Tetraaryl-1,3-dioxolane-4,5-dimethanols as catalysts for the addition of trimethylsilyl cyanide to benzaldehyde and the oxirane ring

Article abstract of DOI:10.1007/s11172-007-0233-7

The synthesis of 1,2-, 1,3-, and 1,4-phenylene-bis[(4R,5R)-4,5- di(hydroxydiphenylmethyl)-1,3-dioxolane]s (ortho-, meta-, and para-bis-(R,R)-TADDOLs) and bis[4-{[(4R, 5R)-4,5-di(hydroxydiphenylmethyl)]-1,3- dioxolan-2-yl}phenyl]methane was carried out. The possibilities of the use of these compounds as catalysts for the C-C bond formation in the addition of Me₃SiCN to benzaldehyde and the oxirane ring opening in cyclohexene oxide by Me₃SiCN were investigated. The catalytic activity of different bis-(R, R)-TADDOLs in this series depends on their structure.

Full text of DOI:10.1007/s11172-007-0233-7

Russian Chemical Bulletin, International Edition, Vol. 56, No. 8, pp. 1507—1514, August, 2007
1507
Tetraarylꢀ1,3ꢀdioxolaneꢀ4,5ꢀdimethanols as catalysts
for the addition of trimethylsilyl cyanide to benzaldehyde
and the oxirane ring
Yu. N. Belokon´,ꢀ V. I. Maleev, Z. T. Gugkaeva, M. A. Moskalenko, A. T. Tsaloev, A. S. Peregudov,
S. Ch. Gagieva, K. A. Lyssenko, V. N. Khrustalev, and A. V. Grachev
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5085. Eꢀmail: yubel@ineos.ac.ru
The synthesis of 1,2ꢀ, 1,3ꢀ, and 1,4ꢀphenyleneꢀbis[(4R,5R)ꢀ4,5ꢀdi(hydroxydiphenylmethyl)ꢀ
1,3ꢀdioxolane]s (orthoꢀ, metaꢀ, and paraꢀbisꢀ(R,R)ꢀTADDOLs) and bis[4ꢀ{[(4R,5R)ꢀ4,5ꢀ
di(hydroxydiphenylmethyl)]ꢀ1,3ꢀdioxolanꢀ2ꢀyl}phenyl]methane was carried out. The possiꢀ
bilities of the use of these compounds as catalysts for the C—C bond formation in the addition
of Me3SiCN to benzaldehyde and the oxirane ring opening in cyclohexene oxide by Me3SiCN
were investigated. The catalytic activity of different bisꢀ(R,R)ꢀTADDOLs in this series depends
on their structure.
Key words: organic catalysis, Brønsted acids, bisꢀ(R,R)ꢀα,α,α´,α´ꢀtetraarylꢀ1,3ꢀdioxolaneꢀ
4,5ꢀdimethanols, mandelonitrile, trimethylsilyl cyanide.
Asymmetric organocatalysis with chiral organic
Brønsted acids and bases is an important field of investiꢀ
gation in modern asymmetric synthesis.1—3 This approach
is very attractive due to the conceptual and experimental
simplicity, the absence of hazardous heavy metal salts in
reaction mixtures, and extremely high efficiency of caꢀ
talysis.4 This class of catalysts includes chiral polyꢀ
functional Brønsted acids, α,α,α´,α´ꢀtetraarylꢀ1,3ꢀdioxoꢀ
laneꢀ4,5ꢀdimethanols ((R,R)ꢀTADDOLs),5 in which the
acidity of one hydroxy group increases due to the presꢀ
ence of another hydroxy group as a result of intramolecuꢀ
lar hydrogen bonding. The structure of (4R,5R)ꢀ2,2ꢀdiꢀ
methylꢀ4,5ꢀdi(hydroxydiphenylmethyl)ꢀ1,3ꢀdioxolane (1)
is given below.
nitroso compounds with enamines9 provide examples of
this catalysis.
Evidently, an increase in the acidity of one hydroxy
group leads to an increase in the basicity of another
hydroxy group, in which the hydrogen atom is involved in
hydrogen bonding.6 Hence, TADDOLs would be expected
to act as chiral bifunctional catalysts by activating both
the electrophilic and nucleophilic components of the reꢀ
action, as exemplified by the hypothetical transition state
(TS1) of the addition reaction10 of Me3SiCN to aldeꢀ
hydes.
Presumably, the presence of two (R,R)ꢀTADDOL
fragments in a single molecule can increase the efficiency
of such catalysts due to the spatially favorable arrangeꢀ
ment of several acidic groups capable of activating subꢀ
strates.
This type of catalysts activated by Brønsted acids is
called Brønsted acid assisted Brønsted acid catalysts.6 The
asymmetric Diels—Alder reactions,7 the Mukaiyama reꢀ
action,8 and the TADDOLꢀpromoted condensation of
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1451—1458, August, 2007.
1066ꢀ5285/07/5608ꢀ1507 © 2007 Springer Science+Business Media, Inc.

1508
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
Belokon´ et al.
The
use
of
cyclohexanedioneꢀbased
chlorosilane in the presence of triethylamine gives
bisꢀOꢀsilyl derivative 2 (see Scheme 1). The condensation
of 2 with 1,2ꢀ, 1,3ꢀ, or 1,4ꢀphthalaldehyde or benzaldeꢀ
hyde in the presence of boron trifluoride diethyl etherate
and trifluoromethanesulfonic acid affords acetals, whose
treatment with phenylmagnesium bromide yields the corꢀ
responding bisꢀ(R,R)ꢀTADDOLs. In the case of the
diphenylmethane derivative, acetal 8 was prepared by reꢀ
fluxing the corresponding dialdehyde and diethyl tartrate
in toluene in the presence of toluenesulfonic acid with
azeotropic distillation of water.
bisꢀTADDOLs11,12 in photochemical reactions was docuꢀ
mented.13 However, these compounds were used in
equimolar amounts with respect to substrates.
