Propanal → HCID 11389404, compound

HRID 1983437Notes

Reaction equation

HRID 1983437 reaction equation
[CH:1](=O)[CH2:2][CH3:3].C(=[O:10])CC(C)C.N1CCC[C@H]1C(O)=O.[CH:19](=[O:23])[CH:20]([CH3:22])[CH3:21]>>[OH:23][C@@H:19]([CH:2]([CH3:3])[CH3:1])[C@H:20]([CH3:22])[CH:21]=[O:10]

Participants

5

Reactant 4

HCID 527Propanal2×HCID 6561IsobutyraldehydeHCID 115523-MethylbutanalHCID 145742L-Proline

Product 1

HCID 11389404HCID 11389404, compoundYield 82%

Procedure

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 antidiastereoselectivity.

Workup

  1. customwas obtained in 88% yield and 97% ee
  2. customto provide a single regioisomer despite the fact that both the aldol donor
  3. customEntries 5-7, corresponding to Examples 5-7, indicate that the aldol reaction
  4. customwere 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)
  5. customthe preparative utility of the reaction

Sources & evidence

ORD record
ord-4abc0ec01b534436b8cf5345d9ce1f95
Source dataset
uspto-grants-2009_06
Patent number
US07541456B2

Reaction notes

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