Enantioselective Direct Mannich Reaction Products with One Stereogenic Center

Enantioselective Direct Mannich Reaction Products with One Stereogenic Center 

Optically active /i-amino ketones (S)-28 with one stereogenic center can be efficiently prepared in the presence of 35 mol% L-proline (S)-27 with acetone as a 

Very recently, the List group applied this proline-catalyzed Mannich reaction efficiently in multi-step syntheses of several a-amino acid derivatives, such as protected 1,2-amino alcohol derivatives and oxazolidin-2-ones [25], 

Interestingly, however, another comparative study [24] revealed the capacity of other amines related to L-proline (S)-27 to function as organocatalysts in the Mannich reaction under modified reaction conditions [24]. As shown for a model reaction using preformed imines derived from o-anisidine, the thiazolidine carboxylic 

Mechanistically it seems that the reactions follow an enamine mechanism, in which the enamine derived from the ketone and proline reacts with the imine formed in situ from the aldehyde and p-anisidine. 

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