Novel optically active pyrazole ligands derived from (+)-3-carene

Article abstract of DOI:10.1016/S0957-4166(01)00477-3

Reactions of chiral β-diketone with racemic hydrazines as well as reaction of chiral pyrazole with cyclohexene epoxide and trans-stilbene epoxide have been examined as the routes to optically active pyrazolylethanols. Diastereomerically pure products have

Full text of DOI:10.1016/S0957-4166(01)00477-3

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 2875–2881
Novel optically active pyrazole ligands derived from (+)-3-carene
Sergey A. Popov,a Yuri V. Gatilov,a Tatjana V. Rybalova,a Oxana A. Kholdeevab and
Alexey V. Tkachevc,*
aN.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Acad. Lavrentjev Ave. 9, Novosibirsk 630090, Russia
bG.K. Boreskov Institute of Catalysis, Acad. Lavrentjev Ave. 5, Novosibirsk 630090, Russia
cNovosibirsk State University, Pirogov St. 2, Novosibirsk 630090, Russia
Received 19 October 2001; accepted 23 October 2001
Abstract—Reactions of chiral b-diketone with racemic hydrazines as well as reaction of chiral pyrazole with cyclohexene epoxide
and trans-stilbene epoxide have been examined as the routes to optically active pyrazolylethanols. Diastereomerically pure
products have been isolated by crystallization or column chromatography in good yields. © 2001 Elsevier Science Ltd. All rights
reserved.
1. Introduction
readily accessible derivatives of the natural monoter-
pene (+)-3-carene. We described earlier the reaction of
Substituted pyrazole-N-alkanols are prospective agents
for diastereoselective synthesis: optically active pyra-
zolylethanols were employed as chiral auxiliaries in the
addition reaction of diethyl zinc to aldehydes,1 whereas
modified polydentate ligands obtained from pyra-
zolylethanols were used to synthesize complexes with
Pd and Re.2
optically active diketone
1 with monosubstituted
hydrazines (hydrazino–ethanol and ethyl hydrazino–
acetate) to proceed regioselectively providing substi-
tuted pyrazoles 3 in good yields.5
Racemic hydrazines 2a and 2b resulting from trans-stil-
bene oxide and cyclohexene oxide, respectively, were
used in the reaction with diketone 1 to give pyrazoles 4
and 5 as ca. 1:1 (according to NMR) mixtures of
diastereomers (Scheme 1). The reaction proceeds
regioselectively to give only one positional isomer of the
substituted pyrazoles.
Optically active epoxides are known to be opened with
pyrazoles at high pressure (10 kbar) to give
diastereomerically pure products (regioisomers resulting
from optically active pyrazoles are separated chromato-
graphically).1 Regioselective reactions of pyrazoles with
cyclohexene epoxide at elevated temperatures providing
chiral products have been described.3,4 Kinetic resolu-
tion of racemic and diastereomeric adducts has been
performed by immobilized lipase3 to give diastereomeri-
cally pure (1S,2S)-derivatives. Pyrazole fused with a
bornane framework has been reported to be alkylated
with ethyl bromoacetate and reduced to give the
regioisomeric pyrazole–ethanols.1
The alternative route to substituted pyrazoles by open-
ing of the epoxide ring in trans-stilbene oxide and
cyclohexene oxide with pyrazole 3 (R=H)6 was also
studied (Scheme 2). Heating of equimolar mixture of
pyrazole 3 (R=H) and trans-stilbene oxide in a sealed
tube at 100–130°C resulted in poor regioselectivity
affording mixtures of regioisomers 4 and 7 in ca. 4:1
ratio (NMR, GC–MS), whereas the reaction of the
pyrazole 3 (R=H) with cyclohexene oxide gave ca. 10:1
mixture of 5 and 8.
