1
784 J . Org. Chem., Vol. 67, No. 6, 2002
Hungerhoff et al.
of these ratios illustrates that the extractive separation
is efficient even in the case when fluorine is in shortage
over hydrogen as in the case of the cyclopentenol deriva-
tive 10. In addition, the selectivity of the partition of the
fluorinated esters and alcohols between perfluoro-n-
hexane and methanol may be increased as a result of the
formation of hydrogen bonds between the enantiomeric
alcohols and methanol. Alternatively, for the isolation of
NMR (CDCl
.4 Hz).
3
) δ 3.25 (2 H, t, J ) 17.1 Hz), 4.54 (2 H, q, J )
8
Tolu en e-4-su lfon ic Acid 1H,1H,2H,2H-P er flu or od ecyl-
ester . To a solution of 1H,1H,2H,2H-perfluorodecane-1-ol (1)
400 g, 0.862 mol) and p-toluenesulfonyl chloride (207.0 g,
.086 mol) in dry THF (800 mL) was added triethylamine
110.0 g, 151.3 mL, 1.086 mol) at room temperature within 10
(
1
(
min. The reaction mixture was refluxed under argon until 1
was completely consumed (∼10 h). The precipitate was filtered
off and washed with tert-butyl methyl ether (500 mL). The
filtrate was concentrated under reduced pressure, and the
remaining residue was partitioned between a mixture of tert-
butyl methyl ether (1000 mL), ethyl acetate (500 mL), and 2
N HCl (500 mL). The organic phase was washed with 2 N
compounds with a low fluorine content, solid-liquid
extraction is a useful separation technique.1b
Regarding price and availability the highly fluorinated
acyl donor 4 cannot compete with the frequently used
inexpensive vinyl acetate but the fluorous label can be
recycled. On the other hand, perfluoro-n-hexane, FC-72,
is a technical product. Its improper use on large scale
can cause environmental problems that could be avoided
by using an appropriate extraction technique different
from separatory funnels as typical for laboratory workup.
K
2
CO
3
(2 × 100 mL) and brine (100 mL) and dried (Na
2 4
SO ).
Evaporation under reduced pressure (up to 95 °C bath tem-
perature/10 mbar) yielded the crude product still containing
p-toluenesulfonyl chloride that was distilled off by rotatory
evaporation (140-154 °C bath temperature, 0.08 mbar). The
slightly brown oily residue crystallized on cooling, affording
toluene-4-sulfonic acid 1H,1H,2H,2H-perfluorodecylester (470.6
g, 88%), which was used in the next step without further
1
Con clu sion s
purification. H NMR (CDCl ) δ 2.47 (3 H, s), 2.51 (2 H, m),
3
4
.31 (2 H, t, J ) 6.9 Hz), 7.37 (2 H, d, J ) 7.8 Hz), 7.81 (2 H,
The highly fluorinated carboxylic ester 4 is an ex-
tremely useful and selective acyl donor for the lipase-
catalyzed enantiomer-selective acylation of alcohols,
whereby the faster reacting enantiomer is equipped with
a fluorous tag in order to be recognized selectively by a
fluorous phase. The enantiomer-selective labeled mixture
of ester and alcohol representing the two enantiomers
can be separated very efficiently by partition in the two-
phase solvent system perfluoro-n-hexane/methanol, avoid-
ing a chromatographic step. Hydrolysis of the fluorinated
enantiomer allows the quantitative recovery of the fluo-
rous tag.
d, J ) 7.8 Hz).
1-Br om o-1H,1H,2H,2H-p er flu or o Deca n e. Caution: the
bromide is a toxic lachrymator. A suspension of the above-
described toluenesulfonate (470.0 g, 0.76 mol) and dry LiBr
(132.0 g, 1.52 mol) in acetone (380 mL) was refluxed for 7 h
and turned to a fluffy suspension. The progress of the reaction
was monitored by 1H NMR of an analytical sample. After
complete conversion the reaction mixture was cooled to room
temperature. Cyclohexane (1000 mL) was added, and the
precipitate was filtered off and washed with a mixture of
cyclohexane (100 mL) and acetone (20 mL) and finally with
pure cyclohexane (3 × 100 mL). The filtrate was concentrated
under reduced pressure, and the oily residue was distilled,
affording the bromocompound (371.8 g, 93%) as a colorless
The method accomplishes existing methods for the
nonchromatographic separation of enantiomeric esters
from the corresponding alcohols.
1
liquid that crystallized at ∼6 °C. Bp 68-72 °C (0.1 mbar); H
NMR (CDCl
3
) δ 2.70 (2 H, tt, J
1
) 8.1 Hz, J ) 8.4 Hz), 3.51
2
(
0
4
2 H, t, J ) 8.4 Hz). Anal. Calcd. for C10H BrF17 C, 23.17; H,
.81. Found: C, 23.01; H, 0.85.
