Preparation of chiral hydroxy carbonyl compounds and diols by ozonolysis of olefinic isoborneol and fenchol derivatives: Characterization of stable ozonides by 1H-, 13C-, and 17O-NMR and electrospray ionization mass spectrometry

Article abstract of DOI:10.1002/(SICI)1522-2675(19990908)82:9<1385::AID-HLCA1385>3.0.CO;2-Y

The allylic and homoallylic alcohols 1-8, prepared from (+)-camphor and (-)-fenchone, were ozonized in Et₂O at -78°and treated with Et₃N or LiAIH₄ to give the chiral hydroxy carbonyl compounds 9-16 and the diols 17- 24, respectively (Scheme 1). In the case of the diols 19 and 24, the formation of new chiral centers proceeded with high diastercoselectivity. These diols were prepared highly diastereoselectively also by LiAIH₄ reduction of the hydroxy carbonyl compounds 11 and 16a, respectively (Scheme 2). The absolute configuration of the new chiral centers in 19 and 24 was determined by X-ray and NMR methods. The ozonization of compounds 2, 3, 7, and 8 provided the relatively stable hydroxy-substituted 1,2,4-trioxolane derivatives (ozonides) 37-40 (Scheme 5) which were characterized by ¹H- and ¹³C-NMR spectra, ESI-MS, and natural-abundance ¹⁷O-NMR spectra.

Full text of DOI:10.1002/(SICI)1522-2675(19990908)82:9<1385::AID-HLCA1385>3.0.CO;2-Y

Helvetica Chimica Acta ± Vol. 82 (1999)
1385
Preparation of Chiral Hydroxy Carbonyl Compounds and Diols by Ozonolysis
of Olefinic Isoborneol and Fenchol Derivatives:
Characterization of Stable Ozonides by 1H-, 13C-, and 17O-NMR and
Electrospray Ionization Mass Spectrometry
by Kalina Kostovaa), Vladimir Dimitrova)*, Svetlana Simovaa), and Manfred Hesseb)*
a) Institute of Organic Chemistry, Bulgarian Academy of Sciences, BG-1113 Sofia
b) Organisch-chemisches Institut, Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich
The allylic and homoallylic alcohols 1 ± 8, prepared from (‡)-camphor and ( )-fenchone, were ozonized in
Et2O at 788 and treated with Et3N or LiAlH4 to give the chiral hydroxy carbonyl compounds 9 ± 16 and the
diols 17 ± 24, respectively (Scheme 1). In the case of the diols 19 and 24, the formation of new chiral centers
proceeded with high diastereoselectivity. These diols were prepared highly diastereoselectively also by LiAlH4
reduction of the hydroxy carbonyl compounds 11 and 16a, respectively (Scheme 2). The absolute configuration
of the new chiral centers in 19 and 24 was determined by X-ray and NMR methods. The ozonization of
compounds 2, 3, 7, and 8 provided the relatively stable hydroxy-substituted 1,2,4-trioxolane derivatives
(ozonides) 37 ± 40 (Scheme 5) which were characterized by 1H- and 13C-NMR spectra, ESI-MS, and natural-
abundance 17O-NMR spectra.
Introduction. ± The cleavage of CˆC bonds by ozone is a very convenient route for
the preparation of carbonyl compounds or alcohols depending on the reducing reagent
used in a second step [1]. The ozonolysis of alkenes has been carried out in various
solvents, e.g., MeOH [2], CH2Cl2 [3], AcOEt [4], as well as other solvents [1]. For the
synthesis of alcohols, LiAlH4 and NaBH4 have been usually applied in the second step.
Dimethyl sulfide (Me2S) has been suggested as the most convenient reagent for the
preparation of carbonyl compounds [1], although other agents, e.g., Et3N or Ph3P, have
been reported to provide excellent results [5][6]. The mechanism formulated by
Criegee (formation of a relatively unstable primary ozonide which is cleaved into a
carbonyl compound and a carbonyl oxide, followed by recombination to the more
stable normal ozonide) [7] to describe the ozonolysis of alkenes in aprotic solvents has
been widely accepted, though some details are not completely understood, thus the
object of further investigations [8][9]. Normal ozonides, which have been recognized
as 1,2,4-trioxolanes by Rieche et al. in 1942 [10] have, in recent years, received increased
attention in studies on their stability, reactivity, and structure [6][11].
