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Synlett 2005(14): 2254-2256  
DOI: 10.1055/s-2005-872229
LETTER
© Georg Thieme Verlag Stuttgart · New York

High-Pressure-Promoted Uncatalyzed Ketalization of Ketones and Oxy-Michael/Ketalization of Conjugated Enones [1]

Koji Kumamoto, Yoshiyasu Ichikawa, Hiyoshizo Kotsuki*
Laboratory of Natural Products Synthesis, Faculty of Science, Kochi University, Akebono-cho, Kochi 780-8520, Japan
Fax: +81(888)448359; e-Mail: kotsuki@cc.kochi-u.ac.jp;
Further Information

Publication History

Received 10 May 2005
Publication Date:
20 July 2005 (online)

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Abstract

A new practical method for ketalization or oxy-Michael/ketalization was developed using the high-pressure-promoted condensation of ketones or α,β-unsaturated ketones with alcohols in the presence of trialkyl orthoformates as water scavengers.

Key words

ketalization - ketones - enones - trialkyl orthoformates - high-pressure reaction

    References

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7

General procedure A mixture of ketone and trimethyl orthoformate (2 equiv) in MeOH was placed in a Teflon reaction vessel (2.0 mL volume), and the mixture was allowed to react at 0.8 GPa at the appropriate temperature and for the specified time (Table [1] ). After the mixture was cooled and the pressure was released, the mixture was concentrated in vacuo. The crude product was purified quickly by column chromatography on alumina (elution with hexane-Et2O) to afford the pure product in good to excellent yields.

8

The use of a stoichiometric amount of this reagent resulted in incomplete conversion.

11

The ease of mono-ketalization of these difunctional substrates can be ascribed to the low electron density at one of the carbonyl groups.

13

Under the normal conditions (1 atm, r.t.) both substrates were recovered unchanged.

14

These reactions were best performed in CH2Cl2 using trimethyl orthoformate (2 equiv) and MeOH (2 equiv).