Background: Hexahydro-2H-pyrano[3,2-c]quinolines are known to have antibacterial, antifungal, and
antitumor properties. Great efforts have been made to develop new synthetic methods that lead to the synthesis of
valuable libraries. Extensive methodologies, low yields, excessive amounts of catalyst and expensive reactants
are some of the limitations of current methodologies.
Aims and Objective: Developing a useful and efficient method to construct diversely substituted hexahydro-2Hpyrano[
3,2-c]quinolines into good to excellent yields through a cationic imino-Diels-Alder/N-debenzylation
Method: The cationic imino-Diels-Alder/N-debenzylation methodology was used for the preparation of substituted
hexahydro-2H-pyrano[3,2-c]quinolines. It involves the use of Sc(OTf)3 for activation of cationic imino-
Diels-Alder cycloaddition reaction of N-benzylanilines, 3,4-dihydro-2H-pyran and paraformaldehyde in MeCN;
and microwave irradiation to shorten reaction time to afford new 6-benzyl-hexahydro-2H-pyrano[3,2-
c]quinolines whose catalytic transfer debenzylation reactions with HCO2NH4 in the presence of Pd/C (10%) and
methanol give the new 5-unsubstituted pyrano[3,2-c]quinolines in excellent yields.
Results: We found that optimal conditions for the preparation of hexahydro-2H-pyrano[3,2-c]quinolines were
Sc(OTf)3 0.5 % and acetonitrile at 160°C for 15 min; and using paraformaldehyde obtained the 6-benzylhexahydro-
2H-pyrano [3,2-c]quinolines with excellent yields, while the N-debenzylation process using ammonium
formate in the presence of Pd/C and methanol resulted in the synthesis of hexahydro-2H-pyrano [3,2-c] quinolines
with quantitative yields (95-98%).
Conclusion: We describe an efficient method to synthesize hexahydro-2H-pyrano[3,2-c]quinolines via the cationic
imino-Diels-Alder/N-debenzylation methodology using Sc(OTf)3 0.5 % as Lewis Acid catalyst. Excellent
yields of the products, use of MW irradiation, short times of reactions, and an efficient and highly diversified
method are some of the main advantages of this new protocol.