New chiral ligands: 1,4-diols prepared from (S)-1-phenylethanol

Article abstract of DOI:10.1134/S1070428010090125

The stereochemistry of condensation of dilithiated 1-phenylethanol with various carbonyl compounds was investigated. In most cases the reaction proceeds nonstreoselectively, and only in the condensation with PhCOBu-t and 2,4-(MeO)₂C₆H₃COPh only one of the diastereomeric diols prevailed. It was shown by XRD analysis that in the prevailing diastereomeric diol the newly formed chiral carbinol center possessed the same configuration as the initial alcohol. The synthesized diols form homochiral dimers in the crystal lattice.

Full text of DOI:10.1134/S1070428010090125

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 9, pp. 1332−1338. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © I.N. Shishkina, E.Yu. Sokolovskaya, K.A. Potekhin, Yu.V. Nelyubina, R.K. Askerov, V.M. Dem’yanovich, 2010, published in Zhurnal
Organicheskoi Khimii, 2010, Vol. 46, No. 9, pp. 1333−1339.
Dedicated to Full Member of the Russian Academy of Sciences
N.S. Zefirov on occasion of his 75th anniversary
New Chiral Ligands: 1,4-Diols
Prepared from (S)-1-Phenylethanol
I. N. Shishkinaa, E. Yu. Sokolovskayaa, K. A. Potekhinb, Yu. V. Nelyubinac,
R. K. Askerovd, and V. M. Dem’yanovicha
a Lomonosov Moscow State University, Moscow, 119899 Russia
e-mail: shish@org.chem.msu.ru
bVladimir State Humanitarian University, Vladimir, Russsia
cNesmeyanov Institute of Organoelemental Compounds, Russian Academy of Sciences, Moscow, Russia
dBaku State University, Baku, Azerbaijan
Received October 22, 2009
Abstract—The stereochemistry of condensation of dilithiated 1-phenylethanol with various carbonyl compounds
was investigated. In most cases the reaction proceeds nonstreoselectively, and only in the condensation with
PhCOBu-t and 2,4-(MeO)2C6H3COPh only one of the diastereomeric diols prevailed. It was shown by XRD
analysis that in the prevailing diastereomeric diol the newly formed chiral carbinol center possessed the same
configuration as the initial alcohol. The synthesized diols form homochiral dimers in the crystal lattice.
DOI: 10.1134/S1070428010090125
The asymmetric synthesis of chiral organic com- to the asymmetric synthesis are 1,4-diols. The main sub-
pounds with a desired absolute configuration of the atoms stances, BINOLs (I) and TADDOLs (II), proved to be
in the carbon skeleton takes a special place in the current highly efficient asymmetry inducing catalysts for, e.g., the
organic synthesis. The growing world-wide interest in diethylzinc addition to aldehydes, the conjugate addition
enantiomerically pure compounds is due to their practical to unsaturated carbonyl compounds, the aldol reaction,
value, mainly as components of new efficient drugs. The the reactions of Diels–Alder, Strecker, Friedel–Krafts,
enantiomers of a chiral biologically active substance often reduction, and oxidation [2, 3].
differently affect the body, and the influence may be not
only neutral, but sometimes negative. The difference may
be not only in the biological effect but also in the phar-
macokinetics and in the metabolism of enantiomers [1].
The main role in the synthesis of chiral compounds
belongs nowadays to the asymmetric synthesis, and in
particular, to the asymmetric catalysis. The main re-
quirement to the chiral ligands is the presence of no less
than two functional groups capable of the formation of a
conformationally rigid transition complex, and the loca-
tion of these groups close to the chiral center of definite
conformation.And certainly, a very important problem is
the availability of the optically active compound.
The example of the practical application of the (S)-
BINOL is its employing as a complex with lanthanum in
the synthesis of one of the key precursors of the fostriecin
(exibiting a high anticancer action) that is a leading com-
pound among the antitumor drugs [4].
