Synthesis of chromeno[2,3-b]carbazole and chromeno[3,2-f]indazole derivatives. A new class of indole- and pyrazole-fused polycyclic compounds using o-quinodimethane chemistry. A reactivity and regioselectivity computational study

Abstract

An efficient route to the new classes of derivatives tetrahydrochromeno[2, 3-b]carbazoles and tetrahydrochromeno[3,2-f]indazoles has been developed. The cycloaddition reactions of chromones 3 and 4 with indole-o-quinodimethane 2 gave a diastereomeric mixture of Diels-Alder cycloadducts 5-8 in good yields, whereas the corresponding reactions of chromones 3 with pyrazole-o- quinodimethane 10 were more regioselective giving only cycloadducts 11 and 12 along with a small amount of the oxidation product 14, which, however, was the main reaction product in the case of formylchromone. Frontier Molecular Orbital theory (FMO) predicted in all cases a HOMO(QDM)-LUMO (chromone) controlled reaction. The observed regioselectivity was explained on account of the Δc difference in absolute values of the p z orbital coefficients of the terminal reacting atoms in HOMO and LUMO, and also from the activation parameters calculated after locating the several transition states (TS) involved. The structure of all new compounds was confirmed by using 1D and 2D NMR data (COSY H-H, NOESY H-H, COSY C-H and COLOC C-H), ms and elemental analysis. Full assignment of all 1H and 13C NMR chemical shifts has been unambiguously achieved. ©ARKAT USA, Inc.