A Simple and Efficient Method for Transesterification of β-Keto Esters Catalyzed by Cesium Fluoride

Abstract

Cesium fluoride is found to be an efficient and reusable catalyst for the transesterification of β-keto esters with various alcohols in good to high yields.

alcohols - β-keto esters - catalysis - cesium fluoride - transesterifications

References and Notes

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<A NAME="RU10007ST-14">14</A>

To the best of our knowledge, there is only one successful report⁴ on the use of this type compound in the transesterification process.

<A NAME="RU10007ST-15">15</A>

CsF was the best catalyst among the cesium salts examined under the identical conditions: CsCl (1%), CsBr (2%), CsI (2%).

Transesterification of β-keto esters with allylic alcohols is rather difficult as it is offset by facile decarboxylative rearrangement:

<A NAME="RU10007ST-16A">16a</A> Carrol MF. J. Chem. Soc.  1940,  704 

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<A NAME="RU10007ST-17">17</A> Conventional acid- and base-catalyzed transesterification of β-keto esters with propargylic alcohols provided in most cases low yields of the products: Mottet C. Hamelin O. Garavel G. Depres J.-P. Greene AE. J. Org. Chem.  1999,  64:  1380 ; and references cited therein

<A NAME="RU10007ST-18">18</A> Cesium fluoride promoted desilylation of tert-butyldimethylsilyl ethers was reported: Cirillo PF. Panek JS. J. Org. Chem.  1990,  55:  6071 

<A NAME="RU10007ST-19">19</A>

Transesterification of normal esters proceeded under similar reaction conditions. The details of this result will be communicated later.

<A NAME="RU10007ST-20">20</A>

Typical Procedure (Table 1, entry 1): In a 65-mL test tube (2.0 × 19 cm) fitted with a Drierite drying tube, a vigorously stirred mixture of methyl acetoacetate (581 mg, 5.0 mmol), 1-octanol (846 mg, 6.5 mmol) and CsF²¹ (76 mg, 0.5 mmol) in commercial toluene without any purification (10 mL) was heated so that the toluene refluxed halfway up the tube (130-135 °C, bath temperature) for 18 h.²² After toluene had been decanted, CsF was washed with Et₂O (5 mL). The combined organic layer was evaporated under reduced pressure. The residue was chromatographed on silica gel (5% EtOAc-hexane) to afford octyl acetoacetate (997 mg, 93%).²³ CsF remained intact and was reused for the subsequent reaction.

<A NAME="RU10007ST-21">21</A>

Purchased from Mitsuwa Chemicals Co., Ltd.

<A NAME="RU10007ST-22">22</A>

The equilibrium was shifted due to the loss of the relatively volatile methyl, ethyl or isopropyl alcohol from the reaction mixture.

<A NAME="RU10007ST-23">23</A>

Selected spectroscopic data:
Octyl 2,2-Dimethyl-3-oxobutyrate: ¹H NMR (CDCl₃): δ = 0.88 (t, J = 7.5 Hz, 3 H), 1.22-1.66 (m, 12 H), 1.36 (s, 6 H), 2.16 (s, 3 H), 4.12 (t, J = 7.0 Hz, 2 H). ¹³C NMR (CDCl₃): δ = 13.9, 21.7, 22.5, 25.5, 25.7, 28.3, 29.0, 31.6, 55.6, 65.3, 173.5, 205.6.
2-Heptynyl 3-Oxohexanoate: ¹H NMR (CDCl₃): δ = 0.91 (t, J = 7.5 Hz, 3 H), 0.93 (t, J = 7.5 Hz, 3 H), 1.36-1.44 (m, 2 H), 1.46-1.53 (m, 2 H), 1.59-1.67 (m, 2 H), 2.22 (tt, J = 2.5, 7.5 Hz, 2 H), 2.53 (t, J = 7.5 Hz, 2 H), 3.47 (s, 2 H), 4.72 (t, J = 2.5 Hz, 2 H). ¹³C NMR (CDCl₃): δ = 13.4, 16.8, 18.3, 21.8, 30.3, 44.7, 48.9, 53.5, 73.3, 88.0, 166.5, 202.1.
8-Oxiranyloctyl 3-Oxohexanoate: ¹H NMR (CDCl₃): δ = 0.93 (t, J = 7.5 Hz, 3 H), 1.25-1.69 (m, 16 H), 2.47 (dd, J = 3.5, 5.0 Hz, 1 H), 2.52 (t, J = 7.5 Hz, 2 H), 2.75 (app t, J = 4.5 Hz, 1 H), 2.88-2.94 (m, 1 H), 3.43 (s, 2 H), 4.13 (t, J = 6.5 Hz, 2 H). ¹³C NMR (CDCl₃): δ = 13.4, 16.8, 25.6, 25.8, 28.3, 28.9, 29.1, 29.2, 32.3, 44.7, 46.9, 49.1, 52.2, 65.3, 167.2, 202.6.
2-(Dimethylamino)ethyl 3-Oxohexanoate: ¹H NMR (CDCl₃): δ = 0.93 (t, J = 7.0 Hz, 3 H), 1.58-1.68 (m, 2 H), 2.28 (s, 6 H), 2.52 (t, J = 7.0 Hz, 2 H), 2.58 (t, J = 5.5 Hz, 2 H), 3.47 (s, 2 H), 4.24 (t, J = 5.5 Hz, 2 H). ¹³C NMR (CDCl₃): δ = 13.3, 16.7, 44.7, 45.4, 49.0, 57.4, 62.6, 167.1, 202.6.
6-Chlorohexyl 3-Oxohexanoate: ¹H NMR (CDCl₃): δ = 0.93 (t, J = 7.5 Hz, 3 H), 1.35-1.82 (m, 10 H), 2.52 (t, J = 7.5 Hz, 2 H), 3.43 (s, 2 H), 3.54 (t, J = 6.5 Hz, 2 H), 4.14 (t, J = 7.0 Hz, 2 H). ¹³C NMR (CDCl₃): δ = 13.4, 16.8, 25.0, 26.3, 28.2, 32.2, 44.7, 49.1, 65.0, 167.1, 202.6.