New chiral ligands based on (+)-α-pinene

Article abstract of DOI:10.1134/S1070428010080014

A number of new chiral ligands were synthesized starting from an accessible monoterpene, (+)-α-pinene. The new ligands were used in the vanadium-catalyzed oxidation of sulfides to chiral sufoxides. Pleiades Publishing, Ltd., 2010.

Full text of DOI:10.1134/S1070428010080014

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 8, pp. 1109–1115. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © E.A. Koneva, D.V. Korchagina, Yu.V. Gatilov, A.M. Genaev, A.P. Krysin, K.P. Volcho, A.G. Tolstikov, N.F. Salakhutdinov, 2010,
published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 8, pp. 1111–1117.
New Chiral Ligands Based on (+)-α-Pinene
E. A. Konevaa, D. V. Korchaginaa, Yu. V. Gatilova, A. M. Genaeva, A. P. Krysina,
K. P. Volchoa, A. G. Tolstikovb, and N. F. Salakhutdinova
a Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences,
pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: volcho@nioch.nsc.ru
b Boreskov Institute of Catalysis, Siberian Division, Russian Academy of Sciences, Novosibirsk, Russia
Received December 21, 2009
Abstract—A number of new chiral ligands were synthesized starting from an accessible monoterpene,
(+)-α-pinene. The new ligands were used in the vanadium-catalyzed oxidation of sulfides to chiral sufoxides.
DOI: 10.1134/S1070428010080014
Optically active monoterpenes and their derivatives
are widely used as source of chirality in asymmetric
synthesis [1]. In the recent time, application of ligands
derived from monoterpenes in asymmetric oxidation of
prochiral sulfides to optically active sulfoxides has
been reported [2–6]. Chiral sulfoxides play an impor-
tant role in asymmetric synthesis [7, 8], and many of
these compounds exhibit strong biological activity [9].
We recently synthesized a large series of new chiral
Schiff bases Ia–Ij on the basis of an accessible mono-
terpene, α-pinene [3]. These compounds were used as
ligands in vanadium-catalyzed asymmetric oxidation
of sulfides. It was found that the largest enantiomeric
excess (ee) in the oxidation of thioanisole (II) to sulf-
oxide III was attained in the presence of ligand Ia
(ee 32%) [3] (Scheme 1). In the oxidation of sulfide V
as precursor of effective antiulcer drug Esomeprazole
(VI), the most efficient was ligand Ib (ee up to 31%)
[4]. Hydrogenation of Schiff bases derived from chiral
α-diamines and substituted salicylaldehydes gave the
corresponding amines which were used as ligands in
asymmetric oxidation of thioanisole (II). As a result,
enantiomeric excess was raised to 95% (in the pres-
ence of initial Schiff bases enantiomeric excess did not
exceed 20%) [10]. Although these data were not repro-
duced (the largest enantiomeric excess of sulfoxide III
was 26% [11]), it is obvious that replacement of Schiff
bases by the corresponding amines should affect the
yield and enantioselectivity of the above transforma-
tions to an appreciable extent.
The goal of the present work was to synthesize new
chiral amines from Schiff bases derived from α-pinene,
and estimate their potential as ligands in vanadium-
catalyzed asymmetric oxidation of sulfides. In addition
to ligands Ia–Ij synthesized previously, by reaction of
amino alcohol (–)-VII with 3-tert-butyl-2-hydroxy-5-
(2-methoxyethyl)benzaldehyde (VIII) we obtained in
quantitative yield new Schiff base Ik having a me-
thoxyethyl group in the para position with respect to
the phenolic hydroxy group (Scheme 2).
By slow evaporation of a solution of compound Ia
in chloroform we succeeded in obtaining for the first
time single crystals of the corresponding hydrate, and
the molecular and crystalline structure of Schiff base
Ia was studied by X-ray analysis (Fig. 1). The hy-
droxyphenylmethylidene fragment C3N1C12-18 is planar
within ±0.059 Å. The C4 atom in the pinane fragment
deviates from the C2C3C5C6 plane by 0.180(4) Å
toward the C1 atom, as in the structure of 3-(methyl-
Me
Me
Me
R3
R2
N
HO
HO
R1
Ia–Ij
R1 = R3 = t-Bu, R2 = H (a); R1 = R2 = R3 = H (b); R1 =
1,7,7-trimethylbicyclo[2.2.1]hept-2-yl, R2 = H, R3 = Me (c);
R1 = R3 = CMe2Ph, R2 = H (d); R1 = R2 = H, R3 = NO2 (e);
R1 = R3 = NO2, R2 = H (f); R1 = R2 = H, R3 = OMe (g); R1 =
OMe, R2 = R3 = H (h); R1 = R3 = H, R2 = NEt2 (i); R1 = Br,
R2 = H, R3 = NO2 (j).
