Optical resolution of racemic 4-hydroxy-3,5-diisobornylbenzaldehyde

Article abstract of DOI:10.1134/S1070428013010119

Optical resolution of racemic 4-hydroxy-3,5-diisobornylbenzaldehyde was accomplished via transformation into diastereoisomeric esters by treatment with (1S)-camphanoyl chloride. The absolute configuration of the enantiomers was determined on the basis of

Full text of DOI:10.1134/S1070428013010119

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 1, pp. 60–66. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © E.V. Buravlev, I.Yu. Chukicheva, K.Yu. Suponitskii, A.V. Kutchin, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49,
No. 1, pp. 69–75.
Dedicated to Full Member of the Russian Academy of Sciences
G.A. Tolstikov on his 80th anniversary
Optical Resolution of Racemic
4-Hydroxy-3,5-diisobornylbenzaldehyde
E. V. Buravleva, I. Yu. Chukichevaa, K. Yu. Suponitskiib, and A. V. Kutchina
a Institute of Chemistry, Komi Scientific Center, Ural Branch, Russian Academy of Sciences,
ul. Pervomaiskaya 48, Syktyvkar, 167982 Russia
e-mail: buravlev-ev@chemi.komisc.ru
b Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
ul. Vavilova 28, Moscow, 119991 Russia
Received November 18, 2012
Abstract—Optical resolution of racemic 4-hydroxy-3,5-diisobornylbenzaldehyde was accomplished via trans-
formation into diastereoisomeric esters by treatment with (1S)-camphanoyl chloride. The absolute configura-
tion of the enantiomers was determined on the basis of the X-ray diffraction data for one diastereoisomeric
camphanate.
DOI: 10.1134/S1070428013010119
Substituted and unsubstituted p-hydroxybenzalde-
hydes are precursors of fused derivatives and phos-
phorus-containing compounds [1–5]; such aldehydes
are especially important for the synthesis of symmetric
and unsymmetric tetraarylporphyrins [6–10]. We pre-
viously described tetrapyrrole condensation of the
meso diastereoisomer of 4-hydroxy-3,5-diisobornyl-
benzaldehyde (meso-I), which produced tetra(meso-
aryl)porphyrin bearing isobornyl substituents as a mix-
ture of atropisomers due to different configurations of
isobornyl fragments in the initial aldehyde molecule
[10]. Enantiopure (or enantiorich) formyl derivatives
with diisobornylphenol fragments attract interest from
the viewpoint of studying their antioxidant and phar-
macological properties. To obtain them it was neces-
sary to synthesize pure enantiomers of 4-hydroxy-3,5-
diisobornylbenzaldehyde (I). The present article
reports on the preparation of its enantiomerically
enriched samples by optical resolution of racemic alde-
hyde rac-I.
Aldehyde rac-I was synthesized by oxidation of
racemic 2,6-diisobornyl-4-methylphenol (rac-II) at the
4-methyl group with bromine in tert-butyl alcohol
according to the procedure for the synthesis of meso-I
[11] (Scheme 1). Enantiomeric isobornyl-substituted
salicylaldehydes and 4-hydroxy-3-isobornyl-5-methyl-
benzaldehydes were previously separated via trans-
formation into the corresponding diastereoisomeric
Schiff bases by treatment with (R)-1-phenylethan-
amine and subsequent fractional crystallization
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
OH
(4'R)
(1R)
(4'S)
OH
OH
(1'S)
(1S)
Me
Me
(1'R)
Me
(2R)
Me
Me
(4S)
(4R)
(2S)
+
(2'R)
(2'S)
H
H
H
H
H
H
CHO
meso-I
R
R
rac-I, rac-II
I, R = CHO; II, R = Me.
60

OPTICAL RESOLUTION OF RACEMIC 4-HYDROXY-3,5-DIISOBORNYLBENZALDEHYDE
61
Scheme 1.
9
Me
Me
Me
Me
Me
Me
Me
8
7
Me
6
5
10
Me
OH
12
OH
1'
1
2Br2, t-BuOH
(R)-MeCH(Ph)NH2
Me
Me
Me
4
2
rac-II
rac-I
+
11
3
13
14
H
H
H
H
16
15
17
N
N
18
Me
Ph
Me
Ph
IV
III
[12, 13]. However, we failed to separate by crystalliza-
tion diastereoisomeric Schiff bases III and IV obtained
in a similar way from rac-I (Scheme 1).
assignment). The diastereoisomeric purity of V and VI
in the course of their separation and the enantiomeric
purity of the isolated aldehydes (+)-I and (–)-I were
determined by analytical HPLC using Chiralcel OD-H
and Chiralpak AD columns.
