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 alpha,b eta -unsaturated carbonyl compounds is reported. Ab initio calculation usin g 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 for med at the early stage of the reaction, the acrolein/BH3 complex as minor c ontributor shows high rate acceleration giving the electronically controlle d endo-isoxazolidine-4-carbaldehyde complex as the major regio- and stereoi someric cycloadduct. On the other hand, the nitrone cycloaddition reaction of acrolein in the presence of BF3 leads to the formation of the correspond ing Michael adduct complex intermediate which then cyclizes to the isoxazol idine-4-carbaldehyde complex. These calculation studies indicate that the n itrone cycloadditions with electron-deficient alkenes may proceed through a stepwise mechanism when catalyzed by a strong Lewis acid. (C) 2001 Elsevie r Science Ltd. All rights reserved.