In
the
present
study,
we
synthesized
bisꢀ(R,R)ꢀTADDOLs and investigated their catalytic acꢀ
tivity in the addition reactions of Me3SiCN with benzꢀ
aldehyde and the oxirane ring opening in cyclohexene
oxide. The known examples of the addition of Me3SiCN
to benzaldehyde in the presence of organic catalysts are few
in number and involve the use of bases and carbenes.14,15
The structures of the resulting bisꢀ(R,R)ꢀTADDOLs
were confirmed by elemental analysis, 1H NMR spectroꢀ
scopy, and mass spectrometry, as well as by the results of
Xꢀray diffraction study of tetramethyl ester 5a´, which is a
related compound of intermediate compound 5a (Fig. 1)
and for which crystals suitable for Xꢀray diffraction
were grown (crystals of 5a were not obtained), and
paraꢀbisꢀTADDOL 6c (Fig. 2).
The Xꢀray diffraction study showed that the crystals of
compound 5a´ contain two independent molecules per
asymmetric unit. The main geometric parameters of two
molecules are virtually identical. The dioxolane rings
adopt an envelope conformation with the C(7) and C(14)
atoms deviating from the plane through the other atoms
Results and Discussion
Monoꢀ(R,R)ꢀTADDOL and bisꢀ(R,R)ꢀTADDOLs
were synthesized starting from diethyl ester of natural
Lꢀtartaric acid, benzaldehyde, the corresponding diformylꢀ
benzenes, and bis(4ꢀformylphenyl)methane (Scheme 1).
2,2´ꢀ(Phenylene)bis[(4R,5R)ꢀ4,5ꢀdi(hydroxydiphenylꢀ
methyl)ꢀ1,3ꢀdioxolane)]s and bis[4ꢀ{[(4R,5R)ꢀ4,5ꢀ
di(hydroxydiphenylmethyl)]ꢀ1,3ꢀdioxolanꢀ2ꢀyl}pheꢀ
nyl]methane were synthesized according to a procedure
analogous to that used earlier16 for the preparation of
monoꢀ(R,R)ꢀTADDOL. The first step affords diethyl
tartrate, and the treatment of the latter with trimethylꢀ
Scheme 1
1,2ꢀ (5a, 6a), 1,3ꢀ (5b, 6b), 1,4ꢀphenyleneꢀbis[(4R,5R)ꢀ4,5ꢀdi(hydroxydiphenylmethyl)ꢀ1,3ꢀdioxolane] (5c, 6c).
Reagents and conditions: i. Me3SiCl/Et3N, PhCH3, 0 °C; ii. 1) BF3•OEt2, 2) CF3SO3H; iii. 4 PhMgBr, THF; iv. 8 PhMgBr, THF.

Bisꢀ(R,R)ꢀTADDOLs in C—C bond formation
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
1509
a rather narrow range from 25.7° to 54.8°. In turn, this
fact allows the conclusion that the rotation of one
dioxolane ring with respect to another ring is hindered by
steric factors. The steric strain can substantially influence
the catalytic properties of bisꢀ(R,R)ꢀTADDOLs prepared
from compounds 5.
C(11)
C(20)
C(16)
O(4)
C(10)
O(3)
O(11)
C(19)
O(12)
C(8)
O(1)
O(6)
C(9)
The Xꢀray diffraction data for paraꢀbisꢀ(R,R)ꢀ
TADDOL 6c (see Fig. 2) show that the crystals of 6c, like
those of 5a´, contain two crystallographically indepenꢀ
dent molecules. Compound 6c crystallizes as a solvate
with two methanol molecules per independent paraꢀbisꢀ
(R,R)ꢀTADDOL molecule. The geometry of two indeꢀ
pendent molecules in the crystal structure of 6c is virtuꢀ
ally identical. Slight differences are observed only in the
conformations, to be more precise, in the orientation of
the dioxolane ring with respect to the central aromatic
ring. In compound 6c, one of the hydroxy groups in
both TADDOL fragments is involved in an intramoꢀ
lecular O—H...O bond (O...O, 2.686(4)—2.791(4) Å),
whereas another OH group forms an intermolecular
hydrogen bond with the methanol solvent molꢀ
ecules (O...O, 2.670(4)—2.850(4) Å) (see Fig. 2). The
bisꢀ(R,R)ꢀTADDOL molecules are linked to each other
by these interactions to form Hꢀbonded chains (Fig. 3).
Initially, we studied the catalytic activity of
bisꢀTADDOLs 6a—c based on three isomeric diformylꢀ
O(10)
C(15)
C(13)
C(12)
O(8)
C(18)
C(14)
O(2)
O(7)
C(7)
C(1)
C(17)
O(5)
C(2)
O(9)
C(6)
C(5)
C(3)
C(4)
Fig. 1. Overall view of tetramethyl ester 5a´ related to comꢀ
pound 5a.