Schiff bases III and IV were characterized by E
configuration with respect to the double C=N bond.
The NOESY spectrum of mixture III/IV revealed
coupling between 17-H and 18-H, indicating spatially
close location of these protons.
The structure of compounds I and III−VI was
confirmed by spectral and analytical data. The absolute
configuration of V was determined on the basis of
anomalous X-ray scattering; it coincided with the
relative configuration determined on the basis of the
known configuration of the camphane fragment. The
chiral centers in the isobornyl fragments of V and (–)-I
have (1S,2R,4R) configuration, while configuration
of the isobornyl substituents in VI and (+)-I is the
opposite, (1R,2S,4S).
Aldehyde rac-I was converted into diastereoiso-
meric esters V and VI by treatment with (1S)-cam-
phanoyl chloride, and stereoisomers V and VI were
separated by fractional crystallization from toluene.
We thus isolated diastereoisomerically enriched cam-
phanates V and VI whose alkaline hydrolysis gave
enantiomerically enriched samples of (–)-I and (+)-I
(Scheme 2; atom numbering in the camphane skeleton
is shown for the sake of convenience in NMR signal
The symmetry-independent part of a unit cell of V
includes one molecule (Fig. 1). The ester fragment is
Scheme 2.
9''
Me
Me
8''
7''
6''
Me
Me
5''
10''
Me
1''
O
O
Me
Me
4''
11''
3''
O
O
O Me
O
Me
Me
Me
Me
Me
Me
Me
C(O)Cl
Me
O
O
Me
Me
Me
Me
rac-I
+
+
O
H
H
H
H
Me
O
CHO
CHO
(1S)-Camphanoyl
V
VI
chloride
HO–
HO–
V
(–)-I
(+)-I
Fractional crystallization
VI
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 1 2013

BURAVLEV et al.
are different. The main factor determining the substit-
62
C10″
C9″
uent orientation in rac-VII was intermolecular inter-
actions, whereas the situation with camphanate V was
different.
C4″
C5″
C8″
O3
C7″
C1″
C6″
To get a deeper insight into the steric structure of V,
conformational analysis was performed by varying
the torsion angles C16C11C2C3 and C14C13C2′C3′, the
relative position of the other substituents remaining
unchanged (as in crystal). The calculations were per-
formed at the B972/6-31G* level of theory (as in [18])
with the aid of GAUSSIAN software package [20].
The potential energy curves shown in Fig. 2 differ
considerably from each other. The dependence of Erel
on the torsion angle C14C13C2′C3′ resembles that found
for isobornylbenzene (weak effect of the ester group),
whereas the dependence of Erel on C16C11C2C3 is quite
different: the torsion angle 100° corresponds to the
global minimum. The reason is that the terpene frag-
ments in molecule V have the same absolute con-
figuration, and mutual orientations of each isobornyl
fragment and the ester group are different. The ester
fragment and isobornyl substituent on C13 appear at the
opposite sides of the aromatic ring, so that there are no
steric hindrances, and the orientation of the isobornyl
fragment is almost the same as in unsubstituted iso-
bornylbenzene. If the torsion angle C16C11C2C3 were
equal to 20°, the isobornyl fragment on C11 and the
ester group would be located at the same side of the
benzene ring. This should lead to steric repulsion and
cause the isobornyl fragment to turn away as observed
in crystal. Thus the conformation of molecule V is
determined mainly by intramolecular interactions.
C3″
O2
O5
C18
O4
C12
C6′
C5′
C6
C3′
C2′
C4′
C7′
C10
C1
C2
C3
C5
C7
C11
C9′
C1′
C10′
C13
C14
C9
C4
C15
C17
C16
C8′
C8
O1
Fig. 1. Structure of the molecule of 4-formyl-2,6-bis-
{(1S,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl}-
phenyl (1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]-
heptane-1-carboxylate (V) according to the X-ray diffraction
data. Non-hydrogen atoms are shown as thermal vibration
ellipsoids with a probability of 50%.
