New chiral ligands from myrtenal and caryophyllene for asymmetric oxydation of sulfides catalyzed by metal complexes

Article abstract of DOI:10.1134/S1070428006110091

From myrtenal and caryophyllene, widespread terpene compounds, three new chiral Schiff bases were prepared suitable for ligands in vanadium ions catalyzed sulfides oxidation to chiral sulfoxides.

Full text of DOI:10.1134/S1070428006110091

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2006, Vol. 42, No. 11, pp. 1653−1661.  Pleiades Publishing, Inc. 2006.
Original Russian Text  T.M. Khomenko, O.V. Salomatina, S.Yu. Kurbakova, I.V. Il’ina, K.P. Volcho, N.I. Komarov, D.V. Korchagina,
N.F. Salakhutdinov, A.G. Tolstikov, 2006, published in Zhurnal Organicheskoi Khimii, 2006, Vol. 42, No. 11, pp. 1666−1673.
New Chiral Ligands from Myrtenal and Caryophyllene
for Asymmetric Oxydation of Sulfides Catalyzed by Metal
Complexes
T. M. Khomenkoa, O. V. Salomatinaa, S. Yu. Kurbakovaa, I. V. Il’inaa, K. P. Volchoa,
N. I. Komarovaa, D. V. Korchaginaa, N. F. Salakhutdinova, andA. G. Tolstikovb
aVorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences,
Novosibirsk, 630090 Russia
e-mail: volcho@nioch.nsc.ru
bBoreskov Institute of Catalysis, Novosibirsk, Russia
Received November 23, 2005
Abstract—From myrtenal and caryophyllene, widespread terpene compounds, three new chiral Schiff bases were
prepared suitable for ligands in vanadium ions catalyzed sulfides oxidation to chiral sulfoxides.
DOI: 10.1134/S1070428006110091
was developed exploiting hydrogen peroxide in the
presence of obtained in situ complexes of vanadium(IV)
acetylacetonate with chiral Schiff bases [11, 12]. These
complexes are used in a catalytic amount (~1%), permit
the application of water solution of hydrogen peroxide,
and the process is carried out in the presence of air. The
system is sufficiently general and often can be used in
oxidation of polyfunctional sulfides. Nowadays only
several accessible ligands exist successfully used in this
catalytic system, for instance, compounds I and II. These
ligands are obtained by reaction of substituted salicyl-
aldehydes with amino acids derivatives. These ligands
made it possible to oxidize various methyl aryl sulfides
into the corresponding sulfoxides with sufficient chemical
and optical yields.Yet it is highly desirable to have available
versatile optically active ligands for conversion of complex
polyfunctional compounds with the use of chiral metal
Chiral sulfoxides constitute an important class of
organic compounds extensively used in asymmetric
synthesis [1, 2]. The interest in chiral sulfoxides is also
supported by discovery of natural substances containing
an asymmetric sulfoxide group [3, 4] and by finding
biologically active sulfoxides of certain configuration [5,
6]. Relatively recently optically active sulfoxides were
patented with an outstanding antiulcer action, derivatives
of 2-mercaptobenzimidazole and 2-mercapto-4,5-
diphenylimidazole [7]. Therefore the development of
efficient procedures for preparation of chiral sulfoxides
by asymmetric oxidation of sulfides was stimulated.
In the beginning of nineteen eighties Kagan et al. [8]
and Modena et al. [9] independently of one another
succeeded in asymmetric oxidation of thioanisole and its
homologs applying a modified Sharpless system [Ti(i-
PrO)4–(+)-diethyl tartrate−t-BuOOH]. Further develop-
ment of the procedure of asymmetric sulfides oxidation
in the presence of chiral titanium alcoholates was directed
to increasing enantioselectivity and chemical yields of
target sulfoxides [10]. The disadvantage of these system
lies in the necessity to carry out the reaction under an
inert gas atmosphere, to control moisture, and to use as a
rule equivalent amount of the oxidating system with
respect to sulfides.
N
OH
N
OH
OH
O2N
OH
As an alternative to the methods of Kagan and
Modena a procedure for asymmetric sulfides oxidation
II
I
1653

KHOMENKO et al.
1654
led to the formation of 3,5-di-tert-butylcyclohexa-3,5-
diene-1,2-dione (VIII) [14]. The reaction of compound
VIII with aqueous ammonia followed by reduction [15]
resulted in the desired aminophenol V in overall yield of
all the three stages 60% (Scheme 1).
complex systems, and therefore the research in the field
of synthesis of new salicylaldimines remains urgent [10].
The target of this study was the synthesis of new
ligands suitable for application to the oxidizing system
with vanadium acetylacetonate based on widespread
optically active terpenes.
