Regioselective 1,4-Addition of P(O)–H Species to In Situ-Formed 1-Benzopyrylium Ion from C3-Substituted 2H-Chromene Hemiketals to Construct C3-Functionalized C4-Phosphorylated 4H-Chromenes

Herein, we report the first example that P(O)-H species including H-phosphonates and H-phosphine oxides could participate in a highly regioselective 1,4-addition to in situ generated 1-benzopyrylium ion from C3-substituted 2H-chromene hemiketals, which provides a brand-new and effective approach for the synthesis of C4-phosphorylated 4H-chromenes with diverse C3-functionality (ketone, ester, sulfonyl, aryl, and alkyl groups). In total, the reaction features the use of inexpensive Zn(ClO₄)₂·6H₂O as a catalyst, low catalyst loading (only 5 mol %), mild reaction conditions (60 °C, 10 min to 24 h), and broad substrate scope (46 examples) as well as good to high yields (>90% yield on average). More importantly, mechanistic experiments demonstrated the essential role of the C3-substituent on 2H-chromene hemiketals in stabilizing the in situ generated 1-benzopyrylium ion and the regioselective 1,4-addition control.