Asymmetric opening of styrene oxide with p-toluidine catalyzed by BINOL polyols and their lithium complexes

Article abstract of DOI:10.1007/s11172-013-0195-x

Opening of racemic styrene oxide with p-toluidine catalyzed by chiral BINOL-derived polyols proceeded regioselectively mainly with the formation of 2-phenyl-2-(p-tolylamino)- ethanol with low ee values.

Full text of DOI:10.1007/s11172-013-0195-x

Russian Chemical Bulletin, International Edition, Vol. 62, No. 6, pp. 1371—1376, June, 2013
1371
Asymmetric opening of styrene oxide with pꢀtoluidine catalyzed by
BINOL polyols and their lithium complexes
Yu. N. Belokon´, V. I. Maleev, M. A. Moskalenko, Yu. V. Samoilichenko, A. S. Peregudov,† and A. T. Tsaloev
aA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (495) 135 5085. Eꢀmail: yubel@ineos.ac.ru
Opening of racemic styrene oxide with pꢀtoluidine catalyzed by chiral BINOLꢀderived
polyols proceeded regioselectively mainly with the formation of 2ꢀphenylꢀ2ꢀ(pꢀtolylamino)ꢀ
ethanol with low ee values.
Key words: asymmetric organic catalysis, chiral polyols, ꢀamino alcohols, kinetic resoluꢀ
tion, oxiranes.
The epoxide ring opening with nucleophiles is an imꢀ
portant reaction in organic chemistry.1 Achiral2 and chiral3
Lewis acids are widely used as catalysts in this reaction.
Attempts to use organic catalysis, including its asymmetꢀ
ric version,4,5 were also undertaken. It is important to note
that the natural enzymes accomplishing the epoxide ring
opening do not contain metal ions, and their active groups
responsible for the catalysis are phenol groups of the proꢀ
tein thyroxine residues.6
Recently, we introduced7 a new chiral organic catalyst
BIMBOL (3,3´ꢀbis[hydroxy(diphenyl)methyl]ꢀ1,1´ꢀbiꢀ
naphthaleneꢀ2,2´ꢀdiol (1)). This tetraol containing two
phenol groups has proved an efficient catalyst of a number
of asymmetric conversions, including synthesis of amino
acids and Michael reaction.7,8 The presence of four hydrꢀ
oxy groups in the structure of one molecule provides their
synergetic interaction in the reaction activated complexes
and, as a consequence, superiority of BIMBOL over diols,
in particular, BINOL (2).8 It could have been expected
that BIMBOL and its more acidic analogs (BICBOL (3);
FBIMBOL (4)) would also be efficient organic catalysts
in the asymmetric opening of epoxide with those nucleoꢀ
philes which are not strong bases. Tetraol BIMBOL, like
diol BINOL, possesses good chelating ability with respect to
metal ions, therefore, its complexes can be efficient cataꢀ
lysts simultaneously exhibiting Lewis acidity due to the
metal ion and Brønsted acidity due to the hydroxy groups.
In the present work, we report an opening of enantioꢀ
merically pure and racemic styrene oxides (5) with pꢀtoluꢀ
idine (6) catalyzed by polyols 1—4, as well as by lithium
derivatives of compound 1 (Scheme 1).
Scheme 1
†
Deceased.
i. Catalyst, solvent.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1371—1376, June, 2013.
1066ꢀ5285/13/6206ꢀ1371 © 2013 Springer Science+Business Media, Inc.

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Belokon´ et al.
Results and Discussion
Catalyst 2 at 55 C in toluene within 11 h provided 36% of
7a without enantiomeric enrichment (entry 10).
The synthesis of compounds 1 and 2 was reported.9,10
Catalysts 3 and 4 were obtained according to the proceꢀ
dures suggested by us earlier.
The catalytic activity of polyols 1—4 clearly enough
correlated with their acidity. Since the acidity of the pheꢀ
nol groups in compounds 1, 3, and 4 differs only slightly,
the main factor determining the difference in their cataꢀ
lytic activity is the acidity of the carboxy and triphenylꢀ
carbinol groups in 3 and in 1, 4, respectively. The pKa
values of this groups in DMSO exceed 25 for 1 (see Ref. 11),
10.8 for 4 (see Ref. 12), and are within 10—12 for 3 (see
Ref. 11). Since the acidity constant of the protonated form
of aniline in DMSO is 3.6, toluidine can ionize neither the
phenol OH groups (pKa 17—18), nor other acid groups in
compounds 1—4, and the catalysts retain their initial acidic
properties in its presence.
