Preparation of a fluorous chiral BINOL derivative and application to an asymmetric protonation reaction

Article abstract of DOI:10.1016/S0040-4020(99)01004-2

Fluorous Chiral Proton Source (R,S)-FDHPEB resulted in a higher enantioselectivity (95% ee) than that of the original nonfluorous (R,S)-DHPEB (87% ee) in an enantioselective protonation of a samarium enolate. (R,S)- FDHPEB was easily recovered by a simple filtration through a fluorous reverse phase silica gel and was recyclable. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(99)01004-2

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 351–356
Preparation of a Fluorous Chiral BINOL Derivative and
Application to an Asymmetric Protonation Reaction
a
b
Yutaka Nakamura,a Seiji Takeuchi,a, Yoshiaki Ohgo and Dennis P. Curran
*
aNiigata College of Pharmacy, 5-13-2 Kamishin’ei cho, Niigata 950-2081, Japan
bDepartment of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
Received 4 October 1999; accepted 12 November 1999
Abstract—Fluorous Chiral Proton Source (R,S)-FDHPEB resulted in a higher enantioselectivity (95% ee) than that of the original nonfluor-
ous (R,S)-DHPEB (87% ee) in an enantioselective protonation of a samarium enolate. (R,S)-FDHPEB was easily recovered by a simple
filtration through a fluorous reverse phase silica gel and was recyclable. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Compounds that have long perfluorinated carbon chains are
“fluorous” and are easily separable from organic compounds
by a simple partitioning procedure with a fluorous solvent
such as FC-72 (CF3(CF2)4CF3) and a standard organic
solvent. In an ideal case, after partitioning work-up, almost
pure products are obtained from the organic phase, and
fluorous product and reagent are recovered quantitatively
from the fluorous phase. The organic products and the
fluorous compounds can also be separated cleanly by a
simple filtration through a fluorous reverse phase (FRP)
silica gel column. Thus, fluorous chemistry is attracting
the growing interest of organic chemists world-wide since
it provides new options for solution phase combinatorial
chemistry.1c,2
In spite of the growing number of articles on fluorous chem-
istry, only a few reports have been published on asymmetric
reactions using fluorous reagents or catalysts.4 The main
reason for this situation seems to be due to the lack of chiral
fluorous ligands available. Therefore, we have attempted to
synthesize such ligands and succeeded in preparing a chiral
fluorous BINOL analogue via short steps and in good over-
all yield.
In this paper, we wish to report the preparation of the chiral
fluorous BINOL and its derivative, and the application of
the compound to an enantioselective protonation of a
samarium enolate.
Another area of fluorous chemistry is a catalytic reaction in
a fluorous and organic biphase system (FBS) using a
fluorous catalyst.1a,b,d,3 Homogeneous transition metal
catalysts whose ligands are highly fluorous are dissolved
only in the fluorous phase of FBS. Reactants in the organic
phase can partition into the fluorous phase or the reaction
can occur at the interface of FBS as well. The products are
obtained from the organic phase by separating the phase
from the fluorous phase after the reaction. The reaction
can be repeated by adding a new organic solution containing
the reactants, as long as the catalyst remains intact in the
Results and Discussion
Preparation of chiral fluorous BINOL and its derivative
The chiral BINOL (III) and its derivative (V) were prepared
by the route shown in Scheme 1.
(R)-6,60-Dibromo-2,20-dimethoxymethoxy-1,10-binaphtha-
lene (I) was prepared from commercially available (R)-6,60-
dibromo-1,10-binaphth-2,2-diol by Pu’s method.5 (R)-6,60-
Bis[tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silyl]-2,20-
dimethoxymethoxy-1,10-binaphthalene (II) was obtained in
91% yield via lithiation at the 6 and 60-positions of I and
then reaction with (C6F13CH2CH2)3SiBr2q according to
Curran’s method.2x The MOM group of II was removed in
hydrochloric acid and THF under reflux and vigorous stirring.
(R)-6,60-Bis[tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-
silyl]-1,10-binaphth-2,20-diol (III; (R)-FBINOL) was isolated
in 97% yield. The enantiomeric excess (ee) of the fluorous
(R)-FBINOL (III) was determined to be higher than 99% by
HPLC using a chiral column, using the (S)-enantiomer of III
´
fluorous phase. Horvath and Gladysz have prepared a
fluorous phosphine ligand P(CH2CH2(CF2)5CF3)3 and
successfully applied this to hydroformylation and hydro-
boration in FBS catalyzed by rhodium complex.3b,f
Keywords: fluorous chiral; enantioselective protonation; samarium enolate.