The addition of vinyl and allyl Grignard reagents to (‡)-(1R)-camphor and ( )-
(1R)-fenchone provided the corresponding allylic and homoallylic alcohols, which are
suitable for ozonolytic cleavage, in high yields on a multigram scale [12]. We have
preliminarily communicated about the ozonolysis of four camphor- and fenchone-
derived homoallylic alcohols which gave, after reduction with LiAlH4, chiral 1,3-diols
in high yields [13]. In continuation of our studies concerning the preparation of
functionalized optically active compounds based on transformations of camphor and
fenchone derivatives [14], we report here the synthesis of new hydroxy carbonyl

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Helvetica Chimica Acta ± Vol. 82 (1999)
compounds and diols, as well as the isolation of stable 1,2,4-trioxolanes (so-called
normal ozonides).
Results and Discussion. ± The ozonolysis of the alcohols 1 ± 8 (Scheme 1) was
carried out in Et2O at 788. The reduction occurred with Et3N or LiAlH4 to give, in
high yields, the hydroxy carbonyl compounds 9 ± 16 and the diols 17 ± 24, respectively. It
is interesting to note that the hydroxy aldehydes 9 and 14 were also formed without
treatment with Et3N directly after the ozonization of 1 and 6, respectively; however the
Et3N treatment is highly recommended since in this case, the products obtained are of
higher purity.1)
The crude hydroxy carbonyl compounds 9 ± 16 were isolated in very good purities.
This is important for further transformations, since the hydroxy aldehydes are unstable
on standing ± compounds 9 and 12 ± 14 decomposed significantly to unidentified
compounds within several hours. The aldehydes 10 and 15, which are more stable
(decomposition within 3 ± 4 weeks), were best purified by bulb-to-bulb distillation
rather than by flash chromatography (FC) because of the higher yields thus realized.
During chromatography and on prolonged contact with silica gel, compound 10
eliminated H2O to give (1,7,7-trimethylbicyclo[2.2.1]hept-2-ylidene)acetaldehyde (25;
see below, Scheme 2)2) as a by-product. The ketones 11 and 16a are stable, but not so
the isomer 16b which decomposed within several weeks. It must be pointed out that the
starting alcohols with the fenchone skeleton were endo/exo-isomeric mixtures 92 :8 for
6 and 7 and 82 :18 for 8. The minor isomers 14b and 15b (with an exo-OH group) could
be observed in the 13C-NMR spectra (content ca. 5%) of the isolated hydroxy
aldehydes 14 and 15 only. It was not possible to isolate them in pure form by FC. The
isomeric hydroxy ketones, 16a and 16b, were separated by FC.
The treatment of the solutions of ozonized compounds 1 ± 8 with LiAlH4 at 788,
followed by slow warming to room temperature and hydrolytic workup, provided the
diols 17 ± 24, which were isolated, after FC or recrystallization, in high yields.
Interestingly, in the crude 17 and 22, significant quantities of isoborneol and endo-
fenchol, respectively, were observed (17/isoborneol 85 : 15, 22/endo-fenchol 85 : 15; by
1H-NMR). A small amount of endo-fenchol was also isolated on chromatography of
diol 24. In the case of diols 23 and 24, the corresponding exo-OH isomers were only
detected as impurities by 13C-NMR, without quantification. Contrarily, in the 13C-NMR
spectrum of 22, signals of the minor exo-OH isomer 22b (content ca. 8%) could be
unambigously assigned (Table 1). Consequently, the minor exo-OH isomers of the diols
23 and 24 are probably not stable and, therefore, could only be detected as impurities.
The diols 19 and 24 were obtained diastereoselectively with respect to the newly
formed chiral center. Compound 19 (diastereoisomer ratio in the crude product: 19a/
19b 75 : 25 by 1H-NMR) was separated into the individual diastereoisomers by
chromatography. Moreover, diastereoisomer 19a could be enriched to a ratio 19a/19b
88 : 12 by a single recrystallization of the crude product from hot hexane. The (2'R)-
configuration1) of 19a was determined by an X-ray crystal-structure analysis; however,
the quality of the crystals of 19a did not allow an exact structure determination
1
)
)
Arbitrary or trivial numbering; for systematic names, see Exper. Part.
