Reactivity, Stereo- And Regioselectivity of Diels-Alder Reactions Between Five-Membered Heterocycles and Danishefsky's Diene

Abstract

Conceptual density functional theory (chemical hardness η, electronic chemical potential µ, global and local electrophilicity index ω and ω k , Fukui function f + k) is used to predict reactivity, stereo-and regioselectivity of the Diels-Alder (DA) reaction between 2-nitropyrrole and its 1tosylated derivative with Danishefsky's diene to yield 5-hydroxyindoles. A detailed mechanistic study of various possible reaction channels is done by DFT [B3LYP/6-31G(d)] calculations. Solvent effects (benzene) are taken into account by the CPCM bulk solvation model. In principle, the nitropyrrole can either act as diene involving the nitro group (hetero Diels-Alder reaction, HAD) or alternatively as alkene in a "normal" Diels-Alder reaction. The experimentally observed product 5-hydroxy-1-tosylindole can be formed either directly by Diels-Alder reaction of the nitropyrrole acting as alkene or by rearrangement of the dihydrooxazine N-oxides. The primary cycloadduct with the nitropyrrole acting as alkene is found to be unstable reacting further by extrusion of nitrous acid to 5-hydroxyindole. Finally, the results are compared with those obtained for the analogous furans, thiophenes, and selenophenes.