It is obvious that the catalysis of the epoxide opening is
provided by the formation of strong hydrogen bonds of the
OH groups of the catalyst with the oxygen atom of styrene
oxide in the activated complex. The presence of the conjuꢀ
gated system of hydrogen bonds in molecules 1, 3, and 4
facilitates the proton transfer from the forming ammoniꢀ
um group to the generating alkoxide group in the transiꢀ
tion state of the amino alcohol formation. This can
explain the superiority of organic catalysts 1, 3, and 4 over 2.
The formation of the excess of isomer 7a allows us
to suggest that the character of the transition state of the
styrene oxide opening is shifted toward the SN1 and
considerable carbocationic character of this state is stabiꢀ
lized by the phenyl ring of styrene oxide. This is also inꢀ
dicated by the decrease in the amount of the second isoꢀ
mer 7b formed when more acidic catalyst 3 is used (see
Table 1, entry 3).
The opening of styrene oxide (5) with pꢀtoluidine (6)
in the presence of polyols 1—4 mainly led to isomer 7a,
namely, 2ꢀphenylꢀ2ꢀ(pꢀtolylamino)ethanol, whereas reꢀ
gioisomer 7b, 1ꢀphenylꢀ2ꢀ(pꢀtolylamino)ethanol, was
formed in considerably lower amounts (Table 1, enꢀ
tries 1—10). The rate of the process was found to very
strongly depend on the catalyst acidity and structure.
Diol 2 (5 mol.%, CH2Cl2, room temperature) catalyzed
the reaction, providing a 12% yield of product 7a within
three days, with the asymmetric induction being absent
(entry 1). The use of 5 mol.% of catalyst 1 under the same
conditions gave product 7a in 28% yield and a slight enanꢀ
tiomeric enrichment, 5% ee (entry 2). When catalyst 3
was used under the same conditions, the yield of 7a was
39% with the enantiomeric excess ee 5% (entry 3), and the
full conversion of styrene oxide was reached within ten
days (entry 4). The catalytic activity of compound 4 was
low, and the yield of the product was only 8% (2.5 mol.%
of catalyst, 72 h, entry 5) at no enantiomeric enrichment.
The reaction was accelerated by the elevation of temꢀ
perature to 55 C (solvent toluene), and after 11 h (5 mol.%
of 1) the yield of product 7a reached 37% (entry 6), howꢀ
ever, the enantioꢀdiscrimination practically disappeared.
As it was expected, diol 3 proved more active catalyst and
under the same conditions gave the product in 36 and 80%
yield on using 5 and 10 mol.% of the catalyst, respectively,
however, without enantiomeric enrichment (entries 7 and 8).
The reaction in toluene without heating catalyzed by diol 3
gave 20% of product 7a with 12% ee within 24 h (entry 9).
It is obvious that an increase in the acidity of polyol
catalyst leads to the increase in its activity in the reaction
Table 1. Opening of racemic styrene oxide with pꢀtoluidine catalyzed by compounds 1—4a
Entry
Polyol
C (mol.%)
Solvent
T/C
t/h
Yieldb (%)
ee (%)
7a
7b
1
2
3
4
5
6
7
8
9
10
(R)ꢀ2
(S)ꢀ1
(R)ꢀ3
(R)ꢀ3
(R)ꢀ4
(S)ꢀ1
(R)ꢀ3
(R)ꢀ3
(R)ꢀ3
(R)ꢀ2
5.0
5.0
5.0
5.0
2.5
5.0
5.0
10.0
5.0
5.0
СH2Cl2
СH2Cl2
СH2Cl2
СH2Cl2
СH2Cl2
Toluene
Toluene
Toluene
Toluene
Toluene
25
25
25
25
25
55
55
55
25
55
72
72
72
240
72
11
11
11
12
28
39
92
18
37
36
80
20
36
2.0
4.5
2.7
6.0
0
5 (R)
5 (S)
—
c
—
0
6.0
4.5
9.0
6.0
1 (R)
0
0
12 (S)
0
24
11
12.0
a Reagents: catalyst (0.0118 mmol), styrene oxide 5 (0.237 mmol), pꢀtoluidine (0.332 mmol), solvent (0.5 mL).
1
b Was determined using H NMR spectroscopy from the ratio of signals for the product 7a at  6.54 (2 H) and the
unreacted styrene oxide at  2.87 (1 H), regioisomer 7b was formed in the trace amounts; unreacted styrene oxide 5
remained in the reaction mixture without changes.
c Trace amounts.

Toluidinolysis of styrene oxide
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 6, June, 2013
1373
Lewis acid
of the styrene oxide opening with pꢀtoluidine. It is known
that the Brønsted acidity of hydroxy groups can be raised
by the activation with Lewis acids (LBA).13 This suggesꢀ
tion was tested by the use of (S)ꢀ1 with the equimolar
additive of lithium tetraphenylborate as the catalytic sysꢀ
tem (Table 2).
Brønsted acid
Basic fragment
The reaction proceeded rapidly (within 20 min) to
reach 18% yield of product 7a and then it stopped: the
yield did not change during the next 2 h (see Table 2,
entries 1—3). This fact indicates the disappearance from
1
the reaction medium of activating species (the H NMR
spectroscopic data showed that the starting pꢀtoluidine
and styrene oxide remained in the mixture). The catalyst 1
itself without activating additives has low activity (entry 2).
This means that lithium ion are completely removed from
the catalytic cycle, probably, by the competing chelation
by the reaction product, ꢀamino alcohol 7a. The reaction
can take place without catalyst 1 only in the presence of
lithium tetraphenylborate, though slower and with low
yield, which can be caused by the same reason (entry 4).
As it was expected, the amount of product 7b decreased
with the increase in the acidity of the catalytic system
resulted from the addition of LiBPh4 (cf. Table 1, entry 2
and Table 2, entries 1—3).
It could have been expected that ionization of 1 upon
the action of a base would make it more efficient catalyst
of this process. The ionized tetraol 1 becomes better chelatꢀ
ing agent, that allows us to suppress the competing chelaꢀ
tion of lithium ions with the forming ꢀamino alcohol,
which leads to the termination of the reaction. In this
case, two additional catalytic centers emerge (Fig. 1). The
first center is basic (the ionized hydroxy group), the secꢀ
ond one is acidic (Lewis acid, Li+ ion). The Lewis acid
together with the Brønsted acid groups (the unionized hyꢀ
Fig. 1. Polyfunctional character of monolithium salt 1[Li].
droxy groups of the catalyst) should activate the oxygen
atom of styrene oxide. At the same time, the ionized
hydroxy group of the catalyst increases the nucleophiliciꢀ
ty of pꢀtoluidine following the general base catalysis
mechanism.
The monolithium salt was obtained by the reaction
of 1 with the equimolar amount of BuLi. The exclusive
formation of the monolithium salt 1[Li] was confirmed by
the mass spectrometry (electrospray ionization). The mass
spectrum exhibited a positive ion with m/z 657 correspondꢀ
ing to the protonated monolithium salt with no signals
corresponding to the higher amount of lithium per one
molecule of 1.
To confirm the suggested hypothesis for the activation
of the catalyst, we carried out a quantitative comparison
of the reaction rates depending on the catalyst used. Figꢀ
ure 2 represents the accumulation of the reaction product
in the catalysis with (R)ꢀ1, (R)ꢀ2, (R)ꢀ3, and lithium salt
(R)ꢀ1[Li]. All the experiments were carried out in NMR
Table 2. Opening of racemic styrene oxide with pꢀtoluidine catalꢀ
yzed by the system (S)ꢀ1—LiBPh4
Yield 7a (%)
a
(R)ꢀ1
(R)ꢀ2
(R)ꢀ3
50
40
30
20
10
(R)ꢀ1[Li]
Entry
t/min
Yieldb (%)
7a
eec (%)
7b
1
2
3
4d
120
160
120
160
18.0
18.0
18.0
11.5
1.0
1.0
1.0
3.5
2 (R)
2 (R)
0
0
a Reagents: (S)ꢀ1 (0.0118 mmol,
5
mol.%), LiBPh4
(0.0118 mmol, 5 mol.%), styrene oxide 5 (0.237 mmol), pꢀtoluidꢀ
ine (0.332 mmol), CH2Cl2 (0.5 mL).
20
40
60
80
100 t/h
b Was determined using 1H NMR spectroscopy from the ratio of
signals for the product 7a at  6.54 (2 H), regioisomer 7b at  4.93
(1 H), and unreacted styrene oxide 5 at  2.87 (1 H).
c Enantiomeric purity of compound 7a was determined by HPLC
(see Experimental).
Fig. 2. Accumulation of product 7a in the course of the opening
of racemic styrene oxide 5 with pꢀtoluidine catalyzed by (R)ꢀ1
(5 mol.%), (R)ꢀ2 (10 mol.%), (R)ꢀ3 (5 mol.%), and lithium salt
(R)ꢀ1[Li] (5 mol.% Li, 5 mol.% (R)ꢀ1) in CD2Cl2 at 25 C. For
the linear dependence of catalysis with lithium salt (R)ꢀ1[Li],
the convergence factor R2 = 0.9927.
d Experiment was carried out with 5 mol.% of LiBPh4 and
without (S)ꢀ1.

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Belokon´ et al.
Table 3. Opening of racemic styrene oxide catalyzed by lithium
salts (R)ꢀ1[Li] and (R)ꢀ2[Li]a
tubes in CD2Cl2, and the reaction progress was monitored
by the changes in the 1H NMR spectra of the reacꢀ
tion mixture.
The yield was determined from the ratio of the integral
intensity of the signal for product 7a at  6.54 (2 H) and
the total integral intensity of the signals for the unreacted
pꢀtoluidine at  6.67 (2 H) and regioisomer 7b at  6.66
(2 H). Allowance was made for the initial excess of pꢀtoluꢀ
idine and its consumption in the formation of some secꢀ
ond isomer 7b.
Entry Polyol
BuLi : Polyol
t/h
Yieldb (%) ee (%)c
(mol.% : mol.%)
7a
7b
1
2
3
4
(S)ꢀ1
(S)ꢀ1
(S)ꢀ1
(R)ꢀ2
5 : 5
10 : 5
2.5 : 5
40 : 40
24
24
24
24
36
18
12
10
3.6
1.2
41
12
17
—
d
—
d
—
a
The formation of a noticeable amount of 7b (up to
6.2%) was observed only when lithium salt 1[Li] was used;
the ratio of regioisomers 7a : 7b = 20 : 3 remained practiꢀ
cally unchanged as the reaction progressed.
Reagents: catalyst (0.0118 mmol, 5 mol.%), styrene oxide
(0.237 mmol), pꢀtoluidine (0.332 mmol), CH2Cl2 (0.5 mL).
b
Was determined using 1H NMR spectroscopy from the ratio of
signals for the product 7a at  6.54 (2 H), regioisomer 7b at  4.93
(1 H), and unreacted styrene oxide 5 at  2.87 (1 H).
c Enantiomeric purity of compound 7a was determined by HPLC
(see Experimental).
Monolithium salt 1[Li] exhibited considerably higher
catalytic activity under the indicated reaction conditions:
the yield was 41% after 93 h, the enantiomeric purity of
the product was 12% (S). The order of activity of the
catalysts other than lithium salts corresponded to their
acidity, which confirmed the data obtained earlier (see
Table 1). As it was expected, the highest reaction rate was
observed in the case of diol (R)ꢀ3, possessing the highest
acidity, in the case of less acidic tetraol (R)ꢀ1, the rate of
the reaction was slower. Despite the fact that the comparꢀ
ison of the catalytic activity in this experiment was carried
out using 10 mol.% of catalyst (R)ꢀ2 containing two OH
groups in the molecule, the reaction turned out to be the
slowest, that agreed with its lowest acidity. A relatively
small increase in the reaction rate when catalyst (R)ꢀ3 was
used as compared to (R)ꢀ1 was caused by the low solubiliꢀ
ty of (R)ꢀ3 (see Experimental).
d Trace amounts.
The ratio of rate constants of the reaction of (R)ꢀstyrꢀ
ene oxide in the presence of (R)ꢀ1[Li] (kRR) and (S)ꢀ1[Li]
(kRS) is kRR : kRS = 2.64 (the ratio of the constants kRR
and kRS is equal to the ratio of the slopes of the correꢀ
sponding straight lines, see Fig. 3). The ratio of rate conꢀ
stants of the reaction of each of the enantiomers is the
stereoselectivity factor (s), whereas its value differing from 1
(2.64), according to the known formula14 s = ln[1 – C(1 +
+ ee´)] : ln[1 – C(1 – ee´)], indicates a possibility of kinetꢀ
ic resolution in this reaction. The low s value indicates
that the further modification of the catalytic system is
necessary in order to increase the efficiency of the resoluꢀ
tion, and such works are in progress.
To select the most efficient catalytic system, we obꢀ
tained lithium salt containing different amounts of lithiꢀ
um by the reaction of tetraol 1 with BuLi taken in different
ratios. The monolithium salt of diol (R)ꢀ2 was obtained
for comparison. The results of the catalytic experiments
are represented in Table 3.
In the experiments on the opening of enantiomerically
pure (R)ꢀstyrene oxide, the enantiomerically enriched
Yield 7a (%)
(R)ꢀ1[Li]
40
As it is seen from these data, the most efficient catalytꢀ
ic system is the one obtained by the reaction of the equimoꢀ
lar amounts of BuLi and tetraol (S)ꢀ1, i.e. salt 1[Li]
(Table 3, entry 1): its amount of 5 mol.% in CH2Cl2 at
room temperature provided the 40% total yield of the reꢀ
action products 7a and 7b within 24 h, the enantiomeric
purity of 7a was 41% (R). Dilithium salt of tetraol 1 was
less active catalyst (entry 2), the catalytic ability of the
system decreased with the decrease in the amount of the
BuLi added (entry 3). It should be noted that monolithiꢀ
um salt (R)ꢀ2[Li] was much less active as compared to the
monolithium salt (S)ꢀ1[Li] (entry 4).
To study the mechanism of the reaction catalyzed by
monolithium salt 1[Li], we measured the reaction rate in
the experiments with enantiomerically pure (R)ꢀstyrene
oxide. The yield of product 7a linearly depends on the
reaction time in the case of catalysis with both lithium salt
(R)ꢀ1[Li] and lithium salt (S)ꢀ1[Li] (Fig. 3).
(S)ꢀ1[Li]
35
30
25
20
15
10
5
20
40
60
80
100 120 140 t/h
Fig. 3. Accumulation of product 7a in the course of the opening
of racemic styrene oxide 5 with pꢀtoluidine catalyzed by monoꢀ
lithium salts (S)ꢀ1[Li] and (R)ꢀ1[Li] (5 mol.% Li, 5 mol.% 1) in
CD2Cl2 at 25 C. The approximation of the linear dependencies
for the catalysis by salt (R)ꢀ1[Li] was made using the equation
y = 0.4938x, the convergence factor R2 = 0.996; for the catalysis
by salt (S)ꢀ1[Li], using the equation y = 0.1852x, R2 = 0.991.

Toluidinolysis of styrene oxide
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 6, June, 2013
1375
H, 5.8. C46H34O4•2H2O•Me2CO. Calculated (%): C, 78.9;
H, 5.9.
product 7a was formed predominantly in (S)ꢀconfiguraꢀ
tion in the case of catalysis with both (R)ꢀ1[Li] and
(S)ꢀ1[Li]. However, the enantiomeric purity of 7a in the
case of catalysis with (R)ꢀ1[Li] is 96.4% (S), whereas in
the case of (S)ꢀ1[Li], 91.3% (S). In the case of the classic
SN1ꢀtype mechanism, the stereochemistry of the reaction
product would have been determined by only the configuꢀ
ration of the catalyst and would have differed depending
on whether (R)ꢀ1[Li] or (S)ꢀ1[Li] was used. It is obvious
that this clearly contradicts to the conclusions drawn earꢀ
lier. On the one hand, the regioselectivity of the styrene
oxide ring opening indicates a considerable degree of the
carbocationic character of the transition state of the proꢀ
cess and, consequently, the SN1 mechanism of the reacꢀ
tion. On the other hand, the retention of the enantioꢀ
meric purity in the reaction product indicates a considerꢀ
able SN2ꢀcharacter of the opening. We suggest that in this
case the reaction follows the SN1 mechanism with one of
the sides of the planar carbocation being shielded by the
alkoxide anion of the forming amino alcohol and, thus,
the SN2 mechanism is simulated.
(R)ꢀBIMBOL ((R)ꢀ1) was synthesized according to the
known procedure9 starting from (R)ꢀBINOL ((R)ꢀ2) (ee 99.9%,
25
tret 5.499 min); []D + 109.8 (c 1.00, CHCl3) (cf. Ref. 9:
[]D20 + 113.4 (c 1.00, CHCl3)).
(R)ꢀMOMꢀBINOL ((R)ꢀ1) was synthesized according to the
known procedure17 starting from (R)ꢀBINOL ((R)ꢀ2).
(R)ꢀBICBOL ((R)ꢀ2,2´ꢀdihydroxyꢀ1,1´ꢀbinaphthaleneꢀ3,3´ꢀ
dicarboxylic acid, (R)ꢀ3). A 2.5 M solution of BuLi in hexane
(14 mL, 0.0348 mol) was added dropwise to a solution of
(R)ꢀMOMꢀBINOL (bisꢀmethoxymethylene ether (R)ꢀBINOL)
(4.36 g, 0.0116 mol) in 1,4ꢀdioxane (50 mL) at –15 C under
argon, and the mixture was stirred for 3 h at –5—0 C. Then dry
CO2 was passed through the reaction mixture over 1 h, followed
by the addition of water (20 mL), diethyl ether (50 mL), and 1%
aqueous HCl until acidic pH. The organic layer was separated,
the aqueous layer was additionally extracted with diethyl ether
(2×50 mL). The combined organic extracts were dried with sodiꢀ
um sulfate, the solvent was evaporated at reduced pressure. The
intermediately obtained (R)ꢀMOMꢀBICBOL was used in the
next step without additional purification. For this, a 6 M solution
of HCl in 1,4ꢀdioxane (30 mL) was added to its solution in THF
(30 mL), and the mixture was kept for 3 h. Then the solvent was
evaporated at reduced pressure, followed by the addition of waꢀ
ter (20 mL) and extraction with ethyl acetate (3×50 mL). The
combined organic layer was dried with sodium sulfate, the solꢀ
vent was evaporated at reduced pressure. The residue was reꢀ
crystallized from a mixture of ethyl acetate—toluene. The yield
of product (R)ꢀ3 was 2.18 g (50%), m.p. >290 C. 1H NMR
(DMSOꢀd6), : 3.20 (br.s, 2 H, COOH); 7.00—7.02 (m, 2 H);
7.32—7.35 (m, 4 H); 8.02—8.04 (m, 2 H); 8.70 (s, 2 H); 11.14
(br.s, OH).
Experimental
1
H, 13C and 19F NMR spectra were recorded on Bruker
AvanceTM 300, 400, 600 spectrometers. Chemical shifts () in
the 1H NMR spectra were measured relative to the residual
protons of the solvent, in the 13C NMR spectra, relative to the
signal of the deuterated solvent, in the 19F NMR spectra, relaꢀ
tive to the external standard CFCl3 ( = 0.00). The spectra were
recorded in CDCl3 and CD2Cl2. Optical rotation was measured
on a Perkin—Elmer 341 polarimeter in a temperatureꢀcontrolled
cuvette (l = 5 cm) at 25 C.
(R)ꢀFBIMBOL (3,3´ꢀbis[(hydroxy)bis(pentfluorophenyl)ꢀ
methyl]ꢀ1,1´ꢀbinaphthamineꢀ2,2´ꢀdiol, (R)ꢀ4).
Step 1. Thionyl chloride (5 mL, 8.19 g, 0.069 mol) was addꢀ
ed dropwise to a solution of compound (R)ꢀ3 (1 g, 0.0027 mol) in
methanol (30 mL), and the reaction mixture was refluxed for 6 h
and then concentrated at reduced pressure. The residue was
treated with water and extracted with ethyl acetate. The comꢀ
bined organic layer was dried with sodium sulfate, then passed
through a short layer of silica gel, and the solvent was evaporated
at reduced pressure. The yield of dimethyl ester of compound
(R)ꢀ3 was 0.93 g (87%). 1H NMR (CDCl3), : 4.07 (s, 6 H);
7.15—7.19 (m, 2 H); 7.34—7.38 (m, 4 H); 7.91—7.95 (m, 2 H);
8.70 (s, 2 H); 10.72 (s, 2 H).
Silica gel 60 purchased from Merck was used in the work.
Enantiomeric purity of BINOL (2) was analyzed on a liquid
chromatograph using a Chiralcel® IBꢀ3 column (eluent hexꢀ
ane—PriOH (90 : 10), the rate of the eluent flow 1.0 mL min–1
,
UV detector ( = 254 nm)).
Enantiomeric purity of 2ꢀ(pꢀtolylamino)ꢀ2ꢀphenylethanol
(7a) was analyzed on a liquid chromatograph using an AmyCoat
column (150×4.6 mm) (eluent hexane—PriOH (95 : 5), the rate
of the eluent flow 1.0 mL min–1, UV detector ( = 254 nm));
t0 = 2 min, tS = 11.4 min, tR = 17.3 min.
All the solvents used were purified according to the standard
procedures.15
Elemental analysis of all the compounds obtained was perꢀ
formed in the Laboratory of Elemental Analysis of A. N. Nesmeꢀ
yanov Institute of Organoelement Compounds, Russian Acadeꢀ
my of Sciences.
Step 2. A 2.5 M solution of BuLi in hexane (0.64 mL,
1.6 mmol) was placed into a flask under argon, followed by the
addition of a solution of C6F5Br (0.395 g, 1.6 mmol) in diethyl
ether (5 mL) at –70 C and the stirring of the mixture at this
temperature for 2 h. A solution of dimethyl ester of (R)ꢀ3 (0.1 g,
0.25 mmol) obtained in step 1 in diethyl ether (40 mL) was
added dropwise to the obtained solution of pentfluorophenylꢀ
lithium18 at –70 C. The mixture was stirred for 16 h, with the
temperature allowing to reach the ambient. Then, 10% aq. HCl
was added dropwise to the reaction mixture, followed by the
extraction with diethyl ether (3×50 mL) and drying with Na2SO4.
Diethyl ether was evaporated at reduced pressure, the product
was isolated by chromatography on silica gel (eluent ethyl acetꢀ
ate—hexane (1 : 4), Rf 0.6). The isolated material was visualized
in the system diethyl ether—hexane (1 : 9) as two spots: comꢀ
(R)ꢀBINOL ((R)ꢀ2) was synthesized according to the known
procedure.10
(S)ꢀBIMBOL ((S)ꢀ1) was synthesized according to the known
procedure9 starting from (S)ꢀBINOL (ee 99.9%, tret 5.058 min);
[]D25 –107.3 (c 1.00, CHCl3) (cf. Ref. 9: [б]D20 –109.5 (c 1.00,
CHCl3). M.p. 186—188 C (cf. Ref. 16: m.p. 176—179 C).
1H NMR (CDCl3), : 4.79 (s, 2 H, OH); 6.70 (s, 2 H,
OH); 7.14—7.17 (m, 2 H, Ar); 7.19 (s, 2 H, Ar); 7.28—7.40
(m, 24 H, Ar); 7.65—7.68 (m, 2 H, Ar). Found (%): C, 79.2;

1376
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 6, June, 2013
Belokon´ et al.
pound (R)ꢀ4 had lower Rf 0.2. The yield of the product was 0.038 g
(15%). 19F NMR (CDCl3), : (–83.74)—(–83.36) (m, 2 F);
(–74.98) (dt, 1 F, J = 55.0, J = 21.3 Hz); (–60.25) (dd, 2 F,
J = 88.4 Hz, J = 19.4 Hz). 13C NMR (CDCl3), : 29.72 (s),
112.53 (s), 117.28 (m), 123.96 (s), 125.43 (s), 128.34 (s), 128.64
(s), 128.89 (s), 129.22 (s), 133.48 (s), 136.26 (m), 139.62 (m),
142.97 (m), 143.65 (m), 146.98 (m), 150.36 (c).
