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Synlett 2009(3): 487-489  
DOI: 10.1055/s-0028-1087534
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Simple and Efficient Procedure for the Synthesis of Ketone Di-sec-alkyl ­Acetals

Fumiaki Ono, Hirotaka Takenaka, Yuko Eguchi, Masato Endo, Tsuneo Sato*
Department of Life Science, Kurashiki University of Science and the Arts, Kurashiki 712-8505, Japan
Fax: +81(86)4401062; e-Mail: sato@chem.kusa.ac.jp;
Further Information

Publication History

Received 22 September 2008
Publication Date:
21 January 2009 (online)

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Abstract

Ketone di-sec-alkyl acetals are obtained in good to excellent yields by treatment of ketones with tri-sec-alkyl orthoformate and the corresponding alcohol in the presence of a catalytic amount of cerium(III) trifluoromethanesulfonate.

Key words

acetals - cerium(III) trifluoromethanesulfonate - ketones - Lewis acids - tri-sec-alkyl orthoformates

    References and Notes

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9

When this reaction was attempted in the absence of i-PrOH or triisopropyl orthformate, diisopropyl acetalization did not proceed at all.

10

None (85%), CH2Cl2 (80%), Et2O (83%), THF (81%), MeCN (76%).

11

Typical Procedure (Table 1, Entry 1)
To a mixture of cyclopentanone (84 mg, 1.0 mmol), Ce(OTf)3 (Alfa Aesar, 5.9 mg, 0.01 mmol), i-PrOH (1 mL), and toluene (1 mL) triisopropyl orthoformate (247 mg, 1.3 mmol)was added at 0 ˚C. After the mixture was kept stirring at the same temperature for 6 h, it was quenched by adding Et3N (101 mg, 1.0 mmol). The resulting mixture was passed through a short plug of neutral Al2O3 (activity III), which was then washed with Et2O (30 mL), and the solvent was removed under reduced pressure. The ¹H NMR (500 MHz) analysis of the crude product showed the absence of
1-cyclopentenyl isopropyl ether. The residue was chroma-tographed on neutral Al2O3 (activity III, hexane) to afford cyclopentanone diisopropyl acetal (168 mg, 90%). ¹H NMR (500 MHz, CDCl3): δ = 1.17 (d, J = 6.1 Hz, 12 H), 1.65-1.70 (m, 4 H), 1.75-1.81 (m, 4 H), 4.01-4.09 (m, 2 H). ¹³C NMR (125 MHz, CDCl3): δ = 21.7, 24.4, 35.6, 63.8, 111.6. 2-Octanone Diisopropyl Acetal
¹H NMR (500 MHz, CDCl3): δ = 0.88 (t, J = 7.1 Hz, 3 H), 1.14 (d, J = 6.4 Hz, 12 H), 1.24-1.37 (m, 8 H), 1.27 (s, 3 H), 1.54-1.59 (m, 2 H), 3.99-4.08 (m 2 H). ¹³C NMR (125 MHz, CDCl3): δ = 14.1, 22.6, 23.7, 24.5, 24.6, 24.8, 29.7, 31.9, 39.8, 62.1, 102.6.
1-Cyclohexyl-1-ethanone Diisopropyl Acetal
¹H NMR (500 MHz, C6D6): δ = 0.92-2.10 (m, 11 H), 1.10 (d, J = 6.0 Hz, 6 H), 1.13 (d, J = 6.0 Hz, 6 H), 1.15 (s, 3 H), 3.97-4.05 (m, 2 H). ¹³C NMR (125 MHz, C6D6): δ = 19.7, 24.6, 25.0, 27.1, 27.2, 29.0, 45.9, 62.0, 104.5.
Acetophenone Diisopropyl Acetal
¹H NMR (500 MHz, C6D6): δ = 0.98 (d, J = 6.5 Hz, 6 H), 1.12 (d, J = 6.0 Hz, 6 H), 1.61 (s, 3 H), 3.96-4.04 (m, 2 H), 7.08-7.76 (m, 5 H). ¹³C NMR (125 MHz, C6D6): δ = 24.2, 24.9, 28.3, 63.7, 101.3, 127.3, 127.6, 145.0.
Cyclohexanone Di- sec -butyl Acetal
¹H NMR (500 MHz, C6D6): δ = 0.87 (t, J = 7.7 Hz, 3 H), 0.88 (t, J = 7.7 Hz, 3 H), 1.14 (d, J = 6.4 Hz, 3 H), 1.16 (d, J = 6.1 Hz, 3 H), 1.26-1.35 (m, 2 H), 1.43-1.74 (m, 12 H), 3.82-3.93 (m, 2 H). ¹³C NMR (125 MHz, C6D6): δ = 9.5, 9.6, 21.3, 21.5, 23.8, 26.1, 31.3, 36.1, 36.2, 36.5, 66.8, 67.0, 101.3.
Cyclohexanone Dicyclohexyl Acetal ¹H NMR (500 MHz, C6D6): δ = 1.10-1.87 (m, 30 H), 3.82-3.89 (m, 2 H). ¹³C NMR (125 MHz, C6D6): δ = 23.8, 24.8, 26.2, 35.2, 36.7, 67.9, 101.5.

12

Other Brønsted and Lewis acids are less effective than Ce(OTf)3 in our reaction system. The reaction of 2-octanone under identical conditions are as follows: TfOH (23%), BF3˙OEt2 (0%), AlCl3 (15%), Mg(OTf)2 (0%), TMSOTf (58%), Sc(OTf)3 (62%), Cu(OTf)2 (63%), Zn(OTf)2 (35%), La(OTf)3 (36%), Gd(OTf)3 (63%), Bi(OTf)3˙4H2O (51%).

13

Reaction of benzophenone (r.t., 24 h) followed by the standard workup gave benzophenone diisopropyl acetal (5%) and the starting ketone (90%).

14

Di-sec-butyl acetalization of cyclohexanone by the Roelofsen method [5] afforded cyclohexanone di-sec-butyl acetal (80%) and sec-butyl 1-cyclohexenyl ether (15%).