One of the most important compound classes applied
1332

NEW CHIRAL LIGANDS: 1,4-DIOLS
1333
However the wide application of BINOLs and TAD-
Me
OH
Me
Li
DOLs is limited by their restricted availability. The
synthesis of chiral BINOLs requires either the use of
auxiliary chiral reagents, often of complex structure, or
the labor-consuming multistage splitting. An important
advantage of TADDOLs is their synthetic accessibility
from the natural D-tartaric acid. Yet only TADDOLs
of the simplest structure were obtained in high yields
containing the same aryl substituents in the α-positions.
BuLi
OLi
IV
V
Me
RR'C=O
OH
OH
Another application field for chiral 1,4-diols may be
their use as precursors of optically active 1,3-dihydroiso-
benzofurans (phthalanes) whose fragment is present
in the composition of the molecules of some biologi-
cally active substances, e.g., the known antidepressant
Citalopram [5]. Up till now this class compounds are
used mainly as racemates, although it is known that
the necessary biological activity of one enantiomer is
considerably higher.
R
R'
VI_XV
R = R' = H (VI); R = Ph, R' = Ph (VII), 2,4-Me2C6H3
(VIII), 3,4-Me2C6H3 (IX), t-Bu (X), 2,4-(MeO)2C6H3
(XI), 3,4-(MeO)2C6H3 (XII), 4-NMe2C6H4 (XIII),
2-NH2C6H4 (XIV); R = 2-MeC6H4, R' = 2,4-Me2C6H3
(XV).
compounds a second chiral carbinol center would be
formed that might result in two diastereomers. In most
cases the reaction proceeds nonstereoselectively. Only the
condensation with tert-butyl phenyl ketone and 2,4-di-
methoxybenzophenone afforded prevailingly one of the
diastereomers (Table 1). The yield and the ratio of the diol
In this study we report on the synthesis of new chi-
ral 1,4-diols III proceeding frome (S)-1-phenylethanol
through the stage of ortho-lithiation followed by con-
densation with carbonyl compounds. We selected this
synthetic method because of mild conditions of the
reaction preventing in many events the formation of
side products.
1
diastereomers was established from the H NMR spectra
of the reaction mixtures; the diastereomeric composition
was estimated from the doubled signal of protons of the
CHCH3 group and from their relative intensity (Table 1).
The procedure of the lithiation of 1-phenylethanol
(IV) and of the subsequent condensation with the car-
bonyl compounds was optimized using the racemic
alcohol by condensation its dilithium derivative V with
2,4-dimethylbenzophenone. It turned out that the amount
of the lithiating agent and ketone, and also the duration
and the temperature of the reaction did not affect the diol
yield. The replacement of ether by THF where the BuLi is
known to be less associated than in ether [6] unexpectedly
has resulted in significant decrease in the yield (from 65
to 22%). There are published examples on improvement
of the lithiation at the addition of the tetramethylethylene-
diamine [7]. In our case the yield of diol in its presence
decreased to 47% and besides the workup of the reaction
mixture became more complex.
Diols VI, VII, one of diastereomers VIIIa, and also
the predominant diastereomer Xa we succeeded to isolate
in the pure state by crystallization. Further their chiral
Table 1. Composition of reaction mixtures in condensation
of dilithiated 1-phenylethanol (IV) with carbonyl compounds
(see the scheme)
Compd.
no.
Diastereomers
ratio
Conversion,%
Yield, %
a
VI
VII
VIII
IX
35
95
62
59
79
56
70
54
34
32
35
95
62
59
50
48
26
42
17
32
–
a
–
1 : 1
1 : 1
3 : 1
2 : 3
1 : 1
1 : 1
1 : 1
1 : 1
Further the lithiation was performed using 2.1 equiv
of BuLi with respect to alcohol IV in ether at room tem-
perature, and after 24 h the ketone was added (see the
scheme). The reaction mixture was maintained no less
than 24 h and after quenching with water it was analyzed
by IR and 1H NMR spectroscopy. As a result a series of
diols VI–XV was synthesized.
X
XI
XII
XIII
XIV
XV
a One enentiomer.
