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Synlett 2010(2): 329-332  
DOI: 10.1055/s-0029-1219221
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© Georg Thieme Verlag Stuttgart ˙ New York

Regiodivergent Carbometalation Reactions of Ynol Ether Derivatives

Anat Levin, Ahmad Basheer, Ilan Marek*
Contribution from the Mallat Family Laboratory of Organic Chemistry, Schulich Faculty of Chemistry, and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, Technion-Israel Institute of Technology, Haifa 32000, Israel
Fax: +972(4)8293709; e-Mail: chilanm@tx.technion.ac.il;
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Publication History

Received 11 October 2009
Publication Date:
04 January 2010 (online)

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Abstract

The stereodivergent carbometalation of substituted ynol ethers is reported and both isomers could be obtained at will depending of the nature of the OR group.

Key words

ynol ether - carbocupration - regioselectivity - enol ether

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Carbometalation of (Hex-1-yn-1-yloxy)cyclohexane To a solution of flame-dried LiBr (0.78 mmol) in THF (5 mL), CuBr (0.39 mmol) was added at ambient temperature. After the entire solid dissolves with formation of a greenish color, the mixture was cooled to -20 ˚C and R2Zn was added (0.39 mL, 1.0 M solution in hexanes). Stirring for 15 min at -20 ˚C, 4 (0.3 mmol, 0.215 M solution in hexanes) was added, and the mixture was stirred at ambient temperature for 6 h. The reaction was hydrolyzed with an aq solution of NH4Cl/NH4OH (2:1). After usual workup the crude was purified on a short silica gel column pre-washed with Et3N (2.5%) using hexane as eluent to give the pure vinyl ether.

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Carbometalation of 2-(Alk-1-yn-1-yloxy)tetrahydro-2 H -pyran Derivatives
To a stirred mixture of CuI (0.476 g, 2.5 mmol) in dry THF (20 mL) at -50 ˚C was slowly added alkyl magnesium bromide (RMgBr, 2.5 mmol) through a syringe. The reaction mixture was allow to warm up to -30 ˚C and was stirred at -30 ˚C for additional 1 h. Then, a solution of 7 (1 mmol) in THF (5 mL) was added dropwise, and the mixture was stirred at this temperature for additional 2 h. The reaction was quenched with an aq solution of NH4Cl:NH4OH (2:1, 50 mL) and Et2O (50 mL) was added. The aqueous phase was extracted twice with Et2O (50 mL), and the combined organic layers were washed with a sat. solution of NaCl (3 × 50 mL) and once with ice-cold H2O (100 mL). The organic layer was dried over Na2SO4, evaporated, and the residue (70-88%) purified by chromatography (5% EtOAc in hexane) to give the α-enol ether as a colorless oil in 61-77% yields.