2. Results and discussion
The mixture of diastereomers 4 can be separated easily
by column chromatography to afford both isomers in
quite good yields. The structure 4a was established by
X-ray crystallography (Fig. 1) showing the intermolecu-
lar hydrogen bonds between the hydroxyl hydrogen and
We have studied the possibility of synthesizing new
optically active pyrazole–N-ethanols starting from
* Corresponding author. Tel.: +7(3832)344855; fax: +7(3832)344752;
e-mail: atkachev@nioch.nsc.ru
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00477-3

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S. A. Popo6 et al. / Tetrahedron: Asymmetry 12 (2001) 2875–2881
Scheme 1. The numbering of the carbons shown does not coincide with the numbering of the system according to IUPAC and
is given for NMR interpretation only.
H
H
H
H
N
+
Ph
N
N
4:7 = 4:1
N
Ph
Ph
O
Ph
Ph
Ph
HO
OH
4
7
H
H
N
4, 5, 7, 8 - 1:1 mixtures of diastereomers
NH
O
3
H
N
H
H
H
5:8 = 10:1
+
N
HO
N
N
OH
5
8
Scheme 2.
the non-substituted pyrazole nitrogen. When a solu-
tion of 4 in acetonitrile is seeded with the pure isomer
4a, the isomer 4a is isolated by crystallization in 11%
yield.
tives. Treatment of 5 with AcCl resulted in the O-acetyl
derivative, which was crystallized from MeCN to give a
2:1 mixture of diastereomers. On the other hand, crys-
tallization of the O-benzoyl derivative 9 allowed us to
prepare benzoate 9a in diastereomerically pure form.
The structure 9a was established by X-ray analysis (Fig.
2). Bond lengths of the tetrahydrocyclopropa[3,4]cyclo-
penta[1,2-c]pyrazolyl fragment of compounds 4a and
9a are identical within experimental error. Overall,
whole all bond lengths including that of pyrazole ring
are close to the average ones.7
Mixtures of isomers 5a and 5b are chromatographically
homogeneous (TLC and GLC); moreover, attempts to
separate 5a and 5b via crystallization failed (Scheme 3).
Problems in separation of the simplest diastereomeric
pyrazole–cyclohexanols have been documented,4 and
therefore we tried to separate their O-acylated deriva-

S. A. Popo6 et al. / Tetrahedron: Asymmetry 12 (2001) 2875–2881
2877
Figure 1. Molecular structure of compound 4a according to
X-ray crystallography. Thermal ellipsoids are shown at 30%
,
probability level. Selected bond lengths (A): C(2)ꢀC(3)
Figure 2. Molecular structure of compound 9a according to
X-ray crystallography. Thermal ellipsoids are shown at 30%
1.387(4), C(3)ꢁC(4) 1.361(4), C(4)ꢀN(4) 1.345(4), N(4)ꢀN(2)
1.372(3), N(2)ꢁC(2) 1.359(4). Bicyclic system C(2)ꢀC(7), N(2),
,
probability level. Selected bond lengths (A): C(2)ꢀC(3)
,
N(4) is planar within 0.032(3) A. Parameters of the
intramolecular hydrogen bond OH···N are as follows:
O(12)···N(2) 2.704(4), O(12)ꢀH 0.99(6), H···N(2) 1.93(6) A,
1.409(5), C(3)ꢁC(4) 1.375(5), C(4)ꢀN(4) 1.340(5), N(4)ꢀN(2)
1.376(4), N(2)ꢁC(2) 1.335(5). Bicyclic system C(2)ꢀC(7), N(2),
,
,
N(4) is planar within 0.028(3) A.
angle O(12)ꢀH···N(2) 133(5)°.
H
H
H
H
N
H
H
H
N
H
PhCOCl - Py
Crystallization
N
N
OH
N
N
OCOPh
H
N
OCOPh
N
OCOPh
H
H
H
5
(46%)
9
9a
9b
MeOH/KOH
MeOH/KOH
96%
9
10
Crystallization: no separation occurs
8
H
H
H
H
7
6
3
5
1
4
2
OH
N
N
OH
H
N
N
11
H
H
H
12
16
13
15
14
5b
5a
40% (counting on 5)
44% (counting on 5)
Scheme 3. The numbering of the carbons shown does not coincide with the numbering of the system according to IUPAC and
is given for NMR interpretation only.

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S. A. Popo6 et al. / Tetrahedron: Asymmetry 12 (2001) 2875–2881
Saponification of 9a with methanolic KOH provided
isomer 5a, whereas the saponification of the mother
liquor (after separation of the isomer 9a) resulted in the
second diastereomer 5b.