of the ring (see Fig. 1). The carboxy substituents in the
dioxolane rings are in the axial positions and have
trans orientations with respect to each other. Slight differꢀ
ences in the geometry of the independent molecules in
the crystal structure of 5a´ are associated with the mutual
arrangement of the dioxolane substituents with respect to
the aromatic ring. The torsion angles characterizing the
rotation of the rings in two independent molecules vary in
C(49)
C(50)
C(48)
C(23)
C(22)
C(51)
C(24)
C(21)
C(47)
C(46)
C(18)
C(25)
C(19)
C(14)
H(3O)
C(40)
C(41)
C(42)
C(20)
C(13)
C(8)
C(17)
C(39)
C(2)
C(3)
O(1)
O(7)
C(43)
O(5)
C(44)
C(45)
C(16)
C(15)
H(7O)
O(3)
C(1)
C(7)
O(2)
C(4)
C(11)
C(10)
C(9)
C(12)
C(64)
H(4O)
O(4)
C(6)
O(8)
C(5)
O(6)
C(62)
C(34)
C(35)
C(38)
H(8O)
C(26)
C(36)
C(63)
C(59)
C(52)
C(53)
C(33)
C(32)
C(61)
C(37)
C(27)
C(28)
C(54)
C(60)
C(31)
C(58)
C(57)
C(55)
C(29)
C(30)
C(56)
Fig. 2. Overall view of paraꢀbisꢀ(R,R)ꢀTADDOL 6c.

1510
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
Belokon´ et al.
Fig. 3. Fragment of the Hꢀbonded chain of paraꢀbisꢀ(R,R)ꢀTADDOL and the methanol molecules of solvation in the crystal
structure of 6c.
benzenes and monoꢀTADDOL 4 in the addition of
Me3SiCN to benzaldehyde and cyclohexene oxide.
The NMR monitoring of the reaction allowed us also
to refute the possibility of silylation (complete or partial)
of alcohol groups in the catalysts. In the course of
the reaction, the signals for the hydroxy protons of
monoꢀTADDOL and all bisꢀ(R,R)ꢀTADDOLs (at δ 3.94
and 3.59) became slightly broader, but their integral inꢀ
tensities remained unchanged, which is evidence that the
catalysts undergo no substantial changes in the course of
the reaction.
The dependence of the yield of Oꢀsilylmandelonitrile
on the reaction time of the addition reaction in the presꢀ
ence of bisꢀ(R,R)ꢀTADDOLs as the catalysts is presented
in Fig. 4. This figure also shows the accumulation of the
product in the reaction catalyzed by monoꢀTADDOL 4
The addition of trimethylsilyl cyanide to benzaldeꢀ
hyde (Scheme 2) was monitored by 1H NMR spectroꢀ
scopy. The reaction was carried out in deuterated benꢀ
zene in an NMR tube. It was found that the reaction does
not proceed in the absence of a catalyst. In the presꢀ
ence of both monoꢀ(R,R)ꢀTADDOL (10 mol.%) and
bisꢀ(R,R)ꢀTADDOLs (5 mol.%),* the reaction produces
the Oꢀsilyl derivative of mandelonitrile. The course of the
reaction can easily be followed based on the disappearꢀ
ance of the signal for the proton at the carbonyl group of
benzaldehyde at δ 9.78 and the appearance of the signal
for the α proton of the trimethylsilyl derivative of mandeloꢀ
1
nitrile at δ 5.36. According to the H NMR specta of the
taken in
a
double amount with respect to
reaction mixture recorded at certain intervals, no byꢀprodꢀ
bisꢀ(R,R)ꢀTADDOLs. As can be seen from these data,
ucts were formed even after 48 h.
Y (%)
100
Scheme 2
9
80
60
It could not be sure that the reaction was not accomꢀ
panied by leaching of sodium ions from the glass surꢀ
face to form the corresponding sodium derivatives of
TADDOL, which can serve as catalysts for the reaction.
To exclude this possibility, we carried out kinetic studies
in a quartz tube with the use of 10 mol.% of compound 6c.
It appeared that, both in quartz and glass tubes, the reacꢀ
tions proceed at the same rate (within the experimental
error). Hence, it can be concluded that the reaction is
catalyzed by free (R,R)ꢀTADDOLs.
6c
40
20
4
6b
6a
0
40
80
120
t/min
Fig. 4. Plot of the yield (Y ) of the reaction product vs. the
time (t) of the addition of trimethylsilyl cyanide to benzaldeꢀ
hyde in C6D6 in the presence of 5 mol.% of 6a—c or 9 and
10 mol.% of 4 as the catalyst at 20 °C; [PhCHO] = 0.94 mol L–1
,
* The ratio PhCHO : TMSCN = 1 : 1.5 at benzaldehyde conꢀ
centrations of 0.94 mol L–1
.
[Me3SiCN] = 1.41 mol L–1
.

Bisꢀ(R,R)ꢀTADDOLs in C—C bond formation
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
1511
Table 1. Reaction of benzaldehyde with trimethylsilyl cyanide
catalyzed by (R,R)ꢀTADDOLs in C6D6 and CH2Cl2
lnC/t
a
–1
TADDOL
Yield of the productb (%)
–2
–3
–4
–5
CH2Cl2
C6D6
4
10
0
5
8
0
1
6a
6b
6c
85
18
a The reaction conditions: benzaldehyde (1 mmol), trimethylsilyl
cyanide (1.5 mmol), the catalysts (5 mol.% in the case of 6a—c
and 10 mol.% in the case of 4), CH2Cl2 (1 mL) or C6D6, argon
atmosphere, 25 °C, 30 min.
–4.5
–4.0
–3.5
–3.0
lnCcat
b The yield of Oꢀsilylmandelonitrile was determined by 1H NMR
spectroscopy.
Fig. 6. Plot of the logarithm of the initial rate of the reaction
PhCHO with Me3SiCN vs. the logarithm of the concentration
of 6c: y = 1.8901x + 3.6504; R2 = 0.9989.
terephthalaldehydeꢀbased paraꢀ(R,R)ꢀTADDOL 6c is
the most efficient catalyst superior to ortho (6a) and
meta isomers (6b), as well as to monoꢀ(R,R)ꢀTADDOL 4.
