Efficient Formation of Ring Structures Utilizing Multisite Activation by Indium Catalysis

• Published in: Journal of the American Chemical Society Vol. 130; no. 50; pp. 17161 - 17167
• Main Authors: Itoh, Yoshimitsu, Tsuji, Hayato, Yamagata, Ken-ichi, Endo, Kohei, Tanaka, Iku, Nakamura, Masaharu, Nakamura, Eiichi
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 17.12.2008; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; UNACTIVATED ALKYNES; BETA-KETOESTERS; ACTIVE METHYLENE-COMPOUNDS; 1,3-DICARBONYL COMPOUNDS; CARBONYL-COMPOUNDS; BIFUNCTIONAL CHAIN MOLECULES; CLOSING METATHESIS; METHINE COMPOUNDS; CONIA-ENE REACTION; MEDIUM-SIZED RINGS
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja805657h

Lewis acidic indium(III) salts, in particular In(NTf2)3, effect the conversion of α-(ω′-alkynyl)-β-ketoesters and ω-alkynyl-β-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 β-ketoester substrate containing an acetylene function. The indium metal activates the β-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.