Monolithium salt (S)ꢀ1[Li]. Tetraol (S)ꢀ1 (7.7 mg, 0.0118 mmol)
and a 0.075 M solution of BuLi (0.158 mL, 0.0118 mmol) in
hexane were placed in a roundꢀbottom flask with a magnetic
stirrer under argon, and the mixture was stirred for 5 min. The
solvent was evaporated at reduced pressure. The solid compound
obtained was directly used as a catalyst in the reaction of the
styrene oxide opening with pꢀtoluidine.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 11ꢀ03ꢀ00206).
References
1. L. P. C. Nielsen, E. N. Jacobsen, in Aziridines and Epoxides
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Reaction of styrene oxide (5) with pꢀtoluidine (general proceꢀ
dure). A. The catalyst (5 mol.% of (S)ꢀ1, 7.7 mg, 0.0118 mmol)
in CH2Cl2 (0.5 mL) was placed in a roundꢀbottom flask with
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0.237 mmol) and pꢀtoluidine (6) (35 mg, 0.332 mmol) were addꢀ
ed. After the reaction reached completion, the mixture was passed
through a short layer of silica gel (eluent light petroleum—ethyl
acetate (5 : 1)). The yields of products 7a and 7b were deterꢀ
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1
mined from the H NMR spectra, which agreed with those deꢀ
scribed in the literature.19,20
2ꢀPhenylꢀ2ꢀ(pꢀtolylamino)ethanol (7a). 1H NMR (CDCl3),
: 2.24 (s, 3 H); 3.72 (dd, 1 H, J = 11.1 Hz, J = 7.4 Hz); 3.93 (dd,
1 H, J = 11.1 Hz, J = 4.2 Hz); 4.49 (dd, 1 H, J = 7.4 Hz, J = 4.2 Hz);
6.54 (d, 2 H, J = 8.2 Hz); 6.96 (d, 2 H, J = 8.3 Hz); 7.35—7.39
(m, 5 H).
1ꢀPhenylꢀ2ꢀ(pꢀtolylamino)ethanol (7b). 1H NMR (CDCl3),
: 2.31 (s, 3 H); 3.30 (dd, 1 H, J = 13.1 Hz, J = 8.7 Hz); 3.43 (dd,
1 H, J = 13.1 Hz, J = 3.9 Hz); 4.93 (dd, 1 H, J = 8.7 Hz,
J = 3.9 Hz); 6.66 (d, 2 H, J = 8.0 Hz); 7.06 (d, 2 H, J = 8.1 Hz);
7.32—7.45 (m, 5 H).
B. NMR experiment. The catalyst (5 mol.% of (S)ꢀ1, 7.7 mg,
0.0118 mmol) in CD2Cl2 (0.6 mL) was placed in an NMR tube,
followed by the addition of styrene oxide (5) (27 L, 0.237 mmol),
shaking, and addition of pꢀtoluidine (6) (35 mg, 0.332 mmol),
then the tube was shaken until its complete dissolution. The
1H NMR spectra were recorded on a Bruker Avance 600 spectroꢀ
meter, chemical shifts () were measured relative to the residual
signal of the undeuterated solvent, CD2Cl2. The yield was deterꢀ
mined from the ratio of the integral intensities of the signal for
the product 7a at  6.54 (2 H) and the total integral intensity of
the signals for the unreacted pꢀtoluidine at  6.67 (2 H) and
regioisomer 7b at  6.66 (2 H). Allowance was made for the
initial excess of pꢀtoluidine and its consumption in the formation
of isomer 7b.
Yield (%) = Rexc•I7a/(I7a + I7b + Itol)•100%,
where Rexc is the initial molar ratio pꢀtoluidine : styrene oxide;
I7a and I7b are the integral intensities of the indicated signals of
products 7a and 7b, respectively; Itol is the integral intensity of
the signal for the unreacted pꢀtoluidine.
The authors are grateful to N. S. Ikonnikov for the
carrying out the mass spectrometric analysis.
Received March 1, 2013