Asymmetric Michael Reactions Using Tartrate-based Magnesium Catalysts

Abstract

Catalysts derived from a combination of dialkyl tartrates and dibutylmagnesium are effective for the asymmetric Michael addition of dibenzyl malonate to enones with ee’s up to 58%.

asymmetric catalysis - asymmetric synthesis - Michael additions - magnesium - nucleophilic additions

References

1 Krause N. Hoffmann-Roder A. Synthesis  2001,  171 

2 Rowlands GJ. Tetrahedron  2001,  57:  1865 

3 Shibasaki M. Sasai H. Arai T. Angew. Chem., Int. Ed. Engl.  1997,  36:  1237 

4 Sasai H. Arai T. Shibasaki M. J. Am. Chem. Soc.  1994,  116:  1571 

5 Sasai H. Arai T. Satow Y. Houk KN. Shibasaki M. J. Am. Chem. Soc.  1995,  117:  6194 

6 Shibasaki M. Sasai H. Pure Appl. Chem.  1996,  68:  523 

7 Xu Y. Ohori K. Ohshima T. Shibasaki M. Tetrahedron  2002,  58:  2585 

8 Kim YS. Matsunaga S. Das J. Sekine A. Ohshima T. Shibasaki M. J. Am. Chem. Soc.  2000,  122:  6506 

9 Yamaguchi M. Shiraishi T. Hirama M. J. Org. Chem.  1996,  61:  3520 

10 Sawamura M. Hamashima H. Shinoto H. Ito Y. Tetrahedron Lett.  1995,  36:  6479 

11 Manickam G. Sundararajan G. Tetrahedron: Asymmetry  1997,  8:  2271 

12 DiMauro EF. Kozlowski MC. Org. Lett.  2001,  3:  1641 

13 Suzuki T. Torii T. Tetrahedron: Asymmetry  2001,  12:  1077 

14 Kumaraswamy G. Sastry MNV. Jena N. Tetrahedron Lett.  2001,  42:  8515 

15 Jha SC. Joshi NN. Tetrahedron: Asymmetry  2001,  12:  2463 

16 Elston CL. Jackson RFW. MacDonald SJF. Murray PJ. Angew. Chem., Int. Ed. Engl.  1997,  36:  410 

17 Jacques O. Richards SJ. Jackson RFW. Chem. Commun.  2001,  2712 

18 Kolb HC. VanNieuwenhze MS. Sharpless KB. Chem. Rev.  1994,  94:  2483 

19

Representative Procedure for the Catalytic Asymmetric Michael Addition. l-Dicyclohexyl tartrate (34.5 mg, 0.11 mmol) and powdered 4 Å molecular sieves (200 mg) were added to a dry 50 mL 2-necked flask under nitrogen. To the stirred mixture was added toluene (0.5 mL) and dibutylmagnesium (1 M in heptane, 100 µL, 0.1 mmol). The resulting mixture was stirred for 30 min to allow complex formation. Freshly distilled cyclohex-2-enone (96.5 µL, 1 mmol) was added by syringe into the flask and allowed to mix for 10 min. Dibenzyl malonate (245 µL, 0.98 mmol) was added to the flask and the resulting mixture heated in an oil bath to 50 °C. The reaction mixture was stirred for 66 h, diluted with diethyl ether and the mixture washed with aq NH₄Cl and aq NaCl. The organic layer was extracted, dried (MgSO₄) and the solvent removed. The resultant gum was purified by flash column chromatography (SiO₂, petrol/ethyl acetate 6/1 v/v) to give the Michael adduct 1 as an off-white solid (200 mg, 52%), which exhibited identical spectroscopic data to that in the literature. [5] The ee of 1 was determined by chiral HPLC analysis [5] (Daicel CHIRALPAK AS, i-PrOH:hexane 1:9, 1 mL/min, 254 nm; ee 58%). Compounds 13-16 exhibited identical spectroscopic data to that in the literature. [8]