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.

catalysis - cuprates - silicon - zinc - copper

References

For comprehensive reviews on the Tamao-Fleming oxidation see:

1a Jones GR. Landais Y. Tetrahedron  1996,  52:  7599 

1b Fleming I. Chemtracts, Org. Chem.  1996,  9:  1 

2a Brook MA. Silicon in Organic, Organometallic, and Polymer Chemistry   Wiley-Interscience; New York: 2000. 

2b Colvin EW. Silicon Reagents in Organic Synthesis   Academic Press; Orlando: 1988. 

3a Lipshutz BH. In Organometallics in Synthesis. A Manual   Schlosser M. Wiley-VCH; Weinheim: 2002.  p.665 

3b Dieter RK. In Modern Organocopper Chemistry   Krause N. Wiley-VCH; Weinheim: 2002.  p.79 

3c Singer RD. In Science of Synthesis   Vol. 4:  Ley SV. Fleming I. Thieme; Stuttgart: 2002.  p.231 

3d Fleming I. In Organocopper Reagents. A Practical Approach   Taylor RJK. Oxford Academic Press; New York: 1994.  p.257 

3e Tamao K. Kawachi A. Adv. Organomet. Chem.  1995,  38:  1 

4a Lipshutz BH. James B. J. Org. Chem.  1994,  59:  7585 

4b For Li[(PhMe₂Si)₂Cu]·LiCN see: Bertz SH. Miao G. Eriksson M. Chem. Commun.  1996,  815 

5a Ager DJ. Fleming I. J. Chem. Soc., Chem. Commun.  1978,  177 

5b Ager DJ. Fleming I. Patel SK. J. Chem. Soc., Perkin Trans. 1  1981,  2520 

5c Fleming I. Newton TW. Roessler F. J. Chem. Soc., Perkin Trans. 1  1981,  2527 

5d For Et₂NPh₂SiCu(CN)Li see: Tamao K. Kawachi A. Ito Y. J. Am. Chem. Soc.  1992,  114:  3989 

5e For Li[PhMe₂SiCuI] as its dimethylsulfide complex see: Dambacher J. Bergdahl M. Chem. Commun.  2003,  144 

6 Gilman H. Lichtenwalter GD. J. Am. Chem. Soc.  1958,  80:  608 

7a Tückmantel W. Oshima K. Nozaki H. Chem. Ber.  1986,  119:  1581 

7b Crump RANC. Fleming I. Urch CJ. J. Chem. Soc., Perkin Trans. 1  1994,  701 

7c Vaughan A. Singer RD. Tetrahedron Lett.  1995,  36:  5683 

8 Lipshutz BH. Sclafani JA. Takanami T. J. Am. Chem. Soc.  1998,  120:  4021 

9a Ito H. Ishizuka T. Tateiwa J.-i. Sonoda M. Hosomi A. J. Am. Chem. Soc.  1998,  120:  11196 

9b See also: Clark CT. Lake JF. Scheidt KA. J. Am. Chem. Soc.  2004,  126:  85 

9c For other catalyst systems see: Hayashi T. Matsumoto Y. Ito Y. J. Am. Chem. Soc.  1988,  110:  5579 

9d Ogoshi S. Tomiyasu S. Morita M. Kurosawa H. J. Am. Chem. Soc.  2002,  124:  11598 

10 Hameon I. Singer RD. In Science of Synthesis   Vol. 4:  Ley SV. Fleming I. Thieme; Stuttgart: 2002.  p.225 

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 

16a Corey EJ. Boaz NW. Tetrahedron Lett.  1985,  26:  6019 

16b Johnson CR. Marren TJ. Tetrahedron Lett.  1987,  28:  27 

16c Horiguchi Y. Komatsu M. Kuwajima I. Tetrahedron Lett.  1989,  30:  7087 

16d Alexakis A. Sedrani R. Mangeney P. Tetrahedron Lett.  1990,  31:  345 

17

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

18a Sharma S. Oehlschlager AC. J. Org. Chem.  1991,  56:  770 

18b Singer RD. Oehlschlager AC. J. Org. Chem.  1991,  56:  3510