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Synthesis 2005(1): 39-46  
DOI: 10.1055/s-2004-834910
PAPER
© Georg Thieme Verlag Stuttgart · New York

Friedel-Crafts Cyclization of 1,1-Difluoroalk-1-enes: Synthesis of Benzene-Fused Cyclic Ketones via α-Fluorocarbocations

Junji Ichikawa*a, Hideharu Jyonob, Takao Kudob, Masaki Fujiwaraa, Misaki Yokotaa
a Department of Chemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Fax: +81(3)58414345; e-Mail: junji@chem.s.u-tokyo.ac.jp;
b Department of Applied Chemistry, Kyushu Institute of Technology, Sensui-cho, Tobata, Kitakyushu 804-8550, Japan
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Publikationsverlauf

Received 10 August 2004
Publikationsdatum:
17. November 2004 (online)

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Abstract

1,1-Difluoroalk-1-enes bearing a phenyl group at the C-3, -4, or -5 position, readily obtained from 2,2,2-trifluoroethyl p-toluenesulfonate, are treated with FSO3H·SbF5 to undergo Friedel-Crafts cyclization in (CF3)2CHOH. The cyclization takes place via α-fluorocarbocations, followed by spontaneous hydrolysis of the C-F bond to afford bicyclic ketones including a five, six, or seven-membered ring in good yield.

Key words

Friedel-Crafts cyclization - difluoroalkene - bicyclic ketone - α-fluorocarbocation - fluoroalcohol solvent

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13

The configuration of 1h was assigned by 1H NMR measurement. The 1H NMR spectrum for the major isomer of 1h exhibits a large geminal coupling constant (J gem = 13.4 Hz) between the protons Hax and Heq at C-3. Hax is coupled to the C-2 and C-4 protons with coupling constant values of 11.3 Hz and 4.6 Hz, which are consistent with typical axial-axial and axial-equatorial values, respectively. In the 1H NMR spectrum of the minor isomer of 1h, two large axial-axial coupling constants are observed between the C-3 axial proton and the C-2 proton and between the C-3 axial proton and the C-4 proton (J 32 = 14.0 Hz, J 34 = 11.9 Hz). Moreover, the observed NOEs between the C-2 axial proton and the methyl proton of the major isomer and between the C-2 axial proton and the C-4 axial proton of the minor isomer support this assignment. Stereochemistry was assigned for 2g on the basis of the proton coupling constants in a similar manner.

14

Vinyl fluoride 14 (X = F) was not detected by 19F NMR measurement of the reaction mixture.