Our studies showed that the catalytic activity of bisꢀ
TADDOLs remains unchanged in going from deuteroꢀ
benzene to toluene or dichloromethane. The reaction
in dichloromethane in the presence of 5 mol.% of cataꢀ
lyst 6c is completed in 30 min to give the product in
85% yield, whereas other bisꢀ(R,R)ꢀTADDOLs and
monoꢀ(R,R)ꢀTADDOL 4 appeared to be inefficient
(Table 1).
The reaction rate substantially increases as the amount
of the catalyst increases from 1 mol.% to 10 mol.% (Fig. 5).
The linearization of the kinetic curves in logarithmic
coordinates allows the calculation of the reaction order
with respect to the catalyst (Fig. 6). The slope is 1.89 (the
correlation coefficient is 0.9989), which is indicative of
the second reaction order with respect to the catalyst
(calculated for 6c).
Taking into account the data on the catalytic activity
of bisꢀTADDOLs, it can be concluded that the distance
between the dioxolane fragments in the molecules of
these compounds is of considerable importance. This
dependence is additionally exemplified by the use of
bisꢀ(R,R)ꢀTADDOL 9 as the catalyst for the addition of
trimethylsilyl cyanide to benzaldehyde, whose catalytic
activity is substantially higher than that of compounds
6a—c (see Fig. 4). The quantitative conversion of benzꢀ
aldehyde in the presence of 5 mol.% of catalyst 9 was
achieved within 15 min, as opposed to compound 6c, in
the presence of which the analogous result was attained
only within 8 h.
The epoxide ring opening with Me3SiCN is another
reaction, which would be catalyzed by Brønsted acids
(Scheme 3). Like the addition of Me3SiCN to aldehydes,
the epoxide cleavage does not proceed in the absence
of catalysts. The asymmetric epoxide cleavage catalyzed
by chiral Lewis acids,17,18 including the reaction with
Me3SiCN,19,20 was studied in detail. However, to our
knowledge, there are no examples of the asymmetric caꢀ
talysis of the epoxide ring opening with Me3SiCN proꢀ
moted by chiral Brønsted acids.
Y (%)
1
80
60
Scheme 3
2
40
20
3
4
0
It appeared that, of all (R,R)ꢀTADDOLs, only
bisꢀ(R,R)ꢀTADDOL 6c (5 mol.%) catalyzes this reacꢀ
tion, which proceeds at room temperature for 4 days and
produces the racemic product in quantitative yield. This
product was detected by 1H NMR spectroscopy (no
byꢀproducts were observed in the reaction mixture). The
50
100
150
t/min
Fig. 5. Plot of the yield (Y ) of the reaction product vs. the
reaction time (t) of the trimethylsilylcyanation of benzaldehyde
in C6D6 in the presence of 10 (1), 5 (2), 2 (3), and 1 mol.% (4) of
paraꢀbisꢀ(R,R)ꢀTADDOL 6c at 20 °C; [PhCHO] = 0.94 mol L–1
,
[Me3SiCN] = 1.41 mol L–1
.

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Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
Belokon´ et al.
Table 2. Principal crystallographic data and the refinement staꢀ
tistics for 5a´ and 6c
concentration of cyclohexene oxide in dichloromethane
was 0.25 mol L–1
.
Therefore, the fixation of two (R,R)ꢀTADDOL fragꢀ
ments at a particular distance in a single organic molecule
is an efficient approach to the design of new organic chiral
BBA catalysts.6 The further modification of the bridge
between two (R,R)ꢀTADDOL fragments, in particular,
an increase in its flexibility, would be expected to result in
even higher activity of the catalysts. Although we preꢀ
pared racemic products, the replacement of the phenyl
groups in the bisꢀ(R,R)ꢀTADDOL fragment by bulkier
substituents would be expected to increase the enanꢀ
tioselectivity of the reactions.21
Parameter
5a´
6c
Molecular formula
Molecular weight
T/K
Crystal system
Space group
Z (Z´)
a/Å
b/Å
c/Å
α/deg
C20H22O12
454.38
193
Triclinic
P1
C66H62O10
1015.16
100
Monoclinic
P21
2 (2)
4 (2)
8.5511(17)
10.887(2)
13.157(3)
67.79(3)
74.92(3)
70.09(3)
1054.0(5)
1.432
20.023(3)
9.0490(11)
29.047(4)
—
100.020(6)
—
β/deg
γ/deg
V/Å
Experimental
5182.7(13)
1.301
dcalc/g cm–3
µ/cm–3
1
The H NMR spectra were recorded on Bruker Avance 300
1.20
0.87
(300.13 MHz), Bruker Avance 400 (400.13 MHz), and Bruker
Avance 600 (600.22 MHz) spectrometers; the chemical shifts
were measured relative to the residual protons of the deuterated
solvent (CDCl3 or C6D6). The optical rotation was measured on
a Perkin—Elmer 241 polarimeter in a 5ꢀcm cell temperatureꢀ
stabilized at 25 °C. The column chromatography was performed
with the use of silica gel Kieselgel 60 (Merck). The catalysts
were prepared from the following commercial reagents: phthalꢀ
aldehyde, isophthalaldehyde, terephthalaldehyde (Aldrich), and
trifluoromethanesulfonic acid (Acros). The elemental analysis
was carried out in the Laboratory of Microanalysis of the A. N.
