Oxidations with Fluorous Iodine(III) Reagents
SCHEME 3. A Possible Waste-Free Recycling Protocol
Rf10), Rf12I (1-Rf12),19 trifluoroacetic anhydride, 1-phenyl-1-propanol
(3a), 1-phenylethanol (3b), menthol (3e), propiophenone (4a),
menthone (4e), 2-octanol (3c), cyclooctanol (3d), 2-octanone (4c),
cyclooctanone (4d), acetophenone (4b), acetone-d6, used as re-
ceived. The ∼80% H2O2 was prepared from 30% H2O2 by reducing
the volume 1/2.7 in vacuo at 50 °C20 and standardized by titration
with KMnO4.32
NMR spectra were recorded on standard 400 or 300 MHz FT
spectrometers at ambient temperatures and referenced as follows:
13C, internal acetone-d6 (δ 29.8); 19F, internal C6F6 (δ -162.0).
GC data were acquired using a capillary column (OPTIMA-5-
0.25 µm; 25 m × 0.32 mm). Other instrumentation has been
described in earlier papers.8,17
symmetrical tetraiodides derived from VII (Figure 1) and the
tetraphenylmethane analogue also quantitatively precipitate from
methanol, enabling facile recycling.6a The diiodide derived from
VIII, which is commercially available, can be similarly
recovered.7b Alternatively, IBX can be utilized under solvent-
free conditions, and the insoluble coproduct can be isolated by
filtration and recycled.7a
Rf7I(OCOCF3)2 (2-Rf7). A round-bottom flask was charged with
H2O2 (∼80%; 0.25 mL, 8.00 mmol)20 and cooled to -10 °C. Then
trifluoroacetic anhydride (1.65 mL, 14.9 mmol) was added with
stirring. The cold bath was removed. After 30 min, the mixture
was cooled to -15 °C, and 1-Rf7 (0.45 mL, 0.91 g, 1.83 mmol)
was added with stirring. The mixture was stirred for 3 h at 0 °C
and then allowed to stand for 48 h at 20 °C. The volatiles were
removed by oil pump vacuum (-78 °C trap), and the residue
collected to give 2-Rf7 as a white solid (1.190 g, 1.648 mmol, 97%),
mp 110.0-111.5 °C dec. Anal. Calcd for C11F21IO4: C, 18.28.
Found: C, 17.58.33MS (FAB+, m/Z): 609 (M+-OCOCF3, 30%),
1330 (2M+-OCOCF3,34 100%). IR (cm-1, thin film): υCO 1739
(ms), 1686 (ms); υCF 1212-1069 (vs). NMR (δ, acetone-d6): 13C-
There are several obvious extensions of the preceding
methodology. First, PhI(OCOCH3)2 has been employed in
conjunction with other relay oxidants, one of which is TEMPO.28
A variety of fluorous TEMPO derivatives are now known, and
one has recently been applied in such oxidations of alcohols,
with recovery and reuse for six cycles.29 The combined use of
2-Rfn and a fluorous TEMPO would seem to offer very attractive
possibilities. Second, it can be anticipated that 2-Rfns like other
iodine(III) speciesswill be effective oxidants for a variety of
other functional groups.1a,c,30 In work to date, several nitrogen-
containing compounds have been oxidized in high yields.31
In our opinion, the ultimate extension of this chemistry would
be the sequence illustrated in Scheme 3. As noted in the
Introduction, analogous reagents derived from higher and more
fluorophilic perfluorocarboxylic acids are likely easily synthe-
sized. The coproducts 1-Rfn and Rfn′CO2H might be recycled
together, with dehydration of the latter to give a fluorous
anhydride that could mediate the reoxidation of 1-Rfn by H2O2
(compare to Scheme 1). The next conceptual stepsa functional
group oxidation using H2O2, with water as the only nonrecycled
coproductswould represent the ultimate in atom economy and
a fluorous-based green process worthy of considerable attention.
In summary, this study has shown that fluorous iodine(III)
reagents 2-Rfn with longer ponytails (n ) 7, 8, 10, 12) are easily
prepared from commercially available primary alkyl iodides
1-Rfn. In conjunction with aqueous KBr, they are highly effective
reagents for the oxidations of secondary alcohols to ketones.
No fluorous or organic solvents are required, and reaction times
are shorter than with other types of hypervalent iodide
reagents.6a,9,24 Methanolic workups allow the facile recovery of
the coproducts 1-Rfn by liquid/liquid or solid/liquid phase
separations. These are easily reoxidized to 2-Rfn.
