A Practical Route for the Preparation of Substituted 6-oxo-2-Hexenoate Derivatives

Abstract

Reaction of 2-hydroxy-3-butenoates with a series of carbonyl derivatives gives substituted 6-oxo-2-hexenoates in good yields under mild acid conditions via Claisen rearrangement of the allyl alkenyl ether intermediate.

Key words

Claisen rearrangement - substituted hexenoates - aldehydes - β-keto esters - tandem Michael-aldol

References

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9

Typical Experimental Procedure: The 2-hydroxy-3-butenoate (20 mmol) and aldehyde (30 mmol) were dissolved in dry toluene (15 mL) at r.t. in the presence of a catalytic amount of p-toluenesulfonic acid (10 mg). The reaction was refluxed for 48 h using a Dean-Stark trap for the removal of water. The reaction mixture was concentrated under reduced pressure and the resulting oil was purified by flash chromatography [typically petroleum ether (bp 30-40 °C)-EtOAc, 80:20] to give the desired product. All new compounds exhibited spectral (¹H NMR, ¹³C NMR, IR, MS) and analytical (HRMS) data fully consistent with the assigned structures.
Spectral Data for Methyl ( E )-5,5-dimethyl-6-oxo-2-hexenoate: R_f 0.20 [Petroleum ether (bp 30-40 °C)-EtOAc, 80:20]. ¹H NMR (300 MHz, CDCl₃): δ = 1.14 [s, 6 H, C(CH ₃)₂], 2.41 (dd, 2 H, J = 7.8 Hz, J = 1.4 Hz, CH ₂), 3.79 (s, 3 H, OCH ₃), 5.93 (dt, 1 H, J = 15.6 Hz, J = 1.4 Hz, =CHCO₂CH₃), 6.93 (dt, 1 H, J = 15.6 Hz, J = 7.8 Hz, CH=CHCO₂CH₃), 9.60 (s, 1 H, CHO). ¹³C NMR (75.5 MHz, CDCl₃): δ = 21.8 [C(CH₃)₂], 39.7 (CH₂), 46.2 [C(CH₃)₂], 51.9 (OCH₃), 124.6 (=CHCO₂CH₃), 144.2 (CH=CHCO₂CH₃), 166.8 (CO₂CH₃), 205.0 (CHO). FT-IR (NaCl): ν = 1803, 1730, 1645 cm^-1. LRMS (EI⁺): m/z = 171 (50) [M⁺ + 1], 139 (100), 109 (79), 81 (73), 41 (33). HRMS (EI⁺) calcd for C₉H₁₄O₃ [M⁺] 170.09429. Found: 170.09400.