(E)-,(Z)-Stereodefined alpha-Chloro-beta-tosyloxy-alpha,beta-unsaturated Esters: Sequential Cross-couplings for (E)-,(Z)-Stereo complementary Synthesis of Fully-substituted alpha,beta-Unsaturated Esters

An (E)-, (Z)-stereocomplementary synthesis of fully-substituted alpha,beta-unsaturated esters has been developed. The present method involves sequential cross-coupling reactions of readily available (E)-, (Z)-stereodefined alpha-chloro-beta-tosyloxy-alpha,beta-unsaturated esters, which were obtained by (Z)- and (E)-stereocomplementary enol tosylation of methyl alpha-chloro-beta-oxoesters using novel reagents, TsCl-NaH-TMEDA(-LiCl) for Z and TsCl-iPr(2)NEt-N-methylimidazole for E. The first highly chemoselective and stereoretentive Suzuki-Miyaura cross-couplings proceeded smoothly at the beta-TsO-position of (E)- and (Z)-alpha-chloro-beta-tosyloxy-alpha,beta-unsaturated esters to afford (Z)- and (E)-beta-aryl(Ar)-alpha-chloroacrylates, respectively by an accessible [Pd(OAc)(2)-PPh3-K2CO3] catalysis (4 examples: 89-94% yield). Subsequent highly stereoretentive Suzuki-Miyaura cross-couplings using the obtained (Z)- and (E)-acrylates were successfully performed by a reactive [Pd(OAc)(2)-SPhos-K2CO3] catalysis to produce a number of (E)- and (Z)- beta-aryl(Ar)-alpha-aryl'(Ar-1) and beta-aryl(Ar)-alpha-n-hexyl acrylates (24 examples, 62-94 %). As a distinct extension, (Z)- and (E)-beta-(p-tolyl)-alpha-chloroacrylate served as appropriate partners for (E)- and (Z)-stereoretentive Sonogashira, Mizoroki-Heck, and Buchwald-Hartwig cross-couplings, which afforded the corresponding enyne, diene, and alpha-aminoolefin types of fully-substituted alpha,beta-unsaturated esters (6 examples: 52-75% yield).