In the condensation with asymmetrical carbonyl
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 9 2010

SHISHKINA et al.
1334
analogs were synthesized by the lithiation of (S)-1-
phenylethanol (IVa) and by condensation of its dilithium
derivative Va with carbonyl compounds along the pro-
cedure developed using racemic alcohol IV. As a result
we obtained chiral 1,4-diols VIIa, VIIIb,VIIIc, Xb, Xc).
The structure of diol VIIa was proved by XRD analysis.
clouds of the phenyl rings along path d.
c
d
Me
O
Me
Me
Me
Me
Me
O
The condensation with 2,4-dimethylbenzophenone
proceeded nonselectively (diastereomers ratio 1 : 1),
and with tert-butyl phenyl ketone, with a low selectivity
(diastereomers ratio 3 : 1).
H
H
Li
Li
O
O
Me
Li
Me
Li
Considering the molecular models and the comparison
with the experimental data (Table 1) allowed us the fol-
lowing assumptions: from two possible approaches of the
carbonyl compound to the molecule of lithiated alcohol
Va only one was realized because of the stric hindrances
from the methyl group; in the reaction complex the mol-
ecule of an unsymmetrical carbonyl compound can be
oriented in two ways (a and b).
XRD data permit interesting conclusions on the
character of hydrogen bonds in the crystalline diols. In
the crystal of diol VIIa two types of crystallographically
independent molecules are present that combine into
dimers; therewith the molecules of one crystallographic
type form intramolecular hydrogen bonds lacking in the
molecules of the second type; but the latter molecules
form with the former molecules the intermolecular hy-
drogen bonds (Fig. 2a). The other hydroxy group of the
second type molecule remains free.
a
b
The XRD study of diol Xa gave even more unexpected
results. We presumed the formation of intramolecular
hydrogen bonds, but the XRD analysis showed that
same as in the crystal of VIIa in the crystal Xa exist two
cristallographically independent molecules, but neither
of them forms intramolecular hydrogen bonds. Instead
in the crystal stracture of diol Xa formed intermolecular
hydrogen bonds O–H⋯O joining the crystallographically
independent molecules into dimers (Fig. 2b). Although
four OH groups are present, only three such bonds form.
In the first crystallographically independent molecule two
OH groups are acceptors and one donor of the hydrogen
bonds. In the other molecule on the contrary two donors
and one acceptor are present.
The building up of the reaction complex starts by the
coordination of C=O group at the bond of higher ionic
character O–Li; further equally probable is the bond for-
mation between the ortho-carbon atom of the lithiated (S)-
1-phenylethanol Va with the differently oriented ketone
molecules that results in the lack of the stereoselectivity.
Although in the crystal molecules of different chirality
are present in contrast to compound VIIa diol Xa crystal-
lizes in the space group with a center of symmetry P21/n,
in the dimer are combined the molecules of equal chiral-
ity. May be it is just the reason why we failed to grow a
crystal suitable for XRD study from the pure diastereo-
mer: Evidently in the case of the racemate the dimers of
different chirality are better packed in the crystal lattice.
In the condensation of compound Va with tert-butyl
phenyl ketone we observed a predominant formation of
one of the diastereomeric diols Xa. From the possible ap-
proaches of the tert-butyl phenyl ketone molecule to the
dilithiated alcohol we suggested that in the diastereomer
Xc the newly formed chiral center should have the (S)-
configuration, namely, the same as the chiral center of
initial compound Va. The XRD analysis of the racemic
diol Xa proved our assumption (Fig. 1b). The steric hin-
drances from the tert-butyl group at this approach (path
c) are less strong than the pushing aside of electronic
The XRD data do not correlate with the data of IR
spectroscopy for diols solutions in CHCl3. The IR spectra
contain the band at 3580 cm–1 characteristic of the free
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 9 2010

NEW CHIRAL LIGANDS: 1,4-DIOLS
1335
(b)
(a)
Fig. 1. Structures of 1-{2-[hydroxy(2,4-dimethylphenyl)phenylmethyl]phenyl}ethanol (VIIIa) (a) and 1-[2-(1-hydroxyethyl)phenyl]-
2,2-dimethyl-1-phenylpropan-1-ol (Xa) (b) by XRD data.
