Synthesis Of Siloxy-Alpha-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.