Role of water in mukaiyama-aldol reaction catalyzed by lanthanide Lewis acid: A computational study

Miho Hatanaka, Keiji Morokuma

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)


Carbon-carbon bond formations, such as Kobayashi modification of the Mukaiyama-Aldol reaction, catalyzed by lanthanide (Ln) Lewis acid in aqueous solution comprise one of the most attractive types of reactions in terms of green chemistry. However, their detailed mechanisms and the role of water molecules remained unclear. In order to explore complex potential energy surfaces for the water and substrate coordination around Eu3+ as well as the detailed mechanism of the Mukaiyama-Aldol reaction between trimethylsilyl (TMS) cylcohexenolate and benzaldehyde (BA) catalyzed by Eu 3+, the recently developed anharmonic downward distortion following (ADDF) and artificial force-induced reaction (AFIR) methods were used with the B3LYP-D3 theory. The most favorable water coordination structures are Eu 3+(H2O)8 and Eu3+(H 2O)9; they are comparable in free energy and are likely to coexist, with an effective coordination number of 8.3. Eu3+(H 2O)8(BA) is the best aldehyde coordinated structure. Starting with this complex, the Mukaiyama-Aldol reaction proceeds via a stepwise mechanism, first C-C bond formation between the substrates, followed by proton transfer from water to BA and then TMS dissociation caused by nucleophilic attack by bulk water molecules. Why did the yield of the Mukaiyama-Aldol reaction catalyzed by Ln3+ in organic solvent dramatically increase upon addition of water? Without water, the reverse reaction (C-C cleavage) takes place easily. Why did this reaction show syn-preference in water? The anti transition state for C-C formation in water is entropically less favored relative to the syn transition state because of the existence of a rigid hydrogen bond between the TMS part and coordination water around Eu3+ in the former.

Original languageEnglish
Pages (from-to)13972-13979
Number of pages8
JournalJournal of the American Chemical Society
Issue number37
Publication statusPublished - 2013 Sept 18
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry


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