Download PDF
Synlett 2013; 24(18): 2423-2426
DOI: 10.1055/s-0033-1340084
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Sterically Hindered Chiral 1,4-Diols from Different Lignan-Based Backbones

Yury Brusentsev
a   Laboratory of Organic Chemistry, Åbo Akademi University, Biskopsgatan 8, 20500 Åbo (Turku), Finland   Email: paeklund@abo.fi
,
Mikko M. Hänninen
b   Department of Chemistry, University of Jyväskylä, P.O. Box 35, 40014, Jyväskylä, Finland
,
Patrik Eklund*
a   Laboratory of Organic Chemistry, Åbo Akademi University, Biskopsgatan 8, 20500 Åbo (Turku), Finland   Email: paeklund@abo.fi
› Author Affiliations
Further Information

Publication History

Received: 06 September 2013

Accepted after revision: 14 October 2013

Publication Date:
21 October 2013 (online)

    Permissions and Reprints All articles of this category


Abstract

Methods for synthetic modifications of the natural dibenzylbutyrolactone lignan hydroxymatairesinol into chiral 1,4-diols with different lignan-derived backbones have been developed. A stepwise procedure, involving alkylation and oxidation, was shown to be successful and several highly substituted 1,4-diols were prepared. Some substituted butyrolactones resisted alkylation and led to the formation unusually stable hemiketals (butyrolactols). The formation of stable hemiketals was investigated in detail, showing that different backbone structures influence the formation and reactivity of the hemiketals.

Key words

hydroxymatairesinol - chiral 1,4-diols - TADDOL - lignans - burtyrolactol

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information

Primary Data

    for this article are available online at ­http://www.thieme-connect.com/ejournals/toc/synlett and can be cited using the following DOI: 10.4125/pd0051th.
  • Primary Data
 