1109

KONEVA et al.
1110
Scheme 1.
O
S
O
S
SMe
Me
Me
O
[O], VO(acac)2, L*
+
II
(S)-III
IV
OMe
OMe
Me
Me
O
S
N
N
[O], VO(acac)2, L*
MeO
MeO
S
Me
Me
NH
N
N
N
H
V
(S)-VI
Scheme 2.
Me
CHO
NH2
Me
Me
OH
Me
N
6
21
OH
OMe
8
+
Me
Me
MeO
Bu-t
7
4
HO
19
20
Me
Me
Me
HO
Bu-t
(–)-VII
VIII
Ik
aminomethyl)pinane hydrobromide [12]. The intra-
molecular hydrogen bond O2–H···N1 has the following
parameters: O–H 1.00(4), H···N 1.57(4) Å, ∠OHN
166(4)°. Molecules Ia in crystal are linked to dimers
via intermolecular O1–H · · · O1′ hydrogen bonds
[0.80(4), 2.07(4) Å, ∠157(4)°], and the dimers are
linked by hydrate water molecules to form chains
along the b axis [O1 · · · O3 2.779(4), O3 · · · O4B
2.618(6) Å]. The azomethine C=N bond has Z con-
figuration.
Chiral Schiff bases Ia, Ib, and Ik were reduced
with sodium tetrahydridoborate in anhydrous methanol
(Scheme 3) to obtain the corresponding amines IXa–
IXc in ~90% yield. Compounds Ik and IXa–IXc were
not reported previously, and their structure was deter-
1
mined on the basis of H and 13C NMR and high-
resolution mass spectra. The NMR spectra of IXa–IXc
contained two sets of signals which were observed
especially distinctly in the 13C NMR spectra. The
fractions of the minor component were ~17, <10, and
~25% for compounds IXa, IXb, and IXc, respectively.
We succeeded in reliably identifying signals of minor
isomers only for compounds IXa and IXc.
Presumably, strong hydrogen bonds formed be-
tween the nitrogen atom and hydroxy group in the aro-
matic fragment fix two different conformers of IXa–
IXc, which are characterized by a high interconversion
barrier. The formation of strong intramolecular hydro-
gen bonds in o-(methylamino)phenol derivatives is
well known; in some cases such interaction even
determines the direction of chemical reactions [13].
C20
O1
C21
C5
C6
C1
O2
C11
C19
C4
C7
C2
C9
C22
C15
N1
C12
C14
C16
C13
C3
C8
C10
C17
C18
C26
C25A
C24
C23
C24A
C25
C26A
Fig. 1. Structure of the molecule of 2,4-di-tert-butyl-6-
[{(1S,2S,3R,5S)-3-hydroxymethyl-2,6,6-trimethylbicyclo-
[3.1.1]hept-2-ylimino}methyl]phenol (Ia) according to the
X-ray diffraction data. Non-hydrogen atoms are shown as
thermal vibration ellipsoids with a probability of 30%. The
The above assumption was verified by conforma-
tional analysis of compound IXa, which was per-
formed in terms of the molecular mechanics approx-
imation, followed by NDDO/PM6 optimization of
geometric parameters. The calculations revealed more
C
24A, C25A, and C26A atoms are characterized by a population
of 0.264(7).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 8 2010

NEW CHIRAL LIGANDS BASED ON (+)-α-PINENE
1111
Scheme 3.
