A facile method for the preparation of hexafluoroisopropanol functionalized derivatives using hexafluoroacetone trihydrate via a carbonyl-ene reaction

Article abstract of DOI:10.1016/j.tetlet.2008.12.056

Hexafluoroacetone trihydrate was shown to undergo an efficient carbonyl-ene reaction with a variety of alkenes in the presence of molecular sieves under microwave heating and conventional heating producing hexafluoroisopropanol functionalized derivatives

Full text of DOI:10.1016/j.tetlet.2008.12.056

Tetrahedron Letters 50 (2009) 1777–1779
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A facile method for the preparation of hexafluoroisopropanol
functionalized derivatives using hexafluoroacetone trihydrate
via a carbonyl-ene reaction
a
a
a
Madabhushi Sridhar a, , Chinthala Narsaiah , Beeram C. Ramanaiah , Vishnu M. Ankathi ,
*
Rajesh B. Pawar b, Shrinandan N. Asthana b
a Fluoroorganics Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India
b High Energy Materials Research Laboratory, Sutarwadi, Pune 411 021, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Hexafluoroacetone trihydrate was shown to undergo an efficient carbonyl-ene reaction with a variety of
alkenes in the presence of molecular sieves under microwave heating and conventional heating produc-
ing hexafluoroisopropanol functionalized derivatives in high yields.
Received 30 October 2008
Revised 8 December 2008
Accepted 11 December 2008
Available online 16 December 2008
Ó 2009 Published by Elsevier Ltd.
Keywords:
Hexafluoroisopropanol functionalized
derivatives
Carbonyl-ene reaction
Alkenes
Hexafluoroacetone trihydrate
Molecular sieves
Microwave reaction
Hexafluoroisopropanol (HFIP) functionality is a very strong
hydrogen bond donor,1 and molecules appended with this group
often exhibit interesting properties.2 Hexafluoroisopropanol func-
tionalized derivatives are widely in use in micro electromechanical
system (MEMS)-based chemical sensors,3 chemical preconcentra-
tors for micro analytical detection techniques4 and analytical and
purification applications.5
In addition, these compounds are also useful as chemical ampli-
fication resists for 157 nm lithography,6 and as pharmaceuticals.7
One of the general methods for the preparation of HFIP func-
tionalized derivatives is the carbonyl-ene reaction of anhydrous
hexafluoroacetone (AHFA) with an alkene having allylic hydrogens.
However, this method has the following drawbacks: AHFA is a
highly toxic gas (bp À26 °C) and is expensive; yields are often very
low and form a mixture of products; and special equipment is
required for handling AHFA. Because of these disadvantages, the
development of a more simple and convenient alternative ap-
proach for this reaction is desired.
Unlike AHFA, HFAT is highly unreactive with alkenes and its car-
bonyl-ene reactions are not known in the literature.
In the course of our recently initiated activity on the develop-
ment of novel HFIP functionalized derivatives for sensor applica-
tions, we discovered that HFAT also gives an efficient carbonyl-ene
reaction with alkenes having allylic hydrogens upon heating in the
presence of a solid such as molecular sieves, silica gel or alumina,
giving HFIP functionalized derivatives in high yields. The results of
the typical carbonyl-ene reactions of AHFA and HFAT with
ylstyrene are shown in Scheme 1.
a-meth-
AHFA is a strong electrophile and the mechanism of its car-
bonyl-ene reaction was known to involve a four-member, cyclic
dipolar addition transition state.8b HFAT is, however, not a strong
electrophile and the mechanism of its carbonyl-ene reaction is
not clear. In a control experiment, no AHFA was generated when
HFAT was heated with molecular sieves. This shows that the
involvement of AHFA in the formation of observed products in
the present study is a remote possibility.
Hexafluoroacetone trihydrate (HFAT) is a widely available and
inexpensive chemical. Since HFAT is a liquid (bp 106–108 °C) at
room temperature, it is highly convenient for handling and storage.
The carbonyl-ene reaction of HFAT with a-methylstyrene was
studied with a variety of solids such as molecular sieves (3 Å, 4 Å
and 5 Å MS), silica gel, alumina, calcium oxide and montmorillon-
ite K10 clay and also with water-tolerant Lewis acid catalysts,
namely, La(OTf)3, Eu(OTf)3, Gd(OTf)3 and Yb(OTf)3, under micro-
wave heating (800W, 100 °C, 10 min). In this study, molecular
* Corresponding author. Tel.: +91 40 2719 1891; fax: +91 40 2716 0387.
E-mail address: smiict@iict.res.in (M. Sridhar).
0040-4039/$ - see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2008.12.056