(–)-Myrtenal (III) reaction with aminophenol V in
acetonitrile under an argon atmosphere led to the
formation of chiral Schiff base IX in 91% yield.Another
optically active Schiff base we obtained from myrtenal
epoxide (X) and aminophenol V in 96% yield. Myrtenal
epoxide (X) was prepared by oxidation of (–)-myrtenal
(III) with hydrogen peroxide in the presence of NaOH
in 74% yield (Scheme 2).
We selected for initial compounds monoterpenoid
(–)-myrtenal (III) and sesquiterpene (–)-caryophyllene
(IV), widely spread in the nature and accessible optically
active substances.
The chiral salicylaldimines are commonly prepared by
reaction of optically active amines with substituted
salicylaldehydes. Since at the use of myrtenal (III) the
chiral precursor was aldehyde, in order to obtain Schiff
base containing a phenol hydroxy group, we synthesized
2,4-di-tert-butyl-6-aminophenol (V). To this end we
prepared from pyrocatechol (VI) 3,5-di-tert-butylbenzene-
1,2-diol (VII) [13], whose oxidation with sodium nitrite
Compound XI proved to be unstable in air and within
several days transformed into a complex mixture of
substances. This transformation was considerably
accelerated in the presence of chloroform. However
under an argon atmosphere at –24°C aldimine XI can be
stored for a long time.
Scheme 1.
OH
NH2
(CH3)3COH,
OH
(1) NH3/H2O
(2) NaBH4
NaNO2
AcOH
OH
OH
H2SO4
O
OH
O
VI
V, 64%
VII, 98%
VIII, 96%
Scheme 2.
20
21
19
18
12
13
OH
OH
3
11
8
2
1
NH2
23
22
14
Hsin
Hanti
CH3CN
CHO
4
10 N
15
+
16
25
24
5
6
17
IX, 91%
III
H2O2
NaOH
V
,
20
19
18
21
OH
12
O
NH2
OH
13
22
CHO
3
11
8
2
CH3CN
23
Hsin
Hanti
+
4
5
14
10 N
1
15
O
16
25
24
6
17
X, 74%
V
XI, 96%
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

NEW CHIRAL LIGANDS FROM MYRTENAL AND CARYOPHYLLENE
1655
oxidative cyclization into benzoxazole XV; the rate of con-
version significantly increased in the presence of chloro-
form. It is known from published data that similar cycliza-
tion into benzoxazole derivatives was observed in reactions
of o-aminophenols with aldehydes in the presence of
various oxidizing systems {oxygen in the presence of
activated carbon [17],Ag2O [18], 2,3-dichloro-5,6-dicyano-
benzoquinone (DDQ) in DMF [19]}, and also at maintain-
ing at 170°C a mixture of phosphorylated acetals with
some o-aminophenols [20]. In our case the cyclization
proceeded at room temperature without special catalysts:
Apparently the air oxygen acted as oxidant, and chloro-
form, as promoter.
Another terpenoid chosen as initial chiral compound
was widespread sesquiterpene caryophyllene (IV). We
showed formerly that keeping caryophyllene diepoxide
(XII) in the presence of H-β-zeolite led to the prevailing
formation of hydroxyaldehyde XIII [16].
Compound XIII we obtained from caryophyllene
diepoxide (XII) in keeping with procedure [16] in 23%
1
yield; its high optical activity was proved by H NMR
spectroscopy using chiral shift reagent Eu(hfc)3 (on
adding Eu(hfc)3 to compound XIII most proton signals
1
in the H NMR spectrum shifted without separation)
(Scheme 3).
The reaction of hydroxyaldehyde XIII with amino-
phenol V in acetonitrile under an argon atmosphere gave
rise to compound XIV in nearly quantitative yield. Thus
we for the first time prepared from sesquiterpene caryo-
phyllene (IV) a chiral Schiff base suitable for application
as a ligand in metal complex catalysts. Compound XIV
on storage in air at room temperature suffered slow
In order to test the possibility of using optically active
Schiff bases IX, XI, and XIV in asymmetric sulfides
oxidation catalyzed by vanadium acetylacetonate we
selected for a substrate sulfide XVI, analog of compound
XVII, the precursor of antiulcer drug esomeprazole [21],
(S)-sulfoxide prepared from sulfide XVII (Scheme 4).
Scheme 3.
HO
O
O
H+
O
[O]
[O]
CHO
H
H
H
H
H
H
H
H
XII, 55%
XIII, 23%
IV
26
17
25
28
26
29
30
25
24
28
17
16
24
27
16
15
29
23
OH
23
15
18
19
27
30
NH2
HO
18
19
CH3CN
14
O 12
14
CHCl3
HO
XIII
+
10
9
12
10
N
N
H
11
11
H
9
HO
8
1
6
1
6
3
3
2
8
2
4
5
22
7
5 4
7
22
20
20
V
H
21
H
21
XIV, 98%
XV
Scheme 4.