Nesmeyanov Institute of Organoelement Compounds of the
Russian Academy of Sciences. All solvents were purified acꢀ
cording to standard procedures. Benzaldehyde and trimethylsilyl
cyanide were freshly distilled.
F(000)
476
58
5909
2152
54
34679
2θmax/deg
Number of measured
reflections
Number of independent
reflections
Number of reflections
with I > 2σ(I )
Number of variables
R1
wR2
GOOF
Residual electron
density/e Å3
5909
4111
22163
11127
585
—
0.0505
0.1081
1.005
0.0842
0.1949
0.999
0.273/–0.229
0.492/–0.361
(dmin/dmax
)
The Xꢀray diffraction study of compounds 5a´ and 6c was
carried out on Syntex P21 (MoꢀKα radiation, graphite monoꢀ
chromator, θ/2θꢀscanning technique) and SMART 1000 CCD
(MoꢀKα radiation, graphite monochromator, ωꢀscanning techꢀ
nique) diffractometers, respectively. The structures were solved
by direct methods and refined anisotropically by the fullꢀmatrix
leastꢀsquared method based on F 2hkl. The hydrogen atoms of
the hydroxy groups were located in difference Fourier maps.
Other hydrogen atoms were positioned geometrically. The hyꢀ
drogen atoms of three methanol molecules in the crystal strucꢀ
ture of 6c were not located. Principal crystallographic data and
the refinement statistics are given in Table 2. All calculations
were carried out with the use of the SHELXTL PLUS program
package.22
a solution of diethyl Lꢀtartrate (1) (11.6 g, 0.066 mol) and triꢀ
ethylamine (17.5 mL) in toluene (100 mL) under argon with
cooling to –5 °C. The white reaction mixture was stirred at
~20 °C for 4 h. Then an aqueous saturated sodium bicarbonate
solution (50 mL) was added, the organic layer was separated, and
the aqueous layer was extracted with ethyl acetate (3×30 mL).
The combined organic layers were washed with a saturated
NaHCO3 solution (2×50 mL), dried over MgSO4, and filtered.
The solvent was removed by evaporation. The yield was 15.4 g
(78%), b.p. 142—145 °C (1 Torr). 1H NMR (CDCl3), δ:
4.59—4.61 (m, 2 H, CH); 4.12—4.24 (m, 4 H, CH2); 1.23—1.32
(m, 6 H, Me); 0.10 (s, 18 H, Me).
The positive ion MALDIꢀTOF mass spectra were obtained
on a Reflex III instrument (Bruker Daltonics) in the linear
mode; the target voltage was set to 20 kV. 2,5ꢀDihydroxybenzoic
acid was used as the matrix. Samples were prepared by dissolving
the compounds in chloroform (c = 10–4—10–6 mol L–1) and
mixing with a solution of the matrix in 30% aqueous acetonitrile
(30 mg mL–1) in a ratio of 1 : 1.
Diethyl Lꢀtartrate (1) was synthesized according to a stanꢀ
dard procedure23 in 95% yield, b.p. 133—135 °C (1 Torr) (cf. lit.
data23: b.p. 113 °C (0.5 Torr)).
2,2´ꢀ(Phenylene)bis[(4R,5R)ꢀ4,5ꢀdi(ethoxycarbonyl)ꢀ1,3ꢀ
dioxolanes] 5a—c (general procedure). Boron trifluoride diethyl
etherate (0.14 mL, 0.1 mmol) was added to a solution of the
corresponding diformylbenzene (1 g, 0.94 mmol) and diethyl
(R,R)ꢀ2,3ꢀbis(trimethylsilyl)tartrate (6.2 g, 1.9 mmol) in CH2Cl2
(25 mL) under argon at 0 °C. The reaction mixture was stirred
for 15 min, and then trifluoromethanesulfonic acid (0.06 mL,
0.4 mmol) was added dropwise. The mixture was stirred at 0 °C
for 30 min, kept at ~20 °C for 16 h, and again cooled to 0 °C.
A saturated sodium carbonate solution (25 mL) was added. The
reaction mixture was allowed to warm to ~20 °C and stirred for
15 min. The organic layer was separated, and the aqueous layer
Diethyl (R,R)ꢀ2,3ꢀbis(Oꢀtrimethylsilyl)tartrate (2). Triꢀ
methylchlorosilane (16 g, 0.147 mol) was added dropwise to

Bisꢀ(R,R)ꢀTADDOLs in C—C bond formation
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
1513
was extracted with dichloromethane (2×25 mL). The combined
organic layers were washed with water (2×100 mL), dried over
MgSO4, and concentrated. The product was recrystallized from
a 1 : 1 hexane—ethyl acetate mixture.
(c 1, CHC13). Found (%): C, 80.36; H, 5.69. C64H54O8. Calcuꢀ
lated (%): C, 80.82; H, 5.72. H NMR (CDCl3), δ: 7.53—7.18
(m, 44 H, H arom.); 5.31 (d, 2 H, CH, J = 5.2 Hz); 5.11 (s, 2 H,
CH); 5.15 (d, 2 H, CH, J = 3.9 Hz); 3.74 (s, 2 H, OH); 2.98
(s, 2 H, OH). UV (CH2Cl2), λmax/nm (logε): 242.6 (4.36),
253 (4.5), 259.2 (4.55). MALDIꢀTOF MS (chloroform), m/z:
973 [M + Na]+, 989 [M + K]+.
1
2,2´ꢀ(1,2ꢀPhenylene)bis[(4R,5R)ꢀ4,5ꢀdi(ethoxycarbonyl)ꢀ
1,3ꢀdioxolane] (5a). The yield was 3.3 g (87%), m.p. 70 °C,
25
[α]D –16.0 (c 1, CHCl3). Found (%): C, 52.78; H, 5.07.
