An Efficient and Versatile Procedure for the Synthesis of Acetals from ­Aldehydes and Ketones Catalyzed by Lithium Tetrafluoroborate

Nao Hamada; Kiyoshi Kazahaya; Hisashi Shimizu; Tsuneo Sato

doi:10.1055/s-2004-820038

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Synlett 2004(6): 1074-1076
DOI: 10.1055/s-2004-820038

LETTER

An Efficient and Versatile Procedure for the Synthesis of Acetals from Aldehydes and Ketones Catalyzed by Lithium Tetrafluoroborate

Nao Hamada, Kiyoshi Kazahaya, Hisashi Shimizu, Tsuneo Sato*
Department of Chemistry and Bioscience, 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 26 January 2004
Publication Date:
25 March 2004 (online)

Abstract
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Abstract

Acetals are obtained in good to excellent yields by treatment of aldehydes and ketones with trialkyl orthoformate and the corresponding alcohol in the presence of a catalytic amount of lithium tetrafluoroborate. Due to the mild reaction conditions, this method is compatible with acid-sensitive substrates.

Key words

acetals - carbonyl compounds - Lewis acids - lithium tetrafluoroborate - protecting groups

References

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6

Other lithium salts and alkali metal tetrafluoroborates are less effective than LiBF₄ in our reaction system. The reaction of benzaldehyde under the identical conditions is as follows: LiCl (19%), LiBr (15%), LiClO₄ (36%), LiOTf (35%), NaBF₄ (8%), KBF₄ (3%).

10

Both methanol and trimethyl orthformate were necessary in order to obtain the products in satisfactory yields. On the reaction of benzophenone (3 mmol) using LiBF₄ (0.3 mmol): HC(OMe)₃ (3.9 mmol) alone (90 °C, 19 h, 15%); MeOH (1.5 cm³) alone (reflux, 19 h, 2%).

15

The spectroscopic data of new compounds are shown as follows.
4-(Methoxymethoxy)benzaldehyde Dimethyl Acetal: ¹H NMR (CDCl₃): δ = 3.32 (s, 6 H), 3.48 (s, 3 H), 5.18 (s, 2 H), 5.35 (s, 1 H), 7.03 (d, J = 8.85 Hz, 2 H), 7.36 (d, J = 8.85 Hz, 2 H). ¹³C NMR (CDCl₃): δ = 52.6, 56.0, 94.4, 103.0, 115.9, 127.9, 131.6, 157.3.
4-(2-Methoxyethoxy)benzaldehyde Dimethyl Acetal: ¹H NMR (CDCl₃): δ = 3.32 (s, 6 H), 3.37 (s, 3 H), 3.53-3.57 (m, 2 H), 3.80-3.84 (m, 2 H), 5.27 (s, 2 H), 5.34 (s, 1 H), 7.05 (d, J = 8.70 Hz, 2 H), 7.36 (d, J = 8.70 Hz, 2 H). ¹³C NMR (CDCl₃): δ = 52.6, 59.0, 67.6, 71.6, 93.4, 103.0, 115.9, 127.9, 131.6, 157.3.
4-(Perhydro-2 H -pyran-2-yloxymethyl)benzaldehyde Dimethyl Acetal: ¹H NMR (CDCl₃): δ = 1.49-1.92 (m, 6 H), 3.33 (s, 6 H), 3.52-3.56 (m, 1 H), 3.89-3.95 (m, 1 H), 4.51 (d, J = 12.2 Hz, 1 H), 4.70 (t, J = 3.35 Hz, 1 H), 4.79 (d, J = 12.2 Hz, 1 H), 5.39 (s, 1 H), 7.37 (d, J = 7.95 Hz, 2 H), 7.43 (d, J = 7.95 Hz, 2 H). ¹³C NMR (CDCl₃): δ = 19.4, 25.5, 30.6, 52.7, 62.1, 68.5, 97.8, 103.1, 126.7, 127.6, 137.3, 138.6.
4-(5,5-Dimethyl-1,3-dioxan-2-yl)benzaldehyde Dimethyl Acetal: ¹H NMR (CDCl₃): δ = 0.80 (s, 3 H), 1.30 (s, 3 H), 3.29 (s, 6 H), 3.65 (d, J = 10.9 Hz, 2 H), 3.77 (d, J = 10.9 Hz, 2 H), 5.40 (s, 1 H), 5.41 (s, 1 H), 7.46 (d, J = 8.25 Hz, 2 H), 7.51 (d, J = 8.25 Hz, 2 H). ¹³C NMR (CDCl₃): δ = 21.9, 23.0, 30.2, 52.4, 77.7, 101.5, 102.6, 126.0, 126.7, 138.6.