For spectral data of 25, see Table 1 and Exper. Part.
2

Helvetica Chimica Acta ± Vol. 82 (1999)
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Helvetica Chimica Acta ± Vol. 82 (1999)
concerning bond lengths and angles. The diol 24 was isolated as a single diaste-
reoisomer demonstrating an extraordinarily high diastereoselectivity of the LiAlH4
reduction of the ozonized 8.
Table 1. 13C-NMR Chemical Shifts (CDCl3, 300 K, d in ppm from SiMe4) of Compounds 9 ± 25 and 31. Tentative
assignments are marked with asterisks; for the numbering (arbitrary or trivial1)) of the C-atoms, see Schemes1,
2, and 4
C(1) C(2)
C(3)
C(4) C(5) C(6) C(7) C(8) C(9) C(10) C(1')
C(2')
C(3')
9
53.00
52.36
52.22
52.68
52.67
84.42 41.54
80.00 46.24
79.30 47.20
80.69 47.80
83.29 46.07
85.81 44.95
84.98 47.24
81.82 43.81
79.84 47.15
81.55 44.32
81.95 45.34
80.63 44.70
82.87 46.16
45.08 27.05 29.74 50.07 20.30 18.91 10.34 205.58
±
±
±
10
11
12
13
44.96 26.65 30.59 48.53 21.20 20.83 10.18
45.03 26.84 30.47 48.73 21.46 20.96 10.52
52.64
50.81
204.07
211.39 31.49
56.32 11.98
53.69 11.68
±
±
205.35
204.83
213.65 31.12
213.12 31.51
44.78 27.39 30.03 49.86 21.34 20.86 10.04 206.10
44.03 27.04 30.14 49.91 21.16 20.95 10.45 206.78
47.89 25.28 29.06 40.34 26.58 22.65 15.75 205.95
45.20 24.78 31.70 41.50 23.16 21.51 14.43 207.87
14a 52.07
14b 54.01
15a 52.01
15b 53.91
16a 52.05
16b 52.76
±
±
±
±
49.23 25.02 28.73 40.46 28.40 21.97 17.60
45.14 24.75 31.64 41.44 23.13 21.48 14.42
49.76 25.35 28.83 40.65 27.97 22.29 17.80
49.44 25.76 30.50 41.03 25.79 24.13 16.62
43.52 26.90 29.98 49.53 21.07 20.22 11.16
44.94 26.84 30.40 49.23 21.37 20.95 10.63
48.99
45.48
48.02
43.89
68.65
39.81
48.49*
45.60*
67.22
66.17
65.55
63.13
36.93
42.66
17
18
51.04
52.35
±
±
±
60.81
19a 52.11
19b 52.63
20
21
22a 50.92
22b 51.28
23
24
25
31
81.74 48.99* 44.74 27.00 30.44 49.98 21.26 20.88 11.77
83.04 44.87* 45.08 26.82 30.36 48.92 21.52 21.02 10.20
66.85 24.80
66.37 24.68
43.42 13.72
41.35 13.86
±
±
52.62
52.64
84.20 47.31
84.23 47.16
80.13 43.40
81.11 44.81
82.60 44.25
81.31 45.32
44.61 27.56 29.76 50.27 21.44 21.04 12.23
44.43 27.64 29.53 50.51 21.48 21.27 12.22
49.26 25.06 30.13 41.15 26.04 22.38 17.37
48.97 25.45 30.27 41.81 25.67 22.66 16.88
49.86 24.86 29.98 40.88 28.01 22.61 17.95
48.77 25.19 29.86 41.28 27.65 21.87 18.63
±
±
±
52.72
53.34
61.26
65.63 23.96
191.76
103.25 52.72
53.76 179.61 35.42
52.17 79.07 47.09
44.21 27.21 33.99 47.84 19.48 18.53 12.04 119.10
44.90 26.97 30.36 49.40 21.28 20.97 11.02 41.13
±
The diols 19 and 24 were prepared also by LiAlH4 reduction of the ketones 11 and
16a, respectively (Scheme 2), with reproduction of the diastereoselectivities observed
on application of the ozonization/reduction procedure described above. Thus, the ratio
19a/19b was 75 :25, and diol 24 was obtained as a single diastereoisomer. Surprisingly,
the LiAlH4 reduction of compounds 11 and 16a provided significant quantities of
isoborneol and endo-fenchol, respectively (19/isoborneol 75 :25, 24/endo-fenchol
68 :32; by 1H-NMR). For the newly formed chiral center in diol 24, we have previously
proposed (2'R)-configuration1) [13]; however, this assumption was incorrect. The (2'S)-
1
configuration1) could now be established on the basis of the measured vicinal H,1H-
coupling constants, distance constraints (NOE measurements), and force-field
calculations, taking into account the known (1R)-configuration of the fenchone
skeleton. Only the diastereoisomer with (2'S)-configuration1) is compatible with the
experimental evidence, as illustrated in Scheme 2.

