Mannich-Type Reactions of Ketone Donors

Conditions Entries 1-7 Ketone (1 mL), N-PMP-protected a-imino ethyl glyoxylate (0.5 mmol, 1 equiv.), (S)-proline (0.1 mmol, 0.2 equiv.), DMSO (4 mL), rt, 2-24 h. Entry 8 After stirring (S)-proline (0.3 mmol) and 2,2,2-trifluoroethanol (1 mL) for 3 min at rt, the ketone (1.0 mmol) was added. After 15 min, the imine (1.0 mmol) was added and the mixture stirred for 20 h at rt. 

The Mannich reactions of ketones were also performed using sulfonamide-containing pyrrolidine 17, and afforded the products with similar regio-, diastereo-, 

Mannich reactions varied from excellent to low depending on the reactants Table 2.16 includes the results of highly enantioselective reactions. Reactions using 2,2-dimethyl-l,3-dioxane-5-one (5) provide for concise syntheses of enantiomerically enriched protected amino sugars (entries 8-10) [91]. In reactions using 5, the addition of 1 to 10 equiv. of H20 increased the rate and stereoselectivity of the reaction. 

1 (a) S. Yamada, K. Hiroi, K. Achiwa, Tetrahedron Lett. 1969, 4233-4236 (b) S. Yamada, G. Otani, Tetrahedron Lett. 1969, 4237-4240. 

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Table 2.15 (S)-Proline-catalyzed Mannich-type reactions of ketone donors and glyoxylate imines.

Table 2.17 ant/ -Mannich-type reactions of ketone donors and /N/-PMP-protected glyoxylate imine catalyzed by (R)-3-pyrrolidine-carboxylic acid (18). 

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