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

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.

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

References and Notes

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Chemoselective deprotection of TMSE esters besides tert-butyl esters (representative examples):

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Chemoselective deprotection of TMSE esters besides benzyl esters (representative examples):

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7 Kramer R. Dissertation   Universität Freiburg; Germany: 2007.  p.279-280  

8 Tricotet T. Brückner R. Eur. J. Org. Chem.  2007,  1069 

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: δ_3-H3  = 2.20 in 8a vs. 2.15 in 13a; δ_3-H2  = 2.51 in 8b vs. 2.47 in 13b; δ_1-H2 = 3.78 in 8c vs. 3.74 in 13c. The β-keto esters were distinguished from the ketone(s) by their alkoxy resonances.

11 Felpin F.-X. Ayad T. Mitra S. Eur. J. Org. Chem.  2006,  2679 

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14

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

15 Still WC. Kahn M. Mitra A. J. Org. Chem.  1978,  43:  2923 

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 [m_c, 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 [m_c, 1′-H₂ (7a and enol-7a)], 4.99 [m_c, 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.

17 Reaction conditions were gleaned from a protocol by: Hogan F. Herald DL. Petit GR. J. Org. Chem.  2003,  69:  4019 

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 (m_c, 1′-H₂); 7b: δ = 4.20 (m_c, 1′-H₂); 7c: δ = 4.21 (m_c, 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.