(a)
(b)
Fig. 2. General view of dimers connected by hydrogen bonds formed from two independent molecules of (a) 1-{2-[hydroxy(diphenyl)
methyl]phenyl}ethanol (VII) and (b) [2-(1-hydroxyethyl)phenyl]-2,2-dimethyl-1-phenylpropan-1-ol (Xa) by XRD data.
hydroxy group and a wide band of the bound HO group
in the region 3300–3450 cm–1; therewith the absence of
the concentration dependence should indicate the intra-
molecular character of the hydrogen bonds.
We measured the spectra of circular dichroism of chi-
ral diols VIIa, VIIIc, Xc in ethanol, and a comparison
was performed with aminoalcohols XVI, XVII obtained
proceeding from (S)-1-phenylethylamine having the
known configuration of the chiral centers (Fig. 3).
It is presumable that the hydrogen bonds in the dimer
are so strong that it is conserved in the solution. In this
case it is regarded as a single molecule not forming inter-
molecular hydrogen bonds (analogously to the absence
of hydrogen bonds between the dimers in the crystal),
and the concentration dependence is not observed. On
the other hand, it is possible that the dimers dissociate in
the solution, and another type of hydrogen bond forms,
intramolecular one.
The spectra of circular dichroism of diol VIIIc and
aminoalcohol (S,S-XVI) having the similar structure
and the identical (S)-configuration of the chiral center
of the initial alcohol and amine are much alike (Fig. 3).
The same pattern is observed for diol Xc and the cor-
responding aminoalcohol (S,S-XVII). We assumed that
the configuration of the newly formed chiral center in
diols VIIIc and Xc is the same as the configuration of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 9 2010

SHISHKINA et al.
1336
θ, deg
The XRD study of compounds VIIIa, Xa was per-
22
formed on a diffractometer Smart 1000 CCD (MoKα-
radiation, graphite monochromator, ω-scanning), VIIa,
on a diffractometer Siemens P3/PC (MoKα- radiation,
graphite monochromator, θ/2θ-scanning). The structures
were solved by the direct method and refined by the least-
mean-squares methos in the anisotropic full-matrix ap-
proximation by F2hkl. The hydrogen atoms of OH groups
in compounds VII, VIIIa, Xa were localized from the
difference Fourier synthesis of the electron density. The
position of the other hydrogen atoms was calculated. All
hydrogen atoms were refined in the isotropic approxima-
tion by the rider model. The main crystallographic data
and refinement parameters are presented in Table 2. All
calculations were performed using software SHELXTL
PLUS [8]. The structures were deposited into the Cam-
bridge Crystallographic Data Center, CCDC 738564
(VII), 738565 (VIIIc), 738563 (Xc).
20
18
16
14
12
10
8
6
4
2
0
220
240
260
280
300
–2
–4
(S)-1-Phenylethanol (IVa) was obtained by cleav-
age of the salt of the acid phthalate of 1-phenylethanola
(IV) with (S)-1-phenylethylamine (optical purity 100%).
Yield 60%, bp 98°C (18 mm Hg.) {86.5–87.5°C (8 mm
Hg) [9]}, [α]D –43.8° (without solvent) {–43.5° (without
solvent) [9]}, optical purity 100%. IR spectrum, ν, cm–1
–6
Fig. 3. Circular dichroism spectra (in ethanol) of (1S)-{2-[(S)-
hydroxy(2,4-dimethylphenyl)phenylmethyl]phenyl}ethanol
(VIIIc) (1), (1S)-{2-[(1S)-hydroxyethyl]phenyl}-2,2-dimethyl-
1-phenylpropan-1-ol (Xc) (2), (1S)-{2-[(1S)-(dimethylamino)
ethyl]phenyl}(2,4-dimethyl-phenyl)phenylmethanol (XVI) (3),
(1S)-1-{2-[(1S)-(dimethyl-amino)ethyl]phenyl}-2,2-dimethyl-
1-phenylpropan-1-ol (XVII) (4).