Helvetica Chimica Acta ± Vol. 82 (1999)
1389
Scheme 2
We tried further to use 16a synthetically for reaction with lithiated ferrocene3),
expecting that the addition to the carbonyl moiety would occur smoothly, resulting in
the formation of the ferrocene derivatives 26 and 27 (Scheme 3). Surprisingly, after the
reaction with the ferrocenyllithium reagent, which proceeded with quantitative
conversion of 16a, only the ferrocene derivatives 28 and 29 were isolated (27 and
14% yield, resp., after FC). The compounds 28 and 29 have been previously prepared
by the addition of lithiated ferrocene to cerium(III) chloride-activated fenchone [14a].
The formation of isoborneol and endo-fenchol from 11 and 16a (Scheme 2) and the
ferrocene derivatives 28 and 29 from 16a (Scheme 3) leads to the assumption that
during the reduction with LiAlH4 or the addition of the ferrocenyllithium reagent,
respectively, the ketones camphor and fenchone were probably formed in situ.
Therefore, we submitted (‡)-camphor and ( )-fenchone to reduction with LiAlH4 and
obtained, indeed quantitatively, isoborneol (containing 5% borneol) and endo-fenchol
(containing 10% exo-fenchol). However, (‡)-camphor and ( )-fenchone did not react
with the ferrocenyllithium reagent without the assistance of anhydrous CeCl3 [14a].
Moreover, it is not clear in which way the cleavage of the side chain in 11 or 16a with
formation of camphor and fenchone would occur. The investigation of these problems
is planned in further experiments.
The choice of Et2O as solvent for the ozonolysis of 1 ± 8 and the reagents Et3N or
LiAlH4 for the preparation of compounds 9 ± 16 and 17 ± 24, respectively, presented in
3
)
The ferrocenyllithium reagent was prepared by lithiation of ferrocene with BuLi ´ TMEDA (Cp2Fe/BuLi/
TMEDA 1 : 2.2 : 1.2; TMEDA ˆ N,N,N',N'-tetramethylethylenediamine); the ratio (LiCp)2Fe/Li(Cp)-
Fe(Cp) 30 : 1 was determined by the procedure described in [14a].

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Helvetica Chimica Acta ± Vol. 82 (1999)
Scheme 3
Scheme 1, was caused by interesting observations (see Scheme 4). We found that the
ozonolysis of 2 in the presence of MeOH, followed by treatment with Me2S, produced
only the dimethyl acetal 31 (Scheme 4, Entry 1). It has previously been described
[6e][7][15 ± 17] that the ozonolysis of olefins in MeOH generate a-methoxyalkyl
hydroperoxides as intermediates like 30, which afford, after suitable workup, aldehydes
or their dimethyl acetals, depending on the propensity towards acetalization. We found
further that Me2S was unable to react completely with the ozonized 2, 3, and 7, giving
only small amounts of the hydroxy carbonyl compounds 10, 11, and 15, respectively,
even after extended reaction times (up to 48 h); the unreacted ozonides remained as
main products after workup of the reaction mixtures (Entry 2, Scheme 4). A similar
observation has been reported [6a]. The third surprising aspect was observed with
NaBH4 as reducing reagent (Entry 3): instead of the diol 18, we isolated, after
ozonolysis of 2 followed by NaBH4 reduction and hydrolytic workup (2n HCl), a
1
mixture of two boron-containing compounds 32 and 33 (1:2 ratio; by H-NMR). The
presence of B-atoms was established by standard chemical analysis. Moreover, in the
mass spectra (EI-MS, CI-MS, and ESI-MS; see Exper. Part) of the mixture, the
molecular-ion peaks for compounds 32 and 33 with the corresponding isotope patterns
1
could be identified. The H-NMR spectra are rather complicated and change with
temperature. They indicate the presence of O
B O six-membered rings. It is
important to note that the NMR spectra of 32/33 were recorded in C6D6; indeed, when
1
using CDCl3 solutions, especially the H signals rather then the 13C signals of the two
different bicyclic moieties were heavily overlapped.