5–10% solutions using standard Bruker NMR Software
System on a Bruker AC 200 instrument (200 MHz for
1H and 50.32 MHz for 13C) and a Bruker DRX-500
1
instrument (500 MHz for H and 125 MHz for 13C)
locked to the deuterium resonance of the solvent
(CDCl3). The chemical shifts were calculated relative to
the solvent signal used as the internal standard: lH 7.24
ppm and lC 76.90 ppm.
Analyses of mixtures of diastereomers in all the cases
were carried out using GC–MS as well as high-field
NMR spectroscopy. NMR parameters for the terpenic
fragments in pyrazolyl cyclohexanols 5a and 5b are
close to those for corresponding N-unsubstituted pyra-
zoles 3 described earlier.5,6
X-Ray data were measured at 296 K on a Bruker P4
diffractometer with graphite monochromated Mo Ka
,
radiation (u=0.71073 A) using q/2q scans. The struc-
Introduction of the 1,2-diphenylethanol moiety gives
tures were solved by direct methods using SHELXS-97
and refined by full-matrix least-squares using
SHELXL-97. Atomic coordinates, bond lengths and
angles have been deposited at the Cambridge Crystallo-
graphic Data Centre.
1
rise to substantial discrepancy of H NMR parameters
between compounds 4a, 4b, and 6 and known N-unsub-
stituted pyrazole 3,5,6 the protons at C-10 being espe-
cially sensitive to remote chiral environment. Thus,
chemical shifts of the H-10 atoms are 0.59, 0.36 and
−0.01 ppm for compounds 4b, 4a, and 6, respectively:
This could be the result of the strong anisotropic effects
caused by the constrained phenyl moieties.
4.2. Synthesis of substituted hydrazines 2a and 2b
from oxides of trans-stilbene and cyclohexene
A solution of epoxide (0.1 M) in methanol (40 ml) was
added dropwise to a stirred solution of hydrazine
hydrate (15 ml) in methanol (30 ml) at ambient temper-
ature. The mixture was refluxed for 2 h and then
concentrated at reduced pressure. The resulting product
was washed with MeCN (10 ml), dried in vacuum over
concentrated H2SO4 for 2 h and was used immediately
in the reaction with diketone 1 without any additional
purification.
3. Conclusion
Thus, pyrazole–N-alkanols derived from (+)-3-carene
and cyclohexene oxide and stilbene oxide were prepared
in preparative yields and in diastereomerically pure
form. Preliminary studies have shown the new pyra-
zole–N-alkanols to form complexes with transition
metal ions allowing one to consider them as new poten-
tial chiral ligands for enantioselective catalysis.
4.3. Synthesis of 4 and 5 from diketone 1 and
substituted hydrazines
A solution of a substituted hydrazine (1,2-diphenyl-2-
hydroxyethyl hydrazine or 2-hydrazinocyclohexanol,
6.0 mmol) in methanol (10 ml) was added dropwise to
a stirred ice-cooled solution of diketone 1 (1.00 g, 6
mmol) in a mixture of methanol (15 ml) and AcOH (1
ml). The mixture was kept at ambient temperature
overnight and then stirred at reflux for 0.5 h. The
solvent was removed under reduced pressure, and the
residue was treated with water (100 ml) and extracted
with benzene (50 ml). The organic phase was washed
with NaHCO3 (0.5 M, 50 ml), dried (Na2SO4) and
evaporated at reduced pressure to give the crude
product, which was chromatographed on a short alu-
mina column (benzene) and crystallized (MeCN) to give
4. Experimental
4.1. General experimental procedures
All the solvents used were reagent quality. Removal of
all solvents was carried out under reduced pressure and
all commercial reagents were used without additional
purification. Analytical TLC plates were Silufol®
(Silpearl on aluminum foil, Czechoslovakia). Prepara-
tive column chromatography was performed on SiO2
(‘KSK’, Russia, 0.04–0.07 mm, air dried and activated
at 140°C for 5 h) or Al2O3 (‘Reachim’, Russia). Dike-
tone 1 and pyrazole 3 (R=H) were prepared as
6
described in Ref. . IR spectra were obtained using a
the pure pyrazoles
diastereomers.