1
(CHCl3): 3370 (OH). H NMR spectrum, δ, ppm: 1.50
d (3H, CH3CH, J 6.5 Hz), 3.31 s (1H, OH), 4.85 q (1H,
CHCH3, J 6.5 Hz), 7.3–7.5 m (14HAr).
Lithiation of 1-phenylethanol (IV) and (S)-(IVa).
General procedure. To a solution of 0.01 mol of alcohol
in 30 ml of anhydrous ether in the atmosphere of dry
argon was added dropwise a solution of BuLi in hexane.
The solution of lithiated derivatives V and Va were left
standing for 24 h.
the chiral center in the initial alcohol IVa. It was proved
by the XRD data for the racemic diol VIIIa (Fig. 1a).
H
Me
(S)
(S)
NMe2
OH
R'
Preparation of diols. General procedure. To a
solution of 0.01 mol of the lithiated alcohol was added
dropwise in the atmosphere of dry argon a solution of
0.095 mol of a carbonyl compound in 20–30 ml of an-
hydrous ethyl ether. After 24 h the reaction mixture was
quenched with 5–10 ml of water. The water layer was
separated and extracted with ethyl ether (3 × 20 ml).
The combined organic solutions were washed with water
and dried with MgSO4, the solvent was distilled off. The
unreacted alcohol was distilled off in a vacuum [bp 93°C
(12 mm Hg)], the residue was crystallized from a mixture
of petroleum ether with ethanol or ethyl ether. The diaste-
reomeric ratio in the diols obtained was determined from
the 1H NMR spectra of the reaction mixtures.
R
S,S-XVI, XVII
R = Ph, R' = 2,4-Me2C6H3 (XVI); R = t-Bu, R' = Ph (XVII).
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer UR-
1
20. H NMR spectra were registered on a spectrometer
Varian XR-400 (400 MHz) in CDCl3, internal reference
20
TMS. [α]D were measured on a polarimeter EPO-1 of
VNIIKIProdmash in ethanol, cells 0.1 and 0.25 dm. The
circular dichroism spectra were measured on a dichrograph
JASCO J-600 in ethanol at the comcentration 1 mg/ml.
1-[2-(Hydroxymethyl)phenyl]ethanol (VI). Parafor-
maldehyde was used as carbonyl compound. Yield 35%,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 9 2010

NEW CHIRAL LIGANDS: 1,4-DIOLS
1337
1
bp 180°C (10 mm Hg). IR spectrum, ν, cm–1 (mineral
oil): 3540 (OH), 3460–3240 (OH). H NMR spectrum,
δ, ppm: 1.51 d (3H, CH3CH, J 6.5 Hz), 3.54 s (1H, OH),
4.40 s (1H, OH), 4.53 d (2H, CH2, J 6.5 Hz), 5.10 q (1H,
CHCH3, J 6.5 Hz), 7.4–7.5 m (4HAr). Found %: C 71.22;
H 7.92. C9H12O2. Calculated %: C 71.03; H 7.95.
(OH). H NMR spectrum, δ, ppm: 1.32 d (3H, CH3CH,
J 6.5 Hz), 2.41 s (1H, OH), 4.25 s (1H, OH), 5.1 q (1H,
CHCH3, J 6.5 Hz), 6.6–7.7 m (14HAr).
1
1-{2-[Hydroxy(2,4-dimethylphenyl)phenylmethyl]
phenyl}ethanol (VIII) (diastereomers ratio 1:1), yield
1
62%. H NMR spectrum, δ, ppm: 1.34 and 1.41 d (3H,
1-{2-[Hydroxy(diphenyl)methyl]phenyl}ethanol
(VII). Yield 95%, mp 152°C (from the mixture petro-
leum ether–ethanol). IR spectrum, ν, cm–1 (KBr): 3370
(OH), 3350–3130 (OH); (CHCl3): 3580 (OH), 3470–3260
(OH). H NMR spectrum, δ, ppm: 1.32 d (3H, CH3CH,
J 6.5 Hz), 2.41 s (1H, OH), 4.25 s (1H, OH), 5.1 q (1H,
CHCH3, J 6.5 Hz), 6.6–7.7 m (14HAr).