* Corresponding author. Tel.: ϩ25-268-1247; fax: ϩ25-268-1230; e-mail:
takeuchi@niigata-pharm.ac.jp
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(99)01004-2

352
Y. Nakamura et al. / Tetrahedron 56 (2000) 351–356
Scheme 1.
Table 1. Partition coefficients of (R)-FBINOL and (R,S)-FDHPEB in
organic solvent and FC-72
purified by silica gel column chromatography as described
in the Experimental Section.
Organic solvent
Organic solvent/FC-72
The approximate partition coefficients of III and V were
determined by a simple method described in the footnote
of Table 1, and the results are summarized in Table 1.
CHCl3
THF
Toluene
1/19
1/3
1/49
(R)-FBINOL (III)
(R,S)-FDHPEB (V)
Recycling the fluorous chiral diol ((R,S)-FDHPEB; V) in
the enantioselective protonation of the samarium enolate
THF
Benzene
19/1
1/32
A mixture of 100 mg of (R)-FBINOL or (R,S)-FDHPEB in FC-72 (2 mL)
and organic solvent (2 mL) was stirred at room temperature for 10 min.
Then the two phases were separated and the solvents were evaporated in
vacuo. The contents of the fluorous compound in each phase were deter-
mined by weighing the residue.
We have reported in the previous paper that the methoxy
group of 2-methoxy-2-phenylcyclohexanone was reduc-
tively cleaved by SmI2 to give the corresponding samarium
enolate. The enolate was protonated by (R,S)-DHPEB to
afford the corresponding chiral ketone in 87% ee (Eq. (1)).6
as a standard. This was prepared by the same procedures as
those of III from the (S)-starting material.
Thus, we examined the reaction by using (R,S)-FDHPEB
instead of (R,S)-DHPEB and tried to reuse the recovered
(R,S)-FDHPEB for the next reaction without purification.
(R,S)-FDHPEB is very insoluble in THF at Ϫ45ЊC and the
reaction mixture seemed to be liquid–liquid biphase system,
although (R,S)-FDHPEB is a glassy solid that is soluble in
THF at room temperature. However, under the same reac-
tion conditions as those shown in Equation (1), almost the
same yield (76%) and enantioselectivity (85% ee) were
obtained after purification of 2-phenylcyclohexanone by
preparative TLC. (R,S)-FDHPEB was recovered quantita-
tively by extraction with FC-72 after quenching the reaction
with 0.1N hydrochloric acid. However, the separation
procedure was much simpler and more effective when
the reaction mixture was filtered through the fluorous
reverse phase silica gel (FRP silica gel).2l,w The product
Next, we tried to synthesize (R)-2,20-di[(S)-2-hydroxy-2-
phenylethoxy]-6,60-bis[tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tri-
decafluorooctyl)silyl]-1,10-binaphthyl (V; (R,S)-FDHPEB)
by the procedures that we have already established for the
preparation of the nonfluorous analogue.6 However, III was
very insoluble in DMF and the yield was very low. Thus,
BTF (CF3C6H5; benzotrifluoride) and Cs2CO3 were used as
a solvent and a base respectively, and the reaction was
carried out at 80–90ЊC for 18.5 h to give IV. The crude
product of IV underwent deprotection to give the desired
compounds V in 75% overall yield from III. In the
procedures mentioned above, the fluorous products II–V
were generally extracted with FC-72 (CF3(CH2)4CF3) and
ꢀ1†

Y. Nakamura et al. / Tetrahedron 56 (2000) 351–356
353
Scheme 2.
Table 2. Enantioselective protonation of the samarium enolate derived
from 2-methoxy-2-phenylcyclohexanone reusing the same chiral proton
source without purification. (Reactions were carried out using 2.0 mol
equiv. of (R,S)-FDHPEB and 2.4 mol equiv. of SmI2)
TLC purification of the sample, the enantiomeric excess
was reduced to 88% ee. Therefore, it is clear that the
enantiomeric excess of the product before purification was
much higher than that of the sample after preparative TLC
purification. It is already known in our previous work that
the product is rather easy to racemize.6 The lower enantio-
meric excess of the purified product must have been brought
about by racemization during purification by preparative
TLC. The wide range of enantiomeric excesses in Table 2
(81–89% ee) is considered to be due to racemization and the
extent of racemization must depend upon the time taken for
the purification procedures. Therefore, the separation
method using FRP silica gel and the determination method
using HPLC with both UV and CD detectors of the
unpurified sample is a very useful method for a high
throughput assessment of the enantioselective reaction,
especially in the case of a product which is easily racemized
during purification procedures.