C24H30O12. Calculated (%): C, 52.86; H, 4.85. 1H NMR
(CDCl3), δ: 7.88—7.85 (m, 2 H, H arom.); 7.51—7.48 (m, 2 H,
H arom.); 6.54 (s, 2 H, CH); 5.03 (d, 2 H, CH, J = 4.23 Hz);
4.89 (d, 2 H, CH, J = 4.26 Hz); 4.39—4.29 (m, 8 H, CH2);
1.43—1.32 (m, 12 H, Me).
2,2´ꢀ(1,2ꢀPhenylene)bis[(4R,5R)ꢀ4,5ꢀdi(hydroxydiphenylꢀ
methyl)ꢀ1,3ꢀdioxolane] (6a) was synthesized analogously. The
yield was 0.49 g (88%), m.p. 118 °C (with decomp.), [α]D25 +100°
(c 1, CHC13). Found (%): C, 80.67; H, 5.65. C64H54O8. Calcuꢀ
1
lated (%): C, 80.82; H, 5.72. H NMR (CDCl3), δ: 7.54—7.11
2,2´ꢀ(1,3ꢀPhenylene)bis[(4R,5R)ꢀ4,5ꢀdi(ethoxycarbonyl)ꢀ
1,3ꢀdioxolane] (5b) was prepared as oil in a yield of 2.5 g (68%),
(m, 44 H, H arom.); 6.18 (s, 2 H, CH); 5.34 (d, 2 H, CH, J =
4.0 Hz); 5.28 (d, 2 H, CH, J = 4.0 Hz); 3.25 (s, 2 H, OH); 1.90
(s, 2 H, OH). UV (CH2Cl2), λmax/nm (logε): 245.2 (4.35), 253.6
(4.46), 259.4 (4.51). MALDIꢀTOF MS (chloroform), m/z: 973
[M + Na]+, 989 [M + K]+.
Bis(4ꢀformylphenyl)methane (7) was synthesized according
to a procedure described earlier24 in 48% yield, m.p. 87 °C
(cf. lit. data24: m.p. 86 °C).
Bis{4ꢀ((4R,5R)ꢀ4,5ꢀdi(ethoxycarbonyl)ꢀ1,3ꢀdioxolanꢀ2ꢀ
yl)phenyl}methane (8). A mixture of bis(4ꢀformylphenyl)methane
(0.5 g, 2.2 mmol), diethyl Lꢀtartrate (0.92 g, 4.46 mmol), and
TsOH (0.05 g, 0.29 mmol) in toluene (5 mL) was refluxed using
a Dean—Stark trap for 20 h to remove the reaction water. Then
the mixture was concentrated on a rotary evaporator. The prodꢀ
uct was isolated as oil by silica gel column chromatography
using toluene as the eluent (Rf 0.3). The yield was 0.67 g (50%),
[α]D25 –4.6° (c 1, CHC13). 1H NMR (CDCl3), δ: 7.56 (d, 4 H,
H arom., J = 8.2 Hz); 7.26 (d, 4 H, H arom., J = 8.0 Hz); 6.18
(s, 2 H, CH); 4.98 (d, 2 H, CH, J = 4.1 Hz); 4.86 (d, 2 H, CH,
J = 4.1 Hz); 4.39—4.31 (m, 8 H, CH2); 4.06 (s, 2 H, CH2);
1.43—1.33 (m, 12 H, Me).
25
[α]D –24.6 (c 1, CHCl3). Found (%): C, 52.81; H, 4.84.
C
24H30O12. Calculated (%): C, 52.86; H, 4.85. 1H NMR
(CDCl3), δ: 7.78 (s, 1 H, H arom.); 7.70 (d, 1 H, H arom., J =
7.47 Hz); 7.69 (d, 1 H, H arom., J = 7.47 Hz); 7.48 (t, 1 H,
H arom., J = 7.4 Hz); 6.21 (s, 2 H, CH); 4.98 (d, 2 H, CH, J =
3.9 Hz); 4.87 (d, 2 H, CH, J = 4.1 Hz); 4.39—4.26 (m, 8 H,
CH2); 1.41—1.30 (m, 12 H, Me).
2,2´ꢀ(1,4ꢀPhenylene)bis[(4R,5R)ꢀ4,5ꢀdi(ethoxycarbonyl)ꢀ
1,3ꢀdioxolane] (5c). The yield was 2.9 g (77%), m.p. 78 °C,
25
[α]D –17.3 (c 1, CHCl3). Found (%): C, 52.80; H, 4.79.
C
24H30O12. Calculated (%): C, 52.86; H, 4.85. 1H NMR
(CDCl3), δ: 7.67 (s, 4 H, H arom.); 6.23 (s, 2 H, CH); 4.99 (d,
2 H, CH, J = 4.0 Hz); 4.87 (d, 2 H, CH, J = 3.8 Hz); 4.42—4.29
(m, 8 H, CH2); 1.44—1.33 (m, 12 H, Me).
2,2´ꢀ(1,2ꢀPhenylene)bis[(4R,5R)ꢀ4,5ꢀdi(methoxycarbonyl)ꢀ
1,3ꢀdioxolane] (5а´) was synthesized analogously to acetals 5а—с
with the use of dimethyl 2,3ꢀbis(oꢀtrimethylsilyl) tartrate acꢀ
cording to the aboveꢀdescribed procedure. The yield was 1.5 g
25
(77%), m.p. 53 °С, [α]D –43 (c 1, СНСl3). Found (%):
С, 52.80; Н, 4.91. С20Н22О12. Calculated (%): С, 52.87;
Н, 4.88. 1Н NMR (CDCl3), δ: 7.86—7.83 (m, 2 Н, Н arom.);
7.50—7.47 (m, 2 Н, Н arom.); 6.44 (s, 2 Н, СН); 4.87 (d, 2 Н,
СН, J = 3.02 Hz); 4.77 (d, 2 Н, СН, J = 3.04 Hz); 3.74, 3.75,
3.77, 3.78 (all s, 12 Н, OМе).