CH3CH, J 6.5 Hz), 2.17, 2.37 s, 2.25, 2.42 s (3H, CH3),
2.94 s (1H, OH), 4.17 s (1H, OH), 5.11 and 5.22 q (1H,
CHCH3, J 6.5 Hz), 6.4–7.9 m (12HAr).
1-{2-[Hydroxy(2,4-dimethylphenyl)phenylmethyl]
phenyl}ethanol (VIIIa), mp 148°C (from the mixture
petroleum ether–ethanol). IR spectrum, ν, cm–1 (KBr):
3556 (OH), 3370–3130 (OH); (CHCl3): 3585 (OH),
1
1
(1S)-{2-[Hydroxy(diphenyl)methyl]phenyl}ethanol
(VIIa). Yield 95%, mp 156°C (from the mixture petro-
leum ether–ethanol), [α]D20 –90.0° (C 1, ethanol), –105.8°
(C 2.1, CHCl3). IR spectrum, ν, cm–1 (KBr): 3370 (OH),
3350–3130 (OH); (CHCl3): 3580 (OH), 3470–3260
3480–3300 (OH). H NMR spectrum, δ, ppm: 1.41 d (3H,
CH3CH, J 6.5 Hz), 2.17 s, 2.37 s (3H, CH3), 2.25 s (1H,
OH), 4.05 s (1H, OH), 5.22 q (1H, CHCH3, J 6.5 Hz),
6.5–7.7 m (12HAr). Found, %: C 83.30; H 7.29. C23H24O2.
Calculated %: C 83.10; H 7.28.
Table 2. Crystallographic data and the main parameters of XRD study of alcohols VIIIa, Xa, VIIa
VIIIa
C25H30O3
378.49
120
Xa
C19H24O2
284.38
120
VIIa
C21H20O2
304.37
293
Empirical formula
Molecular weight
T, K
Crystal system
Monoclinic
C2
Monoclinic
P21/n
Rhombic
P212121
8
Space group
Z
4
8
a, Å
31.138(4)
8.1816(10)
8.2769(10)
95.596(2)
2098.6(4)
1.198
11.7661(8)
15.1512(10)
18.2371(13)
103.963(2)
3155.1(4)
1.197
8.942(3)
10.222(3)
35.803(14)
–
b, Å
c, Å
β, deg
V, A3
dcalc, g cm–3
3272.6(19)
1.236
μ, cm–1
0.77
0.76
0.78
F(000)
816
1232
1296
2θmax, deg
58
55
52
Measured reflections
11582
32018
3655
Independent reflections
2965
7609
3655
Reflections with I>2σ(I)
2478
3722
2635
The number of refined parameters
254
387
417
R1
0.0555
0.1080
1.011
0.0621
0.1484
1.004
0.0406
0.0882
1.006
wR2
GOF
Residual electron density dmin/dmax, e Å –3
0.390/–0.325
0.360/–0.297
0.150/–0.153
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 9 2010

SHISHKINA et al.
1338
(1S)-{2-[Hydroxy(2,4-dimethylphenyl)phenyl-
2.17 s (1H, OH), 3.41 s (1H, OH), 5.17 q (1H, CHCH3,
J 6.5 Hz), 7.1–8.0 m (9HAr). Found, %: C 80.27; H 8.57.
C19H24O2. Calculated, %: C 80.24; H 8.51.
methyl]phenyl}ethanol (VIIIb) (diastereomers ratio
1 : 1), yield 62%. 1H NMR spectrum, δ, ppm: 1.34 and
1.41 d (3H, CH3CH, J 6.5 Hz), 2.17, 2.37 and 2.25, 2.42 s
(3H, 2,4-CH3), 2.94 s (1H, OH), 4.17 s (1H, OH), 5.11
and 5.22 q (1H, CHCH3, J 6.5 Hz), 6.4–7.9 m (12HAr).
