Organocatalytic synthesis of enantiopure spiro acenaphthyl-pyrrolizidine/pyrrolidines: justifying the regioselectivity based on a distortion/interaction model.

An efficient organocatalytic [3 + 2] reaction with Schreiner's thiourea organocatalyst for the synthesis of a small library of novel enantiopure stable spiroacenaphthyl-pyrrolidines/pyrrolizidines with high regio- and diastereoselectivity (up to 99%) is described for the first time. These chiral compounds were synthesized by a three-component 1,3-dipolar cycloaddition of (E)-1-(2-oxoacenaphthylen-1(2H)-ylidene) pyrrolidin-1-ium-2-ide as a dipolar and (S)-cinnamoyl/crotonoyl oxazolidinone as a dipolarophile. The absolute configuration of cycloadducts was confirmed by X-ray diffraction analysis. The origin of catalyst reactivity and regio- and stereoselectivity was investigated through DFT calculations. DFT calculations showed that the regioselectivity was controlled by the distortion (deformation) of reactants and Schreiner's thiourea acts as a LUMO-lowering catalyst.