H,2H,3H,3H-P er flu or ou n d eca n oic Acid (3). Mg (wire,
.16 g, 130 mmol) was heated with iodine (∼100 mg) under
2
Exp er im en ta l Section
3
All reactions, except those that were monitored by HPLC,
were followed by TLC on glass plates coated with a 0.25-mm
layer of silica gel. Compounds were visualized by heating with
argon, and then dry THF (10 mL) was added after cooling.
The mixture was heated to 60 °C, and the above-described
bromocompound (0.53 g, 1 mmol) was added to start the
Grignard reaction. Subsequently, a solution of the bromo-
compound (52.0 g, 98.7 mmol) in dry THF (150 mL) was slowly
added within 1.25 h while keeping the reaction under gentle
reflux. The mixture was refluxed for another 4 h and cooled
in an ice-NaCl bath to -6 °C. Dry carbon dioxide was bubbled
through the reaction mixture, whereby the temperature rose
to 24 °C and a brown solid precipitated (15 min). Then, 2 N
HCl (75 mL) was added slowly at 0 °C. The aqueous mixture
was extracted with tert-butyl methyl ether (1 × 200 mL, 2 ×
50 mL). The combined organic layers were washed with brine
a 1% aqueous solution of KMnO
Ce(SO containing 2.5% of molybdato phosphoric acid and
% of sulfuric acid. Analytical HPLC was carried out employ-
4
or a 1% aqueous solution of
4 2
)
6
ing Daicel columns. Flash chromatography was performed with
1
silica gel 60 (0.040-0.063 mm). H NMR spectra were recorded
at 300 MHz.
2
H,2H-Perfluorodecanoic acid and the corresponding acid
chloride were synthesized starting from commercially available
H,1H,2H,2H-perfluoro decane-1-ol 1 (Avocado/ABCR) accord-
ing to literature procedures and showed consisting spectro-
1
1
3
scopic data.
,2,2-Tr iflu or oeth yl 2H,2H-P er flu or o Deca n oa te (2). To
an ice-cold solution of 2H,2H-perfluoro decanoic acid chloride
20.0 g, 40.3 mmol) and 2,2,2-trifluoroethanol (4.44 g, 3.2 mL,
4.3 mmol) in dry THF (100 mL) containing a catalytic amount
of DMAP (100 mg) was added dropwise over 5 min dry pyridine
3.17 g, 3.23 mL, 40.0 mmol). The cooling bath was removed,
2 4
(50 mL), dried (Na SO ), and concentrated under reduced
pressure, affording crude 3 (42.9 g, 88%) as a brown solid that
was used in the next step without further purification. (If
desired, 3 can be recrystallized from CHCl
acetone) δ 2.57 (2 H, m), 2.69 (2 H, t, J ) 8.1 Hz), 11.0 (1 H,
br s).
2H,2H,3H,3H-P er flu or o Un d eca n oyl Ch lor id e. A solu-
tion of 3 (43.7 g, 88.8 mmol) in dry diethyl ether (150 mL) was
treated with PCl
argon (4 h). The ice-cooled reaction mixture was filtered, and
the filter cake (excess PCl ) was washed with n-hexane (100
mL). The filtrate was concentrated under reduced pressure,
and the resulting brown oily residue was distilled under
reduced pressure, affording the acid chloride (38.0 g, 84%) as
a colorless liquid. Bp 95-97 °C (0.5 mbar); IR (cm ) 1800; H
NMR (CDCl
2,2,2-Tr iflu or oeth yl 2H,2H,3H,3H-P er flu or o Un d eca n -
oa te (4). To an ice-cold solution of the above-described acid
2
1
(
4
3
.) H NMR (d
6
-
(
and the solution was allowed to warm to room temperature.
After stirring for 1 h at room temperature, the precipitate was
filtered off. The filtrate was concentrated under reduced
pressure, and the residue was partitioned between tert-butyl
methyl ether (100 mL) and 2 N HCl (25 mL). The organic layer
5
(37.0 g, 177.6 mmol) and refluxed under
5
2 4
was washed with water (25 mL), dried (Na SO ), concentrated,
and distilled under reduced pressure, affording 2 (19.9 g, 88%)
as a colorless liquid that crystallized at ∼6 °C. Compound 2 is
moisture-sensitive and should be stored under argon at 4 °C.
Prior to use, 2 was always freshly distilled by Kugelrohr
-1
1
3
) δ 2.53 (2 H, m), 3.24 (2 H t, J ) 7.8 Hz).
-
3
-1
1
distillation. Bp 58-60 °C (1 × 10 mbar); IR (cm ) 1809; H
Hungerhoff, Benno