  • References and Notes

  • 1 Holmbom B, Eckerman C, Eklund P, Hemming J, Nisula L, Reunanen M, Sjöholm R, Sundberg A, Willför S. Phytochemistry Rev. 2003; 2: 331
    Crossref
  • 2 Brusentsev Y, Sandberg T, Hotokka M, Sjöholm R, Eklund P. Tetrahedron Lett. 2013; 54: 1112
    Crossref
  • 3 Budragchaa T, Rollerb A, Widhalm M. Synthesis 2012; 44: 3238
    Article in Thieme Connect
  • 4 Gratzer K, Waser M. Synthesis 2012; 44: 3661
    Article in Thieme ConnectPubMed
  • 5 Markus H, Mäki-Arvela P, Kumar N, Kul’kova NV, Eklund P, Sjöholm R, Holmbom B, Salmi T, Murzin DY. Catal. Lett. 2005; 103: 125
    Crossref
  • 6 Cambie RC, Clark GR, Craw PA, Rutledge PS, Woodgate PD. Aust. J. Chem. 1984; 1775
  • 7 The dimethyl lactone 8a, 8b, or 8c (1 mmol) was dissolved in THF (30 mL), the solution was cooled to 0 °C, and MeMgBr (3 mL of 3 M solution in Et2O, 9 mmol) was added dropwise during 30 min. The solution was allowed to warm to r.t. and stirred for 20–72 h. Saturated NH4Cl (10 mL) and H2O (10 mL) were added to the reaction mixture, and the organic phase was separated. The aqueous phase was extracted with CH2Cl2 (2 × 15 mL), and the combined organic phases were dried over Na2SO4, filtered, and the solvent evaporated. The residue was purified by column chromatography using CHCl3–MeOH (70:1) as eluent, to give products 9a–c. Analytical Data for Compounds 9a–c Compound 9a (reaction time 72 h, yield 265 mg, 60%): 1H NMR (600 MHz, CDCl3): δ = 1.06 (s, 6 H), 1.23 (s, 6 H), 2.58 (dd, J = 7.1, 5.1 Hz, 2 H), 2.65 (dd, J = 14.9, 7.1 Hz, 2 H), 2.96 (dd, J = 14.9, 5.1 Hz, 2 H), 3.88 (s, 6 H), 3.90 (s, 6 H), 6.82 (d, J = 7.9 Hz, 2 H), 6.85 (d, J = 1.5 Hz, 2 H), 6.87 (dd, J = 7.9, 1.5 Hz, 2 H) ppm. 13C NMR (151 MHz, CDCl3): δ = 26.3, 30.9, 33.9, 48.3, 55.9, 74.3, 111.2, 112.1, 120.5, 135.3, 147.2, 148.9 ppm. Compound 9b (reaction time 20h, yield 350 mg, 0.81 mmol, 81%) (S)-9b: 1H NMR (600 MHz, CDCl3): δ = 1.01 (s, 3 H), 1.44 (s, 3 H), 1.57 (s, 3 H), 1.77 (dd, J = 12.3, 10.0 Hz, 1 H), 2.07 (dd, J = 12.1, 10.2 Hz, 1 H), 2.13 (br s, 1 H), 2.20 (dd, J = 13.0, 10.2 Hz, 1 H), 2.31 (dd, J = 13.6, 10.0 Hz, 1 H), 2.47 (d, J = 13.0 Hz, 1 H), 2.64 (d, J = 13.6 Hz, 1 H), 3.87 (s, 3 H), 3.89 (s, 3 H), 3.93 (s, 3 H), 3.96 (s, 3 H), 6.68 (s, 1 H), 6.71 (s, 1 H), 6.72 (s, 1 H), 6.74 (s, 1 H) ppm. 13C NMR (151 MHz, CDCl3): δ = 22.9, 26.4, 28.9, 32.8, 33.3, 54.5, 55.2, 56.0, 56.06, 56.1, 56.2, 81.7, 102.9, 112.0, 112.1, 113.4, 113.6, 132.5, 132.6, 133.0, 133.2, 147.0, 147.1, 148.6, 148.7 ppm. (R)-9b: 1H NMR (600 MHz, CDCl3): δ = 1.14 (s, 3 H), 1.28 (s, 3 H), 1.35 (s, 3 H), 1.69 (dd, J = 12.6, 10.6 Hz, 1 H), 2.08 (dd, J = 12.6, 10.0 Hz, 1 H), 2.13 (br. s., 1 H), 2.20 (dd, J = 12.8, 10.0 Hz, 1 H), 2.22 (dd, J = 13.2, 10.6 Hz, 1 H), 2.42 (d, J = 13.2 Hz, 1 H), 2.73 (d, J = 12.8 Hz, 1 H), 3.88 (s, 3 H), 3.89 (s, 3 H), 3.94 (s, 3 H), 3.95 (s, 3 H), 6.66 (s, 1 H), 6.71 (s, 1 H), 6.74 (s, 1 H), 6.80 (s, 1 H) ppm. 13C NMR (151 MHz, CDCl3): δ = 23.6, 24.4, 28.1, 32.9, 33.1, 55.9, 56.0, 56.1, 56.1, 56.1, 56.3, 80.5, 104.5, 111.9, 112.2, 113.3, 113.4, 132.3, 132.8, 132.9, 132.9, 147.0, 147.1, 148.6, 148.7 ppm. Compound 9c (reaction time 48 h, yield 310 mg, 0.66 mmol, 66%): 1H NMR (600 MHz, CDCl3): δ = 1.56 (s, 6 H), 1.65 (s, 6 H), 1.65–1.71 (m, 2 H), 1.87 (d, J = 10.6 Hz, 2 H), 2.06–2.14 (m, 2 H), 2.62 (dd, J = 13.6, 10.6 Hz, 2 H), 2.76 (d, J = 13.6 Hz, 2 H), 3.70 (br s, 2 H), 3.81 (s, 6 H), 4.17–4.23 (m, 2 H), 4.29–4.34 (m, 2 H), 6.26 (dd, J = 8.1, 1.9 Hz, 2 H), 6.44 (d, J = 1.9 Hz, 2 H), 6.50 (d, J = 8.1 Hz, 2 H) ppm. 13C NMR (151 MHz, CDCl3): δ = 23.5, 30.9, 32.9, 37.7, 53.5, 55.9, 67.5, 74.4, 113.3, 113.5, 120.4, 134.5, 144.5, 148.1 ppm.
  • 8 Bee C, Han SB, Hassan A, Iida H, Krische MJ. J. Am. Chem. Soc. 2008; 130: 2746
    CrossrefPubMed
  • 9 Perotti JP, Cravero RM, Luna LE, Grau RJ. A, Vaillard SE. ARKIVOC 2011; (xi): 92