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Synlett 2012; 23(20): 2931-2934
DOI: 10.1055/s-0032-1317519
DOI: 10.1055/s-0032-1317519
letter
Total Synthesis and Stereochemical Assignment of (–)-Zenkequinone B
Further Information
Publication History
Received: 01 September 2012
Accepted after revision: 08 October 2012
Publication Date:
09 November 2012 (online)
Abstract
The first enantioselective total synthesis and a concise racemic synthesis of zenkequinone B are reported here by utilizing a sequential enyne metathesis, Diels–Alder and aromatization reactions.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
-
References and Notes
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- 18 HPLC separation conditions: The ee value was determined by CHIRALCEL OD-H, n-hexane–2-PrOH = 90:10, flow rate: 0.5 mL/min, λ = 256 nm.
- 19 (R)-[(1-Methyl-4-vinylcyclohex-3-enyloxy)methyl]benzene (20) A solution of enyne 21 (500 mg, 2.19 mmol) in CH2Cl2 (60 mL) was treated with Grubbs’ first-generation catalyst (17; 133 mg, 7 mol%) and then refluxed for 8 h. The reaction mixture was cooled to r.t. and stirred with DMSO (50 equiv with respect to the catalyst) for 6 h to remove the metal impurities. Evaporation of the solvent and purification by silica gel flash column chromatography (10% EtOAc in hexanes) provided 1,3-diene 20 (460 mg, 92%); Rf = 0.7 (EtOAc–hexanes, 1:9); [α]D 21 +67.6 (c 3.6, CHCl3). IR (neat): 2929, 2846, 1645, 1614, 1513, 1462, 1378, 1247, 1129, 1098, 1036, 821, 758 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.35–7.28 (m, 4 H), 7.26–7.20 (m, 1 H), 6.37 (dd, J = 17.5, 10.7, Hz, 1 H), 5.64 (s, 1 H), 5.08 (d, J = 17.5 Hz, 1 H), 4.93 (d, J = 10.7 Hz, 1 H), 4.51, 4.44 (ABq, J = 18.0 Hz, 2 H), 2.45 (d, J = 18.2 Hz, 1 H), 2.40–2.32 (m, 1 H), 2.20 (d, J = 18.2 Hz, 1 H), 2.17–2.12 (m, 1 H), 1.97–1.90 (m, 1 H), 1.78–1.71 (m, 1 H), 1.30 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 139.9, 139.5, 135.4, 128.4, 127.4, 127.2, 127.0, 110.6, 73.6, 63.6, 37.6, 32.6, 23.6, 22.1. ESI-HRMS: m/z calcd for C16H20O [M + Na]+: 251.1412; found: 251.1404.
- 20 (R)-2-(Benzyloxy)-2-methyl-1,2,3,4-tetrahydrotetraphene-7,12-dione (27) A solution of naphthoquinone 12 (228 mg, 1.44 mmol) and diene 20 (300 mg, 1.31 mmol) in toluene was heated at 80 °C for 12 h and then at 100 °C for 2 h. After the solvent was removed in vacuo, the crude Diels–Alder adduct was dissolved in CHCl3 (2 mL), treated with Et3N (1 mL) and silica gel (1 g) and stirred for 4 h. The solvent was removed in vacuo and purified by a silica gel flash column chromatography (20% EtOAc in hexanes) to afford the tetracycle 27 (460 mg, 91%) as a pale yellow solid; Rf = 0.6 (EtOAc–hexanes, 1:3); mp 163–165 °C; [α]D 21 –233.55 (c 1.1, CHCl3). IR (neat): 3021, 2961, 2926, 2857, 1663, 1581, 1566, 1454, 1326, 1299, 1270, 1099, 1045, 740 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.24–8.19 (m, 2 H), 8.16 (d, J = 8.0 Hz, 1 H), 7.79–7.71 (m, 2 H), 7.52 (d, J = 8.0 Hz, 1 H), 7.15–7.05 (m, 5 H), 4.53, 4.43 (ABq, J = 11.7 Hz, 2 H), 3.85 (d, J = 19.0 Hz, 1 H), 3.26–3.20 (m, 1 H), 3.22 (d, J = 19.0 Hz, 1 H), 2.92–2.85 (m, 1 H), 2.22–2.17 (m, 1 H), 1.87–1.79 (m, 1 H), 1.56 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 185.9, 183.7, 145.0, 139.6, 138.7, 135.2, 134.3, 134.1, 133.4, 133.3, 132.7, 131.7, 128.2, 127.2, 127.1, 126.5, 125.2, 72.9, 63.8, 39.9, 32.1, 27.6, 25.4. ESI-HRMS: m/z calcd for C26H22O3 [M + Na]+: 405.1467; found: 405.1475.
- 21 (–)-Zenkequinone B (19) A solution of benzyl ether 27 (50 mg, 0.13 mmol) in a mixture of CH2Cl2 (10 mL) and pH 7 buffer (0.5 mL) at 0 °C was treated with DDQ (59 mg, 0.26 mmol) portionwise and allowed to stir at r.t. for 12 h. The reaction mixture was treated with a sat. solution of NaHCO3 and extracted with CH2Cl2. The organic layer was washed with brine, dried (Na2SO4), concentrated, and purified by silica gel column chromatography to afford target compound 19 (33 mg, 87%) as a pale yellow solid; Rf = 0.40 (EtOAc–hexanes, 1:2); mp 202–204 °C; [α]D 21 –195.33 (c 0.06, acetone). IR (neat): 3463, 3082, 2961, 2927, 1663, 1579, 1561, 1368, 1329, 1303, 1275, 1092, 1045, 759 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.21–8.15 (m, 2 H), 8.11 (d, J = 8.0 Hz, 1 H), 7.76–7.70 (m, 2 H), 7.50 (d, J = 8.0 Hz, 1 H), 3.57 (d, J = 18.8 Hz, 1 H), 3.35 (d, J = 18.8 Hz, 1 H), 3.27–3.18 (m, 1 H), 2.91 (dt, J = 16.4, 4.4 Hz, 1 H), 1.98–1.92 (m, 1 H), 1.85–1.77 (m, 1 H), 1.47 (s, 3 H). ESI-HRMS: m/z calcd for C19H16O3 [M + Na]+ 315.0997; found: 315.0994.
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