OAc
O
O
N
S
N
N
H
S
N
N
H
XVI
XVII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

KHOMENKO et al.
1656
Scheme 5.
OH
OAc
12
11
13
OH
CH(OMe)2
HBr
7
Ac2O
6
2
10
1
4
К10
Br
N
8
Br
5
3
9
XVIII
XX, 100%
XIX, 68%
HS
MeONa
N
H
O
OAc
14
15
7
O
13
10
O
N
S
12
H2O2
18
17
22
1
4
2
3
N
6
5
19
20
11
16
VO(acac)2
ligand
S
8
N
H
N
H
9
21
XXI
XVI, 92%
Compound XVI was prepared from 6-tert-butyl-2,4-
dimethylphenol XVIII. In the first stage by bromomethyl-
ation of compound XVIII in keeping with a modified
procedure [22] we obtained 6-tert-butyl-3-bromomethyl-
2,4-dimethylphenol (XIX) in 68% yield (Scheme 5).
MeO COOH
Ph
XXII
H
As seen from the table, the application of ligand II
was ineffective: The reaction product formed in a medium
yield and of very low optical purity. The use of ligand IX
also gave unsatisfactory results. The highest yield of the
target sulfoxide XXI was obtained using the catalytic
system with XIV, and the highest enantiomer excess was
attained with compound XI. Note that on going from the
catalytic system with compound IX to the system with
epoxide XI not only sharply grew the optical purity of the
sulfoxide obtained but also changed the sign of its optical
rotation. The results of experiments show that the most
promising for application as ligands are tridentate com-
pounds XI and XIV with asymmetric centers in direct
proximity to the complexing atoms.
Acylation of phenol XIX with acetic anhydride in the
presence of nonactivated kaolin K10 by method [23] gave
rise in quantitative yield to 6-tert-butyl-3-bromo-methyl-
2,4-dimethylphenyl acetate (XX) that by reaction with
2-mercaptobenzimidazole in the presence of sodium
methylate formed sulfide XVI in 92% yield.
Oxidation of sulfide XVI was performed with aqueous
hydrogen peroxide in the presence of a complex obtained
in situ of vanadium acetylacetonate with ligands IX, XI,
XIV, or commercially available salicylaldimine II. The
reaction progress was monitored by HPLC. Enantiomer
excess was determined using 1H NMR spectra registered
in the presence of a chiral shift reagent, S-(+)-2-methoxy-
2-phenylacetic acid (XXII), and also by comparison of
the angles of optical rotation. The results of reactions
are compiled in the table.
We did not find in the literature mention of compounds
IX, XI, XIV–XVI, and XIX–XXI. Their structure was
established from 1H, 13C NMR, and high-resolution mass
spectra. NMR spectra of compound XXI revealed that
it was present in two forms in 1:1 ratio, apparently, due
to slow proton exchange between the nitrogen atoms of
the benzimidazole ring. On heating the solution to 35 and
further to 45°C the corresponding signals of methyl
groups, protons of aromatic rings, and of NH group
coalesced into singlets; the signals in the 13C NMR spec-
Asymmetric oxidation of sulfide XVI to sulfoxide XXI
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

NEW CHIRAL LIGANDS FROM MYRTENAL AND CARYOPHYLLENE
1657
trum behaved similarly except the signals of aromatic
C17, C22, C18, and C21 which only suffered considerable
broadening; the complete coalescence of these signals
did not occur because apparently the temperature was
not sufficiently high. The changes in the spectra are
reversible: On cooling to 25°C the primary pattern of the
spectra is recovered. The observed reversible changes
in the spectra may be ascribed to the variations in the
exchange rate.
measured on Finnigan MAT-8200 instrument, specific
rotation [α]580 was determined on a spectrometer Polamat
A from solutions in CHCl3 of concentration c, g/100 ml
of solvent.
The purity of initial compounds was checked and the
reaction products were analyzed by HPLC on a Mili-
khromA02 device (stationary phase ProntoSil-120-5-C18
AQ, eluent 90% aqueous MeOH with 0.1% of trifluoro-
acetic acid). Column chromatography was performed on
silica gel (70–230 mesh, Merck).
The assignment of carbon signals in the aromatic part
of compound IX was done using spectra LRJMD. On
decoupling from the atom H8 with a signal at 8.27 ppm in
the downfield part of the LRJMD spectrum appeared
singlets at 149.09 and 134.53 ppm and a doublet at
137.06 ppm that were assigned to atoms C2, C10, and C3
respectively. Decoupling by turn from atoms H13 and H15
with signals at 7.15 and 7.05 ppm respectively made it
possible to attribute all signals of aromatic carbons and
signals of atoms C18 and C22. The assignment of ana-
logous signals in the spectrum of compound XV was
confirmed by selective decoupling from protons of tert-
butyl groups. The close values of the chemical shifts of
signals of the corresponding aromatic carbon atoms and
of tert-butyl groups permitted the assignment for com-
pounds IX, XI, XIV, and XV.