Run
Yield
(%)
% eea
Config.
(Rotn.)b
Recovered
(R,S)-FDHPEB
(%)
1
2
3
4
5
82
81
78
74
73
81
85
86
89
87
R(ϩ)
R(ϩ)
R(ϩ)
R(ϩ)
R(ϩ)
98
97
98
99
99
a Determined by HPLC analysis using DAICEL CHIRALCEL OD-H.
b Specific rotation was measured in benzene at 24ЊC.
and (R,S)-FDHPEB were cleanly separated simply by elut-
ing first with CH3CN and then FC-72 as described in the
Experimental Section. The crude product obtained from the
CH3CN solution was purified by preparative TLC and (R,S)-
FDHPEB recovered from FC-72 solution was used for the
next reaction without further purification (Scheme 2). Thus,
the reaction was repeated five times and the results are
summarized in Table 2.
The strategy of fluorous chemistry described so far is not
only applicable to the other 2-alkyl or 2-aryl-2-hetero-
substituted ketones which have brought about high enantio-
meric excesses (83–94% ee) in asymmetric protonation by
using (R,S)-DHPEB6 but is also expected to be applicable to
other asymmetric protonation reactions such as (R)-BINOL-
SnCl4 catalyzed protonation of silyl enol ethers and esters7
or LnNa3tris((R)-binaphthoxide) catalyzed Michael addition
of thiol to a,b-unsaturated carbonyl compounds8 reported
by Yamamoto and Shibasaki, respectively.
As seen from Table 2, it is clear that the enantioselectivities
were higher than 85% ee on average even if the recovered
(R,S)-FDHPEB was used for the reactions. The recovered
(R,S)-FDHPEB after the fifth reaction in Table 2 showed the
same NMR spectrum as that of a pure sample. Therefore,
the results demonstrated that (R,S)-FDHPEB has almost the
same ability to control the transition state of the enantio-
selective protonation as that of the original nonfluorous
chiral proton source (R,S)-DHPEB but also has completely
different characteristics from (R,S)-DHPEB which makes
(R,S)-FDHPEB recyclable by the simple filtration with the
FRP silica gel.
Experimental
General
The melting point was determined by a Yanagimoto micro-
melting point apparatus and was uncorrected. The IR
spectra were recorded on a Perkin–Elmer 1720-X FT-IR
Finally, we tried to determine the enantiomeric excess of the
product without purification by preparative TLC, because
such a method can afford a high throughput assessment of
the reaction. HPLC data analyzed by both UV and CD
detectors are shown in Fig. 1.
1
spectrometer. The H NMR spectra were obtained on a
JEOL FX-200 and JEOL JNM-A400 spectrometer in
CDCl3 with tetramethylsilane as an internal standard. The
optical rotations were measured with a Perkin–Elmer 241
polarimeter. HPLC analysis was performed with Hitachi
L-7100 flow system and L-7400 UV detector or JASCO
CD-1595 CD detector using DAICEL CHIRALCEL OD
or OD-H column. Preparative TLC was run on Wakogel
B-5F and column chromatography was performed using
Wakogel C-300. Tetrahydrofuran (THF) was distilled
prior to use from sodium benzophenone ketyl under
argon. FC-72 (commercially available from Sumitomo
As seen from Fig. 1, there was no peak due to products other
than the desired product in the chromatograms with the CD
detector although several additional peaks were recorded
by the UV detector. The enantiomeric excesses obtained
by the UV and CD detectors coincided with each other
and the enantiomeric excess of the unpurified sample of
the product reached 95% ee. However, after preparative

354
Y. Nakamura et al. / Tetrahedron 56 (2000) 351–356
Figure 1. Chromatograms of 2-phenylcyclohexanone with UV and CD detectors.