Me
1M0 e
9Me
Me
2
1
Me
N
Me8
12
R2
6
R2
3
13
NaBH4
7
N
H
5
4
14
11
16
HO
HO
15
R1
HO
HO
R1
Ia, Ib, Ik
IX–IXc
R1 = C19(C21H3)3, R2 = C20(C22H3)3 (a); R1 = R2 = H (b); R1 = t-Bu, R2 = MeOCH2CH2 (c, k).
than 100 structures corresponding to minima on the
potential energy surface, and more stable structures
were characterized by strong hydrogen bonds between
the nitrogen atom and hydroxy group in the aromatic
fragment. According to the DFT/PBE/L1 calculations,
the most stable conformer has structure A1 (Fig. 2),
and the energy of no less than 18 conformers was
higher by no more than 5 kcal/mol. The energy of the
most stable conformer among those lacking intramo-
lecular hydrogen bond was higher by 7.0 kcal/mol than
that of A1; therefore, this value can be assumed (as
a first approximation) to be equal to the energy of the
above hydrogen bond.
The calculations showed that rotation about the
C13–C12 and C12–N bonds, as well as inversion of the
nitrogen atom, is hindered, for these processes should
involve rupture of the hydrogen bond. For example,
the energy barrier for the interconversion of con-
formers A1 and A2 (which have similar energies) via
inversion of the nitrogen atom and rotation about the
N–C3 bond is 20 kcal/mol. In this case, the conformers
should appear separately in the NMR spectra (two sets
of signals should be observed). Thus the results of cal-
culations confirmed our assumption that the formation
of strong intramolecular hydrogen bond between the
nitrogen atom and phenolic hydroxy group is re-
sponsible for the presence of double sets of signals in
the NMR spectra of compounds IXa–IXc.
surprising, for the main difference between compounds
Ia and Ik is related to steric shielding of the para-
position with respect to the phenolic hydroxy group,
which is remote from the site of coordination to
metal ion. Considerable increase in the conversion of
sulfide II (from 44% to quantitative) should be noted;
on the other hand, the yield of sulfone IV also in-
creased in this case. When the temperature was
reduced from 20 to –10°C (see table, run no. 4), the
conversion and enantiomeric excess decreased, but the
chemoselectivity increased so that the only product
was sulfoxide III.
Amines IXa–IXc turned out to be less effective in
asymmetric oxidation of thioanisole (II), as compared
to the corresponding Schiff bases Ia, Ib, and Ik. Non-
racemic sulfoxide III was obtained only in the pres-
ence of ligand IXa (see table, run nos. 5–7), but the ee
value decreased from 32 to 8%. Replacement of ligand
Ia by IXa resulted in inversion of configuration of the
major stereoisomer of III (see table, run nos. 1, 5).
The obtained compounds were tested as ligands in
vanadium-catalyzed asymmetric sulfoxidation, specif-
ically in the oxidation of thioanisole (II) to sulfoxide
III as shown in Scheme 1. The reactions were carried
out under the conditions proposed previously (20°C,
methylene chloride as solvent, 70% hydrogen peroxide
as oxidant [3]). Replacement of the tert-butyl group in
the para position with respect to the phenolic hydroxy
group in ligand Ia by 2-methoxyethyl group (com-
pound Ik), resulted in sharp decrease of the ee value
(to 10%; see table, run nos. 2, 3). This was quite
A1
A2
Fig. 2. Calculated conformations of 2,4-di-tert-butyl-6-
{[(1S,2S,3R,5S)-3-hydroxymethyl-2,6,6-trimethylbicyclo-
[3.1.1]hept-2-ylamino]methyl}phenol (IXa) (protons
attached to carbon atoms are not shown).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 8 2010

KONEVA et al.
1112
Vanadium-catalyzed asymmetric oxidation of thioanisole (II) in the presence of ligands Ia, Ib, Ik, and IXa–IXc
Yield,b %
Run no.
Ligand
Time,a h
Conversion, %
ee,c %
III
IV
1
2
3
4
5
6
7
Ia [3]
Ib [3]
Ik
2.5
2
1.5
5
2
2
044
084
100
048
098
099
081
098.0
098.0
081.0
100.0
075.5
072.0
067.0
02.0
02.0
19.0
00.0
24.5
28.0
33.0
32 (R)
04 (S)
10 (R)
06 (R)
08 (S)
00
Ikd
IXa
IXb
IXc
3.5
00
a
b
c
Molar ratio VO(acac)2–ligand–II–H2O2 1:1.5:106:132; 20°C, solvent CH2Cl2 (5 ml).
Calculated on the reacted sulfide II; the product ratio was determined on the basis of the 1H NMR data.
