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Synlett 2017; 28(19): 2647-2649
DOI: 10.1055/s-0036-1588537
letter
© Georg Thieme Verlag Stuttgart · New York

Palladium-Catalysed Sonogashira Reactions of 16-(Hydroxymethylidene)-3-methoxy-α-estrone

Stefan Jopp
a   Universität Rostock, Institut für Chemie, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
,
Marko Liesegang
a   Universität Rostock, Institut für Chemie, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
,
Peter Ehlers
a   Universität Rostock, Institut für Chemie, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
b   Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
,
Eva Frank
c   Department of Organic Chemistry, University of Szeged, Dóm tér 8, 6720 Szeged, Hungary
,
Gyula Schneider
c   Department of Organic Chemistry, University of Szeged, Dóm tér 8, 6720 Szeged, Hungary
,
János Wölfling
c   Department of Organic Chemistry, University of Szeged, Dóm tér 8, 6720 Szeged, Hungary
,
Alexander Villinger
a   Universität Rostock, Institut für Chemie, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
,
Peter Langer*
a   Universität Rostock, Institut für Chemie, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
b   Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
› Author Affiliations
Further Information

Publication History

Received: 02 June 2017

Accepted after revision: 12 July 2017

Publication Date:
17 August 2017 (online)

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Abstract

Sonogashira reactions of steroids have been studied. The reaction of α-estron-16-methylidenyloxy triflate with various alkynes afforded novel alkynylvinylidene steroids. The reactions proceeded in good to quantitative yields, with excellent E-selectivity and with a broad synthetic scope.

Key words

estrone - steroids - Sonogashira coupling - palladium - alkynes

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1588537.
  • Supporting Information
 

  • References and Notes

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  • 9 (E)-16-(3-Phenylprop-2-ynylidene)-3-methoxy-α-estrone (3a) Compound 2 (0.225 mmol, 100 mg), CuI (0.006 mmol, 2.5 mol%, 1.1 mg), Pd(OAc)2 (0.006 mmol, 2.5 mol%, 1.3 mg), XPhos (0.012 mmol, 5.0 mol%, 5.7 mg), and phenylacetylene (0.338 mmol, 35 mg) were dissolved in THF (5 mL) and NEt3 (1 mL). The reaction mixture was stirred at r.t. for 6 h. The solution was diluted with H2O and extracted with EtOAc (3×). The crude product was purified by column chromatography on silica (elution system heptane/EtOAc, 20:1). Yield: 86 mg (97%); mp 54–55 °C. 1H NMR (250 MHz, CDCl3): δ = 0.79–0.88 (m, 3 H), 1.10 (s, 3 H, Me), 1.43–1.51 (m, 2 H), 1.76–1.83 (m, 1 H), 2.09–2.17 (m, 1 H), 2.24–2.32 (m, 2 H), 2.40–2.48 (m, 1 H), 2.79–2.92 (m, 3 H), 3.76 (s, 3 H, OMe), 6.59 (d, 4 J = 2.71 Hz, 1 H), 6.67–6.72 (m, 2 H), 7.18 (d, 3 J = 8.58 Hz, 1 H), 7.36–7.39 (m, 3 H), 7.50–7.54 (m, 2 H).13C NMR (63 MHz, CDCl3): δ = 25.5 (CH3), 28.1, 28.3, 29.9, 30.3, 32.2 (CH2), 41.3, 43.0, 47.6 (CH), 50.8 (C), 55.2 (OCH3), 87.2, 101.0 (C≡C), 111.7, 113.5, 114.5 (CH), 122.7 (C), 126.9, 128.5, 129.2 (CH), 131.8 (C), 131.9 (CH), 138.0, 146.1, 157.5 (C), 207.4 (C=O). IR (ATR,): 2918 (w), 2187 (w), 1711 (w), 1609 (w), 1498 (w), 1448 (w), 1257 (m), 1076 (m), 1016 (s), 870 (w), 793 (s), 755 (m), 688 (m), 531 (w) cm–1. MS (EI, 70 eV): m/z (%) = 397 (16), 396 (M+, 78), 227 (15), 210 (14), 186 (10), 178 (11), 174 (15), 173 (12), 165 (24), 160 (14), 158 (13), 153 (13), 152 (12), 147 (11), 145 (15), 144 (11), 141 (23), 140 (100), 139 (96), 129 (16), 128 (17), 126 (17), 115 (25), 114 (18), 102 (18), 91 (21), 65 (11). ESI-HRMS: m/z calcd for C28H29O [M + H+]: 397.21621; found: 397.21644.