Asymmetric catalytic carbon-carbon bond formations in a fluorous biphasic system based on perfluoroalkyl-BINOLs

Article abstract of DOI:10.1016/S0040-4020(02)00218-1

Optically active 1,1′-binaphthols (BINOLS) substituted at the 4,4′; 6,6′ and 4,4′,6,6′ positions with perfluoroalkyl groups have been synthesized. Asymmetric diethylzinc and triethyl aluminum addition to aryl aldehydes in a fluorous biphasic system catalyzed by these perfluoroalkyl-BINOL-titanium complexes have been accomplished with good enantiomeric excess obtained.

Full text of DOI:10.1016/S0040-4020(02)00218-1

TETRAHEDRON
Pergamon
Tetrahedron 58 *2002) 3951±3961
Asymmetric catalytic carbon±carbon bond formations in a
¯uorous biphasic system based on per¯uoroalkyl-BINOLs
p
Yuan Tian, Qing Chuan Yang, Thomas C. W. Mak and Kin Shing Chan
Department of Chemistry, Open Laboratory of Chirotechnology of the Institute of Molecular Technology for Drug Discovery and Synthesis
ꢀ
University Grants Committee Area of Excellence Scheme, Hong Kong), The Chinese University of Hong Kong, Shatin New Territories,
Hong Kong, People's Republic of China
Received 20 November 2001;revised 23 January 2002;accepted 30 January 2002
0
0
0
0
0
AbstractÐOptically active 1,1 -binaphthols *BINOLS) substituted at the 4,4 ;6,6 and 4,4 ,6,6 positions with per¯uoroalkyl groups have
been synthesized. Asymmetric diethylzinc and triethyl aluminum addition to aryl aldehydes in a ¯uorous biphasic system catalyzed by these
per¯uoroalkyl-BINOL±titanium complexes have been accomplished with good enantiomeric excess obtained. q 2002 Elsevier Science Ltd.
All rights reserved.
1
. Introduction
2. Results and discussion
2.1. Synthesis of ligands
Per¯uorobutyl and per¯uorooctyl BINOL derivatives
Homogeneous asymmetric catalysis has been applied in
countless bench-scale and commodity chemical transforma-
tions. However, for chiral catalysts, which are often expen-
sive and not easy to be prepared, there remains a need for
improving their recovery methodologies. In 1994, a new
type of two-phase catalytic system±¯uorous biphasic
0
0
0
0
substituted at the 4,4 ;6,6 and 4,4 ,6,6 positions were
prepared by per¯uoroalkylation of the corresponding
bromo-BINOL with Cu/R I in DMSO at elevated tempera-
f
7
1
catalysis *FBC) was developed, based on the tempera-
ture of 90 to 1608C. The bromo-BINOLs were prepared
according to literature methods. Bromination of BINOL 1
ture-dependent phase separation of common organic and
per¯uorous solvents. A prerequisite is the use of a per¯uori-
nated catalyst that shows preferential solubility in the
per¯uorous phase. Nowadays, an increasing number of
academic and industrial groups are working on the design
0
8
and 4,4 -dibromo-BINOL 3 at 2788C gave 6,6 -dibromo-
0
0
0
9
BINOL 2 and 4,4 , 6, 6 -tetrabromo-BINOL 4 in excellent
yields *Eqs. *1) and *2)). The bromination of optically active
*R)- and *S)-1 gave *R)- and *S)-2 with excellent optical
purity of over 99% ee.
2
and application of per¯uorinated catalysts. To our know-
ledge, however, only a few papers have been reported
describing asymmetric ¯uorous biphasic catalysis which
include carbon±carbon bond forming reaction, protona-
3
4
5
tion and epoxidation.
ꢀ
ꢀ
1†
2†
We have reported the asymmetric carbon±carbon bond
formation in a ¯uorous biphasic system *AFBC) catalyzed
by a titanium per¯uoroalkyl-BINOL complex and now
6
disclose the full details of our investigation.
Keywords: asymmetric ¯uorous biphasic catalysis;per¯uoroalkyl-
binaphthols.
p
Corresponding author. Tel.: 1852-2609-6376;fax: 1852-2603-5057;
e-mail: ksc@cuhk.edu.hk
Copper-mediated cross-coupling reactions of *R)- and *S)-2
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020*02)00218-1

3952
Y. Tian et al. / Tetrahedron 58 ꢀ2002) 3951±3961
Scheme 1.
Scheme 2.

Y. Tian et al. / Tetrahedron 58 ꢀ2002) 3951±3961
Table 1. Chemical shifts of the diastereomers *S)- and *R)-11±13-*S)-CS *ppm)
3953
Compound
Methylene-H
2.58
Dd
d
S
±d
R
Methyl-H
Dd
S R
d ±d
*
*
*
*
*
*
S)-11-*S)-CS
R)-11-*S)-CS
S)-12-*S)-CS
R)-12-*S)-CS
S)-13-*S)-CS
R)-13-*S)-CS
3.00
3.39
3.16
3.49
3.17
3.49
0.42
0.88
0.40
0.86
0.40
0.85
20.39
0.07
20.33
0.13
20.32
0.13
0.79
0.65
0.82
0.69
0.81
0.68
0.55
0.54
0.61
0.58
0.60
0.58
0.24
0.11
0.21
0.11
0.21
0.10
0.14
0.01
0.13
0.03
0.13
0.02
2.51
2.76
2.63
2.77
2.64
7
with per¯uorobutyl iodide in DMSO at 908C for 5 days
yielded *R)- and *S)-5 in about 50% yield with excellent
optical purity as determined by chiral HPLC on a Diacel
OD-H column *Scheme 1). The per¯urooctylation of *S)-2
required a longer time of 8 days at 908C to give *S)-6 with a
poorer yield of 21%. The optical purity *S)-6 was not deter-
mined as racemic forms of 6 were not resolvable by chiral
HPLC *Diacel OD and AD columns) and *S)-6 was assumed
to be optically pure.
while those of the slower running isomers *more polar
1
4
diastereomers) BINOLs had an *R)-con®guration'. For
the less polar diastereomer *S)-11-*S)-CS, the methylene
group adjacent to the sulfonyl moiety appeared as an AX
system *Jˆ14.8 Hz) at 3.00 and 2.58 ppm and the two
methyl groups appeared at 0.55 and 0.79 ppm as a pair of
singlet peaks. The chemical shift difference between these
AX system peaks was 0.42 ppm. On the contrary, for the
more polar *R)-11-*S)-CS, the chemical shifts of methylene
group were 3.39 and 2.51 ppm, and those of two methyl
groups were 0.54 and 0.65 ppm. The chemical shift differ-
ence between these AX system peaks was 0.88 ppm. In
addition, comparing with the two spectra of *S)-11-*S)-CS
and *R)-11-*S)-CS, most of the chemical shifts of aromatic
protons of *S)-11-*S)-CS were further down ®eld than those
of *R)-11-*S)-CS, the differences range from 0.004 to
0.058 ppm *Table 1). Similar chromatographic and spectral
characteristics were also observed in NMR spectra of 12-
and 13-*S)-CS.
Since the copper-mediated cross-coupling reactions
required elevated temperature which would ruin the optical
purity of the starting bromo-BINOLs, the per¯uoroalkyl-
ations of 3 and 4 were carried out using racemic mixtures.
Furthermore, the optical resolution of 3 and 4 were not very
practical due to their poor solubility in organic solvents and
our unsuccessful diastereomeric resolution by fractional
recrystallization with N-benzylcinchonidium chloride,
H B´SMe -quinine, and H BO -proline. The per¯uoro-
9
1
0
1
1
12
3
2
3
3
butylation and per¯uorooctylation of 3 and 4 required a
higher temperature of 1208C to give satisfactory yields of
0
0
The structure of the less polar 4,4 ,6,6 -tetraper¯uorobutyl-
BINOL camphorsulfonate *S)-12-*S)-CS was characterized
by single crystal X-ray diffraction analysis. In this molecule,
the absolute con®guration of camphor was con®rmed to be
S, due to the con®guration of *S)-*1)-camphorsulfonyl
chloride used. Based on the IUPAC tentative rule for the
7
±9.
2.2. Optical resolution and determination of absolute
con®guration of ligands
1
5
The resolution of optically active ligands of 7±9 were
achieved by sulphonation of racemic 7±9 with *S)-camphor-
nomenclature of organic chemistry, the absolute con-
®guration of the chiral axis in compound *S)-12-*S)-CS
was con®rmed to be S. The torsion angle of C1±C8±
C18±C11 was found to be 97.68. The crystal structure of
*S)-12-*S)-CS is highly disordered due to the four per¯uoro-
butyl chains.
1
3
sulphonyl chloride to yield 11±13. Careful chromato-
graphic separation of 11±13 yielded the diastereomerically
pure compounds which were further converted to the opti-
cally pure 7±9 by saponi®cation *Scheme 2). Since chiral
HPLC using Diacel OD or AD columns was not able to
resolve the racemates 7±9, the optical purities were deter-
0
CD spectra of optically active 4,4 -diper¯uoroalkyl- and
1
0
0
mined by H NMR spectroscopy on the re-formed camphor-
sulphonates.
4,4 ,6,6 -tetraper¯uoroalkyl-BINOLs revealed that all of
the less polar diastereomeric camphorsulfonates related
per¯uoroalkyl-BINOLs of *S)-7±9 exhibited negative
Cotton effects at lˆ208±225 nm and positive Cotton
effects at lˆ238±246 nm. On the contrary, more polar
diastereomeric camphorsulfonates related per¯uoroalkyl-
BINOLs *R)-7±9 had corresponding mirror-image CD
spectra with positive Cotton effects at lˆ208±225 nm
and negative Cotton effects at lˆ238±246 nm. The
absolute con®gurations of *S)-7±9 were further con®rmed
to be S by their CD spectra based on the comparison with the
The absolute con®guration of 7±9 were determined based
on four kinds of physical evidence: relative chromatographic
mobility, proton chemical shift correlation, X-ray diffraction
studies of BINOL camphor sulphonate *S)-12-*S)-CS and
circular dichorism *CD) of BINOLs.
The proton NMR spectra of the diastereomeric mixtures of
1
1±13-*S)-CS exhibited two AX systems arising from the
1
4
diastereotopic methylene groups adjacent to the sulfonyl
moiety and two pairs of singlet peaks contributing to the
diastereotopic methyl groups of camphor with their relative
integrations in the ration of 1:1, indicating the relative
percentage of the two diastereomers. Chow, in the study
of the absolute con®guration of BINOLs, has concluded
that `The axis of all of the faster running isomers *less
polar diastereomers) BINOLs had an *S)-con®guration
spectra of other optically active BINOL derivatives.
2.3. Asymmetric ¯uorous biphasic catalytic diethylzinc
addition
The diethylzinc addition of aldehydes is classical in
asymmetric catalysis and serves as the testing ground for
the ef®ciency of a newly developed catalytic system.

3954
Y. Tian et al. / Tetrahedron 58 ꢀ2002) 3951±3961
Table 2. The result of asymmetric diethylzinc addition to benzaldehyde
catalyzed by BINOL derivatives in dichloromethane
*S)-BINOL derivatives gave *S)-products. Among BINOL
analogs, the substituents at 4 or 6 positions should not affect
the absolute con®guration of product during the same reac-
tion system. Therefore, the absolute con®gurations of 5±8
were further con®rmed.
a
b
Entry
Ligand
Conversion
ee *%)
Conf.
a
b
1
2
3
4
5
*R)-1
*R)-1
*R)-5
*S)-7
*S)-8
99
100
88
92
R
R
R
S
c
c,d
c,d
a
b
97
99
77
79
a
b
With the optically active per¯uoroalkyl-BINOLs in hand,
the ¯uorous biphasic catalysis was attempted. Per¯uoro-
a
97
b
70
S
*
methyldecalin) and hexane were used as the ¯uorous and
a
Determined by proton NMR.
organic solvent, respectively. The approximate partition
coef®cients of per¯uoroalkyl-BINOLs which contain the
different number of ¯uorocarbons were determined and
b
c
d
Determined by HPLC on a Chiracel OD-H column.
Data were from Ref. 17.
Determined by GLC.
18
the results are shown in Table 3. The compounds which
contained more per¯uorocarbons, are more soluble in
¯uorous solvent but less soluble in hexane.
Ti±BINOL complex has been used in this catalysis to give
1
6,17
good to excellent yields and good enantioselectivities.
The application of the newly synthesized optically pure
per¯uoroalkyl-BINOLs as chiral ligands system has been
studied in Ti±BINOL catalyzed reaction in ¯uorous
biphasic version.
The asymmetric catalytic diethylzinc additions to benzalde-
hyde in ¯uorous biphasic system using per¯uoroalkyl-
BINOLs as chiral ligands were carried out in a mixture of
per¯uoro*methyldecalin) and hexane *Eq. *4), Table 6).
Optically pure per¯uoroalkyl-BINOL *20 mol%) was
dissolved in the ¯uorous solvent, Ti*O Pr) *0.5 M solution
in hexane, 1.4 equiv.) was then added to form a two-layer
system at room temperature. Heating the mixture to 458C
i
Initially, monophasic experiments were carried out in
dichloromethane to test the effectiveness of chiral induction.
Optically pure per¯uoroalkyl-BINOLs *20 mol%) was
treated with 1.4 mol equiv. of titanium tetraisopropoxide
at room temperature for 30 min in dichloromethane to
form the co-catalyst, which promoted the addition of
diethylzinc *3.0 mol equiv.) to benzaldehyde at 08C for
4
gave a deep red or orange one-layer solution. Then, Et Zn
2
*1.0 M solution in hexane, 3.0 equiv.) was added and the
reaction mixture was stirred at 458C for 15 min. The color
of the reaction mixture changed into dark gray. After freshly
distilled benzaldehyde *1.0 equiv.) was added, the mixture
changed yellow in color immediately. The reaction mixture
was stirred at 458C as a homogeneous phase for another
30 min. After the reaction mixture was cooled down to
08C, a two-layer mixture formed. The light color upper
layer was withdrawn with a syringe and added into 10%
HCl solution. 1-Phenylpropanol was obtained by usual
5
pure *R)-BINOL *R)-1, *R)-6,6 -diper¯uorobutyl-BINOL
h to afford 1-phenyl-propanol *Eq. *3), Table 2). Optically
0
R)-5, *S)-4,4 -diper¯uorobutyl-BINOL *S)-7 and *S)-
0
,4 ,6,6 -tetraper¯uorobutyl-BINOL *S)-8 have been
*
0
0
4
employed as the chiral ligands. The results showed that all
per¯uoroalkyl-BINOLs were active in the catalytic diethyl-
zinc addition of benzaldehyde. The enantioselectivities of
the reactions catalyzed by *R)-5 and *S)-7 were similar
work up. To the deep color bottom layer, a new batch of
Ti*O Pr) *0.5 M solution in hexane, 1.4 equiv.) was added.
0
0
i
*
entries 3 and 4) and a little higher than that by 4,4 ,6,6 -
4
tetraper¯uorobutyl-BINOL 8 *entry 5). All per¯uoroalkyl-
BINOLs exhibited a slightly poorer enantioselectivities than
the parent BINOL 1.
The second and subsequent reaction cycle was then carried
out similarly *Table 4).
ꢀ3†
ꢀ4†
When *R)-BINOL derivatives were used as the ligands, the
absolute con®gurations of obtained products were R, while
For the parent BINOL 1, which has no ¯uorocarbon, after
the ®rst reaction run, BINOL was removed from the reaction
system since BINOL prefers to dissolve in hexane rather
than ¯uorous solvent. Therefore, the enantioselectivity of
the second run was almost lost. When the ligand was
Table 3. Partition coef®cients of per¯uoroalkyl-BINOLs in organic and
uorous solvent
¯
BINOL
Hexane/
per¯uoro-
methyldecalin)
0
changed to 6,6 -diper¯uorobutyl-BINOL *R)-5, which
a
contained eight ¯uorocarbons and whose partition coef®-
cient in hexane/per¯uoro*methyldecalin) is only 1:2, the
enantiomeric excess of product decreased from 70% in the
*
0
6
4
6
4
,6 -Diper¯uorobutyl-BINOL 5
0
1:2
0
,4 ,6,6 -Tetraper¯uorobutyl-BINOL 8
,6 -Diper¯uorooctyl-BINOL 6
1:15
1:23
1:53
®
rst run to 28% in the second run and then to 5% in the third
0
0
0
0
run. When 6,6 -diper¯uorooctyl-BINOL *S)-6 was used,
which contains 16 ¯uorocarbons and whose partition coef®-
cient in hexane/per¯uoro*methyldecalin) is 1:23, the
decrease of % ee of product along with the reaction runs
was a little slower than that of 1 and 5. After six runs, the
,4 ,6,6 -Tetraper¯uorooctyl-BINOL 9
a
A mixture of 50 mg per¯uoroalkyl-BINOL in per¯uoro*methyldecalin)
1 mL) and hexane *1 mL) was heated to 458C to give a clear solution.
*
Then the solution was cooled down to 08C to obtain a biphasic mixture.
The two phases were separated and the solvents were evaporated in
vacuo. The contents of the BINOLs in each phase were determined by
weighing the residue.
0
0
enantioselectivity was lost. 4,4 ,6,6 -Tetraper¯uorobutyl-
BINOL *S)-8, which has 16 ¯uorocarbons, behaved

Y. Tian et al. / Tetrahedron 58 ꢀ2002) 3951±3961
3955
Table 4. AFBC of diethylzinc addition to benzaldehyde catalyzed by optically pure per¯uoroalkyl-BINOL±titanium complexes
Cpd
Run
*R)-1
*R)-5
*S)-6
*S)-8
*S)-9
a
b
a
b
a
c
a
c
a
c
Con.
ee *%)
Con.
ee *%)
Con.
ee *%)
Con.
ee *%)
Con.
ee *%)
d
1
2
3
4
5
6
7
8
9
98
71
±
±
±
68
5
±
±
±
99
98
57
±
±
±
70
28
5
±
±
99
99
99
83
51
±
64
58
41
15
4
98
99
99
95
76
63
61
41
53
31
15
7
69
54
57
58
55
60
58
57
56
55
25
5
80
79
76
80
79
80
79
79
±
±
±
±
±
±
±
±
3
3
±
±
e
1
1
0
1
73
51
e,f
a
b
c
d
e
f
Conversion determined by HPLC on a Chiracel OD±H column using para-methoxy-phenethyl alcohol as the internal standard.
The product was in *R)-con®guration.
The product was in *S)-con®guration.
The reaction temperature was 408C, the reaction was not homogeneous.
Fresh Ti*O Pr) was not added.
The reaction was carried out at 458C for 14 h.
i
4
0
0
similarly. When 4,4 ,6,6 -Tetraper¯uorooctyl-BINOL *S)-9,
which contains 32 ¯uorocarbons and whose partition coef®-
cient [hexane/per¯uoro*methyldecalin)] is more than 1:50,
was tested in AFBC, to our delight, the enantiomeric excess
of product as well as the chemical yields were maintained
after nine reaction runs, no signi®cant decrease along with
the reaction run was observed *Table 4). The critical
temperature for this biphasic system was 458C, lower
chemical yield and enantioselectivity were obtained when
the reaction temperature was lower than 458C as the reaction
proceeded heterogeneously *Run 1). The addition of fresh
titanium complex in each run was necessary to maintain the
the reaction was a little faster than that with benzaldehyde
and was completed in 45 min according to TLC analysis
with a quantitative yield of 15b being obtained. On the
contrary, the reaction of the more electron-rich 4-methoxy-
benzaldehyde was slower. The yield of 15c was around 90%
after 2 h. The FBC phenomenon has been observed in both
cases. There were no signi®cant changes in the chemical
yield as well as in the enantioselectivities of products after
three reaction cycles.
From the above results, the number of ¯uorocarbon is
important to ensure the reusability of the ligands in FBC.
1
7
0
0
reactivity and selectivity of the catalysis. When the fresh
titanium complex was not added, the reaction rate was
slower, and the % ee of product decreased dramatically
Optically pure 4,4 ,6,6 -tetraper¯uorooctyl-BINOL 9,
which contains 32 ¯uorocarbons, has been found a good
ligand in titanium catalyzed asymmetric diethylzinc
addition to aromatic aldehydes in ¯uorous biphasic system.
*
runs 10 and 11).
2.4. Asymmetric ¯uorous biphasic catalytic triethyl-
aluminum addition
In 1997, the ®rst example of an asymmetric catalytic ethyl-
ation of aldehydes with triethylaluminum in the presence of
ꢀ
5†
i
a chiral titanium alkoxide catalyst prepared from Ti*O Pr)
4
1
7a
and optically pure BINOL was reported by Chan.
In
Other aryl aldehydes also underwent Et Zn addition in this
2
comparison with asymmetric catalytic diethylzinc addition,
the reaction conditions were quite similar and the enantio-
selectivities were a little lower. Therefore, studies extended
to the ¯uorous biphasic system were carried out.
¯
*
uorous biphasic system catalyzed by *S)-9 *Table 5, Eq.
5)). For the more electron-de®cient 4-chlorobenzaldehyde,
Table 5. AFBC of Et
2
Zn addition to aryl aldehydes catalyzed by *S)-9
0
0
a
b
Optically pure *S)-4,4 ,6,6 -tetraper¯uorooctyl-BINOL *S)-
was used as the chiral ligands in per¯uoro*methyldecalin)/
hexane biphasic system *Eq. *6), Table 6). Although the
Run
15b
15c
9
c
d
e
d
%
Yield
ee *%)
% Yield
ee *%)
mixture of *S)-9 *20 mol%) in ¯uorous solvent and
Ti*O Pr) *0.5 M solution in hexane) was heated to 458C
1
2
3
99
98
99
54
51
51
91
92
91
37
41
40
i
4
to become homogeneous deep orange solution, when
Et Al *1.0 M solution in hexane, 3.0 equiv.) was added,
3
a
b
c
Reaction time was 45 min.
Reaction time was 2 h.
Determined by chiral HPLC using 4-methoxyphenethyl alcohol as the
internal standard.
The major isomer had the *S) con®guration.
Determined by chiral HPLC using 3-nitrobenzyl alcohol as the internal
standard.
the mixture could not remain as one-layer solution at 458C
any more. After the addition of benzaldehyde, the reaction
proceeded heterogeneously at 458C for 30 min and gave
59% yield and 63% ee *Run 1). When the temperature
was increased to 538C, the reaction system became homo-
geneous and the yields and ees of product were improved to
d
e

3
956
Y. Tian et al. / Tetrahedron 58 ꢀ2002) 3951±3961
Al addition to benzaldehyde catalyzed by *S)-9-
Table 6. AFBC of Et
titanium complex
3
than that of benzaldehyde.
a
b
Run
Yield *%)
ee *%)
c
1
59
76
88
82
79
82
47
65
78
63
77
79
77
82
80
58
10
0
2
3
4
5
6
7
8
9
ꢀ7†
d
e
3. Conclusion
e
a
The asymmetric catalytic carbon±carbon bond formation in
¯uorous biphasic system based on BINOL chemistry has
been developed. A series of per¯uoroalkyl-BINOLs has
been investigated in AFBC diethylzinc and triethyl-
aluminum addition to aromatic aldehydes. The number of
Determined by chiral HPLC using para-methoxy-phenethyl alcohol as
the internal standard.
The product was in *S)-con®guration.
b
c
d
e
The reaction temperature was 458C, the reaction was not homogeneous.
The reaction was carried out at 258C for 20 h.
was not added.
i
Fresh Ti*O Pr)
4
¯
very important to ensure the reusability of the ligands in
uorocarbons in the ligand molecules has been found to be
0
0
FBC. Optically pure 4,4 ,6,6 -tetraper¯uorooctyl-BINOL
, which contains 32 ¯uorocarbons and whose partition
7
6 and 77%, respectively *Run 2). The following reaction
9
runs were therefore carried out at 538C and gave the similar
results. No signi®cant difference along with the reaction run
was observed during six runs. Therefore, chiral ligand *S)-9
was demonstrated to be a good ligand for AFBC triethyl-
aluminum addition of benzaldehyde. Moreover, the ees of
product were a little higher than that in the AFBC diethyl-
zinc addition using the same ligand. When the temperature
was decreased to room temperature *258C), the reaction was
completed after 20 h, low yield and ee were obtained *Run
coef®cient in hexane/per¯uoro*methyldecalin) is 1:53, has
been found to be an effective ligand in asymmetric diethyl-
zinc and triethylaluminum additions to aromatic aldehydes
in ¯uorous biphasic system.
4. Experimental
4.1. General
7). If the fresh titanium complex was not added, the enantio-
selectivities of the reaction was lost *runs 8 and 9) *Table 6).
Melting points were measured on an Electrothermal melting
apparatus and were uncorrected. H NMR spectra were
1
recorded on a Bruker DPX 300 *300 MHz) spectrometer.
Spectra were referenced internally to the residual proton
resonance in CDCl *d 7.26 ppm), or with tetramethylsilane
3
ꢀ6†
*TMS, d 0.00 ppm) as internal standard. Coupling constants
*
obtained on a Bruker DPX 300 *75 MHz) spectrometer
1
J) were reported in Hertz *Hz). C NMR spectra were
3
Similarly, other aromatic aldehydes were also used as the
substrates in AFBC triethylaluminum addition and the
results are shown in Table 7. The procedure was the same
as the reaction of benzaldehyde. For the electron-de®cient
and were referenced to CDCl *d 77.00 ppm). Mass spectra
3
*EIMS and FABMS) were recorded on a HP 5989B Mass
Spectrometer. High-resolution mass spectra *HRMS) were
recorded on a Bruker APEX 47e FT-ICR Mass Spectro-
meter *ESI-MS). Speci®c rotation were measured on a
Perkin±Elmer 341 polarimeter. The HPLC analyses were
conducted on a Waters 486 system using a Daicel chiral
column. CD spectra were recorded on a JASCO J-20C spec-
tropolarimeter. Elemental Analysis was performed by the
Medac Ltd., Department of Chemistry, Brunel University,
United Kingdom.
4
-chlorobenzaldehyde, the yield was similar and the
enantioselectivity was lower than that of benzaldehyde.
However, for the electron-rich 4-methoxy-BINOL, after
2
h reaction at 538C, only 10% product was obtained. The
ee of product was around 38%. Comparing with AFBC
diethylzinc addition, for the chloro- or methoxy-benzalde-
hydes, the enantioselectivities were similar or slightly lower
Table 7. AFBC of Et
3
Al addition to aryl aldehydes using *S)-9-titanium complex
a
a
b
Reaction
Benzaldehyde
4-Cl-Benzaldehyde
4-MeO-benzaldehyde
c
d
c
d
e
d
Run
Yield *%)
ee *%)
Yield *%)
ee *%)
Yield *%)
ee *%)
1
2
3
59
76
88
63
77
79
66
67
±
48
52
±
10
13
±
38
37
±
a
The reaction was carried out at 538C for 30 min.
The reaction was carried out at 538C for 2 h.
Determined by chiral HPLC using para-methoxy-phenethyl alcohol as the internal standard.
The product was in *S)-con®guration.
Determined by chiral HPLC using 3-nitrobenzyl alcohol as internal standard.
b
c
d
e

Y. Tian et al. / Tetrahedron 58 ꢀ2002) 3951±3961
3957
Unless otherwise noted, all materials were obtained from
commercial suppliers and used without further puri®cation.
Tetrahydrofuran *THF) and diethyl ether *Et O) were
distilled from sodium benzophenone ketyl immediately
prior to use. Hexane was distilled over calcium chloride.
Toluene was distilled from sodium and dichloromethane
was distilled over calcium hydride. Thin layer chromato-
graphy was performed on Merck precoated silica gel 60
F254 plates. Silica gel *70±230 and 230±400 mesh) was
used for column chromatography.
NMR *75.5 MHz, CDCl ) d 110.46, 110.92, 111.38,
3
116.09, 119.04, 119.29, 124.55, 124.74, 125.01, 125.65,
127.23, 128.33, 130.89, 132.56, 132.75, 134.98, 154.73;
SIMS: 1122 *M );Anal. Calcd for C H F O : C, 38.52;
2
1
3
6
12 34
2
H, 1.08. Found: C, 38.78;H, 1.33.
0
binaphthyl-2,2 -diol ꢀ7). A mixture of 4,4 -dibromo-
0
4.1.4. Preparation of racemic 4,4 -diper¯uorobutyl-1,1 -
0
BINOL 3 *111 mg, 0.25 mmol), copper bronze *160 mg,
0
2
1
2.5 mmol) and per¯uorobutyl iodide *346 mg, 0.18 mL,
1.0 mmol) in anhydrous DMSO *3 mL) was degassed
three times, and then heated to 1208C for 4 days in a Telfon
stopper ¯ask. After cooling down, ethyl acetate *10 mL) was
added and the mixture was ®ltered through Celite. The
®ltrate was washed with 10% HCl, water, brine and dried
0
binaphthyl-2,2 -diol ꢀR)-5. A mixture of optically pure
0
4
.1.1. Preparation of ꢀR)-6,6 -diper¯uorobutyl-1,1 -
0
0
20
*
R)-6,6 -dibromo-BINOL *2) *2.22 g, 5.0 mmol), copper
bronze *3.2 g, 50 mmol) and per¯uorobutyl iodide *6.92 g,
.44 mL, 20 mmol) in anhydrous DMSO *50 mL) was
3
over MgSO . After removal of the solvent, the residue was
4
degassed three times, and then heated to 908C for 5 days.
After cooling down, ethyl acetate *150 mL) was added and
the mixture was ®ltered through Celite, the ®ltrate was
washed with 10% HCl, water, brine and dried over
MgSO . After removal of the solvent, the residue was puri-
4
®ed by column chromatography *ethyl acetate/hexaneˆ1:6)
to give *R)-5 *1.25 g, 52%) as a white solid. Mp 65±668C;
puri®ed by column chromatography *ethyl acetate/hexane/
dichloromethaneˆ1:10:0.2) to give 7 *90 mg, 50%) as a
yellow oil. R ˆ0.59 *ethyl acetate/hexane/dichloro-
f
1
methaneˆ1:4:0.2); H NMR *300 MHz, CDCl ) d 5.43
3
*brs, 2H), 7.20 *d, 2H, Jˆ8.3 Hz), 7.41 *dt, 2H, Jˆ0.7,
7.1 Hz), 7.52 *td, 2H, Jˆ1.3, 7.2 Hz), 7.77 *s, 2H), 8.29
1
3
*d, 2H, Jˆ8.5 Hz); C NMR *75.5 MHz, CDCl ) d
3
R ˆ0.28 *ethyl acetate/hexane/dichloromethaneˆ1:3:0.2);
115.63, 115.76, 117.26, 119.45, 120.34 *t, Jˆ10.3 Hz),
124.86, 125.43, 125.47, 125.51, 125.56, 125.60, 125.64,
125.88, 126.13, 128.30, 128.33, 133.93, 151.02;FABMS:
m/z *relative intensity) 723 *[M1H] , 100), 704 *3), 553
*30);HRMS *M ) Calcd for C H O F 722.0544. Found
f
2
0
[
{
a] ˆ225.78 *c 1.0, CHCl );optical purity .99% ee
D
3
chiral Daicel OD-H column *0.46£15 cm), hexane/2-
1
1
propanolˆ9:1, ¯ow rate: 1.0 mL/min, T ˆ5.51 min}; H
R
1
NMR *300 MHz, CDCl ) d 5.30 *brs, 2H), 7.22 *d, 2H,
3
28 12
2 18
Jˆ8.9 Hz), 7.45 *d, 2H, Jˆ8.8 Hz), 7.51 *d, 2H, Jˆ
722.0503.
4.1.5. Preparation of diastereomeric 2,2 -di-[ꢀ1S)-
1
3
9
.0 Hz), 8.11 *d, 2H, Jˆ9.0 Hz), 8.18 *s, 2H); C NMR
0
camphor-10-sulfonyl]-4,4 -diper¯uorobutyl-1,1 -binaphthyl
*
75.5 MHz, CDCl ) d 110.62, 115.80 *q, Jˆ31.7 Hz),
3
0
0
1
1
7
19.29, 124.53, 124.61, 124.77, 128.33, 132.69, 135.05,
54.73;EIMS: m/z *relative intensity) 723 *[M1H] , 82),
04 *7), 553 *100), 525 *7), 485 *5), 333 *12);FABMS: m/z
1
14b
0
ꢀS)-11-ꢀS)-CS and ꢀS)-11-ꢀS)-CS. To a solution of 4,4 -
diper¯uorobutyl-BINOL 7 *680 mg, 0.94 mmol) and *1S)-
camphor-10-sulfonyl chloride 10 *948 mg, 3.8 mmol) in dry
CCl4 *15 mL) at 08C, triethylamine *476 mg, 0.66 mL,
4.7 mmol) was added. The yellow solution was stirred over-
night. Water *15 mL) was added and the reaction mixture
1
*
relative intensity) 722 *M , 100), 704 *8), 694 *2), 584 *2),
1
5
7
69 *2), 553 *59);HRMS *M ) Calcd for C H O F
28 12 2 18
22.0544. Found 722.0513.
0
0
4
.1.2. Preparation of ꢀS)-6,6 -diper¯uorobutyl-1,1 -
0
was extracted with CCl . The combined organic layer was
4
washed with brine and dried over MgSO . After removal of
4
binaphthyl-2,2 -diol ꢀS)-5. The procedure was the same
as that for the preparation of *R)-isomer. Mp 60±638C;
the solvent, the residue was puri®ed by column chromato-
graphy *ethyl acetate/hexaneˆ1:8) to give a mixture of
diastereomers 11-*S)-CS *922 mg, 85%) as a white solid.
2
0
[
*
a]D ˆ126.18 *c 0.5, CHCl );optical purity .99% ee
3
HPLC: Daicel OD-H column *0.46£15 cm), hexane/2-
1
propanolˆ9:1, ¯ow rate: 1.0 mL/min, T ˆ3.61 min).
SIMS: m/z 1151 *[M1H] ).
R
0
0
binaphthyl-2,2 -diol ꢀS)-6. A mixture of optically pure
4
.1.3. Preparation of ꢀS)-6,6 -diper¯uorooctyl-1,1 -
0
Careful column chromatography *hexane/dichloro-
methaneˆ3:5) gave less polar diastereomer *S)-11-*S)-CS.
0
20
1
*
S)-6,6 -dibromo-BINOL 2 *2.22 g, 5.0 mmol), copper
bronze *3.2 g, 50 mmol) and per¯uorobutyl iodide *10.9 g,
.3 mL, 20 mmol) in anhydrous DMSO *50 mL) was
degassed three times, and then heated to 908C for 8 days.
After the reaction mixture was cooled down to room
temperature, ethyl acetate *200 mL) was added and the
mixture was ®ltered through Celite. The ®ltrate was washed
Mp 78±808C; R ˆ0.33 *hexane/dichloromethaneˆ3:5); H
f
NMR *300 MHz, CDCl ) d 0.55 *s, 6H), 0.79 *s, 6H), 1.25±
3
5
1.41 *m, 4H), 1.81 *d, 2H, Jˆ18.5 Hz), 1.81±1.90 *m, 2H),
1.96±2.04 *m, 4H), 2.23 *dt, 2H, Jˆ18.6, 3.6 Hz), 2.58 *d,
2H, Jˆ14.8 Hz), 3.00 *d, 2H, Jˆ14.8 Hz), 7.34 *d, 2H,
Jˆ8.5 Hz), 7.49 *t, 2H, Jˆ8.3 Hz), 7.66 *t, 2H,
1
3
Jˆ8.1 Hz), 8.14 *s, 2H), 8.35 *d, 2H, Jˆ8.6 Hz);
C
with 10% HCl, water, brine and dried over MgSO . After
4
NMR *75.5 MHz, CDCl ) d 19.06, 19.17, 24.71, 26.64,
3
removal of the solvent, the residue was puri®ed by column
42.13, 42.54, 47.67, 49.27, 57.58, 123.47 *t, Jˆ10.3 Hz),
125.21, 127.24, 127.78, 128.27, 128.40, 133.76, 143.98,
212.79.
chromatography *ethyl acetate/hexane/dichloromethaneˆ
1
1
:8:1) to give *S)-6 *1.2 mg, 21%) as a yellow solid. Mp
37±1398C; R ˆ0.36 *ethyl acetate/hexane/dichloro-
f
2
0
1
methaneˆ1:3:0.2);[ a] ˆ124.48 *c 0.5, CHCl ); H
NMR *300 MHz, CDCl ) d 5.26 *br, 2H), 7.23 *t, 2H,
More polar diastereomer *R)-11-*S)-CS. Mp 80±828C;
R ˆ0.27 *hexane/dichloromethaneˆ3:5);
D
3
1
H
*300 MHz, CDCl ) d 0.54 *s, 6H), 0.65 *s, 6H), 1.20±1.31
NMR
3
f
Jˆ8.8 Hz), 7.45 *d, 2H, Jˆ9.2 Hz), 7.48 *d, 2H,
3
1
3
Jˆ9.2 Hz), 8.10 *d, 2H, Jˆ9.0 Hz), 8.18 *s, 2H);
C
*m, 4H), 1.77 *d, 2H, Jˆ18.4 Hz), 1.75±1.77 *m, 4H),

3958
Y. Tian et al. / Tetrahedron 58 ꢀ2002) 3951±3961
1
2
.94±1.96 *m, 2H), 2.22 *dt, 2H, Jˆ3.1, 18.6 Hz), 2.51 *d,
H, Jˆ14.9 Hz), 3.39 *d, 2H, Jˆ14.9 Hz), 7.28 *d, 2H,
bromo-BINOL 4 *4.6 g, 7.6 mmol), copper bronze *7.3 g,
114.6 mmol) and per¯uorobutyl iodide *15.9 g, 7.9 mL,
45.8 mmol) in anhydrous DMSO *40 mL) was degassed
three times, and then heated to 1208C for 5 days. After
cooling down, ethyl acetate *100 mL) was added and the
mixture was ®ltered through Celite, the ®ltrate was washed
Jˆ8.3 Hz), 7.45 *t, 2H, Jˆ8.1 Hz), 7.64 *td, 2H, Jˆ8.5,
1
3
1
.1 Hz), 8.17 *s, 2H), 8.35 *d, 2H, Jˆ8.6 Hz); C NMR
*
75.5 MHz, CDCl ) d 18.91, 24.42, 26.51, 42.03, 42.42,
3
4
1
7.55, 49.41, 57.49, 123.28 *t, Jˆ9.8 Hz), 125.12, 127.18,
27.78, 128.15, 128.40, 133.82, 143.80, 212.74.
with 10% HCl, water, brine and dried over MgSO . After
4
removal of the solvent, the residue was puri®ed by column
chromatography *ethyl acetate/hexaneˆ1:10) to give 8
0
binaphthyl-2,2 -diol ꢀS)-7. To a suspension of *S)-11-
0
4
.1.6. Preparation of ꢀS)-4,4 -diper¯uorobutyl-1,1 -
0
S)-CS *413 mg, 0.36 mmol) in methanol *20 mL), NaOH
14b
*3.16 g, 36%) as a yellow oil. R ˆ0.32 *ethyl acetate/
f
1
*
*
hexaneˆ1:5); H NMR *300 MHz, CDCl ) d 5.93 *brs,
3
1 M, 5 mL) was added. The resulting yellow solution was
2H), 7.28 *d, 2H, Jˆ8.9 Hz), 7.55 *d, 2H, Jˆ9.0 Hz), 7.88
1
*s, 2H), 8.55 *s, 2H); C NMR *75.5 MHz, CDCl ) d
3
re¯uxed for 24 h. After cooling down, 10% HCl was added
to neutralize the solution to pH 7. Methanol was removed in
vacuo and the residue was extracted with ethyl acetate. The
combined organic layer was washed with brine and dried
3
112.17, 115.55, 115.78, 115.99, 116.88, 119.36, 121.83 *t,
Jˆ9.7 Hz), 124.93, 125.21, 125.57, 125.91, 126.23, 126.55,
129.21, 129.50, 129.81, 135.68, 153.05;FABMS: m/z
1
over MgSO . After removal of the solvent, the product was
4
*relative intensity) 1159 *[M1H] , 85), 1141 *17), 990
*100), 853 *3), 820 *19), 772 *18);SIMS: m/z 1158 *M );
1
puri®ed by column chromatography *ethyl acetate/
hexaneˆ1:10) to give *S)-7 *213 mg, 82%) as a pale yellow
Anal. Calcd for C H F O : C, 37.33;H, 0.87. Found: C,
3
6
10 36
2
2
0
1
solid. Mp 78±808C;[ a]D ˆ210.78 *c 1.0, CHCl ); H
37.27;H, 0.92.
3
NMR spectrum was identical with the spectrum of racemic 7.
0
camphor-10-sulfonyl]-4,4 ,6,6 -tetraper¯uorobutyl-1,1 -
4
.1.10. Preparation of diastereomeric 2,2 -di-[ꢀ1S)-
0
binaphthyl-2,2 -diol ꢀR)-7. To a suspension of *R)-11-*S)-
0
0
binaphthyl ꢀS)-12-ꢀS)-CS and ꢀR)-12-ꢀS)-CS. To a solu-
0
0
4
.1.7. Preparation of ꢀR)-4,4 -diper¯uorobutyl-1,1 -
0
CS *407 mg, 0.35 mmol) in methanol *15 mL), NaOH *1 M,
0
0
tion of 4,4 ,6,6 -tetraper¯uorobutyl-BINOL 8 *702 mg,
0.61 mmol) and *1S)-camphor-10-sulfonyl chloride
*609 mg, 2.4 mmol) in dry CCl *15 mL) at 08C, triethyla-
5
mL) was added. The resulting yellow solution was
re¯uxed for 24 h. After cooling down, 10% HCl was
added to neutralize the solution to pH 7. Methanol was
removed in vacuo and the residue was extracted with
ethyl acetate. The combined organic layer was washed
4
mine *306 mg, 0.57 mL, 3.0 mmol) was added. The yellow
solution was stirred at room temperature for 10 h and then
re¯uxed overnight. Water *15 mL) was added and the reac-
with brine and dried over MgSO . After removal of the
4
tion mixture was extracted with CCl . The combined
4
solvent, the product was puri®ed by column chromato-
organic layer was washed with brine and dried over
MgSO . After removal of the solvent, the residue was
graphy *ethyl acetate/hexaneˆ1:10) to give *R)-7
4
*
[
211 mg, 83%) as a pale yellow solid. Mp 78±808C;
puri®ed by column chromatography *ethyl acetate/
hexaneˆ1:8) to give a mixture of diastereomers 12-*S)-CS
2
0
1
a]D ˆ110.68 *c 1.1, CHCl ); H NMR spectrum was
3
1
*800 mg, 83%) as a white solid. SIMS: m/z 1625 *[M1K] ),
the same as the spectrum of racemic 7.
1
609 *[M1Na] );APCIMS: m/z 1609 *[M1Na] ), 1587
1
1
*[M1H] ), 1586 *M ).
0
0
binaphthyl-2,2 -diol ꢀ4). To a solution of 4,4 -dibromo-
0
1
1
4
.1.8.
