Stereoselective Formation of (E)-β-Alkoxy Acrylates from Fischer Carbene Complexes and Chelated Amino Acid Ester Enolates

Abstract

Chelated amino acid ester enolates react with alkyl Fischer carbene complexes via nucleophilic attack on the electrophilic carbene center. Subsequent elimination of the metal fragment and trifluoroacetamide results in the formation of β-alkoxy-α,β-­unsaturated esters in a highly E-stereoselective fashion.

Key words

acrylates - amino acids - carbene complexes - enolates - Fischer carbenes - α,β-unsaturated esters

• References and Notes

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• 14 Preparation of (E)-tert-Butyl 3-Methoxyhept-2-enoate (5a) To a solution of trifluoroacetylated (TFA) tert-butyl glycinate (75 mg, 0.33 mmol) and ZnCl₂ (54 mg, 0.39 mmol) in THF was added LHMDS (1 M, 0.79 mL, 0.79 mmol) dropwise at –78 °C and the reaction mixture was stirred for 30 minutes at the same temperature. Then the Zn-chelated enolate formed was added dropwise to a solution of methoxybutyl carbene complex 3a (140 mg, 0.33 mmol) in THF at –78 °C. The reaction mixture was stirred for 1.5 h while the temperature rose to –50 °C. Stirring was continued for another 1.5 h at 0 °C to complete the reaction, before it was quenched with distilled water. The organic phase was extracted with EtOAc, dried over anhydrous Na₂SO₄, and was evaporated in vacuo. The crude product was purified by column chromatography (PE) affording the title compound 5a (51.4 mg, 0.24 mmol, 73%) as a colorless liquid. [TLC: R_f (5a) = 0.8 (PE)]. ¹H NMR (400 MHz, CDCl₃): δ = 0.89 (t, ³ J _9,8 = 7.2 Hz, 3 H, 9-H), 1.29–1.38 (m, 2 H, 8-H), 1.46 (s, 9 H, 1-H), 1.48–1.54 (m, 2 H, 7-H), 2.69 (t, ³ J _6,7 = 7.6 Hz, 2 H, 6-H), 3.58 (s, 3 H, 10-H), 4.89 (s, 1 H, 4-H). ¹³C NMR (100 MHz, CDCl₃): δ = 13.9 (q, C-9), 22.5 (t, C-8), 28.3 (q, C-1), 29.6 (t, C-7), 31.5 (t, C-6), 55.1 (q, C-10), 79.0 (s, C-2), 92.2 (d, C-4), 167.1 (s, C-3), 175.5 (s, C-5). GC–MS (EI): m/z (%) = 214 (2) [M], 158 (24) [M – 56], 141 (44) [M – 73], 116 (100) [M – 98].