The Efficient Allylations of 2-Oxocarboxylic Acids. Synthesis of 2-Allyl Derivatives of 2-Hydroxycarboxylic Acids

Abstract

2-Oxocarboxylic acids or their sodium salts undergo indium-mediated allylation with allyl bromide cinnamyl bromide and ethyl 4- bromocrotonate to provide the corresponding 2-allyl derivatives of glycolic lactic mandelic and malic acids. In the case of reactions with cinnamyl bromide or ethyl 4-bromocrotonate high diastereoselectivity is achieved.

allylation reactions - hydroxycarboxylic acids - diastereoselective

References

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General Procedure: The 2-oxocarboxylic acid 1 (0.5 mmol), allyl bromide (0.75 mmol), indium metal (0.5 mmol) were taken in THF-H₂O (2:1) mixture and the reaction mixture was stirred at 30 °C until the indium metal dissolved. The turbid reaction mixture was treated with dilute HCl and extracted with CHCl₃. The solvent was distilled off and the residue was column chromatographed (silica gel, 60-120 mesh) to isolate the allyl addition product. In the case of reactions with sodium 2-oxocarboxylate (0.5 mmol), 2 C (1.5 mmol) and indium (1.0 mmol) the pH (4.7) of the reaction was controlled initially by addition of HOAc and during the course of reaction with aq NaOH (2%).

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¹ H NMR spectral data for the representative cases are given here. 3e: δ 2.18 (s,1 H, OH, exchanges with D₂O), 3.86 (dd, J ₁ = 7.6 Hz, J ₂ = 4 Hz, 1 H, CH), 4.59 (d, J = 4 Hz, 1 H, CH), 5.20-5.29 (m, 2 H, =CH₂), 6.17-6.32 (m, 1 H, =CH), 7.22-7.37 (m, 5 H, ArH) (For Na salt: mp >300 °C, found C 61.4; H 5.1%. C₁₁ H₁₁O₃Na requires C 61.7; H 5.1%). 3f: mp 168 °C; δ 4.39 (s, 1 H, OH, exchanges with D₂O), 4.4 (d,
J = 9.5 Hz, 1 H, CH), 4.79-4.99 (m, 2 H, =CH₂), 5.89-6.03 (m, 1 H, =CH), 7.19-7.41 (m, 8 H, ArH), 7.72-7.73 (m, 2 H, ArH) (Found C 76.3; H 5.99%. C₁₇H₁₆O₃ requires C 76.1; H 5.97%). 3g : δ 1.31 (t, J = 7 Hz, 3 H, CH₃), 2.09 (s, 1 H, OH, exchanges with D₂O), 3.62 (dd, J ₁ = 8.4 Hz, J ₂ = 3.6 Hz,
1 H, CH), 4.20 (s, 1 H, OH, exchanges with D₂O), 4.22 (q,
J = 7 Hz, 2 H, OCH₂) 4.47 (d, J = 3.6 Hz, 1 H, CH), 5.26-5.38 (m, 2 H, =CH₂), 5.77-6.07 (m, 1 H, =CH) (For Na salt: mp >300 °C; found C 45.4, H 4.9. C₈H₁₁O₅Na requires C 45.7; H, 5.2%). 3 h: mp 97-98 °C; δ 1.29 (t, J = 7.2 Hz,
3 H,CH₃), 2.20 (s, 1 H, OH, exchanges with D₂O), 4.14 (d,
J = 8.2 Hz, 1 H, CH), 4.22 (q, J = 7.2 Hz, 2 H, OCH₂), 5.02-5.17 (m, 2 H, =CH₂), 5.56-5.68 (m, 1 H, =CH), 7.29-7.42 (m, 8 H, ArH), 7.58-7.63 (m, 2 H, ArH). (Found C 63.3;
H 6.0%. C₁₄ H₁₆O₅ requires C 63.3; H 6.06%).

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Similar increase in both rate of reaction and diastereoselectivity of allylation at pH 4.0 and slowed allylation at pH 7.0 was reported earlier (ref. [2d] ).