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Synlett 2013; 24(6): 705-708
DOI: 10.1055/s-0032-1318366
DOI: 10.1055/s-0032-1318366
letter
Studies Towards the Synthesis of Crotogoudin
Weitere Informationen
Publikationsverlauf
Received: 07. Januar 2013
Accepted after revision: 12. Februar 2013
Publikationsdatum:
05. März 2013 (online)
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Abstract
An effective synthesis of the tricyclic core structure of the new diterpene crotogoudin was achieved. The synthesis features an intermolecular domino Michael reaction to construct a bicyclo[2.2.2]octane motif and an aldol condensation to close ring B. Stork reductive alkylation with allyl bromide proceeded from the β side, resulting in the wrong stereochemistry at C-10.
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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- 17 Enedione 14 Pd(OH)2/C (Pearlman’s catalyst, 20%, 1.1 g, 2.0 mmol) was added to a stirred suspension of enone 10 (10.0 g, 43.0 mmol), K2CO3 (1.5 g. 10.0 mmol) in CH2Cl2 (200 mL), followed by addition of TBHP (5.0–6.0 M in decaline, 43 mL, 215.0 mmol) at r.t. The resulting mixture was stirred overnight at r.t. The reaction mixture was then filtered through a short pad of silica gel, washed with CH2Cl2, and concentrated in vacuo at r.t. The residue was purified by flash chromatography (PE–EtOAc, 1:1) to give 1,4-diketone 12 (8.3 g, 78%) as a colorless oil. Rf = 0.40 (PE–EtOAc, 1:1). 1H NMR (400 MHz, CDCl3, atoms numbered according to the naphthalene system): δ = 1.74–1.79 (m, 1 H, 10-H), 1.84–1.99 (m, 4 H, 5-H, 10-H, 2 × 9-H), 2.11–2.21 (m, 3 H, 2 × 3-H, 5-H), 2.30 (ddd, J = 16.8, 7.3, 5.3 Hz, 1 H, 6-H), 2.45 (ddd, J = 16.7, 9.9, 5.8 Hz, 1 H, 6-H), 2.60 (ddd, J = 5.8, 3.0, 3.0 Hz, 1 H, 2-H), 2.79 (dd, J = 9.6, 6.1 Hz, 1 H, 4-H), 3.63 (s, 3 H, OCH3), 6.50 (s, 1 H, 8-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 22.7 (C-9), 28.0 (C-3), 29.8 (C-5), 31.1 (C-10), 34.4 (C-6), 38.6 (C-4a), 40.4 (C-2), 46.7 (C-4), 52.2 (OCH3), 125.4 (C-8), 152.4 (C-8a), 174.3 (ester), 198.8 (C-7), 201.8 (C-1) ppm. ESI-HRMS: m/z [M + Na]+ calcd for C14H16O4Na: 271.094080; found: 271.094073.
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- 19 Enedione 5 A solution of diazomethane in Et2O (200 mL) was added to a stirred solution of enedione 14 (4.7 g, 0.019 mol) in CHCl3 (150 mL) at 0 °C. The mixture was allowed to warm to r.t. and stirred for 6 h before the solvents were removed with a flow of nitrogen. The residue was purified by flash chromatography (PE–EtOAc, 4:1 to 1:1) to give enedione 5 (3.9 g, 78%) as white crystals (mp 97–98.5 °C). Rf = 0.45 (PE–EtOAc, 1:1). 1H NMR (400 MHz, CDCl3): δ = 1.61–1.68 (m, 1 H, 10-H), 1.78–2.00 (m, 4 H, 5-H, 10-H, 2 × 9-H), 2.06–2.14 (m, 3 H, 2 × 3-H, 5-H), 2.17 (s, 3 H, 8-CH3) 2.34 (ddd, J = 16.4, 6.8, 5.0 Hz, 1 H, 6-H), 2.49 (ddd, J = 16.4, 10.9, 5.8 Hz, 1 H, 6-H), 2.55 (ddd, J = 6.1, 3.0, 3.0 Hz, 1 H, 2-H), 2.69 (dd, J = 8.6, 7.3 Hz, 1 H, 4-H), 3.60 (s, 3 H, OCH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 12.0 (CCH3), 22.6 (C-9), 28.1 (C-3), 29.8 (C-5), 31.1 (C-10), 34.0 (C-6), 39.8 (C-4a), 42.2 (C-2), 47.2 (C-4), 52.0 (OCH3), 138.2 (C-8), 144.6 (C-8a), 174.6 (ester), 199.6 (C-7), 204.7 (C-1) ppm. ESI-HRMS: m/z [M + Na]+ calcd for C15H18O4Na: 285.109730; found: 285.109658.
