Magnesium Chloride-Promoted Michael Addition of Dimethylsilyl Enolates to α-Enones

Abstract

In the presence of MgCl₂, dimethylsilyl (DMS) enolates 1 smoothly reacted with α-enones in DMF to form 1,5-diketones 3 in moderate to high yields. The Michael addition proceeded with moderate to high anti-diastereoselectivity.

diastereoselectivity - enones - Michael additions - magnesium - silicon

References

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1b Narasaka K. Soai K. Aikawa K. Mukaiyama T. Bull. Chem. Soc. Jpn.  1976,  49:  779 

Reviews:

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For Lewis acid-catalyzed asymmetric Michael reactions, see;

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8

Propiophenone TMS enolate was much less reactive toward the Michael addition to 2a even in the presence of an equimolar amount of MgCl₂ (7% yield of 3aa, 30 °C, 24 h).

9

General Procedure for the MgCl ₂ -promoted Michael Addition of DMS Enolates: Under N₂ atmosphere, dry DMF (1 mL) was added to MgCl₂ (12 mg, 0.13 mmol). The mixture was stirred for 10 min at 30 °C, and a DMS enolate (0.75 mmol) and an α-enone (0.50 mmol) were introduced into the resultant solution. After the reaction was completed, concd HCl (1 mL) was added to the reaction mixture. After being stirred for 5 min, the mixture was neutralized with saturated aqueous NaHCO₃ and extracted with EtOAc (3 × 10 mL). The combined organic layer was dried over Na₂SO₄ and evaporated. The crude product was purified by silica gel column chromatography. Compound anti-3aa: CAN [40794-93-2] (ref. [10] ). ¹H NMR (270 MHz, CDCl₃) δ 1.28 (d, J = 6.8 Hz, 3 H), 3.36-3.53 (m, 2 H), 3.89-4.00 (m, 2 H), 7.06-7.27 (m, 5 H), 7.35-7.55 (m, 6 H), 7.83-7.89 (m, 4 H). ¹³C NMR (68 MHz, CDCl₃) δ 14.10 (CH₃), 39.87 (CH₂), 42.76 (CH), 45.93 (CH), 126.51 (CH), 127.91 (CH × 2), 127.95 (CH × 2), 128.12 (CH × 2), 128.34 (CH × 2), 128.46 (CH × 2), 128.58 (CH × 2), 132.86 (CH), 132.88 (CH), 136.72 (C), 137.07 (C), 142.79 (C), 198.43 (C), 203.23 (C). The signal for the methyl group of the minor isomer appears at 1.01 ppm (d, J = 6.6 Hz). According to the report by Heathcock et al., the major isomer was determined to be anti. See ref. [11] Compound anti-3ab: CAN [111873-77-9] (ref. [12] ). ¹H NMR (270 MHz, CDCl₃) δ 1.21 (δ, J = 6.9 Hz, 3 H), 2.00 (s, 3 H), 2.89 (d, J = 7.1 Hz, 2 H), 3.72 (q, J = 7.1 Hz, 1 H), 3.83 (quint., J = 6.9 Hz, 1 H), 7.09-7.26 (m, 5 H), 7.38-7.54 (m, 3 H), 7.80-7.83 (m, 2 H). ¹³C NMR (68 MHz, CDCl₃) δ 14.19 (CH₃), 30.42 (CH₃), 42.71 (CH), 45.08 (CH₂), 45.79 (CH), 126.64 (CH), 127.86 (CH × 2), 128.06 (CH × 2), 128.43 (CH × 2), 128.54 (CH × 2), 132.86 (CH), 136.68 (C), 142.54 (C), 203.20 (C), 207.12 (C). Compound anti-3ac: CAN [95741-11-0] (ref. [13] ). ¹H NMR (270 MHz, CDCl₃) δ 1.07 (δ, J = 6.4 Hz, 3 H), 1.23 (δ, J = 6.9 Hz, 3 H), 2.17-2.79 (m, 2 H), 3.12 (d, J = 14.5, 2.5 Hz, 1H), 3.62 (qd, J = 6.9, 4.9 Hz, 1 H), 7.37-7.58 (m, 6 H), 7.85-8.06 (m, 4 H). ¹³C NMR (68 MHz, CDCl₃) δ 12.94 (CH₃), 18.57 (CH₃), 31.91 (CH), 41.24 (CH₂), 44.92 (CH), 128.00 (CH × 2), 128.21 (CH × 2), 128.47 (CH × 2), 128.66 (CH × 2), 132.89 (CH), 132.94 (CH), 136.91 (C), 137.05 (C), 199.60 (C), 203.89 (C).

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13 Inokuchi T. Kurokawa Y. Kusumoto M. Tanigawa S. Takagishi S. Torii S. Bull. Chem. Soc. Jpn.  1989,  62:  3739