Seiji Aratake

Dry and wet prolines for asymmetric organic solvent-free aldehyde–aldehyde and aldehyde–ketone aldol reactions

Dry and wet prolines were found to catalyze the direct aldol reactions of aldehyde-aldehyde and aldehyde-ketone, respectively, to afford aldols with excellent diastereo- and enantioselectivities, and an organic solvent-free reaction was realized in some cases.

Direct Asymmetric α‐Amination of Cyclic Ketones Catalyzed by Siloxyproline

trans-tert-Butyldimethylsiloxy-L-proline displays greater catalytic activity and affords higher enantioselectivity than the parent proline in the alpha-amination reaction of carbonyl compounds with azodicarboxylate. A quantum mechanical calculation reveals the structure of the transition state. In the presence of a catalytic amount of siloxyproline and water (3-9 equiv), alpha-amino carbonyl derivatives, which are important synthetic intermediates, are obtained in good yield and with excellent enantioselectivity.

Direct Crossed-Aldol Reaction of Acetaldehyde

Significance: The authors report an organocatalytic asymmetric direct crossed-aldol reaction of acetaldehyde. Diaryl prolinol 1 was found to be an effective catalyst and DMF the best solvent for this reaction. Due to the instability of the aldol products they were reduced to the corresponding diols. With 10 mol% of catalyst 1 and 5 equivalents of acetaldehyde, good to high yields (50–92%) and excellent enantioselectivities (er = 98:2 to >99:1) are obtained for different aromatic aldehydes. One aliphatic aldehyde was also used and reasonable enantioselectivity (er = 90:10) was obtained. Comment: Although organocatalytic aldol reactions with acetaldeyhde were early attempted by the groups of Barbas (J. Org. Chem. 2002, 67, 301) and Jørgensen (Chem. Commun. 2002, 621), the desired products were obtained in poor yields or enantioselectivities. In that respect, this report by the authors is very important. It is intriguing that proline, which is the usual catalyst for other aldol reactions, was found to be ineffective in this case. For an independent use of acetaldehyde in Mannich reactions by List and co-workers, see: Nature 2008, 452, 453 and also Synfacts 2008, 532. 50–92% yield er = 90:10 to >99:1