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Synlett 2016; 27(01): 116-120
DOI: 10.1055/s-0035-1560514
DOI: 10.1055/s-0035-1560514
letter
Rapid Generation of Complex Molecular Architectures by a Catalytic Enantioselective Dearomatization Strategy
Further Information
Publication History
Received: 22 September 2015
Accepted after revision: 05 October 2015
Publication Date:
09 November 2015 (online)
Abstract
A catalytic enantioselective dearomatization strategy can be used to convert readily assembled phenols into complex polycyclic architectures. By combining oxidative dearomatization of phenols bearing a pendent nucleophile with enantioselective secondary amine catalysis, high enantiomeric excesses were obtained for the natural product-like products.
Key words
asymmetric catalysis - biomimetic synthesis - phenols - stereoselectivity - tandem reactionsSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1560514.
- Supporting Information
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References and Notes
- 1a Walji AM, MacMillan DW. C. Synlett 2007; 1477
- 1b Wender PA, Miller BL. Nature 2009; 460: 197
- 1c Newhouse T, Baran PS, Hoffmann RW. Chem. Soc. Rev. 2009; 38: 3010
- 2a Ciufolini MA, Braun NA, Canesi S, Ousmer M, Chang J, Chai D. Synthesis 2007; 3759
- 2b Zhuo C.-X, Zhang W, You S.-L. Angew. Chem. Int. Ed. 2012; 51: 12662
- 3a Pouységu L, Deffieux D, Quideau S. Tetrahedron 2010; 66: 2235
- 3b Roche SP, Porco JA. Jr. Angew. Chem. Int. Ed. 2011; 50: 4068
- 4a Imbos R, Minnaard AJ, Feringa BL. J. Am. Chem. Soc. 2002; 124: 184
- 4b Hayashi Y, Gotoh H, Tamura T, Yamaguchi H, Masui R, Shoji M. J. Am. Chem. Soc. 2005; 127: 16028
- 4c Liu Q, Rovis T. J. Am. Chem. Soc. 2006; 128: 2552
- 4d Vo NT, Pace RD. M, O’Hara F, Gaunt MJ. J. Am. Chem. Soc. 2008; 130: 404
- 4e Gu Q, Rong Z.-Q, Zheng C, You S.-L. J. Am. Chem. Soc. 2010; 132: 4056
- 4f Leon R, Jawalekar A, Redert T, Gaunt MJ. Chem. Sci. 2011; 2: 1487
- 4g Wu Q.-F, Liu W.-B, Zhuo C.-X, Rong Z.-Q, Ye K.-Y, You S.-L. Angew. Chem. Int. Ed. 2011; 50: 4455
- 4h Rubush DM, Morges MA, Rose BJ, Thamm DH, Rovis T. J. Am. Chem. Soc. 2012; 134: 13554
- 4i Corbett MT, Johnson JS. Chem. Sci. 2013; 4: 2828
- 4j Xu R.-Q, Gu Q, Wu W.-T, Zhao Z.-A, You S.-L. J. Am. Chem. Soc. 2014; 136: 15469
- 5a Dyke SF, Quessy SN In The Alkaloids: Chemistry and Physiology . Vol. 18. Manske RF. H, Rodrigo RG. A. Academic Press; New York: 1981: 1
- 5b Tsuda Y, Sano T In The Alkaloids: Chemistry and Pharmacology . Vol. 48. Cordell GA. Academic Press; San Diego: 1996: 249
- 5c Parsons AF, Palframan MJ In The Alkaloids: Chemistry and Biology . Vol. 68. Cordell GA. Academic Press; San Diego: 2010: 39
- 6a Lehman AJ. J. Pharmacol. Exp. Ther. 1937; 60: 69
- 6b Folkers K, Unna K. J. Am. Pharm. Assoc. 1938; 27: 693
- 6c Folkers K, Unna K. J. Am. Pharm. Assoc. 1939; 28: 1019
- 6d Craig LE In The Alkaloids: Chemistry and Physiology . Vol. 5. Manske RF. H. Academic Press; New York: 1955: 265
- 7a Marigo M, Wabnitz TC, Fielenbach D, Jørgensen KA. Angew. Chem. Int. Ed. 2005; 44: 794
- 7b Hayashi Y, Gotoh H, Hayashi T, Shoji M. Angew. Chem. Int. Ed. 2005; 44: 4212
- 8 Initially, the syn-diastereomer 3 is formed by the desymmetrizing Michael addition; however, this isomer is configurationally unstable and epimerizes to the more stable anti-diastereomer 4a upon standing.
- 9 When this is performed as a one-pot procedure in 2,2,2-trifluoroethanol, tetracycle 4a is obtained in 50% yield and 82% ee.
