Organocatalyzed Mannich Reaction of Aldehydes with N-Boc-Imines

Significance

A highly efficient and enantioselective proline-catalyzed Mannich reaction of aldehydes 1 with preformed aromatic N-Boc-imines 2 to give β-amino aldehydes 3 is reported. Mannich products 3 are obtained in high yields and with excellent diastereoselectivities and enantioselectivities and can easily be converted into the corresponding α,β-branched-β-amino acids 4 without loss of stereochemical integrity. The β-amino aldehydes 3 either directly precipitate from the reaction mixture and are collected by filtration or are isolated after aqueous workup and trituration with hexanes. An example using a ketone as nucleophile is also given in this manuscript, while the reaction employing a different ketone has been independently described by D. Enders et al. (Synthesis 2006, 2155-2158; Synthesis 2006, 3597-3604).