Preparation
0
of
4,4 ,6,6 -tetrabromo-1,1 -
0
21
2
1
BINOL 3 *2.22 g, 5 mmol) in dichloromethane *50 mL) at
788C, bromine *2.40 g, 0.78 mL, 15 mmol) in dichloro-
Careful column chromatography *hexane/dichloro-
methaneˆ3:5) gave less polar diastereomer *S)-12-*S)-CS.
2
methane *5 mL) was added dropwise. The resulting brown
solution was stirred and warmed up to room temperature for
Mp 134±1358C; R ˆ0.19 *hexane/dichloromethaneˆ3:5);
f
1
H NMR *300 MHz, CDCl ) d 0.61 *s, 6H), 0.82 *s, 6H),
3
2
days. Saturated sodium thiosulfate solution *10 mL) was
1.21±1.30 *m, 4H), 1.81 *d, 2H, Jˆ18.5 Hz), 1.86±2.03 *m,
6H), 2.23 *dt, 2H, Jˆ18.5, 2.7 Hz), 2.76 *d, 2H, Jˆ14.9 Hz),
3.16 *d, 2H, Jˆ14.9 Hz), 7.43 *d, 2H, Jˆ9.0 Hz), 7.65 *t,
added and the solution was stirred for 30 min. The organic
layer was separated and aqueous layer was extracted with
ethyl acetate *2£20 mL), the combined organic layer was
1
3
2H, Jˆ8.9 Hz), 8.27 *s, 2H), 8.63 *s, 2H); C NMR
washed with water, brine and dried over MgSO . After
*75.5 MHz, CDCl ) d 19.09, 19.19, 24.67, 26.58, 42.06,
3
4
removal of solvent, the crude product was puri®ed by
column chromatography *ethyl acetate/hexaneˆ1:8) to
42.57, 47.72, 49.71, 57.63, 115.90, 119.28, 124.82 *t,
Jˆ10.3 Hz), 125.36, 127.34, 127.44, 127.90, 128.40,
128.72, 128.83, 129.12, 129.43, 130.91, 135.15, 145.80,
212.59;Anal. Calcd for C 56H F S O : C, 42.38;H, 2.41.
Found: C, 42.15;H, 2.39. A single crystal was obtained
from hexane/dichloromethane solution. X-Ray crystallo-
graphic data is shown in the supporting information and
has been deposited in Cambridge Crystallographic Data
Centre.
give 4 *2.98 g, 99%) as a pale brown solid. Mp 129±
1
1
NMR *300 MHz, CDCl ) d 5.56 *brs, 2H), 6.96 *d, 2H,
338C *decomp.); R ˆ0.31 *hexane/ethyl acetateˆ3:1); H
f
38 36
2
8
3
Jˆ8.9 Hz), 7.41 *dd, 2H, Jˆ8.9, 2.0 Hz), 7.73 *s, 2H),
1
3
8
1
1
6
.45 *d, 2H, Jˆ1.9 Hz); C NMR *75.5 MHz, CDCl ) d
3
10.6, 119.8, 123.0, 124.7, 126.2, 129.3, 130.0, 131.8,
32.4, 152.5;FABMS: m/z *relative intensity) 603 *2),
1
01 *M , 5), 414 *18), 391 *100), 307 *24), 289 *29), 279
1
*
31), 261 *15);HRMS *M ) Calcd for C H O Br
2
More polar diastereomer *R)-12-*S)-CS. Mp 102±1038C;
R ˆ0.08 *hexane/dichloromethaneˆ3:5);
2
0
10
4
1
5
97.7414. Found 597.7361.
H
300 MHz, CDCl ) d 0.58 *s, 6H), 0.69 *s, 6H), 1.11±1.34
NMR
f
*
3
0
binaphthyl-2,2 -diol ꢀ8). A mixture of 4,4 ,6,6 -tetra-
0
0
4
.1.9. Preparation of 4,4 ,6,6 -tetraper¯uorobutyl-1,1 -
0
*m, 4H), 1.80 *d, 2H, Jˆ18.5 Hz), 1.79±1.81 *m, 4H), 1.99±
0
0
2.00 *m, 2H), 2.26 *dt, 2H, Jˆ2.7, 18.6 Hz), 2.63 *d, 2H,

Y. Tian et al. / Tetrahedron 58 ꢀ2002) 3951±3961
3959
Jˆ14.9 Hz), 3.49 *d, 2H, Jˆ14.9 Hz), 7.40 *d, 2H,
Jˆ8.9 Hz), 7.63 *t, 2H, Jˆ9.0 Hz), 8.30 *s, 2H), 8.63 *s,
*15 mL) was added and the reaction mixture was extracted
with CCl . The combined organic layer was washed with
brine and dried over MgSO . After removal of the solvent,
4
the residue was puri®ed by column chromatography *ethyl
acetate/hexaneˆ1:6) to give a mixture of diastereomers 13-
*S)-CS *1.1 g, 76%) as a white solid.
4
2
Found: C, 42.56;H, 2.54.
H);Anal. Calcd for C H F S O : C, 42.38;H, 2.41.
8
5
6
38 36
2
0
0
4
1
1
.1.11. Preparation of ꢀS)-4,4 ,6,6 -tetraper¯uorobutyl-
0
0
,1 -binaphthyl-2,2 -diol ꢀS)-8. To a suspension of *S)-
2-*S)-CS *1.22 g, 0.77 mmol) in methanol *40 mL),
Careful column chromatography *hexane/dichloro-
methaneˆ10:7) gave less polar diastereomer *S)-13-*S)-
NaOH *1 M, 10 mL) was added. The resulting yellow solu-
tion was re¯uxed for 24 h. After cooling down, 10% HCl
was added to neutralize the solution to pH 7. Methanol
was removed in vacuo and the residue was extracted
with ethyl acetate. The combined organic layer was washed
CS. Mp 127±1288C; R ˆ0.25 *hexane/dichloro-
f
1
methaneˆ10:7); H NMR *300 MHz, CDCl ) d 0.60 *s,
3
6H), 0.81 *s, 6H), 1.27±1.30 *m, 4H), 1.80 *d, 2H,
Jˆ18.6 Hz), 1.85±2.02 *m, 6H), 2.22 *dd, 2H, Jˆ18.6,
2.9 Hz), 2.77 *d, 2H, Jˆ14.9 Hz), 3.17 *d, 2H,
Jˆ14.9 Hz), 7.43 *d, 2H, Jˆ8.9 Hz), 7.65 *t, 2H,
with brine and dried over MgSO . After removal of the
4
solvent, the product was puri®ed by column chromato-
graphy *ethyl acetate/hexaneˆ1:10) to give *S)-8 *0.67 g,
1
3
Jˆ9.1 Hz), 8.29 *s, 2H), 8.64 *s, 2H);
C NMR
2
D
0
7
CHCl ); H NMR spectrum is the same as the spectrum of
5%) as a pale yellow semi-solid. [a] ˆ22.38 *c 0.7,
*75.5 MHz, CDCl ) d 19.11, 19.18, 24.72, 26.58, 42.06,
3
1
42.63, 47.71, 49.77, 57.65, 107.76, 110.94, 114.87,
124.89, 125.34, 127.50, 127.94, 128.85, 129.23, 135.18,
3
racemic 8.
145.86, 212.57;Anal. Calcd for C 72H F S O : C, 36.23;
H, 1.60. Found: C, 36.12;H, 1.86.