3M) and benzotrifluoride were distilled from phosphorous
pentoxide under argon. 0.1 M samarium iodide THF solu-
tion was prepared from samarium metal and diiodoethane
by Kagan’s method.9 The fluorous reverse phase silica gel
was prepared by Curran’s method.2w
was concentrated in vacuo. The resulting syrup was purified
on a silica gel column (hexane:EtOAcˆ20:1) to afford
the FBINOL diMOM ether (II) as a colorless syrup (8.6 g,
91% yield): [a]2D0 ϩ17.5Њ (c 0.827, benzotrifluoride),
20
20
[a] ϩ18.4Њ (c 0.827, benzotrifluoride), [a] ϩ21.5Њ (c
578
546
16
436
0.827, benzotrifluoride), [a]
trifluoride), [a]
ϩ50.3Њ (c 0.827, benzo-
ϩ167Њ (c 0.827, benzotrifluoride); IR
16
365
(R)-6,60-Bis[tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-
octyl)silyl]-2,20-dimethoxymethoxy-1,10-binaphthalene (II).
(R)-6,60-dibromo-2,20-dimethoxylmethoxy-1,10-binaphtha-
lene (I) (2.00 g, 3.76 mmol) was dissolved in THF (20 mL)
and cooled to Ϫ78ЊC under argon. n-Butyl lithium
(1.55 mol dmϪ3, 5.4 mL, 8.3 mmol) was added dropwise,
and the resulting yellow solution was stirred at that
(neat) 2947, 1617, 1473, 1443, 1362, 1240, 1070, 1023,
915, 845, 812, 737, 708 cmϪ1 1H NMR (200 MHz) d
;
1.10–1.30 (m, 12H, –SiCH2–), 1.80–2.20 (m, 12H,
–CF2CH2–), 3.16 (s, 6H, –OCH3), 5.02 and 5.14 (d×2,
2H×2, –CH2O–, Jˆ6.8 Hz), 7.22 (s, 4H, ArH), 7.67 (d,
2H, ArH, Jˆ9.0 Hz), 7.99 (s, 2H, ArH), 8.01 (d, 2H, ArH,
Jˆ9.0 Hz); MS (EI) m/z (relative intensity) 2511 (Mϩϩ1,
100), 2434 (96), 309 (10), 239 (18), 131 (18), 45 (90); Anal.
calcd for C72H44F78O4Si2: C, 34.44; H, 1.77; F, 59.01. Found
C, 33.67; H, 1.57; F, 58.94.
temperature for 50 min.
A
mixture of bromo
tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silane
(10.6 g, 9.22 mmol) in Et2O (50 mL) was added to the reac-
tion mixture. After stirring at room temperature for 1.5 h,
the reaction mixture was quenched with a saturated aqueous
NH4Cl solution (50 mL). The volatiles were removed in
vacuo and CH2Cl2 (80 mL) was added. The mixture was
washed with FC-72 (30 mL×5), the combined FC-72 layer
(R)-6,60-Bis[tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-
octyl)silyl]-1,10-2-binaphthol (III). A mixture of FBINOL
diMOM ether (II) (399 mg, 0.159 mmol), conc. HCl (4 mL)

Y. Nakamura et al. / Tetrahedron 56 (2000) 351–356
355
16
16
and THF (8 mL) was stirred vigorously at 60ЊC for 3 h.
After addition of CH2Cl2 (10 mL), the cloudy biphase was
washed with FC-72 (10 mL×5). The combined FC-72 layer
was concentrated in vacuo to give a syrup, which was
purified on a silica gel column (hexane:EtOAcˆ10:1) to
afford (R)-FBINOL as a colorless syrup which gradually
[a] ϩ8.29Њ (c 1.16, benzotrifluoride), [a] ϩ9.59Њ (c
578
546
16
1.16, benzotrifluoride), [a]
fluoride), [a]
ϩ24.8Њ (c 1.16, benzotri-
ϩ132.6Њ (c 1.158, benzotrifluoride); IR
436
16
365
(neat) 3445, 3065, 3034, 2943, 1736, 1616, 1474, 1240,
904, 845, 812, 707 cmϪ1; H NMR (400 MHz) d 1.10–
1
1.40 (m, 12H, –SiCH2–), 2.00–2.20 (m, 12H, –CF2CH2–
), 3.01 (d, 2H, –OH, Jˆ2.9 Hz), 4.08 (dd, 2H, one proton of
–OCH2–, Jˆ9.3 and 9.8 Hz), 4.20 (dd, 2H, another proton
of –OCH2–, Jˆ2.9 and 9.8 Hz), 4.71 (ddd, 2H, –OCH–,
Jˆ2.9 and 9.3 Hz), 7.13–7.26 (m, 14H, ArH), 7.51 (d, 2H,
ArH, Jˆ9.0 Hz), 8.03 (s, 2H, ArH), 8.06 (d, 2H, ArH,
Jˆ9.3 Hz); MS (EI) m/z (relative intensity) 2662 (Mϩ,
60), 2525 (40), 2434 (22), 245 (20), 131 (32), 77 (100);
