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Synlett 2008(12): 1865-1869  
DOI: 10.1055/s-2008-1078568
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Selective Cleavage and Decarboxylation of β-Keto Esters Derived from(Tri­methylsilyl)ethanol in the Presence of β-Keto Esters Derived fromOther Alcohols

Eva Knobloch, Reinhard Brückner*
Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität Freiburg, Albertstr. 21, 79104 Freiburg, Germany
Fax: +49(761)2036100; e-Mail: reinhard.brueckner@organik.chemie.uni-freiburg.de;
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Publication History

Received 24 March 2008
Publication Date:
02 July 2008 (online)

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Abstract

β-Keto[2-(trimethylsilyl)ethyl esters] are dealkoxycarbonylated at 50 ˚C by 0.75 equivalents of Bu4N+F−˙3H2O in THF. This reaction proceeds chemoselectively in the presence of β-keto(methyl esters), β-keto(tert-butyl esters), β-keto(allyl esters), or β-keto(benzyl esters) as revealed in intermolecular competition experiments.

Key words

chemoselectivity - dealkoxycarbonylation - defunctionalization - β-keto esters - ketones

    References and Notes

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9

After treatment with Bu4N+F-˙3H2O, any such experiment could ‘rightfully’ (i. e., in the absence of side reactions) deliver a mixture of up to four components, namely the unconsumed β-keto esters and the resulting ketones. We distinguished them by ¹H NMR spectroscopy (ref. 10) and quantified their relative amounts by integration of non-superimposed resonances. In addition, we determined the absolute amounts (i. e., absolute yields) of these species by weighing the respective mixture. Thereupon, the mole fraction of each component, its molecular weight, and the gram amount of the mixture allowed for the yields listed in Tables  [³] -  [6] to be calculated.

10

As remote and modest as the aryl group variation in the resulting ketones 8a-c vs. 13a-c may appear, the chemical shift effect accompanying it sufficed for differentiating, among others, the following resonances: δ3-H3  = 2.20 in 8a vs. 2.15 in 13a; δ3-H2  = 2.51 in 8b vs. 2.47 in 13b; δ1-H2 = 3.78 in 8c vs. 3.74 in 13c. The β-keto esters were distinguished from the ketone(s) by their alkoxy resonances.

14

All new compounds gave satisfactory ¹H NMR and ¹³C NMR spectra and provided correct combustion analyses (C and H ± 0.4%).

16

The crude acylation product 18 (1.3 g, 3.8 mmol) was dissolved in toluene (10 mL). Alcohol 1 (0.60 mL, 0.50 g, 4.2 mmol, 1.1 equiv) was added within 5 min. The mixture was stirred at 80 ˚C for 3.5 h. Evaporation of the solvent under reduced pressure and flash chromatography on SiO2 (see ref. 15; eluent: cyclohexane-EtOAc, 15:1) provided a mixture of the two tautomers of 2-(trimethylsilyl)ethyl
4-(4-phenylphenyl)-3-oxobutanoate (7a; 1.324 g, 94%) as a faintly yellow oil. ¹H NMR (400.1 MHz, CDCl3; 90:10 mixture of keto and enol tautomer): δ = 0.06 [s, Si(CH3)3 (7a)], 0.06 [s, Si(CH3)3 (enol-7a)], 1.02 [mc, 2′-H2 (7a and enol-7a)], 3.43 [s, 4-H2 (7a)], 3.56 [s, 4-H2 (enol-7a)], 3.90 [s, 2-H2 (7a)], 4.25 [mc, 1′-H2 (7a and enol-7a)], 4.99 [mc, 2-H (enol-7a)], 7.27-7.61 [m, Ar-H (7a and enol-7a)], 12.23 [s, 3-OH (enol-7a)]. Anal. Calcd (%) for C21H26O3Si (354.5): C, 71.15; H, 7.39. Found: C, 70.90; H, 7.40.

18

General Procedure for the Execution of the Competition Experiments Listed in Tables 3-6
At 0 ˚C Bu4N+F-˙3H2O (47 mg, 0.15 mmol, 0.75 equiv) in THF (0.5 mL) was added dropwise to a mixture of one of the β-keto(TMSE esters) 7a-c (0.20 mmol) and another β-keto ester 9a-c to 12a-c (0.20 mmol) in THF (1.5 mL). The resulting mixture was stirred at 50 ˚C until conversion was complete as judged by TLC. Brine (1.5 mL), H2O (3 mL), and t-BuOMe (3 mL) were added. Extraction with t-BuOMe (3 × 3 mL), drying of the combined extracts with Na2SO4, evaporation of the solvent under reduced pressure, and flash chromatography on SiO2 (ref. 15; eluent: cyclohexane-EtOAc) furnished a mixture of unreacted β-keto ester(s) and newly formed ketone(s) devoid of any byproducts. The yield of each component was determined as described in refs. 9 and 19.

19

The mole fractions of the β-keto ester and ketone constituents of each mixture isolated from one of the experiments summarized in Tables  [³] -  [6] were inferred from the integral ratios over the following ¹H NMR resonances (300 MHz, CDCl3): 7a: δ = 4.22 (mc, 1′-H2); 7b: δ = 4.20 (mc, 1′-H2); 7c: δ = 4.21 (mc, 1′H2); 8a: δ = 2.20 (s, 3-H3); 8b: δ = 2.51 (q, J 3,4 = 7.2 Hz, 3-H2); 8c: δ = 3.78 (s, 1-H2); 9a: δ = 3.64 (s, 1′-H3); 9b,c: δ = 3.70 (s, 1′-H3); 10a-c: δ = 1.46 [s, 1′-(CH3)3]; 11a: δ = 4.61 (ddd, J 1 ′ ,2 ′ = 5.8 Hz, 4 J 1 ′ ,3 ′ ( E ) = 4 J 1 ′ ,3 ′ ( Z ) = 1.4 Hz, 1′-H2); 11b,c: δ = 4.60 (ddd, J 1 ′ ,2 ′ = 5.8 Hz, 4 J 1 ′ ,3 ′ ( E ) = 4 J 1 ′ ,3 ′ ( Z ) = 1.4 Hz, 1′-H2); 12a,c: δ = 5.15 (s, 1′-H2); 12b: δ = 5.14 (s, 1′-H2); 13a: δ = 2.15 (s, 3-H3); 13b: δ = 2.47 (q, J 3,4 = 7.3 Hz, 3-H2); 13c: δ = 3.74 (s, 1-H2). The β-keto ester signals compiled above coincide for the respective keto and enol tautomers if the substitution pattern a is realized and for compound 10b; the enol resonances corresponding to the signals specified for keto tautomers 7b, 9b, 11b, and 12c are shifted downfield by 0.06 ppm.