4 or 5 as 1:1 mixtures of
Specord M-80 spectrometer. UV spectra were obtained
for 1% solutions in EtOH using a Specord UV–vis
spectrometer. A Polamat A polarimeter was used to
measure optical rotation at 578 nm. Melting points
were obtained using a Kofler melting point apparatus.
Mass spectra were obtained on a Finnigan MAT 8200
instrument using the Electron Impact Ionization tech-
nique (50–150°C, 70 eV). GC–MS data were obtained
on a quadrupole MS (Hewlett–Packard MSD 5971)
coupled to a HP 5890/II GC fitted with an HP-5 fused
silica column, injector and detector (MSD) temperature
were 280 and 170°C, respectively. MSD was operated at
70 ev. Purity was determined from constancy of melting
4.4. Synthesis of mixtures 4/7 and 5/8
An equimolar mixture of pyrazole 3 (R=H) and epox-
ide of cyclohexene or epoxide of trans-stilbene was
heated in a sealed tube at 130°C for 6–10 h to give
mixtures 4/7 or 5/8 in 95–98% yield (purity was estab-
lished by NMR and GC–MS data).
4.5. Chromatographic separation of diastereomeric
mixture 4
point together with TLC and NMR data. H and 13C
NMR spectra were recorded at room temperature for
A mixture of diastereomers 4 (0.700 g, 1.95 mmol) was
chromatographed on a silica gel column (l=230 mm,
1

S. A. Popo6 et al. / Tetrahedron: Asymmetry 12 (2001) 2875–2881
2879
¥=20 mm, eluent CCl4, CCl4–EtOAc) to give 4a 250
mg (0.70 mmol, 36%) and 4b 180 mg (0.50 mmol, 26%).
(ddd, J=7.0, 6.6, 1.1, 1H-6), 1.74 (dd, J=6.6, 1.1,
1H-7), 1.03 (s, 3H-9); 0.61 (s, 3H-10), 3.79 (ddd, J=9.9,
9.9, 4.7, 1H-11), 3.58 (ddd, J=12.5, 9.4, 4.2, 1H-12),
2.06 (m, 1H-13a); 1.70–1.80 (m, 2H-15a, 14a), 1.25–1.37
(m, 3H-15b, 14b, 13b), 1.65 (m, 1H-16a), 1.99 (m,
1H-16b), 3.53 (br.s, 1H-OH). 13C NMR (125 MHz):
12.38 (C-1), 150.48 (C-2), 125.59 (C-3), 142.19 (C-4),
24.68 (C-5), 34.02 (C-6), 25.74 (C-7), 22.21 (C-8), 26.18
(C-9), 13.60 (C-10), 65.64 (C-11), 72.61 (C-12), 33.02
(C-13), 23.89 (C-14), 24.702 (C-15), 30.39 (C-16).
4.6. Synthesis of benzoate of pyrazole–cyclohexanol
9 and separation of the diastereomers
Benzoyl chloride 5.0 g (36 mmol) was added to a stirred
mixture of pyrazole 5 (4.3 g, 17 mmol) in CH2Cl2 (30
ml) and pyridine (10 g) and the mixture was allowed to
stay for 48 h. The mixture was sequentially washed with
satd aq. NaHCO3 (100 ml), 1.0 M H2SO4 (100 ml),
dried (Na2SO4) and concentrated under reduced pres-
sure. The resulting light brown viscous oil was dissolved
in MeCN (50 ml) and left in refrigerator. After 24 h
benzoate 9a (3.0 g, 45%) was separated as white crys-
tals. The mother liquor was evaporated to afford a
brownish oil, which contained benzoates 9b and 9a
(10:1 according to NMR) together with impurities.
4.10. (1R,2R)-2-((3bS,4aR)-3,4,4-Trimethyl-3b,4,4a,5-
tetrahydrocyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)-
cyclohexanol 5b
Treatment of 5 (4.5 g, 17 mmol) with benzoyl chloride
followed by separation of 9a (crystallization) resulted in
the mother liquor, which was concentrated and
saponified to give 5b (1.8 g, 40%) as white needles with
mp 131–133°C(MeCN) and [h]2D5=+66 (c 1.25, CHCl3).