1-{2-[Hydroxy(2,4-dimethoxyphenyl)phenyl-
methyl]phenyl}ethanol (XI) (diastereomers ratio 2 : 3),
yield 48%. 1H NMR spectrum, δ, ppm: 1.31 and 1.60 d
(3H, CH3CH, J 6.5 Hz), 3.71, 3.83 and 3.42, 3.57 s (3H,
2,4-OCH3), 5.32 and 5.42 q (1H, CHCH3, J 6.5 Hz),
6.3–7.8 m (12HAr).
(1S)-{2-[(S)-Hydroxy(2,4-dimethylphenyl)phenyl-
methyl]phenyl}ethanol (VIIIc), mp 122°C (from the
mixture petroleum ether–ethanol), [α]D20 –38.0° (C 1,
ethanol), –71.25° (C 2.1, CHCl3). IR spectrum, ν, cm–1
(KBr): 3556 (OH), 3370–3130 (OH); (CHCl3) 3585 (OH),
1-{2-[Hydroxy(3,4-dimethoxyphenyl)phenyl-
methyl]phenyl}ethanol (XII) (diastereomers ratio 1 : 1),
yield 26%. 1H NMR spectrum, δ ppm: 1.18–1.45 d.d (3H,
CH3CH, J 6.5 Hz), 3.82 s, 3.86 s (3H, OCH3), 5.11 and
5.18 q (1H, CHCH3, J 6.5 Hz), 6.5–8.1 m (12HAr).
1
3480–3300 (OH). H NMR spectrum, δ, ppm: 1.41 d (3H,
CH3CH, J 6.5 Hz), 2.17, 2.37 s (3H, 2,4-CH3), 2.25 s (1H,
OH), 4.05 s (1H, OH), 5.22 q (1H, CHCH3, J 6.5 Hz),
6.5–7.7 m (12HAr). Found, %: C 83.30; H 7.29. C23H24O2.
Calculated, %: C 83.10; H 7.28.
1-{2-[Hydroxy(4-dimethylaminophenyl)phenyl-
methyl]phenyl}ethanol (XIII) (diastereomers ratio
1 : 1), yield 42%. 1H NMR spectrum, δ, ppm: 1.30 and
1.40 d (3H, CH3CH), 2.63 and 3.11 s [6H, N(CH3)2], 5.18
and 5.24 q (1H, CHCH3), 6.6–8.1 m (13HAr).
1-{2-[Hydroxy(3,4-dimethylphenyl)phenylmethyl]
phenyl}ethanol (IX) (diastereomers ratio 1 : 1), yield
1
59%. H NMR spectrum, δ, ppm: 1.30 and 1.34 d (3H,
CH3CH, J 6.5 Hz), 2.26, 2.27 and 2.25, 2.28 s (3H, 3,4-
CH3), 3.24 and 3.22 s (1H, OH), 5.22 and 5.22 q (1H,
CHCH3, J 6.5 Hz), 6.7–7.8 m (12HAr).
1-{2-[(2-Aminophenyl)hydroxyphenylmethyl]
phenyl}ethanol (XIV) (diastereomers ratio 1 : 1),
yield 17%. 1H NMR spectrum, δ, ppm: 1.25 and 1.41 d
(3H, CH3CH, J 6.5 Hz), 5.12 and 5.22 q (1H, CHCH3,
J 6.5 Hz), 6.2–8.1 m (13HAr).
1-[2-(1-Hydroxyethyl)phenyl]-2,2-dimethyl-1-
phenylpropan-1-ol (X) (diastereomers ratio 3 : 1),
1
yield 50%. H NMR spectrum, δ, ppm: 0.78 and 1.30 d
(3H, CH3CH, J 6.5 Hz), 1.22 and 1.35 s [9H, (CH3)3C],
3.2–3.4 s (1H, OH), 4.12 s (1H, OH), 5.17 and 5.27 q
(1H, CHCH3, J 6.5 Hz), 7.1–8.0 m (9HAr).
