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

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.

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

References

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<A NAME="RU02804ST-1B">1b</A> Kocienski PJ. In Protecting Groups   Thieme; Stuttgart: 1994.  Chap. 5.

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<A NAME="RU02804ST-6">6</A>

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%).

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<A NAME="RU02804ST-8">8</A> Dimethyl acetalization of citronellal using electrogenerated acid afforded 6-methoxy-3,7-dimethyl-7-octenal dimethyl acetal (18%) as a by-product: Gora J. Smigielski K. Kula J. Synthesis  1986,  586 

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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%).

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<A NAME="RU02804ST-15">15</A>

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.