1778
M. Sridhar et al. / Tetrahedron Letters 50 (2009) 1777–1779
HO
CF3
CF3
OH
CF3
CF3
CF3COCF3(1.0 equi.)
OH
CF3
+
heat, sealed tube
Ph
Ph
CF3
(Ref. 8a)
2:1
OH
CF3
CF3
CF3COCF3(1.0 equi.)
<40 oC, 4h, sealed tube
(Ref. 8b)
Ph
80%
Ph
CF3COCF3.3H2O(1.1 equi.)
No reaction
100 oC, 48h or
MW, 800 W, 100 oC, 10 min.
OH
CF3COCF3.3H2O(1.1equi.),
3A MS
100 oC, 24 h or
MW, 800 W, 100 oC,
10 min.
CF3
CF3
Ph
95% (conventional heating)
97% (microwave heating)
Scheme 1.
Table 1
sieves (3 Å, 4 Å and 5 Å MS) and silica gel were found to be highly
promising in promoting the reaction and alumina was found to be
moderately active. The order of efficiency of these solids in catalyz-
ing the carbonyl-ene reaction is 3 Å MS > 4 Å MS > 5 Å MS > silica
gel > alumina. Calcium oxide was found to be ineffective in catalyz-
ing the reaction. With K10 clay and lanthanide triflates, oligomers
Solid surface mediated carbonyl-ene reaction of hexafluoroacetone trihydrate with
methylstyrene
a-
S. no.
Solid catalyst
Isolated yield of HFA adduct
1
2
3
4
5
6
7
8
3 Å MSa
4 Å MSa
5 Å MSa
Silica gel
Alumina
CaO
92
82
79
75
of a-methylstyrene are essentially formed in the reaction. The rep-
resentative results are shown in Table 1.
57
In our further study, we have investigated the carbonyl-ene
reactions of HFAT with a variety of alkenes under microwave irra-
diation (800 W, 100 °C, 10 min) and also under conventional heat-
ing in an oil bath at 100 °C.9 In this study, the microwave-assisted
reactions were found to proceed very rapidly (in 10 min) giving the
HFIP functionalized derivatives in 62–97% yields. On the other
No reaction
0
0
K10 clayb
b
Ln(OTf)3
Ln = La, Eu, Gd, Yb
a
Powder.
b
Only oligomers of a-methylstyrene were obtained.
Table 2
Carbonyl-ene reactions of hexafluoroacetone trihydrate with alkenes
Entry
Alkene
Adduct
Conventional heating
Microwave Heating
Yielda (%) (reaction time, h)
Yielda (%) (reaction time, min)
OH
CF3
F3C
1
2
95 (24)
82 (24)
97 (10)
93 (10)
OH
CF3
F3C
Cl
Cl
OH
CF3
F3C
3
4
78 (24)
56 (28)
92 (10)
62 (10)
MeO
MeO
OH
CF3
F3C