1
Enantiomeric excess for compound III was determined from the H NMR data using (R)-(–)-3,5-dinitro-N-(1-phenylethyl)benzamide
as chiral shift reagent. The absolute configuration was determined by comparing the sign of optical rotation of sulfoxide III with
published data.
Temperature –10°C.
d
Thus, using accessible α-pinene as starting com-
eter [graphite monochromator, λ(MoKα) = 0.71073 Å,
ω,φ scanning, 2θ < 51.9°]. The purity of the initial
reactants and reaction products was checked by GLC
on a Varian Model 3700 chromatograph (ZB-5 capil-
lary column, 30000×0.25 mm, flame ionization detec-
tor, carrier gas helium, inlet pressure 1 atm).
Quantum-chemical calculations were performed in
terms of the density functional theory (DFT) using
PBE functional [14] (Priroda software [15, 16]) with
no solvent taken into account. The molecular structures
were optimized using L1 basis set (Λ01 [17], an
analog of cc-pVDZ; {6s2p}/[2s1p] for H atoms,
{10s7p3d}/[3s2p1d] for C, N, O). Conformational
analysis was performed using MarvinSketch program
(Conformers plug-in [18]). Each conformer was
optimized by the NDDO/PM6 method [19]
(MOPAC2009 [20]). Identical structures thus obtained
were removed using Conformers program [21], and the
most stable among the remaining structures was
studied at the DFT level.
pound, we synthesized four new chiral ligands Ik and
IXa–IXc. Although asymmetric induction in the oxida-
tion of thioanisole II in the presence of these ligands
was low, they may be promising as ligands in oxida-
tion of other sulfides, as well as in other asymmetric
reactions catalyzed by metal complexes.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded from
solutions in CDCl3–CCl4 (1:1 by volume) on a Bruker
DRX-500 spectrometer at frequencies of 500.13 MHz
(1H) and 125.76 MHz (13C); the chemical shifts were
measured relative to the solvent signals (CHCl3,
δ 7.24 ppm; CDCl3, δC 76.90 ppm). The product struc-
1
ture was determined by analysis of the H NMR spec-
1
tra with the use of H–1H double-resonance and two-
1
dimensional homonuclear H–1H correlation tech-
niques (1H–1H COSY), as well as by analysis of the
13C NMR spectra recorded with the use of two-dimen-
sional heteronuclear correlation techniques 13C–1H
COSY (1JCH = 160 Hz) and COLOC (2,3JCH = 10 Hz).
The multiplicity of signals in the 13C NMR spectra was
determined using J modulation technique (JMOD) or
off-resonance decoupling from protons. The high-
resolution mass spectra (electron impact, 70 eV) were
obtained on a DFS Thermo Scientific instrument
(a.m.u. range 0–500; direct sample admission into the
ion source). The specific optical rotations [α]D were
measured on a PolAAr 3005 polarimeter. X-Ray anal-
ysis of single crystals of compound Ia was performed
at 173 K on a Bruker KAPPA APEX CCD diffractom-
X-Ray diffraction data for compound Ia. Single
crystals of compound Ia hydrate were obtained by
slow evaporation of its solution in chloroform. Rhom-
bic crystals, space group P21212; unit cell parameters:
a = 17.999(1), b = 10.324(1), c = 14.224(1) Å; V =
2642.9(4) Å3; C26H41N1O2 · 1.5 H2O; Z = 4; dcalc
=
1.072 g/cm3; μ = 0.070 cm–1; dimensions 0.14×0.26×
0.54 mm. Absorption by the crystal was taken into
account empirically using SADABS program
(Tmin/Tmax = 0.75/0.95). Total of 10767 reflection in-
tensities were measured; among these, 5035 reflec-
tions were independent (Rint = 0.0587). The structure
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 8 2010

NEW CHIRAL LIGANDS BASED ON (+)-α-PINENE
1113
2
was solved by the direct method. The positions and
temperature parameters of atoms were refined in
anisotropic approximation by full-matrix least-squares
procedure. Hydrogen atoms in the hydroxy groups and
one water molecule (O3) were localized by the dif-
ference synthesis of electron density, and the positions
of the others were set on the basis of geometry consid-
erations. The second water molecule was disordered by
two positions (O4A, O4B), and positions of the corre-
sponding hydrogen atoms were not determined. The
tert-butyl group C23Me3 was also conformationally dis-
ordered by two positions at a ratio of 73.6(7):26.4(7).