Bis[4ꢀ{[(4R,5R)ꢀ4,5ꢀdi(hydroxydiphenylmethyl)]ꢀ1,3ꢀdiꢀ
oxolanꢀ2ꢀyl}phenyl]methane (9). Compound 9 was synthesized
according to the procedure described above for 6a—c, purified
by silica gel chromatography using a 5 : 1 toluene—ethyl acetate
mixture as the eluent (Rf 0.5), and recrystallized from a 1 : 2
toluene—heptane mixture. The yield was 1.2 g (70%), m.p.
2,2´ꢀ(1,4ꢀPhenylene)bis[(4R,5R)ꢀ4,5ꢀdi(hydroxydiphenylꢀ
methyl)ꢀ1,3ꢀdioxolane] (6c). The synthesis was carried out unꢀ
der argon. A solution of compound 5c (0.3 g, 0.59 mmol) was
added at 5 °C to a solution of PhMgBr, which was prepared from
magnesium metal (0.5 g) and PhBr (1.57 g, 10 mmol) in THF
(20 mL). The reaction mixture was heated to boiling, refluxed
for 2 h, and kept at ~20 °C for 16 h. Then the reaction mixture
was quenched with a saturated NH4Cl solution (50 mL). The
organic layer was separated, washed with a saturated NaHCO3
solution (50 mL), and dried over MgSO4. The solvent was reꢀ
moved in vacuo. The resulting oil was recrystallized from acetone.
The yield of the product was 0.44 g (79%), m.p. 271 °C (with
25
160 °C, [α]D +43.1° (c 1, CHC13). Found (%): C, 80.03;
H, 5.91. C71H60O8. Calculated (%): C, 81.90; H, 5.81. 1H NMR
(CDCl3), δ: 7.70—7.10 (m, 48 H, H arom.); 5.38 (d, 2 H, CH,
J = 5.0 Hz); 5.20 (d, 2 H, CH, J = 5.2 Hz); 5.17 (s, 2 H, CH);
3.96 (s, 2 H, CH2); 3.42 (s, 2 H, OH); 2.21 (s, 2 H, OH).
MALDIꢀTOF MS (chloroform), m/z: 1064 [M + Na + H]+,
1080 [M + K + H]+.
Mandelonitrile trimethylsilyl ether. A 10ꢀmL twoꢀneck flask
was heated to 200 °C, evacuated, filled with argon, and cooled.
Then a catalyst (9.2 µg, 9.6 µmol), dichloromethane (0.5 mL),
benzaldehyde (0.05 mL, 0.47 mmol), and Me3SiCN (0.1 mL,
0.74 mmol) were placed in the flask under argon. The reacꢀ
tion mixture was stirred under argon at ~20 °C for 30 min
and passed through a thin layer of silica gel (d = 0.5 cm,
h = 2 cm) to separate the mixture from the catalyst. The filꢀ
trate was concentrated on a rotary evaporator. The residue was
dissolved in CDCl3 and analyzed by 1H NMR spectroscopy
(no signals of other products were observed). 1H NMR (CDCl3),
δ: 7.49—7.39 (m, 5 H, H arom.); 5.36 (s, 1 H, CH); 0.24
25
decomp.), [α]D +68° (c 1, CHC13). Found (%): C, 80.61;
H, 5.57. C64H54O8. Calculated (%): C, 80.82; H, 5.72. 1H NMR
(CDCl3), δ: 7.57—7.15 (m, 44 H, H arom.); 5.33 (d, 2 H, CH,
J = 4.8 Hz); 5.12 (s, 2 H, CH); 5.16 (d, 2 H, CH, J = 2.04 Hz);
3.21 (s, 2 H, OH); 2.14 (s, 2 H, OH). UV (CH2Cl2),
λ
max/nm (logε): 242.3 (3.87), 255 (4.17), 259.4 (4.29).
MALDIꢀTOF MS (chloroform), m/z: 973 [M + Na]+,
989 [M + K]+.
2,2´ꢀ(1,3ꢀPhenylene)bis[(4R,5R)ꢀ4,5ꢀdi(hydroxydiphenylꢀ
methyl)ꢀ1,3ꢀdioxolane] (6b) was synthesized analogously. The
yield was 0.41 g (74%), m.p. 139 °C (with decomp.), [α]D25 +22°
(s, 9 H, Me) (cf. lit. data14 1H NMR (400 MHz, CDCl3), δ:
:
7.49—7.39 (m, 5 H, H arom.); 5.50 (s, 1 H, CH); 0.24
(s, 9 H, Me)).

1514
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
Belokon´ et al.
1H NMR spectroscopic study of the addition of Me3SiCN to
benzaldehyde catalyzed by (R,R)ꢀTADDOLs 6a—c. Kinetic studꢀ
ies of the reaction were carried out on a Bruker Avance 600
instrument. Bisꢀ(R,R)ꢀTADDOL (4.48, 8.96, 22.4, or 44.8 mg,
4.7, 9.4, 23, or 47 µmol, respectively), benzeneꢀd6 (0.5 mL), and
benzaldehyde (0.05 mL, 0.47 mmol) were placed in a standard
NMR tube.* The tube was placed in the NMR spectrometer
magnet, and the initial spectrum was recorded. Then the
NMR tube was taken out, Me3SiCN (0.1 mL, 0.74 mmol) was
added, the solution was vigorously stirred, the tube was again
placed in the spectrometer, and the spectra of the reaction mixꢀ
ture were recorded at certain intervals.
