DFT Investigation of the Diastereoselectivity of the MX 2 and MX 3 Lewis-Acid-Catalyzed Mukaiyama Aldol Reaction between C,O,O-Tris(trimethylsilyl)ketene Acetal and Aldehydes

Benoît Champagne, Hadj Mohamed Slim, Mahmoud Trabelsi

Research output: Contribution to journalArticlepeer-review

Abstract

The kinetics and diastereoselectivity of the Mukaiyama aldol reaction between C,O,O-tris(trimethylsilyl)ketene acetal and aldehydes bearing alkyl, vinyl, and aromatic substituents is influenced by the nature of Lewis acid catalysts. A density functional theory investigation using the M06-2X exchange-correlation functional and the PCM scheme to account for solvent effects has been carried out to characterize the structure and energetics of the transition state when the Lewis acid is ZnBr2 (MX2) or GaCl3 (MX3) in comparison to the uncatalyzed reaction. The main observations are that (i) the pro-syn transition states are always more stable than the pro-anti ones; (ii) for MX2, the transition state presents a cyclic structure, whereas it is open for MX3, owing to steric interactions; (iii) the difference of activation free enthalpy between the pro-anti and pro-syn transition states decreases when the reaction is catalyzed, by either MX2 or MX3, demonstrating a reduction of the diastereoselectivity with respect to the uncatalyzed reaction; (iv) this decrease of diastereoselectivity is larger for MX3- than for MX2-catalyzed reactions; and (v) the MX3-catalyzed reactions are kinetically favored by 1-2 kcal mol-1 with respect to the MX2 ones.
Original languageEnglish
Pages (from-to)1938-1947
Number of pages10
JournalJournal of physical chemistry A
Volume122
Issue number8
DOIs
Publication statusPublished - 1 Mar 2018

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