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Synlett 2008(19): 3031-3035  
DOI: 10.1055/s-0028-1087349
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

N-Tosyl-(S a)-binam-l-prolinamide as Highly Efficient Bifunctional Organocatalyst for the General Enantioselective Solvent-Free Aldol Reaction

Gabriela Guillena*, Carmen Nájera*, Santiago F. Viózquez
Departamento Química Orgánica and Instituto de Síntesis Orgánica, Universidad de Alicante, Apdo. 99, 03080 Alicante, Spain
Fax: +34(965)903549; e-Mail: gabriela.guillena@ua.es; e-Mail: cnajera@ua.es;
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Publication History

Received 30 July 2008
Publication Date:
12 November 2008 (online)

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Abstract

N-Tosyl-(S a)-binam-l-prolinamide (5 mol%) and benzoic acid (1 mol%) were used as catalysts in the enantioselective direct aldol reaction between different ketones and aldehydes under solvent-free conditions in the presence or absence of water. Under these reaction conditions it was possible to reduce the amount of required ketone to two equivalents to give the corresponding aldol products with high yields, regio-, diastereo- and enantioselectivities. The aldol reaction between aldehydes or the intramolecular aldol reaction can be also performed with excellent results.

Key words

organocatalyzed - aldol reactions - solvent-free - enantio­selective - ketone

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12

Representative Experimental Procedure:
Anhydrous Solvent-Free Conditions: To a mixture of the corresponding aldehyde (0.25 mmol), catalyst 2 (0.0125 mmol, 6.5 mg) and benzoic acid (0.0025 mmol, 0.3 mg) at
0 ˚C was added the corresponding ketone (0.5 mmol). The reaction was stirred until the aldehyde was consumed (monitored by TLC). Then, the crude product was diluted in CH2Cl2 (10 mL), silica gel was added and the solvent was evaporated in vacuo. The resulting residue was purified by flash chromatography (hexanes-EtOAc) to yield the pure aldol product.
Wet Solvent-Free Conditions: To a mixture of the corresponding aldehyde (0.25 mmol), catalyst 2 (0.0125 mmol, 6.5 mg), benzoic acid (0.0025 mmol, 0.3 mg), H2O (33 µL) was added at 0 ˚C followed by the corresponding ketone (0.5 mmol). The reaction was stirred until the aldehyde was consumed. The crude product was diluted in CH2Cl2 (10 mL), MgSO4 was added and filtered. To the filtrate, silica gel was added and the above purification procedure was followed to obtain the aldol product.