Synlett 2017; 28(18): 2425-2428
DOI: 10.1055/s-0036-1590838
cluster
© Georg Thieme Verlag Stuttgart · New York

Ether Synthesis through Reductive Cross-Coupling of Ketones with Alcohols Using Me2SiHCl as both Reductant and Lewis Acid

Yong Ho Lee, Bill Morandi*
  • Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany   Email: morandi@kofo.mpg.de
Further Information

Publication History

Received: 05 May 2017

Accepted after revision: 20 June 2017

Publication Date:
20 July 2017 (eFirst)

Published as part of the Cluster Silicon in Synthesis and Catalysis

Abstract

We report that a Lewis acidic silane, Me2SiHCl, can mediate the direct cross-coupling of a wide range of carbonyl compounds with alcohols to form dialkyl ethers. The reaction is operationally simple, tolerates a range of polar functional groups, can be utilized to make sterically hindered ethers, and is extendable to sulfur and nitrogen nucleo­philes.

Supporting Information

 
  • References and Notes

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  • 13 General procedure for the reductive etherification reaction: To a mixture of carbonyl (0.25 mmol) and alcohol (0.275 mmol, 1.1 equiv) in acetonitrile (0.5 mL) was added chlorodimethyl-silane (0.275 mmol, 1.1 equiv) under argon. The reaction mixture was stirred at room temperature (ca. 25 °C) for 12 h. The reaction was then quenched by adding a drop of aqueous NaHCO3 solution under air. The resulting mixture was dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (pentane/DCM or pentane/MTBE).
  • 14 (8R,9S,13S,14S,17S)-17-(Cyclohexyloxy)-13-methyl-7,8,9,11, 12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-ol (Table 3, Entry 7): White solid. 1H NMR (500 MHz, CDCl3): δ = 7.15 (d, J = 8.5 Hz, 1 H), 6.62 (dd, J = 8.5, 2.7 Hz, 1 H), 6.55 (d, J = 2.7 Hz, 1 H), 4.55 (s, 1 H), 3.49 (dd, J = 8.5, 8.5 Hz, 1 H), 3.32–3.23 (m, 1 H), 2.89–2.74 (m, 2 H), 2.31–2.21 (m, 1 H), 2.20–2.11 (m, 1 H), 2.06–1.93 (m, 2 H), 1.94–1.80 (m, 3 H), 1.79–1.69 (m, 2 H), 1.71–1.60 (m, 1 H), 1.58–1.42 (m, 3 H), 1.45–1.36 (m, 1 H), 1.39–1.10 (m, 9 H), 0.79 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 153.4, 138.5, 133.1, 126.7, 115.4, 112.7, 86.5, 77.1, 50.3, 44.2, 43.4, 38.8, 37.9, 33.3, 33.2, 29.8, 29.1, 27.3, 26.6, 26.0, 24.6, 24.5, 23.3, 11.9. HRMS (ESI+): m/z [M+H]+ calcd for C24H35O2: 355.26316; found: 355.26335