- 10 Dearomatization of Aromatic Phenols with Intramolecular Carbon Nucleophiles: General Procedure The appropriate phenol (1.0 equiv) was dissolved in F3CCH2OH (0.034 M), and the solution was cooled to 0 °C or –40 °C. PhI(OAc)2 or PhI(O2CCF3)2 (1.1 equiv) was added, and the mixture was stirred at 0 °C or at –40 °C for 30 min. The reaction was quenched by addition of H2O at 0 °C or at –40 °C, and the mixture was extracted with CH2Cl2 (×2). The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated in vacuo to give a crude product that was either used in the crude state or purified by flash chromatography to give the desired cyclohexadienone. Asymmetric Organocatalytic Conjugate Addition: General Procedure The crude cyclohexadienone was dissolved in anhydrous MeCN (0.056 M), and the mixture was cooled to –40 °C. The appropriate organocatalyst (0.1 equiv) and BzOH (0–0.1 equiv) were added, and the mixture was stirred at –40 °C for the appropriate time. The mixture was then concentrated in vacuo and the residue was dissolved in CH2Cl2 (0.1 M). Et3N (0.1 equiv) was added and the mixture stirred at r.t. for 4 h, then concentrated in vacuo to give the crude product that was purified by flash chromatography.
- 11 15,16-Dimethoxy-2,10-dioxoerythrinan-7-carbaldehyde (4a) White solid; yield: 118 mg (0.35 mmol, 60%, >99% ee); mp 169–170 °C; Rf = 0.52 (CH2Cl2–MeOH, 9:1); [α]D 20 +72 (c = 0.04, CHCl3). IR (film): 3988 (br), 2924, 1630, 1513, 1450, 1411, 1304, 1254, 1233, 1189, 1120, 1100, 1059, 1037 cm–1. 1H NMR (500 MHz, CDCl3): δ = 9.73 (d, J = 1.9 Hz, 1 H), 6.93 (s, 1 H), 6.68 (s, 1 H), 6.57 (dd, J = 10.2, 2.1 Hz, 1 H), 6.02 (d, J = 10.2 Hz, 1 H), 4.04 (dd, J = 12.6, 7.8 Hz, 1 H), 3.89 (s, 3 H), 3.86 (s, 3 H), 3.80 (dd, J = 12.6, 10.2 Hz, 1 H), 3.74 ( d, J = 20.0 Hz, 1 H), 3.60 (d, J = 20.0 Hz, 1 H), 3.39 (ddd, 10.1, 6.0, 2.1 Hz, 1 H), 3.19 (dd, J = 18.3, 6.0 Hz, 1 H), 3.03 (ddd, 18.1, 10.2, 1.89 Hz, 1 H), 2.90 (br d, J = 18.1 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 197.8, 194.3, 167.2, 149.9, 148.7, 147.6, 127.3, 127.0, 124.1, 110.9, 106.6, 64.9, 56.3, 56.1, 53.1, 43.0, 42.8, 38.7, 36.8. HRMS (APCI+): m/z [M + H]+calcd for C19H20NO5: 342.1336; found: 342.1331.
- 12 The analogous para-anisole nucleophile failed to react under the dearomatization conditions, presumably due to its inability to undergo Friedel–Crafts addition at the ortho- and para-positions.
- 13 (4aS,12R,12aS)-8-Methoxy-2-oxo-1,5,6,11,12,12a-hexahydro-2H-naphtho[8a,1,2-de]chromene-12-carbaldehyde (8) Colorless oil; yield: 134 mg (0.45 mmol, 67%, 95% ee) as a colorless oil; [α]D 25 +123 (c = 1.0, CHCl3). IR (film): 2954, 1721, 1677, 1585, 1493, 1443 cm–1. 1H NMR (400 MHz, CDCl3): δ = 9.59 (d, J = 0.7 Hz, 1 H), 6.93 (dd, J = 10.2, 2.0 Hz, 1 H), 6.74 (d, J = 8.2 Hz, 1 H), 6.67 (d, J = 8.2 Hz, 1 H), 6.07 (dd, J = 10.2, 0.9 Hz, 1 H), 4.51 (ddd, J = 11.5, 4.4, 2.7 Hz, 1 H), 4.25 (ddd, J = 12.9, 11.6, 2.5 Hz, 1 H), 3.86 (s, 3 H), 2.98 (m, 2 H), 2.91 (ddd, J = 15.8, 8.2, 0.7 Hz, 1 H), 2.67 (dt, J = 7.7, 3.6 Hz, 1 H), 2.60 (m, 1 H), 2.54 (ddd, J = 17.2, 3.3, 1.0 Hz, 1 H), 2.43 (dt, J = 13.4, 2.5, 1 H), 2.26 (td, J = 13.1, 4.3 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 201.6, 197.0, 154.3, 147.8, 143.1, 129.5, 127.0, 124.0, 119.7, 110.9, 63.7, 56.4, 50.7, 40.6, 39.8, 36.8, 36.4, 28.1. HRMS (ES+): m/z [M + H]+calcd for C18H19O4: 299.1278; found: 299.1277. HPLC: AD-H (15% i-PrOH–hexane, 1.0 mL/min, 210 nm): tR (major) = 26.6 min, tR (minor) = 27.9 min (97% ee).
- 14 Tissot M, Phipps RJ, Lucas C, Leon RM, Pace RD. M, Ngouansavanh T, Gaunt MJ. Angew. Chem. Int. Ed. 2014; 53: 13498
- 15 Liang H, Ciufolini MA. J. Org. Chem. 2008; 73: 4299
For recent reviews of oxidative dearomatization, see:
For recent reviews on oxidative dearomatization in natural product synthesis, see:
For reviews of the Erythrina alkaloid family, see:
For biological activities of the Erythrina alkaloids, see: