Preparation and catalytic applications of partially fluorinated binaphthol ligands

Article abstract of DOI:10.1016/j.jfluchem.2003.11.024

New partially fluorinated binaphthols were obtained using a copper-catalyzed oxidative coupling. The corresponding enantiomerically pure compounds were prepared by fractional crystallization of the corresponding bis(menthyl)carbamates. Nucleophilic aromat

Full text of DOI:10.1016/j.jfluchem.2003.11.024

Journal of Fluorine Chemistry 125 (2004) 517–525
Preparation and catalytic applications of partially
fluorinated binaphthol ligands
Shahla Yekta, Larissa B. Krasnova, Brian Mariampillai, Christine J. Picard,
Gang Chen, Subramanian Pandiaraju, Andrei K. Yudin*
Department of Chemistry, Davenport Research Laboratories, University of Toronto, 80 St. George Street, Toronto, Ont., Canada M5S 3H6
Received 12 October 2003; accepted 17 November 2003
Abstract
New partially fluorinated binaphthols were obtained using a copper-catalyzed oxidative coupling. The corresponding enantiomerically pure
compounds were prepared by fractional crystallization of the corresponding bis(menthyl)carbamates. Nucleophilic aromatic substitution
using oxygen- and carbon-based nucleophiles resulted in functionalized derivatives without concomitant racemization. The titanium(IV)
complexes of these ligands are catalytically active in the asymmetric oxidation of sulfides.
# 2004 Elsevier B.V. All rights reserved.
Keywords: Asymmetric catalysis; Coupling; Fluorine; Ligand; Nucleophilic aromatic substitution; BINOL; F8BINOL; F4BINOL; Chiral; Sulfoxidation
1. Introduction
methyl propiolate and cyclopentadiene are greatly enhanced
when triaryl silyl substituents are used at the 3,30-positions
of the aluminum–binaphthol catalyst [4].
Finding the right balance between the steric and electronic
demands of a chiral ligand is essential in order to optimize a
given catalytic system. Electron deficiency or Lewis acidity
of the metal center is one of the fundamental properties
explored in many asymmetric transformations. In terms of
ligand symmetry, C2 symmetrical ligands possessing axial
chirality have found wide utility in asymmetric catalysis [1].
BINOL (1) and its derivatives have generated particular
interest because their versatile backbones can be modified,
thereby affecting the reaction environment by influencing
the metal center [2]. The strategic placement of substituents
within the binaphthol framework has been shown to provide
improved catalysts. For instance, incorporation of halogens
at the 6,60-positions of BINOL increases enantioselectivity
of the ene reaction by increasing the Lewis acidity of the
corresponding titanium catalysts [3]. While the BINOL–Ti
complex promoted the reaction in 93% yield and 69%
enantioselectivity, the 6,60-Br2BINOL/Ti catalyst gave the
product in 89% e.e. and high yield was maintained. Sub-
stituents at the 3,30-positions are mainly responsible for
controlling the steric requirements around the metal coor-
dinated to the binaphthol ligand [2]. For example, the yield
and enantioselectivity of the Diels–Alder reaction between
Our explorations in the field of binaphthyl catalysis led us
to consider partially fluorinated species. This interest was
driven by the known stability of the C–F bond towards
oxidation [5], propensity of fluoroaromatics to engage in
stabilizing stacking interactions with other aromatic rings
[6], and rich nucleophilic aromatic substitution chemistry of
fluoroaromatic compounds [7]. We recently, published the
synthesis and catalytic applications of polyfluorinated
BINOL ligands such as F8BINOL (3), an electronic isostere
of BINOL [8]. In terms of catalytic applications, we
explored the sulfoxidation [9] as well as the glyoxylate-
ene reaction [10]. It was found that the (R)-F8BINOL–Ti
system catalyzed the sulfoxidation reaction with higher
enantioselectivity (89% in CH2Cl2) than the (R)-BINOL–Ti
system (7% in CH2Cl2 and 22% in CCl4) at 0.05 M con-
centration. Highly enantioselective ‘‘pseudo-meso’’ aggre-
gates were obtained by combining one of the enantiomers of
BINOL with its fluorinated counterpart, F8BINOL, and were
applied in the enantioselective glyoxylate-ene reaction. The
reaction between ethyl glyoxylate and a-methyl styrene in
the presence of 10 mol% (S)-F8BINOL/Ti(OiPr)4 (2:1 ratio)
afforded the corresponding ene-product in 53% yield and
92% e.e. The catalyst produced from (R)-F8BINOL/(S)-
BINOL/Ti(OiPr)4 mixture (1:1:1 ratio) gave the product of
the reaction between ethyl glyoxylate and a-methyl styrene
* Corresponding author. Tel.: þ1-416-946-5042; fax: þ1-416-978-8775.
E-mail address: ayudin@chem.utoronto.ca (A.K. Yudin).
0022-1139/$ – see front matter # 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2003.11.024

518
S. Yekta et al. / Journal of Fluorine Chemistry 125 (2004) 517–525
with excellent enantioselectivity (99%). A significant yield
improvement was also observed in the mixed case compared
to either 1 or 3 alone.
Monitoring the reaction with 19F NMR showed substitutions
at the 5-, 6-, 7-, and 8-positions. All attempts at making the
Grignard reagent from 4 failed. The Suzuki coupling
between the iodo compound 7 and boronic acid 8 gave
the product in less than 10% yield presumably due to the
sensitivity of the Suzuki coupling to steric bulk around the
incipient C–C bond (Scheme 2c) [14].
We were additionally intrigued by facile and regioselec-
tive nucleophilic aromatic substitution at the 6- and
7-positions of the partially fluorinated rings of F8BINOL
[11]. Interested in using this tool, we proceeded to modify
the binaphthol scaffold by placing a variety of substituents at
these positions. Unfortunately, separation of the 6,60- and
7,70-substituted regioisomers proved to be tedious. Our
interest further progressed towards F4BINOL (2) where only
one of the naphthyl rings is fluorinated, minimizing the
number of sites for possible nucleophilic fluorine displace-
ment. Herein, we report the synthesis of F4BINOL and its
application in the asymmetric sulfoxidation reaction.
The Ullmann coupling similar to what had been tried in
the synthesis of 3 gave 9 in only 5% yield [8]. The major
product was the protected F8BINOL derivative, obtained in
85% yield (Scheme 2). Since the Ullmann coupling reaction
is in favor of electron-poor substrates, naphthoic esters 10a
and 10b were used. The yield of the reaction was improved
to 27 and 47% with 11a and 11b, respectively. In the case of
11b, a 1:1 mixture of diastereomers was obtained and they
were separated through fractional crystallization. Since the
carboxylic acids from which 10a and 10b were prepared are
not readily available, we attempted the synthesis using
readily available aldehyde 12 (Scheme 2). Compound 12
was prepared from commercially available 1-bromo-2-
methylnaphthalene in two steps according to literature
procedure [15]. The aldehyde 13 was then oxidized through
a Baeyer–Villiger reaction with mCPBA followed by hydro-
lysis of the corresponding ester to obtain alcohol 14 in
64% yield (two steps). Demethylation with BBr3 afforded
racemic F4BINOL in 92% yield and 28% overall yield.
Enantiomer resolution was accomplished using a procedure
2. Results and discussion
2.1. Synthesis of F4BINOL
2.1.1. Oxidative and reductive coupling methods
Initial attempts at making F4BINOL involved direct cou-
pling methods (for selected examples on Ullman and oxi-
dative coupling see [12,13]). The coupling of Grignard or
lithium derivatives 5 and 6 with 4 afforded the desired
product 9 in less than 10% yield (Scheme 1a and b).
F
20 mol%
NiCl2(PPh3)2
F
F
a
+
OMe
OMe
F
F
THF, <10%
Br
MgBr
4
5
F
F
20 mol%
F
F
F
NiCl2(PPh3)2
OMe
OMe
b
c
+
+
F
OMe
OMe
OMe
OMe
THF, <10%
F
F
Li
Br
4
6
9
10 mol%
Pd(PPh3)4
F
F
Na2CO3, DME
<10%
F
I
B(OH)2
8
7
Scheme 1.
F
F
F
F
F
F
F
F
F
F
F
Cu, 170 oC
OMe
OMe
OMe
OMe
+
F
F
OMe
OMe
OMe
Br
Br
F
F
F
F
F
F
F
F
F
F
F
Cu, 170 o
C
+
COOR
OMe
Br
Br
COOR
10a R = Me
10b R = Menthyl
11a 27%
11b 47%
Scheme 2.

S. Yekta et al. / Journal of Fluorine Chemistry 125 (2004) 517–525
519
F
F
F
F
F
F
F
F
F
F
F
OMe
CHO
Cuo, 165oC
24h
F
4
Br
Br
1) m-CPBA
OMe
CHO
OMe
OH
48%
2) KOH, THF
64%
14
12
13
BBr3, CH2Cl2
92%
F
F
O
iPr
F
F
F
F
F
1) Fractional
O
O
(-)-Menthyl
Chlorofomate
DMAP, Py
F
Crystallization
OH
OH
O
O
(R) and (S) 2
2) LiAlH4, THF
O
Pri
15
2
Scheme 3.
similar to that for F8BINOL through the bis(carbonate)
diastereomers 15 prepared from (À)-menthyl chloroformate
in pyridine with a catalytic amount of dimethyl aminopyr-
idine (Scheme 3). Fractional crystallization of 15 from 5:1
methanol/isopropanol resulted in the diastereomer separa-
tion. Subsequent reduction using LiAlH4 in THF afforded
enantiomerically pure 2 (Scheme 3).
Unlike the Ullmann coupling, oxidative coupling methods
are known to favor the formation of electron-rich aromatics.
Since only one of the naphthyl moieties in 3 is fluorinated,
we opted to try the oxidative coupling between 16 and 2-
naphthol. Oxidative coupling of 2-naphthols can be pro-
moted by several metal catalysts such as complexes of
ruthenium [16], titanium [17], vanadium [18], manganese
[19], copper [20], and iron [21]. Unfortunately, the widely
used FeCl3-catalyzed reaction cannot be used in our case
because the fluorinated 2-naphthol 16 reacts with FeCl3 to
give chlorinated product 17 (Scheme 4) [9].
We were nonetheless able to obtain the product in mod-
erate yields using Cu(OH)ClÁTMEDA as the catalyst
(Scheme 5) [13b]. Temperature played a key role in influen-
cing product ratios. Since 2-naphthol has a lower oxidation
potential (1.54 V versus Ag/AgCl) than the corresponding
5,6,7,8-tetrafluoronaphthol (1.84 V versus Ag/AgCl), it
undergoes oxidative coupling at lower temperature
(40 8C). Heating the reaction mixture containing the two
starting materials (1:1 ratio) to 70 8C resulted only in
BINOL with quantitative yield. Only upon increasing the
temperature to 125 8C, formation of F4BINOL was
observed. The amount of catalyst used was also essential
in achieving the desired conversions. Thus, the use of
10 mol% of the copper catalyst resulted in highest yields
of F4BINOL whereas 25 mol% facilitated the formation of
BINOL. The best reaction conditions were obtained using
1 eq. of 2-naphthol, 0.7 eq. of 5,6,7,8-tetrafluoronaphthol
and 10 mol% of Cu(OH)ClÁTMEDA at 140 8C for 24 h
which afforded F4BINOL in 40% yield. The main by-
product was BINOL, obtained in 50% yield and F8BINOL,
obtained in less than 10% yield.
2.1.2. Other cross-coupling methods
Another attempt at making F4BINOL using the cross-
coupling methods was the Stille coupling [22]. We envi-
sioned that a cross-reaction may occur with the more
nucleophilic aryl stannane. Compound 18 was prepared
via addition of n-butyllithium at low temperature to generate
the lithiated intermediate 6 which was trapped by slow
addition of tributylstannyl chloride. However, the Stille
coupling with 4 in the presence of palladium acetate and
a variety of phosphine ligands resulted in no reaction
(Scheme 6). This is most likely due to the fact that similar
to Suzuki coupling, the Stille reaction is limited to relatively
sterically unencumbered substrates.
Fortuitously, recent work by Motherwell and co-workers
[23] has shown that tethering the two rings with a sulfonate
linkage followed by a radical-induced 1,5-ipso substitution
works best for sterically hindered biaryls. The process
involves intramolecular free radical ipso substitution via
a spirocyclic intermediate capable of re-aromatization
F
F
F
F
F
F
F
F
Cu(OH)Cl.TMEDA
140oC, 24h
OH
OH
OH
OH
F
F
40 %
FeCl3
F
F
F
F
OH
OH
2
F
F
Cl
16
17
TMEDA = tetramethyl ethylenediamine
Scheme 4.
Scheme 5.

520
S. Yekta et al. / Journal of Fluorine Chemistry 125 (2004) 517–525
F
F
Pd(OAc)2
Ligand
F
F
F
F
F
F
F4
+
NR
OMe
SnBu3
18
+
Et3N, CH2Cl2, 1h, rt
64%
OMe
OH
OMe
SO2Cl
O
CuBr
Toluene
Br
Br
Br
SO2
4
21
20
MeO
Ligand: PPh3, dppb, dppe, BINAP
22
Scheme 6.
EPHP, AIBN
benzene
58%
F
1) H2SO4
70oC, 3d
OMe
SO3 Na+
19
2) NaOH/H2O
78%
OMe
F
F
OH
F
POCl2
OMe
Sulfolane
MeCN
70oC,40min
47%
23
Scheme 8.
OMe
SO2Cl
20
65% conversion and 58% yield [24,25]. Demethylation of 23
resulted in racemic F4BINOL.
Scheme 7.
through loss of sulfur dioxide. The presence of bulky groups
avoids the direct addition pathway. We therefore, decided
that a logical solution to this challenge may be addition of
one such linker prior to the coupling step.
2.1.3. Nucleophilic aromatic substitution
Nucleophilic aromatic substitution on F4BINOL pro-
ceeded similar to our previous reports with F8BINOL
[11]. Initially, F4BINOL was protected as the benzyl ether
24 using benzyl bromide and K2CO3. Nucleophilic aromatic
substitution occurred at both the 6- and 7-positions of the
fluorinated ring by using potassium methoxide (Scheme 9).
Deprotection of 25b using a catalytic amount of Pt/C
(10 mol%) in the presence of H2 afforded ligand 27 in
90% yield.
Alkyllithium species have also been used as nucleophiles
to modify the 7-position of the fluorinated ring system. In
this case, the reaction occurs by using unprotected F4BINOL
at À78 8C mixed with three equivalents of the organolithium
reagent (Scheme 10). Lower reaction yields observed com-
pared with alkoxides could be a result of the longer reaction
times required at low temperatures.
The next step involved preparation of the sodium sulfo-
nate salt 19 from 2-methoxynaphthalene by treatment with
concentrated sulfuric acid at 80 8C for 10 min. Precipitation
of the product with aqueous sodium hydroxide yielded the
desired compound in 78% yield. The derivative 19 reacted
with phosphorous oxychloride to generate the corresponding
sulfonyl chloride 20 (Scheme 7). Coupling of alcohol 21,
prepared by demethylation of 4 with boron tribromide
[8], with 20 in the presence of triethylamine gave the
desired intermediate for the radical cross-coupling reaction
(Scheme 8). The cross-coupling was carried out in the
presence of 1-ethylpiperidine hypophosphite (EPHP) and
AIBN in benzene at 70 8C for 2 days and gave the product in
F
MeO
F
OBn
F
OBn
F
F
F
F
F
F
F
F
BnBr, K2CO3
THF, reflux, 15h
MeOH/KOH
reflux, 12h
25a
OBn
OH
OH
+
OBn
F
F
85%
70%
F
25a:25b = 1:5
MeO
OBn
OBn
24
F
F
25b
H2, Pt/C
MeO
F
OH
OH
EtOH, 12h
25b
90%
27
Scheme 9.

S. Yekta et al. / Journal of Fluorine Chemistry 125 (2004) 517–525
521
Table 1
Titanium-catalyzed oxidation of sulfides to sulfoxides
Entry
Ligand
Time (h)
Temperature (8C)
Yield (%)
e.e. (%)
1
2
3
4
5
6
7
(R)-BINOL
(R)-F8BINOL
(R)-F4BINOL
(R)-F4BINOL
(R)-F4BINOL
(R)-27
42
4.5
2
0
69
77
78
46
46
49
32
3
75
80
75
84
28
27
0
0
2
RT
À20
0
18
3
(R)-26
2
0
F
F
F
F
The average pKa of F4BINOL is 9.8, just between that of
F8BINOL (10.3) and BINOL (9.3) [26]. Based on Lewis
acidity, one would, therefore, expect its reactivity to be also
somewhere between the F8BINOL and BINOL. When
ligands (R)-26 and (R)-27 are used, both the yield and
enantioselectivity of the reaction are dramatically decreased
(entries 6 and 7).
F
F
F
RLi (3 eq), THF
-78oC
OH
OH
R
OH
OH
26 R = tBu (40%)
Scheme 10.
2.1.4. F4BINOL in catalysis: sulfoxidation reaction
3. Conclusion
We previously, reported the asymmetric oxidation of
sulfides to sulfoxides using F8BINOL and its 7,70-substituted
derivatives [2,9]. Our initial results indicated that fluorine
substitution is responsible for improved enantioselectivity
where minimum amount of sulfone by-product is formed.
An inverse sense of chiral induction is observed using
our fluorinated ligands. Kinetic studies showed that the
reaction catalyzed by 3/Ti(IV) is five times faster than that
catalyzed by 1/Ti(IV). Optimized reaction conditions were
used to compare our new ligands, F4BINOL as well as its
7-substituted derivatives 26 and 27, with previous examples.
F4BINOL gives the same sense of chiral induction as
F8BINOL. The yields and enantioselectivities obtained
are also similar to those obtained with F8BINOL was used
as ligand (Table 1, entries 2–5).
Lowering the reaction temperature resulted in increased
enantioselectivity, however, the yield decreased (entries 3–5).
The best conditions were obtained at 0 8C where the product
was obtained in 78% yield with 80% enantioselectivity.
Whereas addition of water (2 eq.) increased the enantios-
electivity of the reaction using F8BINOL, no change was
observed when F4BINOL was used as the ligand.
When the reaction was catalyzed by F8BINOL, the sul-
fone by-product was produced in greater amount than the
reaction catalyzed using BINOL [9]. Surprisingly, no sul-
fone by-product was observed when F4BINOL was used as
the ligand. The presence of electron-withdrawing fluorine
atoms on F8BINOL makes the F8BINOL/Ti catalyst more
Lewis acidic than the corresponding BINOL/Ti catalyst. The
overoxidation of sulfoxides to sulfone can, therefore, be
attributed to the higher reactivity of F8BINOL/Ti catalyst.
In summary, new partially fluorinated binaphthols have
been synthesized using oxidative coupling. We have shown
that different substituents can be placed on the fluorinated
naphthyl ring, allowing easy access to a variety of different
ligands. When the substitution is performed on enantiomeri-
callypurestartingmaterials, nochangeinenantioselectivityis
observed. The catalytic applications of F4BINOL in sulfox-
idation show that the ligand produces no sulfone by-product
and gives the product with moderate enantioselectivity.
3.1. General considerations
All commercial reagents were used as such without pur-
ification. Wherever necessary, solvents were dried as per the
standard procedures. Melting points were taken using a
capillary melting point apparatus. Unless otherwise stated,
all 1H NMR measurements were carried out at 400 MHz and
13C NMR at 100 MHz using TMS as internal standard. 19F
NMR measurements were carried out at 300 MHz using
CFCl3 as internal standard. Column chromatographic pur-
ifications were performed using silica gel with 230–400 mesh
size. Compounds 4 and 16 were prepared according to
literature procedures [8]. Characterization for compound
20 was verified according to literature [27].
3.1.1. 2-Methoxy-naphthalene-1-sodium sulfonate (19)
Concentrated sulfuric acid (35 ml) was added to 2-meth-
oxynaphthalene (48 g, 300 mmol) at room temperature. The
white solid immediately turned red. The mixture was heated
to 80 8C for 30 min until all the solid melted and the starting

522
S. Yekta et al. / Journal of Fluorine Chemistry 125 (2004) 517–525
material disappeared on TLC. A solution of 5% NaOH
was slowly added until the solution was basic. The
white precipitate was filtered and dried in vacuo overnight
(65.6 g, 80%). Decomposes at >250 8C 1H NMR (400 MHz,
D2O) d 8.16 ppm(1H, s), 7.86 (2H, t, J ¼ 8:69), 7.68 (1H,
dd, J ¼ 8:69), 7.29 (1H, d, J ¼ 2:38), 7.18 (1H, dd,
J ¼ 9:06), 3.84 (3H, s); 13C NMR (100 MHz, D2O) d
158.3, 137.4, 135.4, 130.5, 127.9, 127.4, 125.4, 122.5,
119.4, 106.3, 55.7. MS-EI m/z found 237.
over Na2SO4 and concentrated in vacuo. Flash column
chromatography with hexanes/ethyl acetate (9:1) resulted
in product as a light yellow solid (20 g, 76%).Mp: 173 8C.
1H NMR (400 MHz, C6D6) d 8.47(s, 1H), 8.01 (dd,
J ¼ 8:8 Hz, J ¼ 1:83 Hz 1H), 7.46 (d, J ¼ 9:2, 1H),
7.34(d, J ¼ 8:6 Hz, 1H), 7.28 (d, J ¼ 9:3 Hz), 7.17
(d, J ¼ 8:0 Hz, 1H), 6.94 (dd, J ¼ 8:8 Hz, J ¼ 2:6 Hz,
1H), 6.66(d, J ¼ 2:4, 1H), 3.23(s, 3H); 19F NMR
(300 MHz, C6D6) d À140.4 (t, J ¼ 16:8 Hz), À148.18
(t J ¼ 19:8 Hz), À155.2 (t, J ¼ 19:8 Hz), À157.5 (t,
J ¼ 22:9 Hz); 13C NMR (100 MHz, C6D6) d 160.8, 147.2,
144.1, 140.3, 138.7, 137.7, 136.7, 134.1, 131.2, 130.7,
130.2, 128, 7, 128.2, 127.4, 124.3, 124.1, 121.1, 116.8,
106.1, 55.7. HREI-MS, m/z: Calcd for C21H11O4F4SBr
513.9497; found 513.9498.
3.1.2. 2-Methoxy-naphthalene-1-sulfonyl chloride (20)
To a solution of 19 (65 g, 239 mmol) in equal amounts of
tetramethylene sulfone (150 ml) and acetonitrile (150 ml)
was added phosphorous oxychloride (41 ml, 441 mmol)
dropwise on ice. The reaction was warmed to room tem-
perature, and then heated to 70 8C for 2 h. The mixture
was cooled to 4 8C in an ice bath. Water was added
dropwise keeping the temperature at 4 8C until all excess
POCl3 was quenched. The resulting mixture was extracted
with dichloromethane and purified by flash column
chromatography (8:2 hexanes:ethyl acetate) to afford a
yellow powder (36 g, 48%). Mp: 65 8C; 1H NMR (CDCl3)
d 8.50 ppm (1H, s), 7.89–7.96 (m, 3H), 7.31 (dd,
J ¼ 2:4 Hz, J ¼ 9:0 Hz, 1H), 7.21 (d, J ¼ 2:56 Hz, 1H),
3.97 (3H, s); 13C NMR (CDCl3) d 161.43, 139.02, 138.10,
131.65, 129.04, 128.79, 127.18, 122.36, 121.66, 106.26,
55.86.
3.1.5. 5,6,7,8-Tetrafluoro-20-methoxyl-
[1,10]binaphthalenyl-2-ol (23)
A solution of 22 and EPHP in benzene (0.5 ml) was
refluxed for 1 h. AIBN (45 mg, 0.27 mmol) was added in
two portions over 30 min and the reaction was refluxed for
additional 3 h, then cooled to room temperature. Water
(2 ml) and ether (2 ml) were added. The organic layer
was separated and the aqueous layer was extracted with
ether (1 ml) twice. The combined organic layers were dried
over Na2SO4 and concentrated in vacuo. Purification by flash
column chromatography on silica gel with hexanes/ethyl
acetate (8:2) afforded the product as a yellow solid (54 mg,
1
3.1.3. Bromo-2-hydroxy-5,6,7,8-tetrafluoronaphthalene
(21)
38%). H NMR (400 MHz, CDCl3) d 8.05 (d, J ¼ 8:8 Hz,
1H), 7.91(d, J ¼ 8:4 Hz, 1H), 7.78(d, J ¼ 10 Hz, 2H), 7.39
(t, J ¼ 9:2 Hz, 2H), 7.25(m, 2H), 3.99(s, 3H). 19F NMR
(300 MHz, CDCl3) d À142.4 (t, J ¼ 15:3 Hz), À150.4
(t, J ¼ 18:3 Hz), À158.46(t, J ¼ 18:3 Hz), À163.3 (t,
J ¼ 19:8 Hz); 13C NMR (100 MHz, CDCl3) d 158.5,
158.4, 152.8, 137.0, 134.5, 134.4, 129.5, 128.9, 128.8,
128.76, 128.7, 128.3, 128.2, 128.0, 127.8, 121.8, 119.8,
119.6, 118.9, 105.8, 55.4. MS-EI, m/z found 372.
To a solution of 4 (927 mg, 3 mmol) in dichloromethane
(15 ml) was added BBr3 (2.25 g, 9 mmol) at room tempera-
ture under nitrogen atmosphere. The reaction was stirred for
15 h at room temperature, then cooled to 0 8C and quenched
by slow addition of water. The aqueous layer was separated
and the organic layer was washed with water (15 ml) twice,
dried over anhydrous MgSO4 and concentrated in vacuo.
The crude solid was purified by flash column chromatogra-
phy on silica gel. Elution with hexanes/ethyl acetate (8:2)
afforded the product as white solid (97%). 1H NMR (CDCl3)
d 7.97 (d, J ¼ 9:16, 1H), 7.35 (d, J ¼ 9:16, 1H), 6.41(s, 1H);
19F NMR (300 MHz, CDCl3): d À145.4, À148.5, À155.8,
À161.3; 13C NMR (100 MHz, CDCl3): d 152.9, 143.4,
141.7, 140.85, 139.2, 137.6, 135.1, 122, 118.7, 99.2.
HREI-MS, m/z: Calcd for C10H3OF4 293.9303; found
293.9313.
3.1.6. 5,6,7,8-Tetrafluoro-[1,10]binaphthalenyl-2,20-diol
(2)
To a mixture of 23 (7 mg, 0.3 mmol) in dichloromethane
(1 ml) was added boron tribromide (15 mg, 0.6 mmol) at
room temperature. The reaction was stirred for 15 h at room
temperature and then cooled to 0 8C and quenched by slow
addition of water. The aqueous layer was separated and the
organic layer was washed with water (1 ml) twice, dried over
anhydrous Na2SO4 and concentrated in vacuo to afford an
orange solid. Purification with flash column chromatography
with hexanes/ethyl acetate (7:3) resulted in pure F4BINOL
3.1.4. 2-Methoxy-naphthalene-1-sulfonic acid
1-bromo-5,6,7,8-tetrafluoro-naphthalen-2-yl ester (22)
To a solution of 20 (14 g, 52 mmol) and 21 (13 g,
52 mmol) in dichloromethane (200 ml) at 0 8C was added
triethylamine (8.7 ml, 62.7 mmol) dropwise. The reaction
was warmed to room temperature and stirred for 24 h. Water
was added and the organic layer was separated. The aqueous
layer was extracted with dichloromethane (100 ml). The
combined organic layers were washed with dilute HCl, dried
1
(7 mg, 65%). H NMR (400 MHz, CDCl3) d 4.87 (s, 1H),
5.35 (s, 1H), 7.09 (d, J ¼ 7:8 Hz, 1H), 7.30–7.40 (m, 3H),
7.48 (d, J ¼ 9 Hz, 1H), 7.88 (d, J ¼ 7:8 Hz, 1H), 7.96
(d, J ¼ 8:7 Hz, 1H), 8.20 (d, J ¼ 7:8 Hz, 1H). 19F NMR
(280 MHz, CDCl3)
d
À147.63, À149.59, À156.91,
À162.25. HRMS (EI) m/z calcd for [C20H10O2F4]
358.0617 found 358.1617.

S. Yekta et al. / Journal of Fluorine Chemistry 125 (2004) 517–525
523
3.2. Oxidative coupling method
3.2.3. 2,20-bis-benzyloxy-5,6,7,8-Tetrafluoro-[1,10]-
binaphthalenyl (24)
A 250 ml round-bottom flask containing a mixture of 16
(1 g, 4.97 mmol), 2-naphthol (500 mg, 3.48 mmol), and
Cu(OH)ClÁTMEDA (107 mg, 0.5 mmol) was placed in an
oven at 130 8C for 24 h, then cooled to room temperature.
Ether (25 ml) was added and the mixture was washed with
water (50 ml) three times, dried over anhydrous Na2SO4 and
concentrated in vacuo. The resulting brown oil was purified
by flash column chromatography with gradient elution from
100% hexanes to a 7:3 mixture of hexanes/ethyl acetate to
afford F4BINOL as a light yellow solid (270 mg, 47%).
To a mixture of 2 (100 mg, 0.28 mmol) and benzyl
bromide (0.34 ml, 2.8 mmol) in THF (10 ml) was added
potassium carbonate (0.31 g, 2.25 mmol). The mixture was
refluxed for 24 h at which point TLC analysis showed
complete consumption of the starting material. A solution
of 5% aqueous HCl was added and the product extracted
with diethyl ether (3 Â 5 ml). The combined organic layers
were dried over anhydrous MgSO4 and concentrated in
vacuo. Purification by flash column chromatography (hex-
ane/EtOAc 8:2) afforded the product as a yellow solid
(105 mg, 70%). 1H NMR (400 MHz, CDCl3) d 4.93 (s,
2H), 5.00 (s, 2H), 6.70–7.40 (m, 15H), 7.80 (t, J ¼ 9 Hz,
2H), 8.05 (d, J ¼ 8:4 Hz, 1H). 19F NMR (300 MHz, CDCl3)
d À144.4 (t, J ¼ 16:8 Hz), À150.3 (t, J ¼ 15:3 Hz), À158.0
(t, J ¼ 18:3 Hz), À162.7 (t, J ¼ 19:8 Hz). 13C NMR
(100 MHz, CDCl3) d 155.6, 153.4, 137.4, 136.6, 133.7,
129.3, 129.2, 128.2, 128.1, 128.0, 127.5, 127.4, 126.6,
126.5, 126.4, 124.5, 123.6, 121.6, 121.0, 120.9, 120.6,
117.7, 117.6, 116.7, 116.0, 115.8, 115.3, 115.2, 71.1, 70.9.
3.2.1. Bis[(À)-menthl]5,6,7,8-tetrafluoro-1,10-binaphthyl-
2.20-biscarbonate (15)
To a solution of 2 (1.0 g, 3 mmol) in dichloromethane
(100 ml), pyridine (4 ml), (À)-menthyl chloroformate
(2.2 g, 10 mmol), and 4-(dimethylamino)pyridine (10 mg)
were added in sequence. The mixture was allowed to stir at
room temperature for 2 h. A solution of 2 M aqueous
hydrochloric acid (50 ml) was added. The organic layer
was separated and the aqueous layer was extracted with
dichloromethane (2 Â 100 ml). The combined organic
layers were dried over anhydrous MgSO4 and concentrated
in vacuo to give a mixture of two diastereomers as brown oil.
This mixture was purified by silica gel flash column chro-
matography (hexane/EtOAc 20:1) to afford a mixture of the
two diastereomers (1.6 g, 80%). Recrystallization in metha-
nol/2-propanol (5:1) afforded (R)-F4BINOL-(À)-menthyl
3.2.4. 2,20-bis-benzyloxy-5,6,8-Trifluoro-7-methoxy-[1,10]-
binaphthalenyl (25b)
A solution of 24 (25 mg, 0.05 mmol) and potassium
hydroxide (26 mg, 0.5 mmol) in methanol (2 ml) was
refluxed for 10 h under N2 atmosphere. The mixture was
cooled to room temperature and diluted with ether (2 ml). A
5% solution of hydrochloric acid was added and the organic
layer was separated. The aqueous layer was extracted with
ether twice. The combined organic phases were dried over
Na2SO4 and concentrated in vacuo. The crude product was
purified by flash column chromatography (hexanes/EtOAc
8:2) to afford the product as a white solid (23 mg, 85%). 1H
NMR (400 MHz, CDCl3) d 8.02 (d, J ¼ 9:3 Hz, 1H), 7.74–
7.80 (m, 3H), 7.68 (s, 1H), 7.52 (m, 3H), 7.31–7.45 (m, 6H),
7.21–7.27 (m, 3H), 7.18–7.20 (m, 3H), 5.24 (s, 2H), 5.08 (s,
2H), 4.09 (s, 3H for 6-substituted product), 3.92 (s, 3H for 7-
substituted product). 19F NMR (300 MHz, CDCl3) d À132.6
(d, J ¼ 16:8 Hz), À152.5 (t, J ¼ 25:2 Hz), À157.0 (d,
J ¼ 18:3 Hz). 13C NMR (100 MHz, CDCl3) d 156.8,
154.7, 137.0, 136.7, 133.5, 132.6, 129.6, 128.8, 128.6,
128.5, 128.4, 128.35, 128.3, 128.25, 128.24, 128.20,
128.0, 127.8, 127.7, 127.6, 127.5, 126.8, 125.8, 121.2,
119.1, 119.0, 116.4, 107.2, 71.5, 70.1, 62.3.
1
carbonate as white crystals. H NMR (400 MHz, CDCl3)
d 0.18 (d, J ¼ 7:2 Hz, 3H), 0.38 (d, J ¼ 6:9 Hz, 3H), 0.53 (d,
J ¼ 6:9 Hz, 3H), 0.67 (d, J ¼ 6:9 Hz, 3H), 0.75–1.90 (m,
24H), 4.15–4.35 (m, 2H), 7.23 (t, J ¼ 8:24 Hz, 1H), 7.32
(td, J ¼ 6:9 Hz, J ¼ 0:9 Hz, 1H), 7.43–7.48 (m 2H), 7.61
(d, J ¼ 9:3 Hz, 1H), 7.90 (d, J ¼ 8:1 Hz, 1H), 7.97 (d,
J ¼ 8:7 Hz, 1H), 8.24 (d, J ¼ 9:6 Hz, 1H). 19F NMR
(280 MHz, CDCl3)
À158.89.
d
À141.13, À149.66, À156.38,
3.2.2. (R)-5,6,7,8-Tetrafluoro-[1,10]binaphthalenyl-2,20-
diol (2)
To 15 (single diastereomer, 0.7 g, 1 mmol) in freshly
distilled THF (20 ml) was added lithium aluminum hydride
portion wise at 0 8C. The mixture was stirred at that tem-
perature for 2 h. A solution of 5% aqueous HCl was added
and the product was extracted with diethyl ether
(3 Â 20 ml). The combined extracts were dried over anhy-
drous MgSO4 and concentrated in vacuo. The product was
purified by flash column chromatography (gradient from
100% hexanes to 30% EtOAc in hexanes) to give (R)-
3.2.5. 7-tert-butyl-5,6,8-Trifluoro-[1,10]-binaphthalenyl-
2,20-diol (26)
To a solution of 2 (50 mg, 0.14 mmol) in dry Et2O (2 ml)
was added t-BuLi (1.7 M in pentane, 0.42 mmol) at À78 8C.
The reaction was stirred at À78 8C for 2 h, then warmed to
room temperature and stirred overnight. Water (5 ml) was
added to quench the reaction. The organic layer was sepa-
rated and washed with a solution of 5% aqueous hydro-
chloric acid (5 ml), dried over Na2SO4 and concentrated in
vacuo. The brown oil obtained was purified using flash
D
F4BINOL (½aꢀ21 ¼ 59ꢁ, c ¼ 1:64, THF) as an off-white
powder (350 mg, 95%). Enantiomeric excess determination
was performed using chiral HPLC analysis (CHIRALPAK
ADcolumn,Daicelco.,Japan,1 ml/min,hexanes : iPrOH9:1,
lmax 230 nm) Rt ¼ 16:51 min, (R)-isomer, Rt ¼ 17:54 min,
(S)-isomer >99% e.e.

524
S. Yekta et al. / Journal of Fluorine Chemistry 125 (2004) 517–525
(b) K. Mikami, M. Terada, T. Nakai, J. Am. Chem. Soc. 112 (1990)
3949–3954;
column chromatography (hexanes/EtOAc 7:3) to afford the
product as white powder (22 mg, 40%). 1H NMR (300 MHz,
CDCl3) d 8.15 (d, J ¼ 11 Hz, 1H), 7.90 (m, 2H), 7.35 (m,
4H), 7.15 (m, 1H), 5.2 (b, 2H), 1.34 (s, 9H). 19F NMR
(300 MHz, CDCl3) d À116.5 (d, J ¼ 6:0 Hz), À139.23
(d, J ¼ 14:7 Hz), À153.4 (t, J ¼ 14:7 Hz). MS-EI, m/z
found 396.
(c) M. Terada, Y. Motoyama, K. Mikami, Tetrahedron Lett. 35
(1994) 6693–6696;
(d) K. Mikami, Y. Motoyama, M. Terada, Inorg. Chim. Acta 222
(1994) 71–75.
[4] K. Maruoka, A.B. Concepcion, H. Yamamoto, Bull. Chem. Soc. Jpn.
65 (1992) 3501–3503.
[5] M. Aizenberg, D. Milstein, Science 265 (1994) 359–361.
[6] (a) A.P. West, S. Mecozzi, D.A. Dougherty, J. Phys. Org. Chem. 10
(1997) 347–350;
3.2.6. 5,6,8-Trifluoro-7-methoxy-[1,10]-binaphthalenyl-
2,20-diol (28)
(b) J.H. Williams, Acc. Chem. Res. 26 (1993) 593–598.
[7] J.T. Welch, D. Peters, R. Miethchen, A.Y. Il’chenko, S. Ru¨diger, J.
Podlech, in: B. Baasner, H. Hagemann, J.C. Tatlow (Eds.), Organo-
Fluorine Compounds, 4th ed., vol. E10b/Part 2, Georg Thieme
Verlag, Stuttgart, 2000, pp. 293–459.
A solution of 25 (20 mg, 0.036 mmol) in EtOH (1 ml) was
stirred under argon for 5 min. Pd/C (10 mg, 10%) was added
and the reaction was stirred under H2 atmosphere at room
temperature for 12 h, then filtered through a pad of silica gel
and concentrated. The crude product was purified using flash
column chromatography (7:3 hexane/EtOAc) to afford the
product as white powder (12 mg, 90%). 1H NMR (400 MHz,
CD3CN/CDCl3) d 7.95 (d, J ¼ 9:2 Hz, 1H), 7.69–7.77 (m,
3H), 7.51 (s, 2H), 7.26–7.33 (m, 2H), 7.21 (s, 1H), 7.12 (dd,
J ¼ 2:5 Hz, J ¼ 8:8 Hz, 1H), 4.04 (s, 3H for 6-substituted
product), 3.87 (s, 3H for 7-substituted product). 19F NMR
(300 MHz, CD3CN/CDCl3) d À135.0 (d, J ¼ 14:5 Hz),
À153.1 (t, J ¼ 16:0 Hz), À159.6 (d, J ¼ 19:1 Hz).
[8] A.K. Yudin, L.J.P. Martyn, S. Pandiaraju, J. Zheng, A. Lough, Org.
Lett. 2 (2000) 41–44.
[9] L.J.P. Martyn, S. Pandiaraju, A.K.J. Yudin, Organomet. Chem. 603
(2000) 98–104.
[10] S. Pandiaraju, G. Chen, A. Lough, A.K. Yudin, J. Am. Chem. Soc.
123 (2001) 3850–3851.
[11] Y. Chen, S. Yekta, L.J.P. Martyn, J. Zheng, A.K. Yudin, Org. Lett. 2
(2000) 3433–3436.
[12] (a) M.S. Newman, J.A. Cella, J. Org. Chem. 39 (1974) 2084–2087;
(b) S. Miyano, M. Tobita, M. Nawa, S. Sato, H. Hashimoto, J.
Chem. Soc. Chem. Commun. 24 (1980) 1233–1234;
(c) S. Miyano, M. Tobita, H. Hashimoto, Bull. Chem. Soc. Jpn. 54
(1981) 3522–3526;
3.2.7. General procedure for the oxidation of methyl
p-tolyl sulfide
(d) R. Hong, R. Hoen, J. Zhang, G.-Q. Lin, Synlett 10 (2001) 1527–
1530;
(e) G.-Q. Ling, R. Hong, J. Org. Chem. 66 (2001) 2877–2880.
[13] (a) R. Pummerer, E. Prell, A. Rieche, Chem. Ber. 59 (1926) 2159;
(b) M. Noji, M. Nakajima, K. Koga, Tetrahedron Lett. 35 (1994)
7983–7984;
To a mixture of (R)-F4BINOL (0.025 mmol, 0.0978 M
solution in chloroform) and Ti(OiPr)4 (0.0125 mmol,
0.669 M solution in chloroform) in 0.5 ml of chloroform
was added water (4.5 ml, 0.25 mmol). The mixture was
stirred under N2 atmosphere for 30 min then cooled to
0 8C for 15 min. Methyl p-tolyl sulfide (33 ml, 0.25 mmol)
and cumyl hydroperoxide (55.5 ml, 0.3 mmol) were added at
an interval of 15 min. The reaction was stirred for 16 h and
loaded onto a short silica gel pad. The product was obtained
as a white solid from elution by EtOAc/hexanes (1:1)
followed by pure ethyl acetate (78%). Enantiomeric excess
was determined by HPLC analysis (CHIRALPAK AS col-
umn, Daicel co., Japan, 1 ml/min, hexane : iPrOH ¼ 7 : 3,
lmax 230 nm) Rt ¼ 16:51 (R)-isomer, Rt ¼ 17:54 min (S)-
isomer (80% e.e.).
(c) M. Nakajima, I. Miyoshi, K. Kanayama, S. Hashimota, M. Noji,
K. Koga, J. Org. Chem. 64 (1999) 2264–2271;
(d) Z. Xin, C. Da, S. Dong, D. Liu, J. Wei, R. Wang, Tetrahedron:
Asymmetry 13 (2002) 1937–1940.
[14] (a) S. Gronowitz, V. Bobosik, K. Lawitz, Chem. Scripta 23 (1984) 120;
(b) S. Gronowitz, A.-B. Honfeldt, Y. Wang, Chem. Scripta 28 (1988)
281;
(c) W.J. Thompson, J. Gaudino, J. Org. Chem. 49 (1984) 5237;
(d) T. Watanabe, N. Miyaura, A. Suzuki, Synlett 3 (1992) 207.
[15] D.M. Hall, E.E. Turner, J. Chem. Soc. 4 (1955) 1242.
[16] T. Hamada, H. Ishida, S. Usui, Y. Watanabe, K. Tsumura, K.
Ohkubo, J. Chem. Soc. Chem. Commun. 11 (1993) 909.
[17] J. Doussot, A. Guy, C. Ferroud, Tetrahedron Lett. 41 (2000) 2545.
[18] W.L. Carrick, G.L. Karapinka, G.T. Kwiatkowski, J. Org. Chem. 38
(1969) 2388.
[19] B. Feringa, H. Wynberg, J. Org. Chem. 46 (1981) 2547.
[20] (a) B. Feringa, H. Wynberg, Tetrahedron Lett. 50 (1997) 4447;
(b) J. Brussee, J.L.G. Groenendijk, M. te, A.C.A. Jansen, Tetra-
hedron 41 (1985) 3313;
Acknowledgements
ˇ
(c) M. Smrcina, J. Polakova, S. Vyskocil, P. Kocovsky, J. Org.
´
´
´
We thank NSERC, Canada Foundation for Innovation,
ORDCF, and University of Toronto for financial support.
Andrei Yudin is a Cottrell Scholar of Research Corporation.
Chem. 58 (1993) 4534.
[21] (a) F. Toda, K. Tanaka, S. Iwata, J. Org. Chem. 54 (1989) 3007;
(b) K. Ding, Y. Wang, L. Zhang, Y. Wu, Tetrahedron 52 (1996) 1005;
(c) H.-J. Deußen, P. Frederiksen, T. Bjørnholm, K. Bechgaard, Org.
Prep. Proced. Int. 28 (1996) 484.
[22] (a) M. Kosugi, K. Fugami, J. Organomet. Chem. 653 (2002) 50–53;
(b) J. Hassan, M. Sevignon, C. Gozzi, E. Schulz, M. Lemaire, Chem.
Rev. 102 (2002) 1359–1469;
References
[1] H.B. Kagan, in: J.D. Morrison (Ed.), Asymmetric Synthesis, vol. 5,
Academic Press, New York, 1985, pp. 1–39.
(c) T. Okujima, S. Ito, N. Morita, Tetrahedron Lett. 43 (2002)
1261–1264;
[2] Y. Chen, S. Yekta, A.K. Yudin, Chem. Rev. 103 (2003) 3155.
[3] (a) K. Mikami, M. Shimizu, Chem. Rev. 92 (1992) 1021–1050;
(d) M.A. Brimble, L.J. Duncalf, Aust. J. Chem. 52 (1999) 19–29;
(e) G.P. Roth, V. Farina, Tetrahedron Lett. 36 (1995) 2191–2194.

S. Yekta et al. / Journal of Fluorine Chemistry 125 (2004) 517–525
525
[23] (a) M. da Mata, W.B. Motherwell, F. Ujjainwalla, Tetrahedron Lett.
[25] (a) S.R. Graham, J.A. Murphy, D. Coates, Tetrahedron Lett. 40
(1999) 2415;
(1997) 137.;
(b) M. da Mata, W. Motherwell, F. Ujjainwalla, Tetrahedron Lett. 1
(1997) 141;
(b) C.G. Martin, J.A. Murphy, C.R. Smith, Tetrahedron Lett. 41
(2000) 1833.
(c) E. Bonfand, L. Forslund, W.B. Motherwell, S. Vazquez, Synlett 4
(2000) 475.
[26] G. Chen, Synthesis and asymmetric catalysis study of fluori-
nated BINOL ligands, M.Sc. Thesis, University of Toronto,
2001.
[24] (a) T. Laird, S.A. Hermitage, U. Tilstam, Org. Process Res. Dev. 6
(2002) 90;
[27] H.J.E. Loewenthal, L. Gottlieb, J. Org. Chem. 57 (1992) 2631.
(b) D.O. Jang, D.H. Cho, C.-M. Chung, Synlett 12 (2001) 1923.