almost orthogonal to the benzene ring plane [torsion
angle C11C12O4C18 −88.66(11)°]. Orientation of the
isobornyl substituents in molecule V is characterized
by the torsion angles C16C11C2C3 99.27(12) and
C14C13C2′C3′ 20.29(15)°. The corresponding torsion
angle in most isobornylphenols studied previously ap-
proaches 20° [11, 12, 14−19]. Conformational analysis
of model isobornylbenzene [18] showed that such
mutual orientation corresponds to the global minimum
on the potential energy surface and that a torsion angle
of about 90° matches a local minimum with an energy
higher by 1.7 kcal/mol. Thus, orientation of one iso-
bornyl substituent in molecule V may be regarded as
optimal, whereas the second one occupies a local
energy minimum, presumably due to the lack of steric
effects of other substituents.
According to the NMR data, introduction of a cam-
phane fragment into molecule rac-I makes the terpene
fragments magnetically nonequivalent, and some
proton signals become distinguishable. The difference
in the signal position may be rationalized by the same
factors as those operating in crystal, which provides
an additional support to the assumption that mutual
orientation of substituents in V is determined by intra-
molecular interactions.
Analogous pattern was observed previously for
diacyl derivative of diisobornyl-substituted resorcinol
rac-VII [18], but factors responsible for the observed
orientations of the terpene fragments in V and rac-VII
Br
Br
Br
Br
O
O
O
O
Me
Me
+
O
O
O
O Me
Me
Me
Me
Me
Me
Me
Me
H
H
Me
Me
H
H
rac-VII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 1 2013

OPTICAL RESOLUTION OF RACEMIC 4-HYDROXY-3,5-DIISOBORNYLBENZALDEHYDE
63
20
(a)
EXPERIMENTAL
The IR spectra were recorded in KBr on
a Shimadzu IR Prestige 21 spectrometer. The H and
15
10
1
13C NMR spectra were measured on a Bruker Avance
II 300 instrument at 300.17 and 75.48 MHz, respec-
tively, from solutions in CDCl3 relative to the residual
proton and carbon signals of the solvent (CHCl3,
δ 7.26 ppm; CDCl3, δC 77.00 ppm). Signals were
assigned on the basis of the J-modulation 13C NMR
spectra and HSQC, COSY, and NOESY experiments.
The melting points were determined on a Kofler hot
stage and were not corrected. The optical rotations
were measured on a P3002RS Kruss Optronic auto-
matic digital polarimeter (λ 589 nm).
5
0
0
20 40 60 80 100 120 140 160 180°
(b)
12
10
8
6
4
2
0
The progress of reactions was monitored by TLC
on Sorbfil plates. Aldehyde I was detected on the
chromatograms by treatment with a solution prepared
from 15 g of KMnO4, 300 ml of H2O, and 0.5 ml of
concd. H2SO4. Esters V and VI were detected by treat-
ment with a solution of Bromocresol Purple, followed
by heating to 100–120°C. HPLC analyses were per-
formed on an Agilent 1100 chromatograph equipped
with a UV detector (λ 219 nm, 20°C). The diastereo-
isomeric purity of compounds V and VI was estimated
using a Chiralcel OD-H column (Daicel, 25 cm×
4.6 mm, grain size 5 μm; eluent hexane–i-PrOH, 99:1,
flow rate 1.0 ml/min); the enantiomeric purity of (+)-I
and (–)-I was estimated using a Chiralpak AD column
(Daicel, 25 cm×4.6 mm, grain size 10 μm; eluent
hexane–i-PrOH, 97:3, flow rate 1.0 ml/min).
0
20 40 60 80 100 120 140 160 180°
Fig. 2. Plots of the relative conformational energy of
compound V versus torsion angles (a) C16C11C2C3 and
(b) C14C13C2′C3′.
measured on a Bruker Smart Apex2 CCD diffractom-
eter (λCuKα = 1.54178 Å, θmax = 67.35°) at 100 K from
a 0.19×0.14×0.11-mm single crystal. The initial array
of reflection intensities was processed with a correc-
tion for absorption using SAINT and SADABS pro-
grams built in APEX2 software package [22]. The
structure was solved by the direct method and was
refined against F2hkl by the full-matrix least-squares
procedure in anisotropic approximation for non-hydro-
gen atoms. Hydrogen atoms were placed into positions
calculated on the basis of geometry considerations and
were refined according to the riding model [Uiso(H) =
nUeq(C, O); n = 1.5 for methyl carbon atoms, n = 1.2
for the other carbon atoms]. The final divergence
factors were wR2 = 0.0643 (for 5596 independent
reflections, Rint = 0.0284) and R1 = 0.0253 [for
5516 reflections with I > 2σ(I)]. All calculations were
performed on an IBM PC using SHELXTL software
[23]. The coordinates of atoms and their temperature
factors were deposited to the Cambridge Crystallo-
graphic Data Centre (entry no. CCDC 910121).
