Propanal → HCID 11389404, compound

Participants

Reaction Steps

Entry 2, representing the addition of propionaldehyde to isovaleraldehyde, indicates that the reaction product was obtained in 88% yield and 97% ee. This indicates that the method of the invention is able to provide a single regioisomer despite the fact that both the aldol donor and accept bear enolizable α-methylene protons. Entries 5-7, corresponding to Examples 5-7, indicate that the aldol reaction can tolerate a range of structural variation in the aldehyde donor (R1=Me, n-Bu, Bn, 19:1 to 24:1 anti:syn, 91 to >99% ee). In contrast to proline mediated ketone additions, lower catalyst loadings (10 mol %) and shorter reaction times (11 to 26 hours) were possible without loss in reaction efficiency (Hajos et al. (1974) Org. Chem. 39:1615; Eder et al. (1971) Angew. Chem. 10:496; Agami et al. (1987) Bull. Chim. Soc. Fr. 2:358). Entry 5 also illustrates the preparative utility of the reaction, insofar as the addition of propionaldehyde to isobutyraldehyde was performed on a 25 mmol scale to afford 2.65 g (82% yield) of (2S,3S)-3-hydroxy-2,4-dimethylpentanal in >99% ee with 24:1 anti-diastereoselectivity.

Provenance & Evidence