3. T. Akiyama, Y. Saitoh, H. Morita, and K. Fuchibe, Adv.
Synth. Catal., 2005, 347, 1523.
4. G. Guillena and D. Ramon, Tetrahedron: Asymmetry, 2006,
17, 1465.
5. E. Juaristi, A. Beck, J. Hansen, T. Matt, T. Mukhopadhyay,
M. Simson, and D. Seebach, Synthesis, 1993, 1271.
6. H. Yamamoto and K. Futatsugi, Angew. Chem., Int. Ed.,
2005, 44, 1924.
7. Y. Huang, A. Unni, A. Thadani, and V. Rawal, Nature,
2003, 424, 146.
8. J. McGilvra, A. Unni, K. Modi, and V. Rawal, Angew. Chem.,
Int. Ed., 2006, 45, 6130.
1ꢀCyanoꢀ2ꢀtrimethylsilyloxycyclohexane. The Schlenk flask
was evacuated and filled with argon. A catalyst (0.08 g,
0.084 mmol), dichloromethane (4 mL), cyclohexene oxide
(0.1 mL, 0.98 mmol), and Me3SiCN (0.27 mL, 2.02 mmol)
were placed in the flask. The reaction mixture was stirred at
~20 °C for 60 h. Then the mixture was passed through a layer of
silica gel (d = 0.5 cm, h = 2 cm) to separate the mixture from the
catalyst, and the filtrate was concentrated on a rotary evaporaꢀ
tor. To determine the yield of the product, the residue was
dissolved in CDCl3 and analyzed by 1H NMR spectroscopy
(no signals of byꢀproducts were observed). 1H NMR (CDCl3),
δ: 3.77—3.69 (m, 1 H, CH); 2.50—2.42 (m, 1 H, CH); 2.18—2.12
and 2.00—1.94 (both m, 1 H each, CH2); 1.79—1.61 and
1.36—1.23 (both m, 3 H each, CH2); 0.23 (s, 9 H, Me) (cf. lit.
9. N. Momiyama and H. Yamamoto, J. Am. Chem. Soc., 2005,
127, 1080.
10. M. North, Tetrahedron: Asymmetry, 2003, 14, 147.
11. K. Tanaka, S. Honke, Z. UrbanczykꢀLipkowska, and
F. Toda, Eur. J. Org. Chem., 2000, 3171.
12. K. Tanaka, T. Fujiwara, and Z. UrbanczykꢀLipkowska, Org.
Lett., 2002, 19, 3255.
13. K. Tanaka, R. Nagahiro, and Z. UrbanczykꢀLipkowska, Org.
Lett., 2001, 10, 1567.
14. S. Denmark and W.ꢀJ. Chung, J. Org. Chem., 2006, 71, 4002.
15. Y. Suzuki, M. Abu Bakar, K. Muramatsu, and M. Sato,
Tetrahedron, 2006, 62, 4227.
16. D. Seebach, A. Beck, and A. Heckel, Angew. Chem., Int. Ed.,
2001, 40, 92.
17. S. Matsunaga, J. Das, J. Roels, E. Vogl, N. Yamamoto,
T. Iida, K. Yamaguchi, and M. Shibasaki, J. Am. Chem.
Soc., 2000, 122, 2252.
data19
:
1H NMR (400 MHz, CDCl3), δ: 3.64—3.70 (m, 1 H);
2.38—2.44 (m, 1 H); 2.08—2.11 (m, 1 H); 1.90—2.07 (m, 1 H);
1.55—1.75 (m, 3 H); 1.25—1.33 (m, 3 H); 0.17 (s, 9 H)).
18. S. Tosaki, R. Tsuji, T. Ohshima, and M. Shibasaki, J. Am.
Chem. Soc., 2005, 127, 2147.
This study was financially supported by the Russian
Foundation for Basic Research (Project No. 05ꢀ03ꢀ
32243a) and the Russian Academy of Sciences (Program of
the Presidium of the Russian Academy of Sciences No. 8).
19. S. Schaus and E. Jacobsen, Org. Lett., 2000, 7, 1001.
20. K. Shimizu, B. Cole, C. Krueger, K. Kuntz, M. Snapper,
and A. Hoveyda, Angew. Chem., Int. Ed., 1997, 36, 1703
21. Y. Belokon, S. Harutyunyan, E. Vorontsov, A. Peregudov,
V. Chrustalev, K. Kochetkov, D. Pripadchev, A. Sagyan,
A. Beck, and D. Seebach, ARKIVOC, 2004, (iii), 132.
22. G. M. Sheldrick, SHELXTL, V5.10, Bruker AXS Inc.,
Madison (WIꢀ53719), 1997.
References
1. M. Terada, K. Machioka, and K. Sorimachi, Angew. Chem.,
Int. Ed., 2006, 45, 2254.
2. S. Saito and H. Yamamoto, Acc. Chem. Res., 2004, 37, 570.
23. D. Seebach and W. Langer, Helv. Chim. Acta, 1979, 62, 1710.
24. K. Peng, S. Chen, and W. Fann, J. Am. Chem. Soc., 2001,
123, 11388.
* The amount of bisꢀ(R,R)ꢀTADDOL was chosen so that the
total concentration of the catalyst in the reaction mixture was 1,
2, 5, and 10 mol.%, respectively.
Received December 25, 2006;
in revised form June 21, 2007