The products were purified by column chromatog-
raphy (wet packing) on silica gel (70–230 μm, Alfa
Aesar). Toluene was dried over anhydrous CaCl2 and
distilled over metallic sodium. 4-Å Molecular sieves
were activated by calcination at 140°C over a period of
3 h. Commercial (R)-1-phenylethanamine (ChiPros®,
enantiomeric purity >99%), (1S)-camphanoyl chloride
(Alfa Aesar), 4-dimethylaminopyridine (Acros
Organics), and triethylamine (Sigma–Aldrich) were
used without additional purification. Racemic 2,6-di-
isobornyl-4-methylphenol (rac-II) was isolated from
the alkylation products of p-cresol with camphene
according to modified procedure [21].
Single crystals of V suitable for X-ray analysis
were obtained by slow evaporation of its solution in
benzene. Colorless crystals (C37H50O5, M 574.77);
rhombic crystal system, space group P212121; unit cell
parameters: a = 7.10570(10), b = 20.8831(3), c =
4-Hydroxy-3,5-bis(1,7,7-trimethylbicyclo[2.2.1]-
heptan-2-exo-yl)benzaldehyde (rac-I). Compound
rac-II, 8.4 g (22 mmol), was dissolved in 420 ml of
tert-butyl alcohol on slight heating, the solution was
cooled to ~40°C, and 2.27 ml (44 mmol) of bromine
was added in small portions. The mixture was stirred
for 3 h at room temperature and left overnight. The
21.3122(3) Å; V = 3162.50(8) Å3; Z = 4; dcalc
=
1.207 g/cm3. Total of 43373 reflection intensities were
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 1 2013

BURAVLEV et al.
64
solvent was distilled off, 80 ml of chloroform was
added to the residue, the mixture was washed with
a saturated solution of Na2S2O3 (3×50 ml) and water
(2×50 ml) and dried over anhydrous sodium sulfate,
the solvent was distilled off, and the residue was
recrystallized from petroleum ether. Yield 4.1 g (47%),
colorless powder, mp 190–192°C (possibly with de-
composition). IR spectrum, ν, cm–1: 3591, 3296 (OH),
Schiff bases III and IV. A mixture of 1.38 g
(3.5 mmol) of rac-I dissolved in 25 ml of toluene,
0.45 ml (3.5 mmol) of (R)-(+)-1-phenylethanamine,
and 6.5 g of 4-Å molecular sieves was heated for 3.5 h
under reflux while stirring in a stream of argon. The
solution was filtered through a glass filter, the molec-
ular sieves were washed with chloroform, and the
filtrate was evaporated. The residue was recrystallized
in succession from pentane, hexane, cyclohexane, ben-
zene, and toluene.
1
2951, 2878, 1448 (Me, CH2), 1665 (C=O). H NMR
spectrum, δ, ppm: 0.75 s (6H, 10-H, 10′-H), 0.85 s
(6H, 9-H, 9′-H), 0.90 s (6H, 8-H, 8′-H); 1.31–1.50 m,
1.59–1.79 m, and 1.82–2.02 m (4H each, 3-H, 3′-H,
4-H, 4′-H, 5-H, 5′-H, 6-H, 6′-H), 2.26–2.35 m (2H,
3-H, 3′-H), 3.06 t (2H, 2-H, 2′-H, J = 8.7 Hz), 5.40 s
(1H, OH), 7.72 s (2H, 14-H, 16-H), 9.84 s (1H, CHO).
13C NMR spectrum, δC, ppm: 12.49 (C10, C10′), 20.34
(C9, C9′), 21.33 (C8, C8′), 27.52 (C5, C5′), 34.46 (C3,
C3′), 40.17 (C6, C6′), 45.43 (C4, C4′), 46.12 (C2, C2′),
48.36 (C7, C7′), 49.80 (C1, C1′), 128.06 (C14, C16),
128.45 and 129.53 (C11, C13, C15), 159.57 (C12), 191.65
(CHO). Found, %: C 81.98; H 9.91. C27H38O2. Calcu-
lated, %: C 82.18; H 9.71.
