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

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Vol. 122; no. 8; pp. 1938 - 1947
• Main Authors: Mohamed, Slim Hadj, Champagne, Benoît, Trabelsi, Mahmoud
• Format: Journal Article
• Language: English
• Published: United States 01.03.2018
• ISSN: 1089-5639; 1520-5215
• DOI: 10.1021/acs.jpca.7b11186

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 ZnBr (MX ) or GaCl (MX ) 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 MX , the transition state presents a cyclic structure, whereas it is open for MX , 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 MX or MX , demonstrating a reduction of the diastereoselectivity with respect to the uncatalyzed reaction; (iv) this decrease of diastereoselectivity is larger for MX - than for MX -catalyzed reactions; and (v) the MX -catalyzed reactions are kinetically favored by 1-2 kcal mol with respect to the MX ones.