1H NMR (500 MHz, CDCl3): 2.14 (s, 3H-1), 2.50 (ddd,
J=16.6, 1.3, 1.6, 1H-5a), 2.80 (dd, J=16.6, 7.0, 1H-
5b), 1.68 (ddd, J=7.0, 6.5, 1.3, 1H-6), 1.75 (dd, J=6.5,
1.6, 1H-7), 1.07 (s, 3H-9), 0.63 (s, 3H-10), 3.80 (ddd,
J=10.5, 9.5, 4.8, 1H-11), 3.56 (ddd, J=12.3, 9.4, 4.2,
1H-12), 1.35 (m, 1H-13a), 2.08 (m, 1H-13b), 1.32 (m,
1H-14a), 1.77 (m, 1H-14b), 1.30 (m, 1H-15a), 1.78 (m,
1H-15b), 1.66 (dddd, J=12.5, 12.5, 12.5, 3.9, 1H-16ax),
1.99 (m, 1H-16eq), 3.36 (br.s, W1/2=90, 1H-OH). 13C
NMR (125 MHz): 12.45 (C-1), 150.58 (C-2), 125.50
(C-3), 142.14 (C-4), 24.66 (C-5), 34.11 (C-6), 25.95
(C-7), 22.27 (C-8), 26.31 (C-9), 13.68 (C-10), 65.68
(C-11), 72.52 (C-12), 33.15 (C-13), 24.05 (C-14), 24.90
(C-15), 30.47 (C-16). IR, UV, and MS data were identi-
cal to those of 5a.
4.7. Saponification of benzoates 9a and 9b
A solution of 9a (1.0 g, 2.7 mmol) or solution of the
mother liquor (1.0 g) in MeOH (10 ml) and KOH (1 g,
17.8 mmol) were heated at 70°C for 1 h. The mixture
was evaporated at reduced pressure. Water (40 ml) was
added to the residue and the mixture was extracted with
CCl4 (2×20 ml). The combined organic extracts were
washed with 1 M aq. H2SO4 (3×15 ml). The combined
aqueous extracts were neutralized with conc. aq. NH3
(20 ml) and extracted with CH2Cl2 (3×15 ml) to afford
a solid, which was crystallized from MeCN to give
pyrazolocyclohexanol as pale yellow crystals.
4.8.(1S,2S)-2-((3bS,4aR)-3,4,4-Trimethyl-3b,4,4a,5-tetra-
hydrocyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)cyclo-
hexanol and (1R,2R)-2-((3bS,4aR)3,4,4-trimethyl-
3b,4,4a,5-tetrahydrocyclopropa[3,4]cyclopenta[1,2-c]-
pyrazol-1-yl)cyclohexanol 5
4.11. (1S,2S)-Benzoic acid-2-((3bS,4aR)-3,4,4-trimethyl-
3b,4,4a,5-tetrahydrocyclopropa[3,4]cyclopenta[1,2-c]-
pyrazol-1-yl)cyclohexyl ester 9a
Reaction of diketone 1 (1.65 g, 10.0 mmol) with 2-
hydrazinocyclohexanol led to
a
mixture of
Treatment of 5 (4.5 g, 17 mmol) with benzoyl chloride
followed by crystallization of the crude product 9 from
MeCN led to 9a (2.9 g, 46%) as white needles with mp
167–169°C (MeCN, dec.) and [h]2D1=+179 (c 1.7,
CHCl3). UV (EtOH) umax/nm 231 (m 17000); 269 (m 900).
IR (CHCl3) w/cm−1 1716 (CꢁO). MS (m/z, %): 364.2143
(M+, 45%, C23H28N2O2, requires 364.2151), 349 (79),
259 (28), 242 (11), 227 (93), 201 (10), 173 (4), 161 (24),
diastereomers 5 (2.20 g, 84%) as yellow crystals. Heat-
ing a mixture of pyrazole 3 (R=H) (3.6 g, 2.2 mmol)
and cyclohexene oxide led to a mixture of pyrazoles 5
and 8 (5.44 g, 95%, 5:8=10:1 according to NMR and
GC–MS).