2,6-Bis{(1R,2S,4S)-1,7,7-trimethylbicyclo[2.2.1]-
heptan-2-yl}-4-{(E)-[(R)-1-phenylethylimino]-
methyl}phenol (III) and 2,6-bis{(1S,2R,4R)-1,7,7-
trimethylbicyclo[2.2.1]heptan-2-yl}-4-{(E)-[(R)-1-
phenylethylimino]methyl}phenol (IV) (mixture of
diastereoisomers at a ratio of ~1:1). Yield 1.71 g
(98%), red–orange caramel-like material. IR spectrum,
ν, cm–1: 3597, 3418 (OH); 2949, 2876, 1456 (Me,
CH2); 1641 (C=N); 1699 (C=O); 1290 (C–O).
1H NMR spectrum, δ, ppm: 0.74/0.76* s (6H, 10-H,
10′-H), 0.85 s and 0.92 s (6H each, 8-H, 8′-H, 9-H,
9′-H), 1.30−1.47 m (4H, 5-H, 5′-H, 6-H, 6′-H),
1.54/1.56* d (3H, 19-H, J = 6.2/6.4 Hz), 1.61−1.74 m
(4H, 3-H, 3′-H, 6-H, 6′-H), 1.81−1.98 m (4H, 4-H,
4′-H, 5-H, 5′-H), 2.24−2.47 m (2H, 3-H, 3′-H), 3.06 t
(1H, 2-H, 2′-H, J = 8.6 Hz), 4.49 q (1H, 18-H, J =
6.6 Hz), 5.02 br.s (1H, OH), 7.16−7.45 (5H, C6H5),
7.63/7.64* s (14-H, 16-H), 8.27 br.s (1H, 17-H).
13C NMR spectrum, δC, ppm: 12.42/12.47* (C10, C10′),
20. 21/20. 33, * and 21. 43 (C9, C9 ′, C8, C8 ′),
25.12/25.43* (C19), 27.59 (C5, C5′), 34.46/34.49* (C3,
C3′), 40.15/40.19* (C6, C6′), 45.51 (C4, C4′), 46.17 (C2,
C2′), 48.28 (C7, C7′), 49.70 (C1, C1′), 69.41 (C18);
125.95, 126.48/126.64,* 128.22/128.28,* 129.02 (C14,
C16, C21, C21′, C22, C22′, C23); 127.68 and 128.71 (C11,
C13, C15), 146.21 (C20), 156.21 (C12), 159.49/159.62*
(C17). Found, %: C 84.09; H 9.94. C35H47NO. Calculat-
ed, %: C 84.45; H 9.52.
4-Methyl-2,6-bis(1,7,7-trimethylbicyclo[2.2.1]-
heptan-2-exo-yl)phenol (rac-II). A mixture of 10.5 g
(97 mmol) of p-cresol, 26.4 (194 mmol) of camphene,
and 1.05 g (3 mmol) of (4-MePhO)3Al as catalyst was
heated at 180°C until complete conversion of p-cresol
(TLC, eluent petroleum ether). The mixture was
cooled, diluted with diethyl ether until it turned homo-
geneous, and washed with 18% aqueous HCl to de-
compose the catalyst. The ether extract was washed
with 5% aqueous NaOH to remove unreacted p-cresol
and with water to neutral reaction and dried over anhy-
drous sodium sulfate. The solvent was distilled off, and
the residue was subjected to column chromatography
using petroleum ether–diethyl ether as eluent to isolate
8.9 g (24%) of rac-II as colorless powder with
mp 169–172°C. IR spectrum, ν, cm–1: 3505, 3442
(OH), 2988, 2947, 2874, 1458 (Me, CH2), 1178 (C–O).
