Efficient formation of ring structures utilizing multisite activation by indium catalysis.
Lewis acidic indium(III) salts, in particular In(NTf(2))(3), effect the conversion of alpha-(omega'-alkynyl)-beta-ketoesters and omega-alkynyl-beta-ketoesters to the corresponding cyclic products in a manner known as the Conia-ene reaction. This reaction can lead to the creation of five- to fifteen-membered-ring carbocycles and heterocycles in good to excellent yields. The synthetic features of the reaction are a relatively low catalyst loading, as low as 0.01 mol % in the best case, as well as no requirement of solvent for five-membered-ring formation and the requirement of only moderately dilute reaction conditions for medium-sized-ring formation. The high reactivity of indium salts is due to the double activation of the beta-ketoester substrate containing an acetylene function. The indium metal activates the beta-ketoester moiety by the formation of an indium enolate, and this indium metal electrophilically activates the alkyne moiety. Such a strong push-pull activation of the substrate by a single metal circumvents the disadvantage of entropic and enthalpic factors generally associated with the formation of medium- and large-sized rings. The reaction allows the ready formation of a fifteen-membered-ring carbocycle, from which dl-muscone has been synthesized.
Itoh
Yoshimitsu
Y
Department of Chemistry, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Tsuji
Hayato
H
Yamagata
Ken-ichi
K
Endo
Kohei
K
Tanaka
Iku
I
Nakamura
Masaharu
M
Nakamura
Eiichi
E