4.9. (1S,2S)-2-((3bS,4aR)-3,4,4-Trimethyl-3b,4,4a,5-tet-
rahydrocyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)-
cyclohexanol 5a
1
147 (98), 132 (7), 105 (100), 77 (54), 41 (13). H NMR
(CCl4–CDCl3, 200 MHz): 2.05 s (3H-1), 2.48 d (J=
16.0, 1H-5a), 2.77 dd (J=16.0, 7.0, 1H-5b), 2.32 m
(1H), 1.1–1.71 m (5H), 1.75–2.1 m (4H), 3.96 m (1H-
11), 5.22 m (1H-12); aromatic protons: 7.25–7.50 m
(3H), 7.80–7.90 m (2H). 13C NMR (50 MHz): 12.28
(C-1), 149.34 (C-2), 124.72 (C-3), 141.33 (C-4), 23.69
(C-5), 33.77 (C-6), 25.99 (C-7), 21.98 (C-8), 26.11 (C-9),
13.33 (C-10), 62.06 (C-11), 74.49 (C-12), 31.41 (C-13),
23.69 (C-14), 24.61 (C-15), 31.20 (C-16), 164.55 (CꢁO),
aromatic carbons: 127.67 d (2C), 129.34 d (2C), 130.20
s (1C), 132.15 d (1C).
Saponification of benzoate 9a (2.9 g, 8.0 mmol) led to
5a (2.0 g, 96%) as white crystals with mp 138–140°C
(MeCN). [h]2D5=+102 (c 1.0, CHCl3). MS (m/z, %):
260.18886 (M+, 35%, C16H24N2O, requires 260.18885);
245 (73), 227 (28), 217 (3), 189 (3), 175 (30), 163 (55),
147 (100), 133 (7), 120 (3), 106 (8), 91 (7), 81 (9), 65 (3),
55 (3), 45 (4). IR (CHCl3) w/cm−1 3592, 3346, 1551,
1518; 1485, 1451; 1432, 1373, 1333, 1291, 1262, 1215;
1173, 1121, 1072, 1045, 982. IR (CHCl3) w/cm−1 3592
1
(OꢀH). UV (EtOH) umax/nm 238 (m 5300). H NMR
(500 MHz, CDCl3): 2.14 (s, 3H-1), 2.52 (ddd, J=16.8,
1.1, 1.1, 1H-5a), 2.75 (dd, J=16.8, 7.0, 1H-5b), 1.67
4.11.1. Crystal data for 9a. C23H28N2O2, M=364.47,
monoclinic, space group P21, a=5.8010(8), b=

2880
S. A. Popo6 et al. / Tetrahedron: Asymmetry 12 (2001) 2875–2881
,
18.834(2), c=9.541(1) A, i=95.77(1)°, V=1037.1(2)
127.71 d (2C), 128.55 d (2C), 135.50 s (1C), 139.98 s
(1C). IR, UV, and MS data were identical to those of 4.
3
A , Z=2, Dcalcd=1.167 g cm−3, v=0.074 mm−1,
,
F(000)=392, crystal size 0.19×0.38×1.10 mm. Absorp-
tion corrections were applied by integration method
(min. and max. transmission 0.93–0.99) for 1859 mea-
sured intensities (q<25°) of which 1581 were considered
as observed (I>2|). Data/restraints/parameters: 1859/1/
246. Goodness-of-fit on F2: 1.028. Final R indices
[I>2|(I)]: R1=0.0469, wR2=0.1254. R indices (all
data): R1=0.0558, wR2=0.1344. Absolute structure
parameter: 2(2). Extinction coefficient: 0.004(4). The
positions of hydrogen atoms were refined using riding
model. C(1) methyl group is disordered with occupation
factors 40:60. Crystallographic data (excluding struc-
ture factors) for the structure 9a have been deposited
with the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 172663.
Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge,
CB2 1EZ, UK [fax: +44(0)-1223-336033 or e-mail:
deposit@ccdc.cam.ac.uk].
