Selective Lewis Acid Catalyzed Assembly of Phosphonomethyl Ethers: Three-Step Synthesis of Tenofovir

Organic Letters 17(4), 820-823, DOI: 10.1021/ol503612h

Described herein is a novel Lewis acid catalyzed rearrangement−coupling of oxygen heterocycles and bis (diethylamino)chlorophosphine that provides direct formation of the phosphonomethyl ether functionality found in several important antiretroviral agents. A wide range of dioxolanes and 1,3-dioxanes may be employed, furnishing the desired products in good yield. The utility of this method is demonstrated in a novel synthesis of tenofovir, an antiretroviral drug used in the treatment of HIV/AIDS and hepatitis B.