1-{2-[Hydroxy(2,4-dimethylphenyl)(2-methyl-
phenyl)methyl]phenyl}ethanol (XV) (diastereomers
1
ratio 1 : 1), yield 32%. H NMR spectrum, δ, ppm: 1.32
1-[2-(1-Hydroxyethyl)phenyl]-2,2-dimethyl-1-
phenylpropan-1-ol (Xa), mp 157°C (from the mixture
petroleum ether–ether). IR spectrum, ν, cm–1 (mineral
oil): 3590–3240 (OH); (CCl4): 3620 (OH), 3570–3300
and 1.39 d (3H, CH3CH, J 6.5 Hz), 2.15, 2.36, 2.38 and
2.23, 2.41, 2.44 s (3H, 2,4,2'-CH3), 5.16 and 5.24 q (1H,
CHCH3, J 6.5 Hz), 6.9–7.9 m (11HAr).
1
(OH). H NMR spectrum, δ, ppm: 0.78 d (3H, CH3CH,
REFERENCES
J 6.5 Hz), 1.22 s [9H, (CH3)3C], 2.17 s (1H, OH), 3.41 s
(1H, OH), 5.17 q (1H, CHCH3, J 6.5 Hz), 7.1–8.0 m
(9HAr). Found, %: C 80.27; H 8.57. C19H24O2. Calculated,
%: C 80.24; H 8.51.
1. Chirality in Drug Research, Francotte, E. and Lindner, W..
Eds., Weinheim: WILEY-VCH, 2006, p. 189.
2. Brunel, J.M., Chem. Rev., 2005, vol. 105, p. 857.
3. Seebach, D., Beck, A.K., and Heckel, A., Angew. Chem.,
Int. Ed. 2001, vol. 40, p. 92.
4. Fujii, K., Maki, K., Kanai, M., and Shibasaki, M., Org.
Lett., 2003, vol. 5, p. 733.
5. Lundbeck, H., Europe Patent 0 347 066, 1989; Сhem. Аbstr.,
1990, vol. 113, 78150.
6. Bergander, K., He, R., Chandrakurmar, N., Eppes, O., and
Gunter, H., Tetrahedron, 1994, vol. 50, p. 5861.
7. Chadwick, S.T., Ramirez,A., Gupta, L., and Collum, D.B.,
J. Am. Chem. Soc., 2007, vol. 129, p. 2259.
8. Sheldrick, G.M., SHELXTL v. 5.10. Structure Determination
Software Suit, Wisconsin: Bruker AXS, USA, 1998.
9. Hossa, A. and Kenyon J., J. Chem. Soc. 1930, p. 2260.
1-{2-[(1S)-Hydroxyethyl]phenyl}-2,2-dimethyl-
1-phenylpropan-1-ol (Xb) (diastereomers ratio 3 : 1),
yield 50%. 1H NMR spectrum, δ, ppm: 0.78 and 1.30 d
(3H, CH3CH, J 6.5 Hz), 1.22 and 1.35 s [9H, (CH3)3C],
3.2–3.4 s (1H, OH), 4.12 s (1H, OH), 5.17 and 5.27 q
(1H, CHCH3, J 6.5 Hz), 7.1–8.0 m (9HAr).
(1S)-{2-[(1S)-Hydroxyethyl]phenyl}-2,2-dimethyl-
1-phenylpropan-1-ol (Xc), mp 172°C (from the mixture
petroleum ether–ether), [α]D20 –96° (C 1, ethanol). IR
spectrum, ν, cm–1 (mineral oil): 3590–3240 (OH); (CCl4):
1
3620 (OH), 3570–3300 (OH). H NMR spectrum, δ, ppm:
0.78 d (3H, CH3CH, J 6.5 Hz), 1.22 s [9H, (CH3)3C],
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 9 2010