4.13.1. Crystal data for 4a. C24H26N2O, M=358.47,
orthorhombic, space group P212121, a=5.867(1), b=
3
,
,
13.713(2), c=25.385(4) A, V=2042.5(6) A , Z=4,
D
calcd=1.166 g cm−3, v=0.071 mm−1, F(000)=768,
crystal size 0.08×0.09×2.30 mm. Of 2081 measured
intensities with q<25° 1510 were considered observed
(I>2|). No absorption corrections were applied, min.
and max. transmission 0.85–0.99. Data/restraints/
parameters: 2081/0/251. Goodness-of-fit on F2: 1.040.
Final R indices [I>2|(I)]: R1=0.0451, wR2=0.1073. R
indices (all data): R1=0.0688, wR2=0.1224. Absolute
structure parameter: 1(3). Extinction coefficient:
0.0079(17). The positions of hydrogen atoms were
refined using riding model. Crystallographic data
(excluding structure factors) for the structure 4a have
been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication number
CCDC 172662. Copies of the data can be obtained, free
of charge, on application to CCDC, 12 Union Road,
Cambridge, CB2 1EZ, UK [fax: +44(0)-1223-336033 or
e-mail: deposit@ccdc.cam.ac.uk].
4.12. Diastereomeric mixture of (1R,2S)-1,2-diphenyl-2-
((3bS,4aR)-3,4,4-trimethyl-3b,4,4a,5-tetrahydrocyclo-
propa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)ethanol and
(1S,2R)-1,2-diphenyl-2-((3bS,4aR)-3,4,4-trimethyl-
3b,4,4a,5-tetrahydrocyclopropa[3,4]cyclopenta[1,2-
c]pyrazol-1-yl)ethanol 4
4.14. (1R,2S)-1,2-Diphenyl-2-((3bS,4aR)-3,4,4-trimethyl-
3b,4,4a,5-tetrahydrocyclopropa[3,4]cyclopenta[1,2-c]-
pyrazol-1-yl)ethanol 4b
Mp 109–111°C (MeCN). [h]2D1=−39 (c 1.59, CHCl3); 1H
NMR (CCl4–CDCl3, 200 MHz): 2.23 (s, 3H-1), 2.17–
2.24 (m, 2H-5), 1.53 (m, 1H-6), 1.69 (d, J=7.0, 1H-7),
1.02 (s, 3H-9), 0.59 (s, 3H-10), 4.84 (d, J=3.5, 1H-11),
5.63 (d, J=3.5, 1H-12), 5.55 (br.s (OH)); aromatic
protons: 6.74–6.79 (m, 2H), 7.04–7.16 (m, 8H). 13C
NMR (50 MHz): 12.70 (C-1), 151.68 (C-2), 125.43
(C-3), 142.03 (C-4), 23.65 (C-5), 26.72 (C-6), 34.50
(C-7), 22.31 (C-8), 26.52 (C-9), 13.90 (C-10), 69.39
(C-11), 75.13 (C-12), aromatic carbons: 126.82 d (2C),
127.28 d (1C), 127.56 d (3C), 127.74 d (2C), 128.69 d
(2C), 136.13 s (1C), 140.41 s (1C). IR, UV and MS data
were identical to those of 4.
Treatment of diketone 1 (1.3 g, 7.9 mmol) with 1,2-
diphenyl-2-hydroxyethyl hydrazine 2a resulted in a mix-
ture of diastereomers 4 (1.4 g, 50%, 4a:4b=1:1
according to NMR and GC–MS) as pale yellow crys-
tals. IR (CHCl3) w/cm−1 3327 (OH). UV (EtOH) umax
/
nm 240 (m 4360). MS (m/z, %): 358.20457 (M+, 2%,
C24H26N2O, requires 358.20450), 325 (10), 308 (2), 284
(2), 251 (100), 237 (4), 221 (5), 209 (6), 194 (3), 175 (33),
147 (13), 117 (4), 105 (11), 91 (15), 77 (15), 65 (3), 51
(2).
