Catalytic Synthesis of γ-Alkoxy-α-keto Esters

Abstract

Copper(II) triflate effectively catalyzes the reaction of (trimethylsilyloxy)acrylic esters and acetals to form γ-alkoxy-α-keto esters. The reaction proceeds under mild conditions providing products in good to excellent yields. The substrate scope was investigated, and it was demonstrated that the products could be converted into related compounds such as γ-hydroxy-α-keto esters and ­α-oximes.

copper(II)triflate - acetals - (trimethylsilyloxy)acrylic ester - γ-alkoxy-α-keto ester - α-oximes - γ-hydroxy-α-keto ester - ­Mukaiyama-aldol

References and Notes

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14

General Procedure for the Synthesis of the γ-Alkoxy-α-keto Esters Cu(OTf)₂ (0.04 mmol) was dissolved in dry CH₂Cl₂ (2 mL) and cooled to 0 ˚C. The acetal (0.4 mmol) and the acrylic ester (0.6 mmol) were added, and the reaction was monitored by TLC. After consumption of the starting material, the crude reaction mixture was directly subjected to column chromatography to yield the pure products 3a-o.
Ethyl 4-Methoxy-4-phenyl-2-oxobutyrate (3a) ^¹7
¹H NMR (400 MHz, CDCl₃): δ = 1.36 (t, J = 7.14 Hz, 3 H, CH₃), 2.98 (dd, J = 16.8, 4.4 Hz, 1 H, CH₂), 3.20 (s, 3 H, OCH₃), 3.41 (dd, J = 16.8, 9.2 Hz, 1 H, CH₂), 4.31 (q, J = 7.14 Hz, 2 H, CH₂), 4.73 (dd, J = 9.2, 4.4 Hz, 1 H, CH), 7.29-7.40 (m, 5 H, Ar) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 13.9 (CH₃), 47.5 (CH₂), 56.7 (OCH₃), 62.4 (CH₂), 78.9 (CH), 126.4 (Ar), 128.0 (Ar), 128.5 (Ar), 140.1 (Ar), 160.6 (CO), 191.8 (CO) ppm.

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