M. Sridhar et al. / Tetrahedron Letters 50 (2009) 1777–1779
1779
Table 2 (continued)
Entry
Alkene
Adduct
Conventional heating
Microwave Heating
Yielda (%) (reaction time, h)
Yielda (%) (reaction time, min)
CF3
OH
MeO
5
6
68 (28)
88 (10)
MeO
F3C
CF3
OH
CF3
63 (28)
64 (28)
94 (10)
85 (10)
CF3
OH
CF3
CF3
OH
CF3
7
8
73 (28)
89 (10)
67 (10)
OH
CF3
CF3
9
60 (28)b
a
Isolated yields. Yields are based on alkene. All products gave satisfactory 1H NMR, IR and mass spectral data.
This reaction was carried out in a sealed pressure tube.
b
4. Voiculescu, I.; Zaghloul, M.; Narasimhan, N. Trends Anal. Chem. 2008, 27, 327–
343.
5. McGill, R. A. J. Fluoropolym. Sci. Technol. 2001, 14, 583–593.
6. Ito, H.; Wallraff, G. M.; Fender, N.; Brock, P. J.; Larson, C. E.; Truong, H. D.; Breyta,
G.; Miller, D. C.; Sherwood, M. H.; Allen, R. D. J. Fluoropolym. Sci. Technol. 2001,
14, 583–593.
hand, the reactions under conventional heating also gave the prod-
ucts in comparable yields (56–95%), but the reaction times were
comparatively very long (>24 h). The results obtained in this study
are presented in Table 2.
In summary, the present work describes a simple, efficient and
economical method for the preparation of hexafluoroisopropanol
functionalized derivatives with high selectivity by a carbonyl-ene
reaction of hexafluoroacetone trihydrate with alkenes having
allylic hydrogens under microwave heating and also under conven-
tional heating. This work is the first study on the carbonyl-ene
reactions of hydrated hexafluoroacetone using simple solid cata-
lysts, which are inexpensive, easily recoverable and recyclable.
7. Dehmlow, H.; Kuhn, B.; Masciadri, R.; Panday, N.; Ratni, H.; Wright, M.B. U.S.
Patent 7,253,282, 2005.
8. (a) Urry, W. H.; Niu, J. H. Y.; Lundted, L. G. J. Org. Chem. 1968, 33, 2302–2310. and
references cited therein; (b) Adelman, R. J. Org. Chem. 1968, 33, 1400–1410; (c)
Kobayashi, Y.; Nagal, T.; Kumadaki, I. Chem. Pharm. Bull. 1984, 32, 5031–5035.
9. Typical experimental procedure for solid surface mediated carbonyl-ene reaction of
hexafluoroacetone trihydrate with alkenes under microwave heating is as follows:
a
-Methylstyrene (0.5 g, 4.2 mmol), hexafluoroacetone trihydrate (1.01 g,
4.6 mmol) and 3 A MS (0.5 g, powder) were taken in a 10 ml pressure tube
and subjected to microwave heating (CEM discover, 800 W, 100 °C, 16 psi) for
10 min. Next, the reaction mixture was diluted with dichloromethane (5 ml) and
filtered. The molecular sieves were rinsed with dichloromethane (2 Â 5 ml) and
the combined extracts were concentrated and purified by normal column
chromatography to obtain the corresponding addition product, 1,1,1-trifluoro-
4-phenyl-2-(trifluoromethyl)pent-4-ene-2-ol in the form of colourless oil
(1.38 g, 97%).
Procedure for reaction under conventional heating: The reaction mixture was
taken as described above into a 25 ml round-bottomed flask fitted with a
condenser and a calcium chloride guard tube. The mixture was heated on an oil
bath at 100 °C for 24 h and after completion of the reaction (TLC) it was
extracted with dichloromethane following the procedure above. The extract was
concentrated under reduced pressure. Purification of the crude by normal
column chromatography afforded the corresponding addition product (1.35 g)
in 97% yield. The product obtained gave the following spectral data: 1H NMR
(300 MHz, CDCl3): d 2.8 (1H, s, exchange with D2O), 3.3 (2H, s), 5.38 (1H, s), 5.6
(1H, s), 7.3–7.6 (5H, m); 13C NMR (75 MHz, CDCl3): d 35.6, 121.0, 125.2, 127.0,
129.0, 130, 140.9; 19F NMR (282 MHz, CDCl3): d À77, IR (neat, cmÀ1): 3540,
3061, 1628, 1494, 1447, 1393, 1207, 1149, 107, 988, 778, 669; EIMS (m/z,%): 284
(M+, 35), 221 (15), 197 (15), 177 (15), 147 (20), 128 (20), 115 (100), 103 (35), 91
(70);); exact mass observed for C12H10F6O: 284.065 (calcd: 284.063).
Acknowledgement
C.N., B.C.R. and V.M.A. are thankful to the Director, IICT, for pro-
viding financial support in the form of project JRF.
References and notes
1. (a) Maiti, N. C.; Zhu, Y.; Carmichael, I.; Serianni, S. S.; Anderson, V. E. J. Org. Chem.
2006, 71, 2878–2880; (b) Berrien, J. F.; Ourevitch, M.; Morgant, G.; Ghermani, N.
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4954–4955.
3. (a) Andrew, M.; Abraham, M. H.; Grate, J. W. Chemtech 1994, 27–37; (b) Grate, J.
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