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 Joppa, Marko Lieseganga, Peter Ehlersa, b, Eva Frankc, Gyula Schneiderc, János Wölflingc, Alexander Villingera, Peter Langer*a, b
  • aUniversität Rostock, Institut für Chemie, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
  • bLeibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
  • cDepartment of Organic Chemistry, University of Szeged, Dóm tér 8, 6720 Szeged, Hungary
Further Information

Publication History

Received: 02 June 2017

Accepted after revision: 12 July 2017

Publication Date:
17 August 2017 (eFirst)

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.

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.