6-Amino-2,4-di-tert-butylphenol (V). To a suspen-
sion of 2.75 g (25 mmol) of pyrocatechol (VI) in 7 ml
(5.5 g, 74 mmol) of tert-butanol cooled by ice was added
dropwise 2.5 ml of concn. H2SO4, and the mixture was
stirred for 8 h at room temperature. Then a mixture of
25 ml of water and 1.2 ml of dioxane was added, the
separated precipitate was filtered off, washed with water
till neutral pH, and dried in air. We obtained 5.43 g (98%)
of 3,5-di-tert-butylbenzene-1,2-diol (VII), the substance
was recrystallized from hexane, mp 100–101°C. 1H NMR
spectrum of compound VII coincided with analogous
spectrum published before [24].
To a suspension of 0.44 g (2 mmol) of compound VII
in 1 ml of CH3COOH was added by portions a solution
of 0.28 g (4 mmol) of NaNO2 in 1 ml of H2O. The mixture
was stirred for 1 h at room temperature, then diluted with
water. The separated precipitate was filtered off, washed
with water, and dried in air. We obtained 0.42 g (96%) of
3,5-di-tert-butylcyclohexa-3,5-diene-1,2-dione (VIII) of
Thus starting with widespread terpene compounds
myrtenal and caryophyllene we synthesized three new
chiral Schiff bases suitable for application as ligands in
oxidation of sulfides into chiral sulfoxides catalyzed by
1
brick-red color, mp 114–115°C. H NMR spectrum of
vanadium ions.
compound VIII coincided with the spectrum previously
published [25].
EXPERIMENTAL
To a solution of 2.35 g (11 mmol) of compound VIII
in 60 ml of methanol was added 20 ml of concn. NH4OH,
and the mixture was stirred for 10 min. The red solution
turned yellow, NaBH4 was added by portions till the
solution became completely colorless (~0.4 g). The
separated precipitate was filtered off, washed with a mix-
ture methanol–aqueous ammonia, 3:1 v/v, dried, and
recrystallized from a mixture chloroform–hexane. Yield
1.5 g (64%), mp 164–165°C. 13C NMR spectrum of
compound V coincided with the spectrum previously
published [26].
1H and 13C NMR spectra were registered on a spec-
trometer Bruker AM-400 (operating frequencies 400.13
and 100.61 MHz respectively) from solutions of com-
pounds in CDCl3, in a mixture CDCl3–CCl4, ~1:1 v/v, in
deuteroacetone, or DMSO-d6. For internal reference
were used signals of chloroform (δH 7.24, δC 76.90 ppm),
deuteroacetone (δH 2.04, δC 29.80 ppm), or DMSO-d6
(δH 2.50, δC 39.50 ppm). The structure of compounds
1
obtained was established from analysis of H NMR
spectra involving also double resonance 1H–1H spectra,
and also from analysis of 13C NMR spectra using spectra
with off-resonance decoupling from protons, two-dimen-
sional correlation 13C–1H spectra on direct constants
(COSY, 1JC,H 135 Hz), and one-dimensional correlation
13C–1H spectra on long range constants (LRJMD, nJC,H
10 Hz, n = 2, 3). High resolution mass spectra were
4,6-Di-tert-butyl-2-{(6,6-dimethylbicyclo-[3.1.1]-
hept-2-en-2-yl)methyleneamino}phenol (IX).
To a solution of 0.044 g (0.2 mmol) of compound V in
4.5 ml of acetonitrile was added at stirring under an argon
atmosphere 0.035 g (0.23 mmol) of (–)-myrtenal (III)
{Aldrich, 98%, [α]D22 –15° (oil); publ.: [α]D20 –15.8° (oil)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

KHOMENKO et al.
1658
(C4), 40.87 d (C5), 40.95 s (C6), 26.04 t (C7), 162.43 d
(C8), 135.63 s (C10), 149.05 s (C11), 135.36 s (C12),
123.82 d (C13), 142.20 s (C14), 111.80 d (C15), 20.76 q
(C16), 26.72 q (C17), 35.12 C (C18), 29.80 q (C19–C21),
35.46 s (C22), 31.87 q (C23–C25). Found M 369.26682.
C24H35NO2. Calculated M 369.26676.
