N-PEGylated (L)-Prolinamide: A Homogeneous, Solvent-Free, and Recyclable Catalyst for Scalable Enantioselective Aldol Reaction

The unique physicochemical properties of PEG-400 were imparted to (L)-prolinamide to afford a homogeneous, solvent-free, recyclable organocatalyst for scalable enantioselective aldol reaction between acetone and benzaldehyde to afford (R)-4-hydroxy-4-phenylbutan-2-one. The reaction was scaled up to afford 41 g of ketol in 95% yield and an ee of 91% using 30 mol% catalyst, 10 mol% trifluoroacetic acid (TFA), and 135 equivalent moles of acetone with respect to benzaldehyde. The catalyst was recycled 4 times with no obvious loss of activity. The role of PEG is discussed at the molecular level. This type of catalyst may provide new possibilities for the so-far-thwarted attempts at large-scale application of proline organocatalysis to asymmetric aldol reactions.