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

Hidefumi Nakatsuji; Kanako Ueno; Tomonori Misaki; Yoo Tanabe

doi:10.1021/ol800480d

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

Org Lett. 2008 Jun 5;10(11):2131-4. doi: 10.1021/ol800480d. Epub 2008 May 9.

Authors

Hidefumi Nakatsuji¹, Kanako Ueno, Tomonori Misaki, Yoo Tanabe

Affiliation

¹ Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo, Japan.

PMID: 18465867
DOI: 10.1021/ol800480d

Abstract

We have developed a general, robust, and cost-effective method for the (E)- or (Z)-stereocomplementary enol tosylation of beta-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. beta-Ketoesters underwent (E)-selective tosylation using TsCl-NMI-Et3N and (Z)-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.