[27]} in 1.3 ml of acetonitrile, and the mixture was stirred
at 28°C for 4 h. The solvent was distilled off. Yield
0.064 g(91%), mp 141–142°C (from acetonitrile), [α]D27
+
1.7° (c 2.6, CHCl3). 1H NMR spectrum (CDCl3–CCl4),
δ, ppm (J, Hz): 0.84 s (3H, C16H3), 1.18 d (1H, H7anti
,
J7anti,7syn 9.5), 1.32 s (9H, C23H3, C24H3, C25H3), 1.40 s
(3H, C17H3), 1.42 s (9H, C19H3, C20H3, C21H3), 2.22 m
(1H, H5, J5,7syn 5.5, J5,1 5.5, J5,4 3, J5,3 1.2), 2.53 d.d.d
(1H, H7syn, J 9.5, J7syn,1 5.5, J7syn,5 5.5), 2.46–2.62 m
(2H, H4), 3.20 d.d.d (1H, H1, J1,5 5.5, J1,7sin 5.5, J1,3 1.2),
6.29 m (1H, H3, J3,4 3.5, J3,1 1.2, J3,5 1.2), 7.05 d (1H,
H15, J15,13 2.2), 7.15 d (1H, H13, J 2.2), 8.27 s (1H, H8).
13C NMR spectrum, δ, ppm: 40.02 d (C1), 149.09 s (C2),
137.06 d (C3), 32.82 t (C4), 40.94 d (C5), 37.77 s (C6),
31.30 t (C7), 155.72 d (C8), 134.53 s (C10), 148.68 s (C11),
134.75 s (C12), 122.52 d (C13), 140.82 s (C14), 109.58 d
(C15), 21.07 q (C16), 26.15 q (C17), 34.55 s (C18), 29.50 q
(C19–C21), 34.87 s (C22), 31.76 q (C23–C25). Found
M 353.27221. C24H35NO. Calculated M 353.27185.
(2aR,4aR,5R,7aR,7bS)-[7a-(3,5-Di-tert-butyl-2-
hydroxyphenylimino)methyl]-2,2,4a-trimethyl-
decahydro-1-cyclobuta[e]indene-5-ol (XIV).
(2aR,4aR,5R,7aR,7bS)-5-Hydroxy-2,2,4a-trimethyl-
decahydro-1H-cyclobuta[e]indene-7a-carbaldehyde
(XIII) was obtained from caryophyllene diepoxides (XII)
20
in keeping with procedure [16] in 23% yield, [α] –5.3°
580
(c 3.7, CHCl3). To a solution of 0.032 g (0.14 mmol) of
compound V in 4.5 ml of acetonitrile was added at 28°C
while stirring under an argon atmosphere a solution of
0.040 g (0.16 mmol) of aldehyde XIII in 1.3 ml of
acetonitrile, and the stirring was continued for 4 h. The
solution was dried with Na2SO4, then filtered, and the
20
solvent was distilled off. Yield 0.063 g, [α] +33.2°
4,6-Di-tert-butyl-2-{(7,7-dimethyl-3-oxatricyclo-
[4.1.1.02,4]oct-2-yl)methyleneamino}phenol (XI). To
a solution of 3 g (20 mmol) of (–)-myrtenal (III) in 30 ml
of methanol at 12–15°C was added 6 ml of 30% H2O2,
then 1.5 ml of 6 N aqueous NaOH, and the mixture was
stirred for 2 h, maintaining the temperature in the indicated
range. The reaction mixture was poured into water, the
product was extracted into ethyl ether. The combined
ether extracts were washed with water, dried over
MgSO4, and the solvent was distilled off. We obtained
580
1
(c 2.35, CHCl3). H NMR spectrum (CDCl3–CCl4), δ,
ppm (J, Hz): 1.09 s (3H, C21H3), 1.10 s (3H, C22H3),
1.18 s (3H, C20H3), 1.22-1.50 m (5H, H3, 2H6, 2H7),
1.29 s (9H, C28H3, C29H3, C30H3), 1.41 s (9H, C24H3,
C25H3, C26H3), 1.61 m (1H, H5), 1.73 d.d (1H, H32 , J32 ,3
10, J32 ,2 7), 1.89 m (1H, H10), 2.11 m (2H, H11), 2.40 m
(1H, H2), 2.43 m (1H, H102 ), 3.77 d.d (1H, H9, J9,102 6.5,
J9,10 1.5), 6.84 d (1H, H19, J19,17 2.2), 7.12 d (1H, H17,
J 2.2), 8.20 c (H12). 13C NMR spectrum, δ, ppm: 55.71 s
(C1), 37.54 d (C2), 38.70 t (C3), 38.70 s (C4), 46.28 d
(C5), 23.24 t (C6), 37.00 t (C7), 52.96 s (C8), 82.11 d
(C9), 32.88 t (C10), 26.47 t (C11), 170.74 d (C12), 135.59 s
(C14), 147.50 s (C15), 134.74 s (C16), 121.95 d (C17),
141.05 s (C18), 110.61 d (C19), 21.01 q (C20), 30.39 q
(C21), 17.13 q (C22), 34.44 s (C23), 29.57 q (C24–C26),
34.87 s (C27), 31.75 q (C28–C30). Found M 439.34822.
C29H45NO2. Calculated M 439.35624.
