Proline-catalysed Mannich reactions of acetaldehyde

摘要: Traditionally, catalysts for organic chemical reactions have been either enzymes or metal complexes. But small molecules, known as organocatalysts, recently burst on to the scene. Organocatalysts are effective in promoting a wide range of useful transformations, including carbon–carbon bond forming process Mannich reaction. frustratingly, these always failed when simplest possible substrate, acetaldehyde, was used. Yang et al. now filled this gap organocatalysis spectrum by establishing catalytic conditions with acetaldehyde. This greatly expands 'toolkit' chemists, and will be especially making chiral, biologically active compounds. paper has market devising organocatalytic expanding chemists. Small molecules emerged third class broadly asymmetric that direct yield predominantly one chiral product, complementing complexes1. For instance, amino acid proline its derivatives activation carbonyl compounds via nucleophilic enamine intermediates. Several important bond-forming reactions, reaction, developed using approach2, all which relevant Remarkably, despite attempts3,4, nucleophiles, could not used way. Here we show acetaldehyde is powerful nucleophile asymmetric, proline-catalysed N-tert-butoxycarbonyl (N-Boc)-imines, yielding β-amino aldehydes extremely high enantioselectivities—desirable products drug intermediates synthesis other molecules. Although biological such aldolases5 thiamine-dependent enzymes6, also employed indirectly7,8,9, use an inexpensive versatile two-carbon small-molecule catalysis find many practical applications.