General, robust, and stereocomplementary preparation of β-ketoester enol tosylates as cross-coupling partners utilizing TsCl-N-methylimidazole agents

We have developed a general, robust, and cost-effective method for the (E)- or (2)-stereocomplementary enol tosylation of ss-ketoesters using TsCl-N-methylimidazole (NMI)-Et3N or LiOH. TsCl coupled with NMI formed a highly reactive N-sulfonylammonium intermediate. Stereocongested secondary alcohols were smoothly sulfonylated using Ts(Ms)Cl-NMI-Et3N. ss-Ketoesters underwent (E)-selective tosylation using TsCl-NMI-Et3N and (2)-selective tosylation using TsCl-NMI-LiOH (total of 23 examples; 60%-99% yield). Stereoretentive Negishi and Sonogashira couplings using enol tosylates proceeded successfully to give trisubstituted alpha, beta-unsaturated esters.