 2018; 83: 7276
  • 14 Silica gel-induced acceleration was also observed in the reactions of 2-(1,1-dimethylallyloxy)xanthone derivatives as illustrated in Scheme 7, which, incidentally, led to the selective isoprenylation at the C1 position. General aspects of the silica gel catalysis in the Claisen rearrangement of xanthone derivatives will be reported in due course.
  • 15 Silica gel: Kanto Chemical Co. Inc. (63–210 mesh for chromatography), Florisil: FUJIFILM Wako Pure Chemical, Ltd. (100–200 mesh for chromatography), MS 4Å: FUJIFILM Wako Pure Chemical, Ltd, MS 13X: Kanto Chemical Co. Inc., neutral alumina: MP Biomedicals (Alumina N, Act-I for chromatography), Montmorillonite K10: Sigma-Aldrich Co. LLC.
  • 16 Typical Procedure of the SNAr Reaction/Claisen Rearrangement Sequence for the Synthesis of 5a A flame-dried two-necked round-bottomed flask was charged with NaH (60% dispersion in mineral oil, 160 mg, 4.0 mmol) and DMF (2.0 mL). Then, 1,1-dimethylallyl alcohol 2 (0.63 mL, 6.0 mmol) was added dropwise at 0 °C. After stirring for 30 min at 25 °C, the net concentration of the alkoxide was adjusted to 1.0 M by adding DMF (1.3 mL), ready to use for the SNAr reactions. This solution of the alkoxide (1.0 M, 0.94 mL, 0.94 mmol) was added dropwise to a solution of fluoroxanthone 1a (100 mg, 468 μmol) in DMF (0.95 mL), and the stirring was continued for 1 h at 25 °C. The reaction was quenched with phosphate buffer (0.1 M, pH 7), and the products were extracted with Et2O (3×). The combined extracts were washed with water, brine, dried over Na2SO4, and concentrated in vacuo. The residue was azeotropically dried with toluene and used for the next step without further purification. Silica gel (100 mg), placed in a two-necked round-bottomed flask, was dried in vacuo by heating it with a heating gun and then suspended in toluene (1.3 mL). To this suspension was added a solution of the above-stated crude material of ether 3a in toluene (1.0 mL) at 0 °C, and the mixture was stirred for 5 h at 25 °C. After removal of silica gel by filtration through a sintered glass filter, the filtrate was concentrated in vacuo. The residue was purified by column chromatography (silica gel, ­hexane/EtOAc = 9:1) to give xanthone 5a (124 mg, 95%) as yellow solids and a small amount of 1-hydroxyxanthone (4a, 2 mg). Mp 124.5–127.0 °C (yellow needles from hexane/EtOAc). 1H NMR (400 MHz, CDCl3): δ = 1.75 (s, 3 H), 1.77 (s, 3 H), 3.39 (d, 2 H, J = 7.2 Hz), 5.34 (br t, 1 H, J = 7.2 Hz), 6.87 (d, 1 H, J = 8.4 Hz), 7.37 (dd, 1 H, J = 8.0, 7.2 Hz), 7.44 (d, 1 H, J = 8.4 Hz), 7.47 (d, 1 H, J = 8.4 Hz), 7.72 (ddd, 1 H, J = 8.4, 7.2, 1.6 Hz), 8.27 (dd, 1 H, J = 8.0, 1.6 Hz), 12.91 (s, 1 H). 13C NMR (100 MHz, CDCl3): δ = 17.8, 25.8, 26.9, 106.2, 108.5, 117.8, 120.5, 121.7, 122.9, 123.8, 126.0, 133.4, 135.4, 136.8, 154.5, 156.2, 159.0, 182.5. IR (ATR): 2962, 2902, 1607, 1574, 1472, 1458, 1440, 1424, 1374, 1306, 1277, 1237, 1220, 1202, 1154, 1119, 1056, 998, 918, 876, 851, 809, 790, 779, 753, 666, 636, 606, 576, 524, 481, 454, 426 cm–1. HRMS (ESI-TOF): m/z calcd for C18H16O3Na [M + Na]+: 303.0997; found: 303.0996. Anal. Calcd for C18H16O3: C, 77.12; H, 5.75. Found: C, 77.11; H, 5.71.
  • 17 See the Supporting Information for HOMOs of 3b and 3c, obtained by theoretical calculations (HF/6-311G(d,p)//B3LYP/6-31G (d)).
    • 18a Jung ME, Gervay J. Tetrahedron Lett. 1988; 29: 2429
    • 18b Jung ME, Gervay J. J. Am. Chem. Soc. 1991; 113: 224
    • 18c Jung ME, Piizzi G. Chem. Rev. 2005; 105: 1735
    • 18d Beesley RM, Ingold CK, Thorpe JF. J. Chem. Soc., Trans. 1915; 107: 1080
  • 19 DFT calculations performed at B3LYP/6-31G(d,p) level of theory suggested that the reaction of 3m is energetically more preferable than the reaction of 3l in 3.8 kcal/mol (ΔΔG ). For details including the optimized TS structures and energies, see the Supporting Information.