1H NMR spectrum, δ, ppm: 0.78 s (6H, 10-H, 10′-H),
0.88 s and 0.93 s (6H each, 9-H, 9′-H, 8-H, 8′-H);
1.40–1.50 m, 1.58–1.71 m, and 1.89–1.90 m (4H each,
3-H, 3′-H, 4-H, 4′-H, 5-H, 5′-H, 6-H, 6′-H), 2.22–
2.31 m (2H, 3-H, 3′-H), 2.31 s (3H, 17-H), 3.08 t (2H,
2-H, 2′-H, J = 9.0 Hz), 4.64 s (1H, OH), 6.99 s (2H,
14-H, 16-H). 13C NMR spectrum, δC, ppm: 12.44 (C10,
C10′), 20.32 and 21.46 (C8, C8′, C9, C9′, C17), 27.60 (C5,
C5′), 34.40 (C3, C3′), 40.14 (C6, C6′), 45.43 and 46.12
(C2, C2′, C4, C4′), 48.17 and 49.61 (C1, C1′, C7, C7′),
125.95 (C14, C16), 127.39 and 128.23 (C11, C13, C15),
151.60 (C12). Found, %: C 85.38; H 10.33. C27H40O.
Calculated, %: C 85.20; H 10.59.
Esters V and VI. A mixture of 2.37 g (6.0 mmol)
of rac-I dissolved in 25 ml of toluene, 1.56 g
(7.2 mmol) of (1S)-camphanoyl chloride, 1.0 ml
(7.2 mmol) of triethylamine, and 0.073 g (0.6 mmol)
of 4-dimethylaminopyridine was heated for 4 h under
reflux while stirring in a stream of argon. The solution
was evaporated, and the residue was subjected to
column chromatography using cyclohexane–chloro-
form as eluent to isolate 2.87 g (83%) of a mixture of
diastereoisomers V and VI. The isomer mixture was
dissolved in 25 ml of hot toluene, and the solution was
left to stand for crystallization at –20°C over a period
* Signals from different diastereoisomers.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 1 2013

OPTICAL RESOLUTION OF RACEMIC 4-HYDROXY-3,5-DIISOBORNYLBENZALDEHYDE
65
of 48 h. The colorless precipitate was separated and
dried under reduced pressure. Yield of V 1.05 g (61%),
diastereoisomeric purity >95%. The second diastereo-
isomer was isolated from the mother liquor after two
additional crystallizations. Yield of VI 1.38 g (80%),
diastereoisomeric purity >85%.
20.48 and 20.56 (C9, C9′), 21.53 and 23.27 (C8, C8′),
27.28 (C5, C5′), 28.90 (C5″), 32.17 (C6″), 34.19 and
43.36 (C3, C3′), 39.02 and 40.09 (C6, C6′), 45.51 (C4,
C4′), 45.81 and 46.83 (C2, C2′), 48.29 and 48.47 (C7,
C7′), 50.51 (C1, C1′), 54.50 (C4″), 54.85 (C7″), 90.23
(C1″), 127.83 and 128.08 (C14, C16); 132.93, 136.59,
140.37 (C11, C13, C15); 153.80 (C12), 166.05 and 177.74
(C3″, C11″), 191.81 (C17). Found, %: C 74.05; H 8.24.
C28H36O5. Calculated, %: C 74.31; H 8.02.
4-Formyl-2,6-bis{(1S,2R,4R)-1,7,7-trimethylbi-
cyclo[2.2.1]heptan-2-yl}phenyl (1S,4R)-4,7,7-tri-
methyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbox-
ylate (V). Colorless finely crystalline powder,
mp 250–252°C, [α]D21 = –103.7° (c = 0.36, CHCl3);
retention time (HPLC) 9.53 min. IR spectrum, ν, cm–1:
2959, 2878, 1458 (Me, CH2), 1798, 1755 (C=O, ester),
Enantiomerically enriched aldehydes (+)-I and
(–)-I (general procedure). Camphanate V or VI, 0.3 g
(0.52 mmol), was dissolved in 6 ml of THF (com-
pound V was dissolved on slight heating), 6 ml of
12 M aqueous KOH was added, and the mixture was
heated for 12 h under reflux with vigorous stirring. The
organic phase was separated, washed with several
portions of a saturated solution of sodium chloride, and
dried over anhydrous sodium sulfate, the solvent was
distilled off, and the residue was subjected to column
chromatography using benzene as eluent.