20
2.47 g (74%) of myrtenal epoxide (X), [α] –114.5° (c
580
2.3, CHCl3) {publ.: [α]20 –89.4° (CHCl3) [28]}. 1H NMR
spectrum of compoundDX coincided with the correspond-
ing spectrum previously published [29].
To a solution of 0.023 g (0.1 mmol) of compound V in
2 ml of acetonitrile was added at 25°C while stirring under
an argon atmosphere a solution of 0.022 g (0.13 mmol)
of myrtenal epoxide (X) in 0.8 ml of acetonitrile. The
stirring was continued for 0.5 h, the solvent was distilled
On keeping in chloroform solution for 48 h compound
XIV virtually completely converted into
(2aR,4aR,5R,7aR,7bS)-7a-(5,7-di-tert-butylbenzo[d]-
oxazol-2-yl)-2,2,4a-trimethyldecahydro-1H-
cyclobuta[e]inden-5-ol (XV), [α]25080 +37.0° (c 0.7,
27
off. We obtained 0.037 g (96%) of compound XI, [α]
580
+2.6° (c 2.1, CH3CN). 1H NMR spectrum (acetone-d6),
δ, ppm (J, Hz): 0.91 s (3H, C16H3), 1.28 s (9H, C23H3,
C24H3, C25H3), 1.40 s (3H, C17H3), 1.41 s (9H, C19H3,
C20H3, C21H3), 1.70 d (1H, H7anti, J7anti,7syn 10), 1.81 m
(1H, H5, J5,7syn 5.5, J5,1 5.5, J5,4 3, J5,3 2), 2.10 m (2H,
H4), 2.17 d.d.d (1H, H7syn, J7syn,7anti 10, J7syn,1 5.5, J7syn,5
5.5), 2.94 d.d (1H, H1, J1,5 5.5, J1,7syn 5.5), 3.63 m (1H,
H3, J 2–3), 7.23 d and 7.25 d (2H, H13, H15, J 2.2),
7.69 br.s (1H, OH), 7.88 s (1H, H8). 13C NMR spectrum,
δ, ppm: 40.26 d (C1), 63.47 C (C2), 56.50 d (C3), 27.89 t
1
CHCl3). H NMR spectrum (CDCl3–CCl4), δ, ppm (J,
Hz): 0.99 s (3H, C22H3), 1.11 s (3H, C21H3), 1.20 s (3H,
C20H3), 1.23–1.52 m (4H, 2H6, 2H7), 1.35 s (9H, C28H3,
C29H3, C30H3), 1.46 s (9H, C24H3, C25H3, C26H3), 1.52 d.d
(1H, H3, J3,32 10, J3,2 10), 1.68 m (1H, H5), 1.92 d.d (1H,
H32 , J32 ,3 10, J32 ,2 7), 2.05 d.d.d (1H, H11, J11,112 10,
J11,10 10, J11,102 3), 2.11 m (1H, H10), 2.31 m (1H, H112 ),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

NEW CHIRAL LIGANDS FROM MYRTENAL AND CARYOPHYLLENE
1659
2.58 m (1H, H102 ), 2.61 m (1H, H2), 3.61 br.d (1H, H9,
J9,102 7), 7.18 d (1H, H17, J17,19 2), 7.46 d (1H, H19, J 2).
13C NMR spectrum, δ, ppm: 53.12 s (C1), 37.49 d (C2),
39.39 t (C3), 38.39 s (C4), 46.03 d (C5), 23.42 t (C6),
37.30 t (C7), 52.43 s (C8), 82.46 d (C9), 34.12 t (C10),
29.99 t (C11), 173.13 s (C12), 140.53 s (C14), 146.02 s
(C15), 133.38 s (C16), 118.66 d (C17), 147.36 s (C18),
113.76 d (C19), 20.93 q (C20), 30.32 q (C21), 17.51 q (C22),
34.30 s (C23), 29.91 q (3C, C24–C26), 35.06 s (C27),
31.94 q (3C, C28–C30). Found M 437.33213. C29H43NO2.
Calculated M 437.34059.
20 ml of methanol was added dropwise at stirring
a solution of sodium methylate in methanol prepared from
0.31 g (13.5 mmol) of sodium and 12 ml of methanol.
After several minutes white precipitate started to form.
The suspension was stirred for 2.5 h at room temperature.
The precipitate was filtered off, washed on the filter with
40 ml of 50% aqueous methanol, 40 ml of 25% aqueous
methanol, and 40 ml of water, and dried in a vacuum. We
obtained 4.68 g (92%) of compound XVI, mp 219°C.
1H NMR spectrum (DMSO-d6), δ, ppm: 1.26 s (9H,
C11H3, C12H3, C13H3), 2.08 s (3H, C7H3), 2.33 s (3H,
C15H3), 2.37 s (3H, C9H3), 4.57 m (2H, H8), 7.09 s (1H,
H5), 7.14 m (2H, H19, H20), 7.47 m (2H, H18, H21).
