Synlett 2002(8): 1269-1272
DOI: 10.1055/s-2002-32978
LETTER
© Georg Thieme Verlag Stuttgart · New York

Mannich-type Reaction Catalyzed by HBF4 in Water: Effect of the Loading of Surfactant

Takahiko Akiyama*, Junji Itoh, Kohei Fuchibe
Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1, Mejiro, Toshima-ku, Tokyo 171-8588, Japan
Fax: +81(3)59921029; e-Mail: takahiko.akiyama@gakushuin.ac.jp;
Further Information

Publication History

Received 26 May 2002
Publication Date:
25 July 2002 (online)

Abstract

The HBF4 (0.1 equiv)-catalyzed Mannich-type reactions of ketene silyl acetals with aldimines proceeded smoothly in water in the coexistence of as low as 1 mol% of SDS. Furthermore, the Mannich-type reaction also took place in water in the absence of SDS by means of 0.3 equiv of HBF4 to afford the corresponding β-amino esters in high yields.

10

We optimized the loading of SDS by use of a silyl enol ether as a substrate in ref. [8]

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General Experimental Procedure for Protocol A (entry 3 of Table 1). Aq solution of HBF4 (8 µL, 0.0080 mmol, 1.3598 mol/L) was added to a mixture of N-benzylidene-p-anisidine(1) (17 mg, 0.0805 mmol), ketene silyl acetal(2a) (48 µL, 0.241 mmol), SDS (8 µL, 0.0080 mmol, 0.10027 mol/L solution) in H2O (0.5 mL) at r.t. After being stirred at the temperature for 0.5 h, the reaction was quenched by addition of sat. NaHCO3 and CH2Cl2. The aq layer was extracted with CH2Cl2 and the combined organic layers were washed with brine, dried over anhyd Na2SO4, and concentrated to dryness. Purification of the crude mixture by preparative TLC (SiO2, hexane:ethyl acetate = 10:1, v/v) gave 3a in 94% yield.

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Because H3PO4 also worked equally as a Brønsted acid for the present Mannich-type reaction, presence of the fluoride ion, which might be generated from HBF4, is not essential for the Mannich-type reaction. Authors are grateful to a referee for pointing out the issue.

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General Experimental Procedure for Protocol B (entry 5 of Table 1). Aq solution of HBF4 (48 µL, 0.0480 mmol, 1.0 mol/L) was added to a mixture of N-benzylidene-p-anisidine(1) (33.6 mg, 0.159 mmol), ketene silyl acetal (2a) (99 µL, 0.477 mmol) in H2O (1.0 mL) at r.t. After being stirred at the temperature for 0.5 h, the reaction was quenched by addition of sat. NaHCO3 and CH2Cl2. The aq layer was extracted with CH2Cl2 and the combined organic layers were washed with brine, dried over anhyd Na2SO4, and concentrated to dryness. Purification of the crude mixture by preparative TLC (SiO2, hexane:ethyl acetate = 10:1, v/v) gave 3a in 81% yield.