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Synlett 2013; 24(2): 189-192
DOI: 10.1055/s-0032-1317704
DOI: 10.1055/s-0032-1317704
letter
Concise Asymmetric Synthesis of (+)-Conocarpan and Obtusafuran
Further Information
Publication History
Received: 27 August 2012
Accepted after revision: 07 November 2012
Publication Date:
21 December 2012 (online)
![](https://www.thieme-connect.de/media/synlett/201302/lookinside/thumbnails/10.1055-s-0032-1317704-1.jpg)
Abstract
The asymmetric synthesis of three natural products: (+)-conocarpan, both (+)- and (–)- obtusafuran is disclosed. The highlights of the synthesis are the enantioselective hydrogenation of prochiral ketones via dynamic kinetic resolution to afford chiral alcohols. Intramolecular ring closure via either SNAr reaction or metal-catalyzed C–O bond formation led to the construction of the trans-dihydrobenzofuran core.
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References and Notes
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- 8b Procedure for the preparation of (+)-conocarpan from bromophenol 16: To bromophenol 16 (0.60 g, 1.966 mmol) in toluene (7.20 mL) was added potassium carbonate (0.815 g, 5.90 mmol), water (3.00 mL), trans-1-propen-1-ylboronic acid (0.338 g, 3.93 mmol) and [1,1′-bis(diphenylphospino)ferrocene]dichloropalladium(II) (0.072 g, 0.098 mmol). The mixture was degassed via nitrogen/vacuum followed by heating to 95 °C and kept at this temperature for 3 h to complete the coupling reaction. The reaction mixture was cooled to ambient temperature and the aqueous layer was removed. The organic layer was dried over MgSO 4 , concentrated and the residue was subjected to biotage separation to afford (+)-conocarpan (0.482 g, 1.809 mmol, 92% yield) as a white solid: mp 136–138 °C. 1 H NMR (500 MHz, CDCl 3 ): δ = 1.41 (d, J = 6.8 Hz, 3 H), 1.89 (d, J = 1.6, 6.7 Hz, 3 H), 3.42 (m, 1 H), 5.0 (br s, 1 H), 5.10 (d, J = 8.6 Hz, 1 H), 6.10 (dq, J = 6.7, 15.5 Hz, 1 H), 6.40 (dd, J = 1.6, 15.5 Hz, 1 H), 6.78 (d, J = 8.1 Hz, 1 H), 6.83 (m, 2 H), 7.16 (m, 2 H), 7.31 (m, 2 H). 13 C NMR (125 MHz, CDCl 3 ) δ = 17.8, 18.4, 45.2, 92.6, 109.3, 115.5, 120.7, 123.0, 126.3, 127.9, 130.8, 131.3, 132.4, 132.9, 155.7, 158.3. The enantiopurity of (+)-conocarpan was determined to be 99.6% using the reported method cited in reference 7a.
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- 16 Procedure for the preparation of (+)-obtusafuran: Obtusafuran OTIP ether (22, 0.40 g, 0.969 mmol) and tetrabutylammonium fluoride trihydrate (0.459 g, 1.454 mmol) in THF (4.00 ml) were stirred at ambient temperature for 12 h to complete the desilylation reaction. Methyl tert-butylether (5 mL) was added. The organic layer was washed with water (2 × 5 mL), dried (Na2SO4) and concentrated in vacuum to an oil. The oil was chromatographed over silica gel, eluted with methyl tert-butylether–hexanes (1:3), to afford (+)-obtusafuran (0.234 g, 0.931 mmol, 94% yield) as a solid. mp 111–113 °C. [α]D 25 +50 (c 0.33, MeOH) [lit. 4 [α]D 25+47 (c 0.86, MeOH). 1H NMR (500 MHz, CDCl3) δ = 1.41 (d, J = 6.7 Hz, 3 H), 3.40 (m, 1 H), 3.90 (s, 3 H), 5.14 (d, J = 8.5 Hz, 1 H), 5.29 (s, 1 H), 6.54 (s, 1 H), 6.76 (s, 1 H), 7.40 (m, 5 H). 13C NMR (125 MHz, CDCl3) δ = 18.5, 45.7, 56.3, 92.8, 94.2, 109.5, 122.9, 126.0, 128.2, 128.6, 140.0, 141.0, 146.3, 152.4. The enantiopurity of (+)-conocarpan was determined to be 99.1% using Chiralcel OZ column (250 × 4.6 mm), gradient method: 4% MeOH/25 mM IBA/CO2 for 4 min, then ramp at 6%/min to 40% MeOH, hold 5 min, 15 min runtime, 200 bar, 35 °C, 3 mL/min, 215 nm, retention time: 9.56 min.