Development of the First Spiro Bis(isoxazoline)Ligands (SPRIXs) and Their Applications to Catalytic Enantioselective Reactions

Abstract

The first chiral isoxazoline ligands bearing spiro skeleton are developed. The spiro bis(isoxazoline) ligands (SPRIXs) are readily synthesized from diethyl malonate via double intramolecular nitrile oxide cycloaddition as a key step. The complex of (M, S, S)-R-SPRIX and Pd(OCOCF3)2 promoted the catalytic asymmetric Wacker-type cyclization of alkenyl alcohols to give optically active cyclic ethers for the first time. Furthermore, starting from dialkenyl alcohol, the enantioselective tandem cyclization via oxy-palladation was achieved with up to 95% ee. Asymmetric ligands other than SPRIKs promote neither the Wacker-type reaction nor the tandem reaction.