Ethyl (2E)-3-methyl-4-oxo-2-butenoate → Ethyl 3-methyl-4-oxobutanoate

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Reaction Steps

In another example, an all-trans-13,14-dihydroretinol can be synthesized as follows. All reagents can be purchased from Sigma or Fluka and used without additional purification. Solvents can be dried under standard procedures prior to use. All operations with retinoids may be performed under dim red light unless otherwise specified. B-Ionone can be condensed with triethyl phosphonoacetate in anhydrous tetrahydrofuran in the presence of NaH to give ethyl trans-β-ionylideneacetate. This ester may then be reduced with LiAlH4 to alcohol and reacted overnight with triphenylphosphine hydrobromide to give Wittig salt. Ethyl 4-oxo-3-methylcrotonate can be hydrogenated in methanol with H2 using 10% palladium on carbon as a catalyst to yield ethyl 4-oxo-3-methylbutyrate, which may then be reacted with Wittig salt using t-BuOK as a base in anhydrous CH2Cl2 in the presence of 18-crown-6. The obtained mixture of ethyl 11-cis and all-trans-13,14-dihydroretinoates can be reduced with LiAlH4 to 13,14-dihydroretinols, and all-trans-isomer separated from 11-cis-dihydroretinol by flash chromatography of silica gel using 5% ethyl acetate in hexane. NMR data can be recorded on a Bruker 500-MHz spectrometer using CDCl3 as an internal standard. 1H NMR analysis of synthetic all-trans-13,14-dihydroretinol can yield: NMR (CDCl3, δ, ppm) 6.41 (dd, 1H, H-12, J=11.3, 14.75 Hz), 6.10-6.12 (m, 3H, H-7, H-8, H-10, J=15.7 Hz), 5.6 (dd, 1H, H-11, J=8.34, 14.95 Hz), 3.67 (m, 2H, CH2-15), 2.41 (m, 1H, H-13, J=6.7 Hz), 1.96 (m, 2H, CH2-14), 1.90 (s, 3H, CH3-9), 1.69 (s, 3H, CH3-5), 1.46 (m, 2H, CH2-2), 1.6 (m, 4H, CH2-3, CH2-4), 1.06 (d, 3H, CH3-13 J=6.7 Hz), 1.00 (s, 6H, 2×CH3-1).

Provenance & Evidence