1
2
{1H} (partial) 114.1 (q, JCF ) 287.5 Hz, CF3CO), 160.9 (q, JCF
) 41.2 Hz, CF3CO); 19F -73.67 (s, 6F, CF3CO), -77.79 (t, JFF
4
4
) 15.1 Hz, 2F, CF2I), -78.97 (t, JFF ) 10.0 Hz, 3F, CF3CF2),
-113.42 (m, 2F, CF2), -119.31 (m, 2F, CF2), -119.66 (m, 2F,
CF2), -120.55 (m, 2F, CF2), -124.05 (m, 2F, CF2).35
Rf8I(OCOCF3)2 (2-Rf8). H2O2 (∼80%; 0.25 mL, 8.00 mmol),20
trifluoroacetic anhydride (1.65 mL, 14.9 mmol), and 1-Rf8 (0.50
mL, 1.00 g, 1.83 mmol) were combined in a procedure analogous
to that for 2-Rf7. An identical workup gave 2-Rf8 as a white solid
(1.385 g, 1.795 mmol, 98%), mp 112.0-113.5 °C dec. Anal. Calcd
for C12F23IO4: C, 18.65. Found: C, 18.38. MS (FAB+, m/Z): 659
(M+-OCOCF3,34 50%), 1431 (2M+-OCOCF3, 100%). IR (cm-1
,
thin film): υCO 1741 (ms), 1687 (ms); υCF 1216-1096 (vs). NMR
(δ, acetone-d6): 13C{1H} (partial) 114.1 (q, 1JCF ) 287.3 Hz, CF3-
2
CO), 160.9 (q, JCF ) 41.2 Hz, CF3CO); 19F -73.73 (s, 6F, CF3-
CO), -78.10 (t, 4JFF ) 14.0 Hz, 2F, CF2I), -79.02 (t, 4JFF ) 10.2
Hz, 3F, CF3CF2), -113.44 (m, 2F, CF2), -119.36 (m, 4F, CF2),
-119.71 (m, 2F, CF2), -120.55 (m, 2F, CF2), -124.09 (m, 2F,
CF2).35
R
f10I(OCOCF3)2 (2-Rf10). H2O2 (∼80% 1.19 mL, 38.0 mmol),20
trifluoroacetic anhydride (7.00 mL, 63.2 mmol), and 1-Rf10 (1.182
g, 1.830 mmol) were combined in a procedure analogous to that
for 2-Rf7. An identical workup gave 2-Rf10 as a white solid (1.413
g, 1.620 mmol, 89%), mp 115.0-116.5 °C dec. Anal. Calcd for
C14F27IO4: C, 19.27. Found: C, 18.49.33 MS (FAB+, m/Z): 759
(M+-OCOCF3, 46%), 1631 (2M+-OCOCF3,34 100%). IR (cm-1
,
thin film): υCO 1745 (ms), 1691 (ms); υCF 1216-1096 (vs). NMR
(δ, acetone-d6): 13C{1H} (partial) 114.1 (q, 1JCF ) 287.4 Hz, CF3-
CO), 160.9 (q, JCF ) 41.1 Hz, CF3CO); 19F -73.71 (s, 6F, CF3-
2
CO), -77.77 (t, 4JFF ) 13.3 Hz, 2F, CF2I), -79.04 (t, 4JFF ) 10.1
Experimental Section
General Data. Chemicals were treated as follows: methanol
and CHCl3, distilled; CF3C6F11, Rf7I (1-Rf7), Rf8I (1-Rf8), Rf10I (1-
(32) Huckaba, C. E.; Keyes, F. G. J. Am. Chem. Soc. 1948, 70, 1640.
(33) Although some microanalyses were marginal, the best available data
are given.
(28) (a) De Mico, A.; Margarita, R.; Parlanti, L.; Vescovi, A.; Piancatelli,
G. J. Org. Chem. 1997, 62, 6974. (b) Dondoni, A.; Massi, A.; Minghini,
E.; Sabbatini, S.; Bertolasi, V. J. Org. Chem. 2003, 68, 6172. (c) Vescovi,
A.; Knoll, A.; Koert, U. Org. Biomol. Chem. 2003, 1, 2983. (d) Sakurantani,
K.; Togo, H. Synthesis 2003, 21.
(29) Holcknecht, O.; Cavazzini, M.; Quici, S.; Shepperson, I.; Pozzi, G.
AdV. Synth. Catal. 2005, 347, 677.
(30) Spyroudis, S.; Varvoglis, A. Synthesis 1975, 445.
(31) Bescherer, K. Diploma Thesis, Universita¨t Erlangen-Nu¨rnberg,
Nuremberg, Germany, 2005.
(34) The mass spectra of iodine(III) compounds often show signals for
di(iodine) species: Silva, L. F., Jr.; Lopes, N. P. Tetrahedron Lett. 2005,
46, 6023.
(35) (a) All compounds with (CF2)7CF3 ponytails exhibit very similar
19F NMR chemical shifts, which have been assigned by detailed 2D NMR
experiments: Gladysz, J. A. In Handbook of Fluorous Chemistry; Gladysz,
J. A., Curran, D. P., Horva´th, I. T., Eds.; Wiley/VCH: Weinheim, Germany,
4
3
2004; pp 43-44. (b) The triplets represent JFF and not JFF values. See:
(i) White, H. F. Anal. Chem. 1966, 38, 625. (ii) Foris, A. Magn. Reson.
Chem. 2004, 42, 534.
J. Org. Chem, Vol. 71, No. 19, 2006 7439