Chemoselective and diastereodivergent synthesis of new spirooxindolo-pyrrolizidines and pyrrolidines stemming from unsymmetrical 1,3-bis(arylidene)tetral-2-ones: a combined experimental and theoretical study

Abstract

A theoretical and experimental study of a three-component one-pot cycloaddition reaction involving unstabilized azomethine ylides and unsymmetrical exocyclic dienones featuring a tetralone core was performed. Two new families of highly substituted dispirooxindolo-pyrrolizidine/pyrrolidines were obtained with moderate to good yields. To rationalize the origin of the reactivity difference between the two exocyclic double bonds of the starting dienones, a topological QTAIM (Quantum theory of Atoms in Molecules) analysis study has been performed. To rationalize the observed regio- and stereoselectivity of the [3+2] cycloaddition, a computational approach was realized by means of density functional theory (DFT) at the B3LYP/6-311G(d,p) level of theory. The calculations corroborate the experimental findings. It was demonstrated that the double bond located at the 3-position of the enone scaffold is more reactive than its analogue at the 1-position and that the aforementioned reaction occurs in a chemoselective manner through a two-step mechanism. Moreover, it progresses under kinetic control to offer a mixture of two dispirooxindolo-pyrrolidines/pyrrolizidines with a high diastereomeric excess. The relative stereochemistry of derivative 4k was confirmed by an X-ray crystallography study. The intermolecular N–H–O hydrogen bonding occurring in the difluorinated spiro-compound 4k has been investigated by Hirshfeld surface analysis. Furthermore, the electronic absorption and fluorescence properties of several derivatives have been studied.