13C NMR spectrum, δ, ppm: 146.24 s (C1), 130.78 s (C2),
131.55 s (C3), 134.44 s (C4), 126.67 d (C5), 140.36 s
(C6), 12.93 q (C7), 31.47 t (C8), 19.48 q (C9), 34.20 s
(C10), 30.31 q (3C, C11–C13), 169.15 s (C14), 21.13 q
(C15), 149.89 s (C16), 139.61 s (C17, C22), 114.05 d (C18,
C21), 121.72 d (C19, C20). In the 13C NMR spectrum the
signals at 139.61 and 114.05 ppm are strongly broadened
presumably due to a slow proton exchange between
nitrogen atoms of benzimidazole ring. On heating to
30 and then to 45°C the signals in the spectra recorded
at these temperatures contain these signals in somewhat
narrower form. In the 1H NMR spectrum the signals of
two H8 protons proved to be sensitive to the temperature,
and at 45°C these signals became one singlet.At recording
the 1H NMR spectrum in a mixture CDCl3–CCl4 at 25°C
the spectral pattern slightly changed apparently due to
the slower exchange. 1H NMR spectrum (CDCl3–CCl4),
δ, ppm (J, Hz): 1.29 s (9H, C11H3, C12H3, C13H3), 2.12 s
(3H, C7H3), 2.25 s (3H, C9H3), 2.35 s (3H, C15H3),
4.39 br.d (1H, H8, J8,82 12) and 4.54 br.d (1H, H82 , J 12),
AB system, 6.90 s (1H, H5), 7.14 br.s and 7.15 br.s (2H,
H19, H20), 7.65 br.s and 9.35 br.s (2H, H18, H21). In the
13C NMR spectrum recorded in the mixture CDCl3–CCl4
the signals from atoms C17, C18, C21, and C22 were not
observed because of great width of the signals; the
chemical shifts of the other peaks were close to the values
given for the spectrum in DMSO-d6. Found M 382.18917.
C22H26N2O2S. Calculated M 382.17149.
3-{(1H-Benzo[d]imidazol-2-ylsulfanyl)methyl}-6-
tert-butyl-2,4-dimethylphenyl acetate (XVI).
3-(Bromomethyl)-6-tert-butyl-2,4-dimethylphenol (XIX)
was obtained in 68% yield by bromomethylation of
2-tert-butyl-4,6-dimethylphenol (XVIII) with methylal in
the presence of HBr in keeping with a modified procedure
1
[22]. mp 76–77°C. H NMR spectrum (CDCl3 –CCl4),
δ, ppm (J, Hz): 1.43 s (9H, C11H3, C12H3, C13H3), 2.28 s
(3H, C7H3), 2.37 s (3H, C9H3), 4.56 s (2H, H8), 4.75 s
(1H, OH), 6.98 s (1H, H5). 13C NMR spectrum, δ, ppm:
150.81 s (C1), 122.95 s (C2), 132.10 s (C3), 128.58 s (C4),
126.40 d (C5), 136.29 s (C6), 11.29 q (C7), 29.88 t (C8),
18.97 q (C9), 34.26 s (C10), 29.67 q (3C, C11–C13). The
assignment of carbon signals belonging to the aromatic
part of compound XIX was carried out with the help of
LRJMD spectra. Found M 270.06005. C13H19BrO.
Calculated M 270.06197.
6-tert-Butyl-3-bromomethyl-2,4-dimethyl-phenyl
acetate (XX). To a solution of 8.00 g (30 mmol) of com-
pound XIX in 40 ml of CH2Cl2 was added at stirring 6 g
of clay kaolin K10 (Fluka) and 6.5 ml (6.02 g, 59 mmol)
of acetic anhydride. The solution was heated at reflux
with stirring for 4 h. The solvent was distilled off, the
residue was diluted with 100 ml of ethyl ether and
thoroughly washed with water. The ether solution was
dried with MgSO4, the solvent was distilled off. Yield
9.23 g (100%), yellow oily substance solidifying at
standing, mp 41°C. 1H NMR spectrum (CDCl3–CCl4),
δ, ppm (J, Hz): 1.33 s (9H, C11H3, C12H3, C13H3), 2.12 s
(3H, C7H3), 2.34 s (3H, COCH3), 2.40 s (3H, C9H3), 4.50
m (2H, H8), 7.05 s (1H, H5). 13C NMR spectrum, δ, ppm:
