Iron(III) Chloride Catalyzed Formation of 3,4-Dihydro-2H-pyrans from α-Alkylated 1,3-Dicarbonyls. Selective Synthesis of α- and β-Lapachone.

A mild, catalytic method for the synthesis of 3,4-dihydro-2H-pyrans is described. The FeCl3-catalyzed transformation of aryl- and alkyl β-diketones enables synthetic access to functionalized pyran core structures incorporated in many natural products and biologically active target structures. The method represents a mild alternative to currently available reaction protocols relying on stoichiometric reagents and harsh reaction conditions. This FeCl3-catalyzed transformation has enabled the selective synthesis of α-lapachone in two synthetic transformations and subsequently β-lapachone in three synthetic transformations, which is currently undergoing clinical trials as a potent anticancer agent.