Double crystallization of 4 (100 mg, 0.28 mmol)
resulted in 4a (11 mg, 11%) as white crystals, while
column chromatography of 4 gave 4a (36% yield) and
4b (26%).
4.15. (1S,2R)-Benzoic acid-1,2-diphenyl-2-((3bS,4aR)-
3,4,4-trimethyl-3b,4,4a,5-tetrahydrocyclopropa[3,4]cyclo-
penta[1,2-c]pyrazol-2-yl)ethyl ester 6
4.13. (1S,2R)-1,2-Diphenyl-2-((3bS,4aR)-3,4,4-trimethyl-
3b,4,4a,5-tetrahydrocyclopropa[3,4]cyclopenta[1,2-c]-
pyrazol-1-yl)ethanol 4a
Treatment of 4 (100 mg, 0.28 mmol) with benzoyl
chloride followed by crystallization of the crude
product from MeCN led to 6 (36 mg, 28%) as white
crystals with mp 155°C (MeCN, dec.) and [h]2D1=+119
(c 0.5, CHCl3). MS (m/z, %): 462.2313 (M+, 3%,
C31H30N2O2, requires 462.2307), 447 (2), 325 (10), 284
(2), 251 (100), 235 (4), 209 (4), 179 (4), 146 (5), 105 (40),
77 (20), 57 (4). IR (CHCl3) w/cm−1 1723 (CꢁO). 1H
NMR (400 MHZ, CDCl3): 2.13 (s, 3H-1), 2.03 (ddd,
J=16.5, 1.3, 1.3, 1H-5a), 2.56 (dd, J=7.0, 16.2, 1H-
5b), 1.48 (ddd, J=7.0, 6.3, 1.3, 1H-6), 1.58 (dd, J=6.3,
1.3, 1H-7), 0.92 (s, 3H-9), −0.01 (s, 3H-10), 5.25 (d,
J=10.0, 1H-11), 6.86 (d, J=10.0, 1H-12); aromatic
protons: 7.11–7.22 (m, 4H), 7.24–7.32 (m, 4 H), 7.38–
Mp 159–160°C (MeCN), [h]2D1=+298 (c 1.34, CHCl3).
1H NMR (400 MHz, CDCl3): 2.24 (s, 3H-1), 1.87 (d,
J=17.0, 1H-5a), 2.47 (dd, J=17.0, 7.0 1H-5b), 1.56
(dd, J=7.0, 7.0, 1H-6), 1.75 (dd, J=7.0, 1.3, 1H-7),
0.97 (s, 3H-9), 0.36 (s, 3H-10), 4.92 (d, J=3.0, 1H-11),
5.69 (d, J=3.0, 1H-12); aromatic protons: 6.66–6.79
2H, 6.95–7.15 (m, 8H). 13C NMR (100 MHz): 12.71
(C-1), 151.41 (C-2), 125.49 (C-3), 141.63 (C-4), 23.62
(C-5), 26.27 (C-6), 34.13 (C-7), 21.95 (C-8), 26.40 (C-9),
13.48 (C-10), 68.77 (C-11), 74.83 (C-12), aromatic car-
bons: 126.70 d (2C), 127.28 d (3C), 127.47 d (1C),

S. A. Popo6 et al. / Tetrahedron: Asymmetry 12 (2001) 2875–2881
2881
7.45 (m, 3H), 7.76 (m, 2H). 13C NMR (100 MHz):
References
12.70 (C-1), 150.61 (C-2), 124.90 (C-3), 142.70 (C-4),
23.35 (C-5), 26.30 (C-6), 33.93 (C-7), 22.04 (C-8), 26.31
(C-9), 13.20 (C-10), 68.10 (C-11), 75.98 (C-12),
164.43 (CꢁO), aromatic carbons: 127.12 d (2C), 128.05
d (1C), 128.09 d (2C), 128.17 d (2C), 128.27 d (3C),
128.31 d (2C), 129.46 d (2C), 130.08 s (1C), 132.65 d
(1C), 137.58 s (1C), 138.39 s (1C).
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Acknowledgements
The authors thank the Russian Foundation for Basic
Research (Grant No. 01-03-32369) and INTAS
(Grant No. 97-0217) for financial support of this
work.