Synthesis of siloxy-α-lapachone derivatives by chemo- and regioselective Diels-Alder reactions of 3-methylene-1,2,4-naphthotriones with silyl enol ethers

o-Quinone methides, generated in situ from the Knoevenagel condensation of 2-hydroxy-1,4-naphthoquinone with aliphatic and aromatic aldehydes, take part in chemoselective hetero-Diels-Alder reactions with silyl enol ethers to give a series of siloxy-containing naphtho[2,3-b]pyran-5,10-dione (alpha-lapachone) derivatives in moderate to high yield. These reactions regioselectively gave a-lapachone derivatives with an acetal structure. This regioselectivity can be rationalized by considering the frontier molecular orbital interactions of the o-quinone methide with the silyl enol ether, and by taking into account the energetically more favorable pathway leading to a zwitterion-like transition state of lower energy in a Michael addition between the two reactants.