Asymmetric Mannich reactions, metal-free

Recently, direct catalytic asymmetric Mannich-type reactions were reported via C-H activation of carbonyl compounds. The transformations are catalyzed both by organometallic complexes and metal-free organic catalysts. 

Another important means of mediation of metal-free catalytic enantioselective Mannich-type reactions is via electrophilic activation of the preformed imines by chiral Bronstedt acids [7, 8, 46], By using this strategy Terada and coworkers performed chiral phosphoric acid-catalyzed direct asymmetric Mannich-type reactions between Boc-protected imines and acetoacetone that furnished aryl /3-amino... 

The scope of this chapter does not allow nor attempt a comprehensive account of all developed processes to date. A detailed summary, in particular of aldol, Mannich, or ot-functionalisation reactions, can be found in excellent reviews written on the topic." Barbas and List reported an asymmetric, direct, intermolecular aldol reaction of acetones and aldehydes (Scheme 5.4), presumably via enamine formation of proline and acetone. As compared to its metal-catalysed alternatives, no preformation of the respective enolate is required, a mode of action that mimics metal-free aldolase enzymes. ... 

EXAMPLES OF METAL-FREE DIRECT CATALYTIC ASYMMETRIC MANNICH-TYPE REACTIONS USING AM I NOCATALYSIS... 

The influence of pressure on organic reactions catalyzed by chiral metal-free organic molecules was studied for selected asymmetric Michael, Baylis-Hillman, aldol, Mannich, Friedel-Crafls, and Diels-Alder reactions-the essential part of this work was done in Japan. In the early stages of those investigations the high-pressure technique was applied to reactions catalyzed by cinchona alkaloids and in most cases low or moderate enantioselectivities were observed. Since 2002 some examples of high-pressure reactions catalyzed by proUne, thioureas, and modified cinchona alkaloids have appeared. 

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