The attempts to hydrolyze the mixture 32/33 with conc. HCl solution were success-
ful, yielding the products 35 and 36, which were isolated and analyzed (see Exper. Part).
Thus, under acidic conditions and in the presence of boron as a Lewis acid, the
elimination of H2O to 35 and the rearrangement to 36, obviously via the carbonium ion

Helvetica Chimica Acta ± Vol. 82 (1999)
1391
Scheme 4
34, is preferred. We have recently reported [14c,d] a similar behavior of compounds
containing the camphor skeleton.
In view of the observation described in Entry 2 (Scheme 4), we ozonized
compounds 2, 3, 7, and 8 and worked the reaction mixtures up without prior treatment
by the reduction reagent (Scheme 5). In the case of the unsubstituted homoallylic
alcohols 2 and 7, the crude reaction mixtures after ozonolysis contained the
corresponding ozonides 37 (diastereoisomer mixture 37a/37b 71:29) and 39 (diaster-
eoisomer mixture 39a/39b 47:53), besides the hydroxy aldehydes 10 (4%) and 15
(10%) respectively. The diastereoisomeric ozonide resulting from the exo-OH isomer
of 7 could not be observed. The ozonides 37a, 37b, 39a, and 39b could be isolated as
individual diastereoisomers by FC. Compounds 37 and 39 decomposed slowly over
several days giving a mixture of unidentified products and small amounts of aldehydes
10 and 15, respectively.
The ozonolysis of compound 3 gave nearly pure ozonide 38 as crude product. The
ratio of the diastereoisomers 38a/38b, concerning the newly formed chiral center of the
trioxolane ring, was 75 :25. This ratio corresponds to that observed for the diols 19a/19b
prepared after reduction of ozonized 3 with LiAlH4. The diastereoisomers 38a and 38b
could not be separated by column chromatography. The ozonide 38 is quite stable,
remaining unchanged after several months at room temperature.
After the ozonolysis of the homoallylic alcohol 8 without reductive workup, the
crude reaction mixture was rather complicated. The following compounds could be

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Helvetica Chimica Acta ± Vol. 82 (1999)
Scheme 5
isolated by FC: a mixture of the ozonides 40b/40c (ratio 66 :34; yield 8%), a mixture of
the ozonides 40b/40c/40d (ratio 29 :11:60; 8%), ozonide 40a as a single diaste-
reoisomer (16%), ketone 16b (5%), and ketone 16a (29%). Therefore, in this case, we
could observe all four diastereoisomeric ozonides resulting from endo-OH isomer 8a
and exo-OH-isomer 8b. A significant amount of the ozonides decomposed during the
reaction, giving the hydroxy ketones 16a and 16b, similarly to the observations made in
the case of the ozonolysis of compounds 1 and 6, as described above. The isolation of
only one diastereoisomeric diol 24 (Scheme 1) after LiAlH4 reduction of ozonized 8
means that the formation of 24 proceeds in two steps via primary generation of the
hydroxy ketone 16a from ozonides 40a/b. Actually, we demonstrated in Scheme 2 that
16a was reduced with LiAlH4 completely diastereoselectively to diol 24.
The ozonides 37 ± 40 were characterized by NMR and ESI mass spectra (see Table2
and Exper. Part). For ozonide 38, it was possible to obtain the natural-abundance 17O-
NMR spectrum (see Scheme 5). The chemical shifts for the ether O-atom and for
the peroxide O-atoms are comparable with the data observed recently for several
different ozonides [11c]. The chemical nonequivalence of the two peroxide O-atoms
in the unsymmetrically substituted trioxolane, confirmed the observation by Gries-
baum et al. [11c] that this nonequivalence can be caused also by hydrocarbon
substituents and not only by electron-withdrawing heteroatom substituents. It was
not possible to differentiate between the diastereoisomers 38a/b because of the
considerable linewidth of the 17O-signals (2000 Hz for the peroxide and 1300 Hz for the
ether signals). Comparing the 17O-chemical shifts with literature data for cyclic

Helvetica Chimica Acta ± Vol. 82 (1999)
1393
Table 2. 13C-NMR Chemical Shifts (CDCl3, 300 K, d in ppm relative to SiMe4) of Ozonides 37 ± 40. Tentative
assignments are marked with asterisks; for the numbering (arbitrary or trivial1)) of the C-atoms, see Scheme 5.