The final divergence factors were wR2 = 0.1502, S =
1.027 (all reflections) and R1 0.0566 [3520 reflections
with I ≥ 2σ(I)]. All calculations were performed using
SHELX software package.
5-H), 2.20 d.d.d.d (syn-7-H, J = 10.3, Jsin-7,2 = 6.0,
Jsyn-7,6 = 6.0, Jsyn-7,syn-5 = 2.2 Hz), 2.36 m (4-H), 2.75 t
(21-H, J21,22 = 7.1 Hz), 3.31 s (C23H3), 3.51 t (22-H,
2
2J22,21 = 7.1 Hz), 3.54 d.d (11-H, J = 10.3, J11,4
=
2
2
6.0 Hz), 3.73 d.d (11′-H, J = 10.3, J11′,4 = 7.4 Hz),
6.90 d (18-H, J18,16 = 2.3 Hz), 7.07 d (16-H, J16,18
=
13
2.3 Hz), 8.24 s (12-H), 14.26 br.s (14-OH). C NMR
spectrum, δC, ppm: 38.75 s (C1), 53.84 d (C2), 64.87 s
(C3), 41.84 d (C4), 31.42 t (C5), 40.14 d (C6), 29.50 t
(C7), 28.32 q (C8), 23.60 q (C9), 28.27 q (C10), 66.11 t
(C11), 161.60 d (C12), 118.49 s (C13), 159.25 s (C14),
127.16 s (C15), 129.78 d (C16), 137.23 s (C17), 129.72 d
(C18), 34.67 s (C19), 29.36 q (C20), 35.45 t (C21), 73.81 t
(C22), 58.38 q (C23). Found: m/z 401.2927 [M]+.
C25H39NO3. Calculated: M 401.2924.
2,4-Di-tert-butyl-6-({(1S,2S,3R,5S)-3-(hydroxy-
methyl)-2,6,6-trimethylbicyclo[3.1.1]hept-2-yl-
amino}methyl)phenol (IXa). Sodium tetrahydrido-
borate, 0.129 g, was added under stirring at room tem-
perature to a solution of 0.170 g of phenol Ia in 20 ml
of anhydrous methanol. The mixture was stirred for
1 h, the solvent was distilled off, and 20 ml of diethyl
ether and 10 ml of water were added to the residue.
The organic phase was separated, the aqueous phase
was extracted with diethyl ether (2×10 ml), the ex-
tracts were combined with the organic phase and dried
3-tert-Butyl-2-hydroxy-5-(2-methoxyethyl)benz-
aldehyde (VIII). A mixture of 10.6 g of 2-tert-butyl-4-
(2-methoxyethyl)phenol [22], 7.8 g of powdered hexa-
methylenetetramine, and 15 ml of glacial acetic acid
was stirred for 1 h at 70°C and then for 2 h at 120–
130°C. The mixture was cooled to 75°C, a solution of
3 ml of concentrated sulfuric acid in 15 ml of water
was added, and the mixture was heated for 1 h at
105°C. The mixture was cooled, the organic phase was
separated and dissolved in diethyl ether, the solution
was washed with water until neutral reaction, the
solvent was distilled off, and the residue (7.7 g) was
distilled under reduced pressure. Yield 4.5 g (40%),
over MgSO4, and the solvent was distilled off. Yield
26
0.154 g (90%), [α]
= –11.67° (c = 0.12, CHCl3).
589
1H NMR spectrum, δ, ppm: 1.11 s (C9H3), 1.18 d (anti-
2
1
7-H, J = 10.1 Hz), 1.28 s (t-Bu), 1.41 s (t-Bu), 1.32 s
bp 145–149°C (4 mm). H NMR spectrum, δ, ppm:
(C10H3), 1.40 s (C8H3), 1.52 d.d.d (anti-5-H, J = 13.2,
2
1.39 s (t-Bu), 2.75 t (7-H, J7, 8 = 7.5 Hz), 3.27 s
Janti-5,4 = 8.2, Janti-5,6 = 2.0 Hz), 1.9–32.04 m (syn-5-H,
(CH3O), 3.46 t (8-H, J8,7 = 7.5 Hz), 7.15 d (6-H, J6,4
=
6-H), 2.11 d.d (2-H, J2,syn-7 = 6.0, J2,6 = 5.5 Hz),
2.3 Hz), 7.26 d (4-H, J4,6 = 2.3 Hz), 9.8 s (CHO),
11.7 s (OH). Found: m/z 236.14107 [M]+. C14H20O3.
Calculated: M 236.14123.
2
2.23 d.d.d.d (syn-7-H, J = 10.1, Jsyn-7,2 = 6.0, Jsyn-7,6
=
6.0, Jsyn-7,syn-5 = 2.2 Hz), 2.31 m (4-H), 3.57 d (12-H,
2J = 13.1 Hz), 3.72 d.d (11-H, J = 10.3, J11,4
=
2
2-tert-Butyl-6-({(1S,2S,3R,5S)-3-hydroxymethyl-
2,6,6-trimethylbicyclo[3.1.1]hept-2-ylimino}meth-
yl)-4-(2-methoxyethyl)phenol (Ik). A solution of
0.167 g of aldehyde VIII in 5 ml of methanol was
added under stirring at room temperature to a solution
of 0.209 g of alcohol (–)-VII {synthesized from
(+)-α-pinene according to the procedure described in
[3]} in 4 ml of anhydrous methanol. The mixture was
stirred for 48 h at room temperature, the solvent was
distilled off, and the residue was recrystallized from
diethyl ether. Yield 0.284 g (100%), [α]D24 = +6.88° (c =
2
5.0 Hz), 3.79 d.d (11′-H, J = 10.3, J11′,4 = 8.2 Hz),
2
3.81 d (12′-H, J = 13.1 Hz), 6.79 d (18-H, J18,16
=
13
2.4 Hz), 7.15 d (16-H, J16,18 = 2.4 Hz). C NMR spec-
trum, δC, ppm: 38.36 s (C1), 50.64 d (C2), 58.83 s (C3),
41.49 d (C4), 30.42 t (C5), 39.96 d (C6), 28.68 t (C7),
26.64 q (C8), 23.74 q (C9), 28.84 q (C10), 64.61 t (C11),
45.97 t (C12), 122.99 s (C13), 154.75 s (C14), 135.77 s
(C15), 122.55 d (C16), 140.09 s (C17), 122.97 d (C18),
34.91 s (C19), 34.11 s (C20), 29.69 q (C21), 31.77 q
(C22). Found: m/z: 401.3292 [M]+. C26H43NO2. Cal-
culated: M 401.3288.
1
0.31, CHCl3). H NMR spectrum, δ, ppm: 1.16 s
1
(C9H3), 1.27 d (anti-7-H, 2J = 10.3 Hz), 1.28 s (C10H3),
Minor isomer. H NMR spectrum, δ, ppm: 1.14 s
1.40 s (t-Bu), 1.42 s (C8H3), 1.54 d.d.d (anti-5-H, J =
(C9H3), 1.29 s (C8H3), 1.35 s (C10H3), 1.42 s (t-Bu),
4.07 d (12-H, 2J = 14.0 Hz), 4.13 d.d (11-H, 2J = 11.2,
J11,4 = 3.2 Hz), 6.77 d (18-H, J18,16 = 2.4 Hz), 7.12 d
2
13.3, Janti-5,4 = 7.8, Janti-5,6 = 2.0 Hz), 1.92 d.d (2-H,
J2,syn-7 = 6.0, J2,6 = 5.5 Hz), 1.98 m (6-H), 2.13 m (syn-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 8 2010

KONEVA et al.
1114
13
2
(16-H, J16,18 = 2.4 Hz). C NMR spectrum, δC, ppm:
38.88 s (C1), 50.45 d (C2), 57.63 s (C3), 37.97 d (C4),
31.10 t (C5), 40.22 d (C6), 29.97 t (C7), 25.25 q (C8),
23.37 q (C9), 29.81 q (C10), 62.20 t (C11), 41.90 t (C12),
121.60 s (C13), 147.54 s (C14), 137.32 s (C15), 121.92 d
(C16), 143.13 s (C17), 121.20 d (C18), 35.01 s (C19),
34.25 s (C20), 29.96 q (C21), 31.64 q (C22).
