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DOI: 10.1055/s-0028-1087349
N-Tosyl-(S a)-binam-l-prolinamide as Highly Efficient Bifunctional Organocatalyst for the General Enantioselective Solvent-Free Aldol Reaction
Publication History
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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References and Notes
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.