C(1) C(2) C(3) C(4) C(5) C(6) C(7) C(8)
C(9)
C(10) C(3') C(5') C(6') C(7')
37a 52.44 79.65 46.33 44.99 26.90 30.54 49.23 21.36 21.06 10.60 102.59 93.76 41.00
37b 52.63 79.57 45.88 45.12 26.87 30.51 49.01 21.45 21.09 10.32 102.76 93.86 40.20
±
±
38a 53.35 78.85 47.11 45.23 26.85 29.72 48.15 23.58 21.31 9.91
38b 53.09 79.00 47.11 45.23 26.80 29.84 48.23 23.90 21.36 9.91
110.53 93.67 43.89 20.92
110.53 93.17 44.50 20.92
39a 52.57 79.36 44.30 49.63 24.97 29.83 40.89 27.88 22.17 17.75 102.71 93.56 37.96
39b 52.68 79.64 44.30 49.91 24.91 29.79 40.78 27.94 22.13 17.67 102.77 93.73 37.30
±
±
40a 53.05 80.78 44.60 50.07 25.13 29.87 40.51 28.75 21.16 18.53 110.38 93.01 39.78 26.23
40b 53.31 80.49 44.43 50.03 25.05 29.85 40.54 28.58 21.33 18.22 110.30 94.20 38.75 26.14
40c 54.13 80.38 45.19 49.31 25.67 29.65 40.59 25.40* 25.10* 15.93 110.25 93.95 36.02 25.00*
40d 53.88 80.51 45.37 49.35 25.73 29.64 40.61 25.40* 25.12* 15.97 110.34 93.26 37.19 24.80*
peroxides [18], it is possible to propose a relatively low C
O O C dihedral angle in
the trioxolane ring, because of the relatively high d values for the peroxide O-atoms
of 38.
In conclusion, we demonstrated a very convenient way to prepare of new chiral,
diastereoisomerically pure hydroxy carbonyl compounds and diols via ozonolysis of
allylic and homoallylic alcohols having camphor and fenchone skeletons. These chiral
compounds can be prepared on a multigram scale, being thus of practical interest for
further transformations and applications.
We thank Dr. A. Linden, Dr. D. Rentsch, Dr. L. Bigler, and N. Bild, Organisch-chemisches Institut der
Universität Zürich, for X-ray analysis of compound 19a, for the 17O-NMR spectra, for the ESI-MS, and for EI-
and CI-MS, respectively. Support of the Bulgarian National Fund for Scientific Research (project X-711) and of
the Swiss National Science Foundation is gratefully acknowledged.
Experimental Part
General. The alcohols (1R,2S)-2-ethenyl-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol, (1), (1R,2R)-1,7,7-tri-
methyl-2-(prop-2-enyl)bicyclo[2.2.1]heptan-2-ol (2), (1R,2S)-1,7,7-trimethyl-2-(2-methylprop-2-enyl)bicyclo-
[2.2.1]heptan-2-ol (3), (1R,2S)-1,7,7-trimethyl-2-[(1R)- and (1S)-1-methylprop-2-enyl]bicyclo[2.2.1]heptan-2-
ol (4 and 5, resp.), (1R,2R)-2-ethenyl-1,3,3-trimethylbicyclo[2.2.1]heptan-2-ol (6), (1R,2R)-1,3,3-trimethyl-2-
(prop-2-enyl)bicyclo[2.2.1]heptan-2-ol (7), and (1R,2R)- and (1R,2S)-1,3,3-trimethyl-2-(2-methylprop-2-enyl)-
1,3,3-trimethylbicyclo[2.2.1]heptan-2-ol (8a and 8b, resp.; ratio 82 :18) were prepared according to [12]. The org.
