Copper-Catalyzed Conjugate Addition of a Bis(triorganosilyl) Zinc and a Methyl(triorganosilyl) Magnesium

Abstract

A practical copper-catalyzed conjugate silylation of α,β-unsaturated carbonyl compounds 4 utilizing bis(triorganosilyl) zinc reagent 3 is described. Moreover, mixed methyl(triorganosilyl) magnesium 7 also transfers its silyl ligand to simple enones 4 under copper catalysis.

Key words

catalysis - cuprates - silicon - zinc - copper

References

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• 11 For a single report on the preparation of 3 and an appli-cation in a silyl metalation reaction see: Morizawa Y. Oda H. Oshima K. Nozaki H. Tetrahedron Lett.  1984,  25:  1163 ; this seminal publication also includes the magnesium reagent 7
• 12a

  Preparation of Zinc Reagent 3: Phenyldimethylsilyl chloride (1, 0.828 mL, 854 mg, 5.00 mmol, 2.50 equiv) was maintained with freshly cut lithium (large excess) in THF (10 mL) at -8 °C under argon atmosphere for 18 h. In order to separate 2 (4.00 mmol, ca. 80% conversion; for a titration procedure see ref. [3d] ) from unreacted lithium metal, the resulting dark red solution was transferred to another flask via a double-ended cannula. At 0 °C, ZnCl₂ (2.00 mL, 2.00 mmol, 1.00 equiv, 1 M in Et₂O) was added accompanied by a color change from red to yellowish brown. The reaction mixture was maintained at this temperature for further 15 min and was ready to use.

• 12b

  Method A: A suspension of CuX (5.0 mol%) and THF (5 mL) was pre-cooled to -78 °C and treated with 3 (2.00 mmol, 1.00 equiv) via syringe. The auburn reaction mixture was allowed to warm to 0 °C and maintained at this temperature for 20 min. Addition of enone 4 (2.02 mmol, 1.01 equiv) to the re-cooled (-78 °C) reaction mixture was followed by stirring for 2 h at -78 °C. Upon completion of the reaction, the reaction mixture was poured into sat. aq NH₄Cl (25 mL) and the flask was rinsed with MTBE (25 mL). The aqueous phase was separated and extracted with MTBE (3 × 25 mL). The combined organic phases were extracted with H₂O (25 mL) and brine (25 mL). After drying (Na₂SO₄), the solvents were evaporated under reduced pressure and the resulting crude product 5 was purified by flash chromatography on silica gel using cyclohexane-MTBE solvent mixtures.

• 12c

  Method B: A mixture of enone 4 (2.02 mmol, 1.01 equiv), CuX (5.0 mol%), and toluene (5 mL) was cooled to -20 °C. To this mixture was then added 3 (2.00 mmol, 1.00 equiv) via syringe. The reaction mixture was maintained at -20 °C for >6 h and poured into sat. aq NH₄Cl (25 mL). Work-up and purification of 5 as described for Method A.

• 13a

  This also applies to triorganosilyl zinc chlorides (R₃SiZnCl) prepared from R₃SiLi and equimolar amounts of ZnCl₂.

• 13b

  Only traces of conjugate addition products 5 were seen with R₃SiZnCl under copper catalysis.

• 14a It should be noted that Me₃SiLi undergoes rapid 1,4-additon to β-monosubstituted ketones in the absence of any copper catalyst. See: Still WC. J. Org. Chem.  1976,  41:  3063 
• 14b

  Conversely, we have isolated substantial amounts of the 1,2-adduct when treating enone 4a with PhMe₂SiLi (2).

• 15 Cu(OTf)₂ is believed to be reduced in situ as described for the conjugate addition of dialkylzincs: Feringa BL. Naasz R. Imbos R. Arnold LA. In Modern Organocopper Chemistry   Krause N. Wiley-VCH; Weinheim: 2002.  p.224 
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17

The generation of 3 from 1 produces a fourfold excess of LiCl, which might function as a Lewis acid.