Highly diastereo- and enantioselective direct aldol reactions of aldehydes and ketones catalyzed by siloxyproline in the presence of water

Seiji Aratake, Takahiko Itoh, Tsubasa Okano, Norio Nagae, Tatsunobu Sumiya, Mitsuru Shoji, Yujiro Hayashi

Research output: Contribution to journalArticlepeer-review

157 Citations (Scopus)

Abstract

Proline-based organocatalysts have been developed for a highly enantioselective, direct aldol reaction of aldehydes and ketones in the presence of water. While several surfactant-proline combined catalysts have proved effective, proline derivatives with a hydrophobic moiety such as rraw-siloxy-L-proline and cis-siloxy-D-proline, both of which are easily prepared from the same commercially available 4-hydroxy-L-proline. have been found to be the most effective organocatalysts examined in this study, affording the aldol product with excellent diastereo- and enantioselectivities, these two catalysts generating opposite enantiomers. Water affects the selectivity, and poor results are obtained under neat reaction conditions or in dry organic solvents. More than three equivalents of water are required for the best diastereo- and enantioselectivities. while three equivalents is the recommended amount from a synthetic point of view. The reaction proceeds in the organic phase, and also proceeds in the presence of a large amount of water. The large-scale preparation of aldols with the minimal use of an organic solvent, including in the purification step. is described.

Original languageEnglish
Pages (from-to)10246-10256
Number of pages11
JournalChemistry - A European Journal
Volume13
Issue number36
DOIs
Publication statusPublished - 2007
Externally publishedYes

Keywords

  • Aldol reaction
  • Asymmetric synthesis
  • Organocatalysis
  • Proline
  • Sustainable chemistry
  • Water

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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