Synthesis of Medium-Sized Cyclic Ethers by Endo-Selective Pd(0)/B(C6F5)3-Catalyzed Hydroalkoxylation of Enynols and Enynedi- ols

Medium-sized cyclic ethers are present in many natural products and therapeutic agents. Herein we describe a mild catalytic method for the synthesis of 6-to-8-membered oxacycles by endo-selective hydroalkoxylation of enynols and enynediols. The utility of this method is demonstrated through the total synthesis of (±)-Corypsoriol D and E. Experimental and computational mechanistic studies re- vealed a syn-outer-sphere proton transfer mechanism involving a rate-determining reductive elimination.