38 68 2 8
0
0
4
1
1
.1.12. Preparation of ꢀR)-4,4 ,6,6 -tetraper¯uorobutyl-
0
0
,1 -binaphthyl-2,2 -diol ꢀR)-8. To a suspension of *R)-
2-*S)-CS *392 mg, 0.25 mmol) in methanol *15 mL),
More polar diastereomer *R)-13-*S)-CS. Mp 109±1108C;
1
NaOH *1 M, 5 mL) was added. The resulting yellow solu-
tion was re¯uxed for 24 h. After cooling down, 10% HCl
was added to neutralize the solution to pH 7. Methanol was
removed in vacuo and the residue was extracted with ethyl
acetate. The combined organic layer was washed with
R ˆ0.19 *hexane/dichloromethaneˆ3:5);
H
*300 MHz, CDCl ) d 0.58 *s, 6H), 0.68 *s, 6H), 1.23±1.34
NMR
f
3
*m, 4H), 1.80 *d, 2H, Jˆ18.6 Hz), 1.78±1.81 *m, 4H), 1.98±
1.99 *m, 2H), 2.25 *dt, 2H, Jˆ18.6, 2.6 Hz), 2.64 *d, 2H,
Jˆ14.9 Hz), 3.49 *d, 2H, Jˆ15.0 Hz), 7.40 *d, 2H,
Jˆ8.9 Hz), 7.63 *t, 2H, Jˆ9.1 Hz), 8.30 *s, 2H), 8.64 *s,
2H);Anal. Calcd for C H F S O : C, 36.23;H, 1.60.
brine and dried over MgSO . After removal of the
4
solvent, the product was puri®ed by column chromato-
graphy *ethyl acetate/hexaneˆ1:10) to giv2e *R)-8
7
2
38 68
2
8
Found: C, 36.11;H, 1.52.
0
*
204 mg, 71%) as a pale yellow semi-solid. [a] ˆ12.18
D
1
c 1.0, CHCl ); H NMR spectrum is the same as the
0
0
*
spectrum of racemic 8.
4.1.15. Preparation of ꢀS)-4,4 ,6,6 -tetraper¯uorooctyl-
0
3
0
1,1 -binaphthyl-2,2 -diol ꢀS)-9. To a suspension of *S)-
3-*S)-CS *239 mg, 0.10 mmol) in methanol *10 mL) and
1
0
octyl-1,1 -binaphthyl-2,2 -diol ꢀ9).
0
4
.1.13. Preparation of racemic 4,4 ,6,6 -tetraper¯uoro-
0
CCl4 *10 mL), NaOH *1 M, 5 mL) was added. The
resulting yellow solution was stirred at 608C for 24 h.
After cooling down, 10% HCl was added to neutralize
the solution to pH 7. Methanol was removed in vacuo
0
A
mixture of
0
0
4
,4 ,6,6 -tetrabromo-BINOL 4 *1.0 g, 1.66 mmol), copper
bronze *1.6 g, 25 mmol) and per¯uorobutyl iodide *5.46 g,
.6 mL, 10 mmol) in anhydrous DMSO *15 mL) was
2
and the residue was extracted with CCl and ethyl acetate.
4
degassed three times, and then heated to 1608C for 3 days.
After cooling down, ethyl acetate *50 mL) was added and
the mixture was ®ltered through Celite, the ®ltrate was
washed with 10% HCl, water, brine and dried over
The combined organic layer was washed with brine and
dried over MgSO . After removal of the solvent, the
4
product was puri®ed by column chromatography
*ethyl acetate/hexaneˆ1:10) to give *S)-9 *167 mg,
2
D
0
MgSO . After removal of the solvent, the residue was
4
85%) as a yellow oil. [a] ˆ215.78 *c 0.15, ethyl
1
acetate); H NMR spectrum is the same as the spectrum of
racemic 9.
puri®ed by column chromatography *ethyl acetate/
hexaneˆ1:10) to give 9 *1.48 g, 46%) as a yellow oil.
1
R ˆ0.17 *ethyl acetate/hexaneˆ1:10);
H
300 MHz, CDCl ) d 5.86 *brs, 2H), 7.27 *d, 2H,
NMR
f
0 0
4.1.16. Preparation of ꢀR)-4,4 ,6,6 -tetraper¯uorooctyl-
*
3
0
0
Jˆ7.6 Hz), 7.56 *d, 2H, Jˆ8.9 Hz), 7.87 *s, 2H), 8.55 *s,
1,1 -binaphthyl-2,2 -diol ꢀR)-9. To a suspension of *S)-
13-*S)-CS *184 mg, 0.08 mmol) in methanol *5 mL) and
CCl *5 mL), NaOH *1 M, 2 mL) was added. The resulting
1
H);FABMS: m/z *relative intensity) 1159 *[M1H] , 85),
2
1
1
0
141 *17), 990 *100), 853 *3), 820 *19), 772 *18);SIMS: m/z
959 *[M1H] );Anal. Calcd for C H F O : C, 31.89;H,
.89. Found: C, 32.02;H, 0.73.
4
1
yellow solution was re¯uxed for 24 h. After cooling
down, 10% HCl was added to neutralize the solution to
pH 7. Methanol was removed in vacuo and the residue
was extracted with CCl4 and ethyl acetate. The
combined organic layer was washed with brine and
5
2
10 68
2
0
camphor-10-sulfonyl]-4,4 ,6,6 -tetraper¯uorooctyl-1,1 -
4
.1.14. Preparation of diastereomeric 2,2 -di-[ꢀ1S)-
0
0
binaphthyl ꢀS)-13-ꢀS)-CS and ꢀR)-13-ꢀS)-CS. At 08C, to a
0
dried over MgSO . After removal of the solvent, the
4
0
0
solution of 4,4 ,6,6 -tetraper¯uorooctyl-BINOL 9 *1.18 g,
.60 mmol) and *1S)-camphor-10-sulfonyl chloride
product was puri®ed by column chromatography *ethyl
acetate/hexaneˆ1:10) to give *R)-9 *122 mg, 79%) as a
0
2
D
0
*
605 mg, 2.4 mmol) in dry CCl *20 mL), triethylamine
4
yellow oil. Mp [a] ˆ115.68 *c 0.96, ethyl acetate);
1
*304 mg, 0.57 mL, 3.0 mmol) was added. The yellow solu-
tion was re¯uxed for 2 days. After cooling down, water
H NMR spectrum is the same as the spectrum of
racemic 9.

3960
Y. Tian et al. / Tetrahedron 58 ꢀ2002) 3951±3961
4
.2. The typical procedure of the asymmetric catalytic
Acknowledgements
addition of diethylzinc to aryl aldehyde in ¯uorous
biphasic system
We thank Hong Kong Research Grants Council of Hong
Kong for ®nancial support *CUHK4023/98P).
To a solution of optically pure BINOL derivative
*
0.025 mmol) in dry per¯uoro*methyldecalin) *1 mL),
titanium tetraisopropoxide *350 mL, 0.5 M in hexane,
.175 mmol) was added and the resulting solution was
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*
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.3. The typical procedure of the asymmetric catalytic
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uorous biphasic system
*
1
9
¯
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0
0
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reaction was cooled down to 08C, a two-layer mixture was
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isopropoxide *350 mL, 0.5 M in hexane, 0.175 mmol) was
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4
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