DFT Investigation of the Diastereoselectivity of the MX₂ and MX₃ Lewis-Acid-Catalyzed Mukaiyama Aldol Reaction between C,O,O-Tris(trimethylsilyl)ketene Acetal and Aldehydes

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 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.

Structural Characterization, DFT Calculation, NCI, Scan-Rate Analysis and Antifungal Activity against Botrytis cinerea of (E)-2-{[(2-Aminopyridin-2-yl)imino]-methyl}-4,6-di-tert-butylphenol (Pyridine Schiff Base)

“…L1 geometry was obtained from the B3LYP hybrid exchange/correlation (XC) functional and Gaussian basis set 6-311+G (2d,p) [ 46 , 47 ]. The geometrical parameters agree with the X-ray crystallographic data [ 34 ].…”