(syn-7-H, J = 10.2, Jsyn-7,2 = 6.0, Jsyn-7,6 = 6.0,
Jsyn-7,syn-5 = 2.2 Hz), 2.30 m (4-H), 2.76 t (2H, 21-H,
J21,22 = 7.3 Hz), 3.35 s (22-OCH3), 3.55 t (2H, 22-H,
2
J22,21 = 7.3 Hz), 3.56 d (12-H, J = 13.0 Hz), 3.70 d.d
2
2
(11-H, J = 10.4, J11,4 = 5.2 Hz), 3.78 d.d (11′-H, J =
2
10.4, J11′,4 = 8.0 Hz), 3.80 d (12′-H, J = 13.0 Hz),
6.71 d (18-H, J18,16 = 2.1 Hz), 6.99 d (16-H, J16,18
=
2.1 Hz). 13C NMR spectrum, δC, ppm: 38.19 s (C1),
50.43 d (C2), 58.73 s (C3), 41.40 d (C4), 30.36 t (C5),
39.82 d (C6), 28.52 t (C7), 26.46 q (C8), 23.54 q (C9),
28.62 q (C10), 64.61 t (C11), 45.41 t (C12), 123.91 s
(C13), 155.50 s (C14), 136.46 s (C15), 126.03 d (C16),
127.75 s (C17), 126.48 d (C18), 34.50 s (C19), 29.43 q
(C20), 35.49 t (C21), 74.03 t (C22), 58.41 q (C23). Found:
m/z 403.3100 [M]+. C25H41O3N. Calculated:
M 403.3081.
2-({(1S,2S,3R,5S)-3-(Hydroxymethyl)-2,6,6-tri-
methylbicyclo[3.1.1]hept-2-ylamino}methyl)phenol
(IXb). Sodium tetrahydridoborate, 0.144 g, was added
under stirring at room temperature to a solution of
0.185 g of phenol Ib in 20 ml of anhydrous methanol,
and the mixture was stirred for 1 h and treated as
described above for the synthesis of IXa. Yield 0.166 g
26
1
(89%), [α] = +18.82° (c = 0.33, CHCl3). H NMR
589
spectrum, δ, ppm: 1.08 s (C9H3), 1.15 d (anti-7-H, 2J =
10.3 Hz), 1.30 s (C10H3), 1.36 s (C8H3), 1.51 m (anti-
5-H), 1.90–2.00 m (syn-5-H, 6-H), 2.08 d.d (2-H,
J2,syn-7 = 6.0, J2,6 = 5.5 Hz), 2.21 m (syn-7-H), 2.26 m
1
Some signals of the minor isomer in the H NMR
spectrum were overlapped by those of the major com-
ponent; therefore, the chemical shifts and coupling
constants are given below only for some separately
(4-H), 3.58 d (12-H, 2J = 13.1 Hz), 3.68 d.d (11-H, 2J =
2
1
10.5, J11,4 = 8.0 Hz), 3.71 d.d (11′-H, J = 10.5, J11′,4
=
observed signals. H NMR spectrum, δ, ppm: 1.06 d
5.0 Hz), 3.80 d (12′-H, 2J = 13.1 Hz), 6.68 d.d.d (17-H,
J17,16 = J17,18 = 7.6, J17,15 = 1.0 Hz), 6.74 d.d (15-H,
(anti-7-H, J = 9.8 Hz), 1.13 s (C9H3), 1.30 s (C8H3),
2
1.33 s (C10H3), 1.41 s (t-Bu), 2.13 m (syn-7-H),
2.17 d.d (2-H, J2,syn-7 = 6.0, J2,6 = 5.5 Hz), 2.78 t (2H,
21-H, J21,22 = 7.3 Hz), 3.35 s (22-OCH3), 3.56 t (2H,
J15,16 = 8.2, J15,17 = 1.0 Hz), 6.90 d.d (18-H, J18,17
=
7.6, J18,16 = 1.5 Hz), 7.07 d.d.d (16-H, J16,15 = 8.2,
J16,17 = 7.6, J16,18 = 1.5 Hz), 5.78 br.s (11-OH, NH).