Anal. calcd for C84H52F78O4Si2: C, 37.88; H, 1.97; F,
55.64. Found C, 37.75; H, 1.77; F, 55.45.
crystallized (379 mg, 98% yield): mp 80–81ЊC, [a]D26
26
Ϫ16.9Њ (c 0.463, FC-72), [a] Ϫ17.5Њ (c 0.463, FC-72),
578
[a]52466 Ϫ20.1Њ (c 0.463, FC-72), [a]42366 Ϫ25.1Њ (c 0.463, FC-
26
365
72), [a] ϩ65.2Њ (c 0.463, FC-72); IR (KBr) 3500, 2946,
1614, 1470, 1207, 1144, 1071, 1019, 900, 844, 746,
708 cmϪ1 1H NMR (200 MHz) d 1.00–1.30 (m, 12H,
;
–SiCH2–), 1.80–2.20 (m, 12H, –CF2CH2–), 5.14 (s, 2H,
–OH), 7.22 (d, 2H, ArH, Jˆ8.3 Hz), 7.31 (d, 2H, ArH,
Jˆ8.3 Hz), 7.47 (d, 2H, ArH, Jˆ9.0 Hz), 7.99 (s, 2H,
ArH), 8.04 (d, 2H, ArH, Jˆ9.0 Hz); MS (EI) m/z (relative
intensity) 2422 (Mϩ, 100); Anal. calcd for C68H36F78O2Si2:
C, 33.71; H, 1.50; F, 61.16. Found C, 33.12; H, 1.25; F,
60.93. The enantiomeric excess (ee) of the product was
determined to be Ͼ99% ee by HPLC analysis using a
chiral column (DAICEL CHIRALCEL OD, hexane:2-
propanolˆ95:5, flow rateˆ1.0 mL/min): tRˆ8.9 min.
Typical procedure for the enantioselective protonation
of the samarium enolate derived from 2-methoxy-2-
phenylcyclohexanone with (R,S)-FDHPEB. A SmI2
solution (0.1 mol dmϪ3, 6.2 mL, 0.62 mmol) was added
to a suspension of 2-methoxy-2-phenylcyclohexanone
(52.8 mg, 0.259 mmol) and (R,S)-FDHPEB (1.317 g,
0.495 mmol) in THF (5 mL) with stirring under argon at
Ϫ45ЊC. After stirring 2 h at that temperature, the reaction
mixture was quenched with 0.1N hydrochloric acid (6 mL).
The mixture was washed with FC-72 (8 mL×6) and then the
THF-H2O layer was extracted with Et2O (20 mL×3). The
combined ether layer was washed with brine (15 mL), dried
over anhydrous MgSO4, and concentrated in vacuo. The
crude product was purified by preparative TLC (hexane:
EtOAcˆ4:1) to give 2-phenylcyclohexanone (34.1 mg,
76% yield) in 85% ee as a colorless solid: [a]2D4 ϩ96.4Њ
(c 0.276, benzene). The absolute configuration was deter-
mined to be R by comparison of its optical rotation with the
reported one. The enantioselectivity was determined by
HPLC analysis using DAICEL CHIRALCEL OD-H,
hexane:2-propanolˆ95:5, flow rateˆ0.5 mL/min). (R,S)-
FDHPEB was recovered almost quantitatively from FC-72
washings without a loss of optical purity.
(S)-fluorous BINOL was prepared from (S)-6,60-dibromo-
2,20-dimethoxylmethoxy-1,10-binaphthalene by the proce-
dure similar to that of (R)-FBINOL (54% overall yield):
26
[a]2D6 ϩ15.7Њ (c 0.594, FC-72), [a]
ϩ16.3Њ (c 0.594,
578
26
26
FC-72), [a] ϩ18.9Њ (c 0.594, FC-72), [a] ϩ22.4Њ (c
0.594, FC-72), [a] Ϫ70.7Њ (c 0.594, FC-72). The ee of
546
436
26
365
the product was determined to be Ͼ99% ee by HPLC
analysis using a chiral column (DAICEL CHIRALCEL
OD, hexane:2-propanolˆ95:5, flow rateˆ1.0 mL/min):
tRˆ5.3 min.
