Ab initio study of Lewis acid catalyzed nitrone cycloaddition to electron deficient alkenes. Does a Lewis acid catalyst change the reaction mechanism?

Theoretical study of Lewis acid catalyzed nitrone cycloadditions to α,β-unsaturated carbonyl compounds is reported. Ab initio calculation using the 6-31++G∗∗ basis set has been applied to the model reaction between the parent nitrone (CH2N(O)H) and acrolein (CH2CHCHO) in the presence of BH3 or BF3 catalyst. Although the nitrone/BH3 complex is predominantly formed at the early stage of the reaction, the acrolein/BH3 complex as minor contributor shows high rate acceleration, giving the electronically controlled endo-isoxazolidine-4-carbaldehyde complex as the major regio- and stereoisomeric cycloadduct. On the other hand, the nitrone cycloaddition reaction of acrolein in the presence of BF3 leads to the formation of the corresponding Michael adduct complex intermediate which then cyclizes to the isoxazolidine-4-carbaldehyde complex. These calculation studies indicate that the nitrone cycloadditions with electron-deficient alkenes may proceed through a stepwise mechanism when catalyzed by a strong Lewis acid.