146.36 s (C1), 130.76 s (C2), 132.94 s (C3), 134.38 s
(C4), 126.86 d (C5), 141.34 s (C6), 12.62 q (C7), 29.08 t
(C8), 19.40 q (C9), 34.44 s (C10), 30.37 q (3C, C11–
C13), 168.46 s (COCH3), 21.20 q (COCH3). Found M
312.07043. C15H21BrO2. Calculated M 312.07253.
Asymmetric oxidation of 3-{(1H-benzo[d]imid-
azol-2-ylsulfanyl)methyl}-6-tert-butyl-2,4-dimethyl-
phenyl acetate (XVI). a. A mixture of 1 mg (4 µmol) of
vanadium acetylacetonate, 2 mg (6 µmol) of (S)-(−)-2-
(3,5-di-tert-butylsalicylideneamino)-3,3-dimethyl-1-
butanol (II) (Aldrich), and 1 ml of CH2Cl2 was stirred till
complete dissolution of components (~ 30 min). To the
solution obtained was added at stirring 200 mg
(0.52 mmol) of compound XVI in 4 ml of CH2Cl2, and
To a solution of 4.16 g (13.3 mmol) of compound XX
and 2.00 g (13.3 mmol) of 2-mercaptobenzimidazole in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 11 2006

KHOMENKO et al.
1660
60 µl (0.58 mmol) of 33% H2O2 was added within
30 min in three portions 20 µl each. The reaction mixture
was stirred at room temperature for 5.5 h (HPLC
monitoring), twice washed with water, and the washings
were extracted with CH2Cl2. The combined organic
solutions were dried with MgSO4, and the solvent was
distilled off. The yellow residue (0.234 g) was
the Russian Foundation for Basic Research (grant
no. 06-03-32052).
REFERENCES
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Patai, S., Rappoport, Z., and Stirling, C.J.M., Eds., J. Wiley
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recrystallized from 2 ml of ethanol. Yield 155 mg (74%),
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20
[α]5
+3.6° (C 1.1, acetone); enantiomer excess 3%
80
1
according to H NMR spectrum with a chiral shift
1
reagent. XXI, mp 168°C. H NMR spectrum (CDCl3–
CCl4), δ, ppm (J, Hz): 1.33 s (9H, C11H3, C12H3, C13H3),
2.10 br.s (3H, C7H3), 2.28 br.s and 2.30 br.s (3H, C15H3),
2.38 br.s and 2.39 br.s (3H, C9H3), 4.69 br.s (2H, 2H8),
7.07 br.s and 7.09 br.s (1H, H5), 7.27 m (2H, H19, H20),
7.38 br.s and 7.76 br.s (2H, H18, H21), 12.08 br.s and
12.14 br.s (1H, NH). 13C NMR spectrum, δ, ppm: 146.72 s
(C1), 125.94 s and 126.19 s (C2), 131.89 s and 132.42 s
(C3), 135.46 s and 136.29 s (C4), 127.25 d (C5), 141.68 C
(C6), 14.00 q and 14.18 q (C7), 57.07 t and 57.22 t (C8),
20.86 q and 21.03 q (C9), 34.55 s (C10), 30.95 q (3C,
C11–C13), 168.55 s (C14), 21.19 q (C15), 152.85 s (C16),
134.47 s and 144.06 s (C17, C22), 112.40 d and 120.15 d
(C18, C21), 123.02 d and 124.19 d (C19, C20). Found
M 398.16737. C22H26N2O3S. Calculated M 398.16640.
b. By oxidation of 200 mg (0.52 mmol) of compound
XVI with 60 µl (0.58 mmol) of 33% H2O2 in the presence
of 1 mg (4 µmol) of vanadium acetylacetonate and 3 mg
(8 µmol) of compound IX in 4 h we obtained 143 mg
(69%) of compoundÿ XXI, [α]25080+1.5° (c 1.2, acetone),
enantiomer excess 1%.
c. By oxidation of 200 mg (0.52 mmol) of compound
XVI with 60 µl (0.58 mmol) of 33% H2O2 in the presence
of 1 mg (4 µmol) of vanadium acetylacetonate and 3 mg
(8 µmol) of compound XI in 4 h 45 min we obtained 124
20
mg (60%) of compoundÿ XXI, [α] –33° (c 1.5,
580
acetone), enantiomer excess 21%.
d. By oxidation of 200 mg (0.52 mmol) of compound
XVI with 60 µl (0.58 mmol) of 33% H2O2 in the presence
of 1 mg (4 µmol) of vanadium acetylacetonate and 3 mg
(7 µmol) of compound XIV in 4 h we obtained 197 mg
20
(95%) of compound XXI, [α] +7.1° (c 1.4, acetone),
580
enantiomer excess 5%.
The study was carried out under a financial support of
Presidium of the RussianAcademy of Sciences (complex
program no. 25, State contract no. 10104-71/P-25/155-
256/290404-008), of the FederalAgency for Science and
Innovation (State contract no. 02.434.11.2026), and of
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and von Unge, S., Tetrahedron: Asymmetry, 2000, vol. 11,
p. 3819.
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NEW CHIRAL LIGANDS FROM MYRTENAL AND CARYOPHYLLENE
1661
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