ChemInform Abstract: Highly Enantioselective Synthesis of 3‐Substituted Furanones by Palladium‐Catalyzed Kinetic Resolution of Unsymmetrical Allyl Acetates.

Abstract

The Pd-catalyzed asymmetric allylic alkylation (AAA) holds a prominent position among the most versatile methods for C C bond formation that are widely applied in natural product synthesis. This transformation typically features broad functional group tolerance and excellent regioand enantioselectivity. In particular, Pd-catalyzed kinetic resolutions of symmetrical allylic substrates and dynamic kinetic transformations have been developed recently, which extends their potential in synthetic chemistry. However, Pd-catalyzed kinetic resolutions of unsymmetrical acyclic allylic substrates with high yield and enantioselectivity are rare. Furthermore, the enantioselective allylic alkylation of silyl enol ethers is still a challenging reaction. Graening and Hartwig reported a highly enantioselective alkylation of monosubstituted allylic substrates with silyl enol ethers catalyzed by an Ir complex. Although excellent results of allylic alkylations have been reported with enolates that are preformed or generated in situ, to the best of our knowledge, Pd-catalyzed AAAwith a nonstabilized silyl enol ether as nucleophile remains an elusive goal (Scheme 1). Herein, we present the Pd-catalyzed kinetic resolution of 1,3-disubstituted unsymmetrical allylic substrates with nonstabilized silyl enol ethers as nucleophiles, which provides a highly regioand enantioselective synthesis of 3-substituted g-butenolides. The g-butyrolactone skeleton is present in more than 13000 natural products, which have attracted considerable attention because of the range of important biological activities associated with this class of compounds. As part of our program to develop catalytic enantioselective methods to access optically active g-butenolides and lactones, we envisioned the possibility of using 2-trimethylsilyloxyfuran (TMSOF) as nucleophile in a Pd-catalyzed AAA reaction. Initially, we examined the allylic substitution of carbonate 1a by utilizing TMSOFas nucleophile and a chiral Pd catalyst based on Trost Ligand L1 (Table 1, entry 1). The 3-substituted product 3 and 5-substituted product 4 were obtained in a 2:1 ratio and in 36% ee for product 3 (Table 1, entry 1). Using a lower temperature (0 8C), the ee value only slightly increased (49% ee, Table 1, entry 2). With tert-butyl carbonate as the leaving group, the regioselectivity shifted in favor of the formation of the 5-substituted product (3/4= 1:2, Table 1,