( S )-Proline-catalyzed Mannich-type reaction of aldehydes with α-imino ethyl glyoxylate affords syn -products, while the reaction utilizing (3R, 5R)-5-methyl-3-pyrrolidinecarboxylic acid gives anti -selective product (Scheme 15).

Scheme 15. Anti and Syn Selectivity in Mannich reaction

In addition , (R )-3-pyrrolidinecarboxylic acid catalyzes the Mannich-type reactions of ketones with α-imino ethyl glyoxylate to give anti -products, while (S)- proline based reactions give syn -products (Scheme 17). Thus, the position of the carboxylic acid group on the pyrrolidine ring directs the stereoselection of the catalyzed reaction providing either syn - or anti -Mannich products.

Scheme 16. Anti and syn Mannich-type Reactions of Ketones

10.1.3 Michael Reaction

In 2001, the first example for a direct asymmetric Michael reaction employing an enamine-activated donor appeared. The proline-catalyzed reaction of acetone and cyclopentanone with benzalmalonate and nitrostyrene affords the Michael product with low enantiomeric excess. However, the use of chiral diamine improves the ee significantly with both nitrostyrene and alkylidene malonates as acceptors and ketone donors (Scheme 17).

Scheme 17