Superacid-catalyzed intramolecular cyclization reaction of arylcyanopropionate: geminal substitution effect on superelectrophilicity.
We present superacid-catalyzed intramolecular cyclization reactions of arylcyanopropionates to give cyclized five- and six-membered beta-enamino esters in moderate to high yields. Known intramolecular ring-closing reactions of protonated nitrile to aromatic carbon atom are limited to the 6-membered case. Interestingly, a significant synergistic increase of reactivity of the cyano functionality was observed, and the cyano nitrogen atom was converted into an amino group, when an ester group was present in a geminal arrangement. Deuterium exchange experiments excluded the involvement of deprotonation of the alpha-proton in the cyclization process. The acidity dependence of the cyclization reactions and (13)C NMR studies of a model compound, methyl cyanoacetate, in various acidic media were consistent with the involvement of the O, N-diprotonated dication of methyl cyanoacetate, a distonic dication, in strong acid, and this is considered to be the de facto electrophile in the present cyclization reaction of arylcyanopropionates.
Nakamura
Satoshi
S
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Sugimoto
Hiromichi
H
Ohwada
Tomohiko
T
D000143:Acids / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D009682:Magnetic Resonance Spectroscopy; D011422:Propionates / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
D000143:Acids; D011422:Propionates