13C NMR spectrum, δC, ppm: 38.34 s (C1), 50.38 d
(C2), 59.16 s (C3), 41.04 d (C4), 30.10 t (C5), 39.93 d
(C6), 28.40 t (C7), 26.53 q (C8), 23.69 q (C9), 28.73 q
(C10), 64.05 t (C11), 44.99 t (C12), 123.40 s (C13),
158.18 s (C14), 116.31 d (C15), 128.42 d (C16), 118.72 d
(C17), 128.10 d (C18). Found: m/z 289.2053 [M]+.
C18H27NO2. Calculated: M 289.2036.
2
22-H, J22,21 = 7.3 Hz), 3.69 br.d (11-H, J = 11.2 Hz),
2
3.79 m (12-H), 4.07 d (12′-H, J = 14.3 Hz), 4.14 d.d
(11′-H, 2J = 11.2, J11′,4 = 3.2 Hz), 6.68 d (18-H, J18,16
=
2.1 Hz), 6.96 d (16-H, J16,18 = 2.1 Hz). 13C NMR spec-
trum, δC, ppm: 38.71 s (C1), 50.21 d (C2), 57.56 s (C3),
37.77 d (C4), 30.94 t (C5), 40.11 d (C6), 29.79 t (C7),
25.07 q (C8), 23.18 q (C9), 29.58 q (C10), 62.30 t (C11),
41.43 t (C12), 122.54 s (C13), 148.22 s (C14), 137.90 s
(C15), 125.34 d (C16), 130.94 s (C17), 124.74 d (C18),
34.62 s (C19), 29.70 q (C20), 35.54 t (C21), 73.77 t (C22),
58.44 q (C23).
2-tert-Butyl-6-({(1S,2S,3R,5S)-3-(hydroxymeth-
yl)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ylamino}-
methyl)-4-(2-methoxyethyl)phenol (IXc). Sodium
tetrahydridoborate, 0.091 g, was added under stirring
at room temperature to a solution of 0.164 g of phenol
Ik in 20 ml of anhydrous methanol, and the mixture
was stirred for 1 h and treated as described above for
the synthesis of compound IXa. The residue was puri-
fied by column chromatography on silica gel (gradient
elution with hexane–ethyl acetate, 0 to 100% of the
latter). Yield 0.141 g (86%), [α]52869 = –10.4° (c = 0.5,
Asymmetric oxidation of thioanisole (II). A mix-
ture of 2 mg (8 μmol) of VO(acac)2 and 12 μmol of the
corresponding ligand in 2 ml of anhydrous methylene
chloride was stirred until it became homogeneous
(~20 min). A solution of 0.105 g (847 μmol) of thio-
anisole (II) in 3 ml of methylene chloride was added
under stirring, and the mixture was cooled if necessary.
Aqueous hydrogen peroxide (70%), 45 μl (1060 μmol),
was then added, and the progress of the reaction was
monitored by GLC. When the reaction was complete,
10 ml of water was added, the organic phase was sepa-
rated, the aqueous phase was extracted with methylene
chloride (2×5 ml), and the extracts were combined
with the organic phase (2×10 ml), washed with water,
CHCl3). H NMR spectrum, δ, ppm: 1.10 s (C9H3),
1
1.15 d (anti-7-H, J = 10.2 Hz), 1.31 s (C10H3), 1.38 s
2
(C8H3), 1.41 s (t-Bu), 1.49 d.d.d (anti-5-H, J = 13.2,
2
Janti-5,4 = 8.2, Janti-5,6 = 1.9 Hz), 1.95–1.98 m (6-H),
2
2.00 d.d.m (syn-5-H, J = 13.2, Jsyn-5,4 = 13.2 Hz),
2.10 d.d (2-H, J2,syn-7 = 6.0, J2,6 = 5.5 Hz), 2.23 d.d.d.d
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 8 2010

NEW CHIRAL LIGANDS BASED ON (+)-α-PINENE
1115
8. Carreno, M.C., Hernandez-Torres, G., Ribagorda, M.,
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sulfide II and the ratio of products III and IV were
1
9. Volcho, K.P. and Salakhutdinov, N.F., Usp. Khim., 2009,
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vol. 78, p. 494.
meric excess of sulfoxide III was calculated from the
1H NMR spectrum (CCl4–CDCl3) recorded in the pres-
ence of an equal amount (in weight) of (R)-(–)-3,5-di-
nitro-N-(1-phenylethyl)benzamide.
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