1
1699 (C=O, aldehyde), 1258 (C–O). H NMR spec-
trum, δ, ppm: 0.72 s (3H) and 1.17 s (6H) (10-H,
10′-H, 10″-H), 0.83 s and 0.96 s (3H each, 9-H, 9′-H),
0.87 s and 1.09 s (3H each, 8-H, 8′-H), 1.14 s (3H,
9″-H), 1.23 s (3H, 8″-H); 1.14–1.36 m (3H), 1.38–
1.52 m (1H), 1.53–1.72 m (4H), 1.72–1.92 m (5H),
1.95–2.14 m (2H), 2.17–2.40 m (2H), and 2.44–2.57 m
(1H) (3-H, 3′-H, 4-H, 4′-H, 5-H, 5′-H, 5″-H, 6-H, 6′-H,
6″-H); 2.63 t and 2.78 t (1H each, 2-H, 2′-H, J = 8.6,
8.7 Hz); 7.82 s and 7.86 s (1H each, 14-H, 16-H),
9.94 s (1H, 17-H). 13C NMR spectrum, δC, ppm: 9.58
(C10″), 12.32 and 14.73 (C10, C10′), 16.94 and 17.09
(C8″, C9″), 20.57 (C9, C9′), 21.54 and 23.22 (C8, C8′),
27.21 and 27.50 (C5, C5′), 28.97 (C5″), 31.74 (C6″),
34.26 and 43.50 (C3, C3′), 39.30 and 39.37 (C6, C6′),
45.49 (C4, C4′), 45.74 and 46.53 (C2, C2′), 48.49 (C7,
C7′), 50.50 (C1, C1′), 54.09 (C4″), 54.71 (C7″), 90.07
(C1″), 127.80 and 128.02 (C14, C16); 133.01, 136.78,
139.83 (C11, C13, C15); 153.62 (C12), 166.10 and 177.66
(C3″, C11″), 191.84 (C17). Found, %: C 74.05; H 8.24.
C28H36O5. Calculated, %: C 74.31; H 8.02.
4-Hydroxy-3,5-bis{(1S,2R,4R)-1,7,7-trimethylbi-
cyclo[2.2.1]heptan-2-yl}benzaldehyde (–)-(I). Yield
0.161 g (78%), enantiomeric purity 98.7%, colorless or
light brown powder, mp 227–229°C (possibly with
decomposition), [α]D23 = –41.9° (c = 0.32, CHCl3);
retention time (HPLC) 9.36 min.
4-Hydroxy-3,5-bis{(1R,2S,4S)-1,7,7-trimethylbi-
cyclo[2.2.1]heptan-2-yl}benzaldehyde (+)-(I). Yield
0.167 g (81%), enantiomeric purity 85%, colorless or
light brown powder, mp 219–222°C (possibly with
decomposition), [α]D23 = +40.2° (c = 0.27, CHCl3);
retention time (HPLC) 11.45 min.
This study was performed under financial support
by the Ural Division of the Russian Academy of
Sciences (Competition of Research Projects of Yong
Scientists and Post-Graduate Students, project no. 13-
3-NP-13). The authors thank E.N. Zainullina (Physico-
chemical Methods Laboratory) for recording the NMR
spectra and T.V. Timofeeva (New Mexico Highlands
University, US) for providing computation facilities
for quantum-chemical calculations.
4-Formyl-2,6-bis{(1R,2S,4S)-1,7,7-trimethylbi-
cyclo[2.2.1]heptan-2-yl}phenyl (1S,4R)-4,7,7-tri-
methyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbox-
ylate (VI). Light brown powder, mp 192–194°C,
[α]D21 = +58.5° (c = 0.33, CHCl3); retention time
(HPLC) 10.36 min. IR spectrum, ν, cm–1: 2955, 2880,
1458 (Me, CH2), 1798, 1753 (C=O, ester), 1699 (C=O,
1
aldehyde), 1258 (C–O). H NMR spectrum, δ, ppm:
0.74 s (3H), 1.18 s (6H), 1.20 s (6H) (8″-H, 9″-H,
10-H, 10′-H, 10″-H); 0.83 s and 0.95 s (3H each, 9-H,
9′-H); 0.87 s and 1.06 s (3H each, 8-H, 8′-H); 1.12–
1.45 (3H), 1.49–1.93 (10H), 1.93–2.13 (2H), 2.13–
2.43 (2H), and 2.45–2.61 (1H) (3-H, 3′-H, 4-H, 4′-H,
5-H, 5′-H, 5″-H, 6-H, 6′-H, 6″-H); 2.61–2.84 m (2H,
2-H, 2′-H); 7.85 s and 7.87 s (1H each, 14-H, 16-H),
9.94 s (1H, 17-H). 13C NMR spectrum, δC, ppm: 9.65
(C10″), 12.43 and 14.99 (C10, C10′), 16.83 (C8″, C9″),
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