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- 22 Allylation of Dienolate of Enedione 5 to 15: Methyl (2S,4S,4aS,8S)-8-Allyl-1-(allyloxy)-8-methyl-7-oxo-3,4,5,6,7,8-hexahydro-2H-2,4a-ethanonaphthalene-4-carboxylate (15) Lithium (60 mg, 8.82 mmol) was added in small portions to stirred liquid NH3 (10 mL) at –78 °C. The resulting blue solution was stirred for 1 h before it was treated with a solution of diketone 5 (50 mg, 0.19 mmol) in THF (4 mL). After complete addition stirring was continued for 2 h at the same temperature. Then, allyl bromide (1.6 mL, 18.90 mmol) was added dropwise at –78 °C and the mixture stirred for 30 min before the cooling bath was removed and the NH3 was allowed to evaporate. The resulting white suspension was diluted with H2O (20 mL) and extracted with Et2O (3 × 10 mL). The combined organic layers were washed with sat. NaCl solution (20 mL), dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (PE–EtOAc, 4:1) to give ketone 15 (41 mg, 63%) as a colorless oil. Rf = 0.64 (PE–EtOAc = 1:1). 1H NMR (400 MHz, CDCl3): δ = 1.29–1.76 (m, 7 H, 2 × 3-H, 5-H, 2 × 9-H, 2 × 10-H), 1.33 (s, 3 H, 8-CH3), 1.85 (ddd, J = 12.6, 9.7, 2.8 Hz, 1 H, 3-H), 2.01–2.08 (m, 1 H, 5-H), 2.25 (ddd, J = 8.5, 5.1, 2.9 Hz, 2 H, 2 × 6-H), 2.45 (dd, J = 9.8, 5.8 Hz, 1 H, 4-H), 2.51 [dd, J = 13.1, 7.6 Hz, 1 H, 8-(CH 2CH=CH2)], 2.80–2.86 [m, 2 H, 2-H, 8-(CH 2CH=CH2)], 3.60 (s, 3 H, OCH3), 4.30–4.39 [m, 2 H, 1-(OCH 2CH=CH2)], 4.87–4.89 [m, 2 H, 8-(CH2CH=CH 2)], 5.22 [ddd, J = 12.1, 1.5, 1.5 Hz, 1 H, 1-(OCH2CH=CH 2)], 3.56 [ddd, J = 17.2, 3.3, 1.6 Hz, 1 H, 1-(OCH2CH=CH 2)], 5.55 [dddd, J = 17.2, 10.0, 7.4, 7.4 Hz, 1H, 8-(CH2CH=CH2)], 5.99 [dddd, J = 17.2, 10.4, 5.2, 5.0 Hz, 1 H, 1-(OCH2CH=CH2)] ppm. 13C NMR (100 MHz, CDCl3): δ = 24.8 (8-CH3), 26.1 (C-9), 30.4 (C-2), 30.8 (C-5), 32.4 (C-3), 34.7 (C-10), 37.3 (C-6), 41.0 (C-4a), 42.9 [8-(CH2CH=CH2)], 49.2 (C-4), 51.6 (OCH3, C-8), 68.8 [1-(OCH2CH=CH2)], 116.8 [8-(CH2CH=CH2), 1-(OCH2CH=CH2)], 118.5 (C-8a), 134.2 [1-(OCH2 CH=CH2)], 136.1 [(8-(CH2 CH=CH2)], 154.5 (C-1), 175.9 (ester), 215.2 (C-7) ppm. ESI-HRMS: m/z [M + Na]+ calcd for C23H30O4Na: 393.203631; found: 393.203799.
For a recent example of Baeyer–Villiger oxidation on a polycyclic ketone, see:
For the synthesis of atisane-type natural products, see ref. 8 and 9. See also:
For a review, see: