L. Basset et al. / Tetrahedron Letters 49 (2008) 1551–1554
1553
ortho-substituted aniline yielded only one conformer
(methyl and tosyl groups in anti conformation),4 meta-
substituted aniline yielded syn and anti conformers in
almost the same ratio (entries 10 and 11).
The fluorination of N-tosyl-5-aminoindan (entry 13)
confirmed the ability to use such a technology to access
polycyclic fluorinated building blocks.
O
O
S
N
H
H
In summary, the reaction of N-tosyl-para-substituted
anilines in the presence of PIDA and PPHF was studied
and afforded an easy access to new 4-fluorinated cyclo-
hexa-2,5-dienimines.
F
Scheme 1.5
This reaction is a novel example of the great scope of the
hypervalent iodine compounds in organic synthesis.
Furthermore, this investigation sets the stage for the appli-
cation to more elaborated substrates and makes this tech-
nology an attractive route to synthetic, highly valued
fluorinated building blocks.
tion to N-para position and/or N-iodophenylation of ace-
tanilides was observed.8 Furthermore, no reaction occurred
with 4-tert-butylacetanilide in the presence of PIFA and
Et3NÁ3HF in CH2Cl2 at room temperature and only 4-flu-
oroacetaniline was obtained in a modest yield after one day
at reflux.9
References and notes
The presence of
a
more electron withdrawing
group such as tosyl makes sulfonamides weak organic
acids, with a pKa in the region of that of phenols.10 As a
result the following mechanism could be proposed:
(Scheme 2).
1. (a) Cartwright, D. In Organofluorine Chemistry: Principles and
Commercial Applications; Banks, R. E., Smart, B. E., Taltow, J. C.,
Eds.; Plenum: New York, 1994; p 237; (b) Mann J. Chem. Soc. Rev.
1987, 16, 346–381; (c) Welch, J. T. Tetrahedron 1987, 43, 3123–3197;
´
´
(d) Begue, J. P.; Bonnet-Delpon, D. Tetrahedron 1991, 47, 207–3258;
(e) Resnati, G.; Soloshonok, V. A. Tetrahedron 1996, 52, 1–330.
Tetrahedron Symposia-in-Print No. 58; (f) Isanbor, C.; O’Hagen, D.
It implies the reaction of the hypervalent iodine deriva-
tive with nitrogen atom, the resulting intermediate being
trapped by the nucleophilic fluoride ion.
However, we cannot exclude the mechanism proposed
by Langlois co-workers9 in which the initial binding of
the hypervalent iodine compound occurred on an oxygen
atom of the sulfonamide moiety.
Substitution on the para position of the aromatic moiety
was also studied. The presence of an electron withdrawing
substituent prevented from any reaction (entry 8) whereas
substitution with an electron donating group (except with
the more oxidizable and bulkiest bromine atom) made this
reaction easier (entries 3–7).
It must be also noticed that substitution at the ortho
position of tosylated anilines clearly disfavoured the
reaction yield probably due to steric effect, which was con-
firmed by the absence of reaction starting from di-ortho-
substituted aniline (entry 12).
´
´
J. Fluorine Chem. 2006, 127, 303–319; (g) Begue, J. P.; Bonnet-
Delpon, D. Chimie Bioorganique et Me´dicinale du Fluor; Eds, EDP
Sciences; CNRS Editions, 2005.
2. (a) Karam, O.; Jacquesy, J. C.; Jouannetaud, M. P. Tetrahedron Lett.
1994, 35, 2541–2544; (b) Martin, A.; Jouannetaud, M. P.; Jacquesy, J.
C.; Cousson, A. Tetrahedron Lett. 1996, 37, 43. pp. 7735–7738; (c)
Karam, O.; Martin, A.; Jouannetaud, M. P.; Jacquesy, J. C.;
Cousson, A. Tetrahedron Lett. 1999, 40, 4186–4193; (d) Karam, O.;
Martin, A.; Jouannetaud, M. P.; Jacquesy, J. C.; Cousson, A.
Tetrahedron 2004, 60, 6629–6638.
3. (a) Zawada, P. V.; Banfield, S. C.; Kerr, M. A. Synlett 2003, 7, 971–
974; (b) Wells, G.; Berry, J. M.; Bradshaw, T. D.; Buerger, A. M.;
Seaton, A.; Wang, B.; Westwell, A. D.; Stevens, M. F. G. J. Med.
Chem. 2003, 46, 532–541.
4. Selected spectral data: Product entry 5: 1H NMR (300 MHz, CDCl3,
TMS as an internal standard): d 6.44 (dd, J = 10.1 Hz, J = 2.3 Hz,
1H), 6.70–6.78 (m, 2H), 7.26 (s, 3H), 7.37 (d, J = 8.0 Hz, 2H), 7.74
(dd, J = 10.1 Hz, J = 2.3 Hz, 1H), 7.88 (d, J = 8.3 Hz, 2H). 13C NMR
(75 MHz, CDCl3): d 21.6, 109.4 (t, J = 225 Hz), 124.6 (t, J = 9 Hz),
127.5, 132.9, 133.1 (t, J = 9 Hz), 135.7 (t, J = 25 Hz), 136.1 (t,
J = 25 Hz), 136.9, 144.7, 160.9 (t, J = 5 Hz). 19F {H} NMR
(282 MHz, CDCl3 external standard C6F6 (dF—162.90)): d À97.1.
Steric influence of the substitution was also demon-
strated after the submission of the ortho and meta methyl
substituted anilines on reaction conditions: while mono-
I
Ts
Ts
H
Ts
CH3COO
PhI(OCOCH3)2
N
N
N
-
- CH3CO2
- CH3CO2H
- PhI
F
-
F
Scheme 2.