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

Abstract

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 (CH 2N(O)H) and acrolein (CH 2CHCHO) in the presence of BH 3 or BF 3 catalyst. Although the nitrone/BH 3 complex is predominantly formed at the early stage of the reaction, the acrolein/BH 3 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 BF 3 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.