Organocatalytic Asymmetric Mannich Reactions in the Preparation of Enantio-enriched beta(3)-Amino Acid Derivatives

Organocatalytic, asymmetric Mannich reactions giving beta3-amino acid derivatives have been reviewed. The Mannich-type addition of an acetate anion to an imine represents in fact one of the most direct routes to this particular class of beta-amino acids. However, due to the low acidity of simple acetates, synthetic equivalents of acetate anions had to be used. These include preformed enolates (silylketeneacetals), carbonylic compounds with improved reactivity (acetophenones and their enamines/enamides), acetates equipped with a removable group enhancing their acidity (malonates, nitroacetates, sulfonylacetates, diazoacetates), acetates able to undergo decarboxylative enolate formation (malonic acid half thioesters), and finally acetaldehyde. Each of these equivalents was combined with the requisite organocatalytic strategy, giving very powerful and effective methods for the preparation of beta3 -amino acid precursors. The simple and straightforward manipulations, used to convert these products into the target beta3-amino acid compounds, are also described.