(R)-2,2 0-Bis[(S)-2-hydroxy-2-phenylethoxy]-6,6 0-
Bis[tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-octyl)-
silyl]-1,10-binaphthyl (V). A suspension of (R)-FBINOL
(500 mg, 0.206 mmol) and cesium carbonate (161 mg,
0.495 mmol) in benzotrifluoride (2 mL) was stirred
vigorously at 80ЊC for 30 min. To the suspension was
added (S)-2-phenyl-2-tetrahydropyranyloxy-1-p-toluene-
sulfonyloxyethane (186 mg, 0.495 mmol) and the reaction
mixture was stirred at 80ЊC. After 6 h, the tosylate (186 mg,
0.495 mmol), cesium carbonate (161 mg, 0.495 mmol) and
benzotrifluoride (2 mL) were added again to the reaction
mixture, and then stirred at that temperature for 12 h.
After cooling, the reaction mixture was diluted with Et2O
(50 mL) and the insoluble material was filtered off. The
filtrate was concentrated in vacuo to give a syrup, which
was purified on a silica gel column (hexane:EtOAcˆ20:1
then 10:1) to afford the diether derivative (IV) as a viscous
syrup. A mixture of the syrup, conc. HCl (2 mL) and THF
(4 mL) was stirred vigorously at 70ЊC for 2 h. The reaction
mixture was extracted with Et2O (15 mL×3), and washed
with a saturated aqueous NaHCO3 solution (10 mL) and
then with brine (10 mL). The organic layer was dried over
anhydrous MgSO4 and then concentrated in vacuo. The
resulting oil was diluted with benzene (20 mL) and washed
with FC-72 (10 mL×6). The combined FC-72 layer was
concentrated in vacuo to give a syrup, which was purified
on a silica gel column (hexane:EtOAcˆ5:1) to afford the
(R,S)-FDHPEB (V) as a colorless viscous syrup (413 mg,
75% overall yield): [a]1D6 ϩ7.94Њ (c 1.16, benzotrifluoride),
Solid phase extraction with fluorous reverse phase silica
gel: The reaction was quenched with 0.1N hydrochloric acid
(6 mL) and extracted with Et2O (20 mL×4). The combined
organic layer was washed with brine (15 mL), dried over
anhydrous MgSO4 and concentrated in vacuo. The residue
was dissolved in Et2O (2 mL). To the solution was added
(1H,1H,2H,2H)-perfluorooctyl)dimethylsilyl bound silica
gel (1 g), then the solvent was evaporated to dryness. The
powder obtained was loaded on
a
column of
(1H,1H,2H,2H)-perfluorooctyl)dimethylsilyl bound silica
gel (4 g) and then eluted successively with acetonitrile
(30 mL) and FC-72 (40 mL). The acetonitrile fraction was
evaporated in vacuo to give crude 2-phenylcyclohexanone.
(R,S)-FDHPEB was recovered almost quantitatively from
FC-72 fraction without a loss of optical purity.
Acknowledgements
The authors wish to express their thanks to Professor Akira
Kato and Professor Hidetoshi Fujiwara, Niigata College of
Pharmacy, for the measurements of MS spectra, and to the
Laboratory for Organic Elemental Microanalysis, Faculty of

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Y. Nakamura et al. / Tetrahedron 56 (2000) 351–356
1996, 9, 75–87. (a0) Curran, D. P.; Hoshino, M. J. Org. Chem.
1996, 61, 6480–6481.
3. (a) Quici, S.; Cavazzini, M.; Ceragioli, S.; Montanari, F.; Pozzi,
G. Tetrahedron Lett. 1999, 40, 3647–3650. (b) Juliette, J. J. J.,
Pharmaceutical Sciences, Kyoto University, for the elemen-
tal analysis. We also would like to thank to Miss Ayako
Abe, Miss Takako Kazama, Miss Mayako Sato, and Miss
Chiharu Suzuki for preparation of the fluorous compounds.
This work was partially supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education,
Science, Sports, and Culture, Japan.
´
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