Bu₄N⁺-Controlled Addition and Olefination with Ethyl 2-(Trimethylsilyl)acetate via Silicon Activation

Published as part of the Cluster Silicon in Synthesis and Catalysis

Abstract

Catalytic Bu₄NOAc as silicon activator of ethyl 2-(trimethylsilyl)acetate, in THF, was utilized for the synthesis of β-hydroxy esters, whereas employing catalytic Bu₄NOTMS gave α,β-unsaturated esters. The established reaction conditions were applicable to a diverse range of aromatic, heteroaromatic, aliphatic aldehydes and ketones. Reactions were achieved at room temperature without taking any of the specialized precautions that are in place for other organometallics. A stepwise olefination pathway via silylated β-hydroxy esters with subsequent elimination to form the α,β-unsaturated ester has been demonstrated. The key to selective product formation lies in use of the weaker acetate activator which suppresses subsequent elimination whereas stronger TMSO^– activator (and base) facilitates both addition and elimination steps. The use of tetrabutyl ammonium salts for both acetate and trimethylsilyloxide activators provide enhanced silicon activation when compared to their inorganic cation counterparts.

Key words

tetrabutyl ammonium - acetate - trimethylsilyl oxide - silicon activation - addition - olefination

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• 21 General Procedure for Addition Reactions A solution of ethyl 2-(trimethylsilyl)acetate (1, 137 μL, 0.75 mmol) and aldehyde (0.50 mmol) in anhydrous THF (2.5 mL) was treated with dried Bu₄NOAc (0.05 mmol) under N₂. The resulting solution was stirred at r.t. for 1 h. Aqueous HCl (2 M, 10 mL) was added and stirred for 30 min. The residue was extracted with Et₂O (3 × 15 mL), organic layers combined, washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure gave the crude product. Ethyl 3-(2-chlorophenyl)-3-hydroxypropanoate (3b) A solution of ethyl 2-(trimethylsilyl)acetate (1, 137 μL, 0.75 mmol) and 2-chlorobenzaldehyde (70 mg, 0.50 mmol) in anhydrous THF (2.5 mL) was treated with dried Bu₄NOAc (15 mg, 0.05 mmol) under N₂. The resulting solution was stirred at r.t. for 1 h. Aqueous HCl (2 M, 10 mL) was added and stirred for 30 min. The residue was extracted with Et₂O (3 × 15 mL), organic layers combined, washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by silica gel chromatography eluting with cyclohexane–EtOAc (90:10) afforded 3b as a colorless oil (91 mg, 80%). ¹H NMR (400 MHz, CDCl₃): δ = 7.63 (dd, J = 7.7, 1.6 Hz, 1 H), 7.36–7.27 (m, 2 H), 7.22 (td, J = 7.6, 1.7 Hz, 1 H), 5.49 (dd, J = 9.7, 2.5 Hz, 1 H), 4.20 (q, J = 7.1 Hz, 2 H), 3.61 (br s, 1 H), 2.86 (dd, J = 16.6, 2.7 Hz, 1 H), 2.58 (dd, J = 16.6, 9.7 Hz, 1 H), 1.28 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 172.7, 140.0, 131.5, 129.5, 128.9, 127.3, 127.2, 67.2, 61.1, 41.5, 14.3 ppm. ESI–MS: m/z cald for C₁₁H₁₄O₃Cl [M + H]⁺: 229.1; found: 229.0.
• 22 General Procedure for Olefination Reactions A solution of ethyl trimethylsilylacetate (1, 137 μL, 0.75 mmol) and aldehyde (0.50 mmol) in THF (2.5 mL) was treated with dried Bu₄NCl (0.15 mmol) and TMSOK (0.15 mmol) under N₂, and the resulting reaction mixture was stirred at r.t. for 2 h. The reaction mixture was quenched with aq 2 M HCl (10 mL) and stirred for 5 min at r.t. The residue was extracted with EtOAc (3 × 15 mL). Organic layers were combined and washed with water and brine, dried over Na₂SO₄, and concentrated under reduced pressure to give the crude product.
• 23 (E)-Ethyl-3-(3,4,5-trimethoxyphenyl)acrylate (4l) A solution of 3,4,5-trimethoxybenzaldehyde (98 mg, 0.50 mmol) and ethyl trimethylsilylacetate (1, 137 μL, 0.75 mmol) in THF (2.5 mL) was treated with dried Bu₄NCl (42 mg, 0.15 mmol) and TMSOK (19 mg, 0.15 mmol) under N₂, and the resulting reaction mixture was stirred at r.t. for 2 h. The reaction mixture was quenched with 2 M aq HCl (10 mL) and stirred for 5 min at r.t. The residue was extracted with EtOAc (3 × 15 mL). Organic layers were combined and washed with water and brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by Al₂O₃ chromatography eluting with cyclohexane–EtOAc (90:10) yielded 4l (95 mg, 71%) as a colorless solid, mp 53–55 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.59 (d, J = 16.0 Hz, 1 H), 6.74 (s, 2 H), 6.33 (d, J = 16.0 Hz, 1 H), 4.25 (q, 2 H), 3.87 (s, 9 H), 1.33 (t, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 166.9, 153.4, 144.5, 140.1, 129.9, 117.5, 105.2, 60.9, 60.4, 56.1, 26.9, 14.3. MS (EI): m/z calcd for C₁₄H₁₈O₅ [M]⁺: 266.1; found: 266.2.