solvents were distilled prior to use. Ozonolysis: ozone generator 502 Fischer (3 ± 5 g O3/h). TLC: precoated
silica gel 60 F254 plates (Merck); visualization by irradiation with UV light or by Ce(SO4)2/phosphomolybdic
acid soln. Flash chromatography (FC): silica gel Merck 60 (0.040 ± 0.063 mm). M.p.: Mettler FP-5/FP-52. Optical
1
rotation: Perkin-Elmer-241 polarimeter. IR Spectra (CHCl3): Perkin-Elmer 781; nÄ in cm 1. H- and 13C-NMR
Spectra (300 K): Bruker-AC-300, Bruker-ARX-300, Bruker DRX-250, Bruker AM-400, or Varian XL-200
spectrometer; d in ppm rel. to Me4Si (ˆ 0 ppm), J in Hz; unless stated otherwise, CDCl3 soln.; C-multiplicities
were assigned by DEPT techniques. 17O-NMR Spectra: Bruker AMX-600, 81.37 MHz, d in ppm rel. to external
water, number of scans 102400, pulse angle 13 ms, relaxation delay 20 ms, spectral width 62.5 kHz, 4 K time-
domain points, transformed to spectrum size 32 K, exponential multiplication with a broadening factor of
400 Hz. EI- (70 eV) and CI-MS (NH3 as reactant gas): Finnigan MAT 90 or Finnigan SSQ 700; fragment ions in
m/z with rel. intensities (%) in parenthesis. ESI-MS: Finnigan MAT TSQ 700.
General Procedure (GP) for the Ozonolysis of Alcohols 1 ± 8. A flow of ozonized oxygen was bubbled (G2
frit) through a soln. of the corresponding alcohol at 788 until appearance of blue color indicated an excess of
O3. After blowing out the excess of O3 with dry N2, the corresponding reducing reagent (Et3N or LiAlH4) was
introduced at 788 and the mixture allowed to warm to r.t. and stirred for 1 h at r.t. Workup: a) when treated
with Et3N, the reaction mixture was washed with 1n HCl, 5% aq. NaHCO3 soln., and H2O, dried (MgSO4), and

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Helvetica Chimica Acta ± Vol. 82 (1999)
evaporated; b) when treated with LiAlH4, the reaction mixture was hydrolyzed (2n HCl), washed with 5% aq.
NaHCO3 soln. and H2O, dried (MgSO4), and evaporated. For removing the last traces of the solvent, the
isolated compounds were properly dried under high vacuum (oil pump).
(1R,2R)-2-Hydroxy-1,7,7-trimethylbicyclo[2.2.1]heptane-2-carbaldehyde (9). Following the GP, 1 (0.16 g,
0.89 mmol) in Et2O (20 ml) was ozonized and then treated with Et3N (0.20 g, 1.98 mmol): 0.16g (quant.) of pure
(by TLC and NMR) 9. Colorless oil. IR: 3500 br. (OH), 2960, 2870, 2740 (CHO), 1715 (CˆO), 1490, 1450,
1390, 1355, 1315, 1245, 1145, 1120, 1080, 980, 940. 1H-NMR (ARX-300)1): 9.66 (s, H C(1')); 3.56 (s, OH); 2.00
(dt, J ˆ 13.4, 3.6, Hexo C(3)); 1.93 ± 1.81 (m, Hendo C(3), H C(4), Hexo C(5)); 1.63 ± 1.53 (m, Hexo C(6));
1.46 ± 1.42 (m, Hendo C(6)); 1.39 ± 1.28 (m, Hendo C(5)); 1.11 (s, Me(8)); 0.87 (s, Me(9)); 0.82 (s, Me(10)). CI-
‡
‡
MS: 200 (28, [M ‡ 18] ), 183 (11, [M ‡ 1] ), 170 (40), 108 (31), 95 (100).
(1R,2S)-2-Hydroxy-1,7,7-trimethylbicyclo[2.2.1]heptane-2-acetaldehyde (10). Following the GP, 2 (2.01 g,
10.34 mmol) in Et2O (35 ml) was ozonized and then treated with Et3N (2.10 g, 20.75 mmol): crude 10 (1.91 g)
of satisfactory purity (by TLC and NMR). The crude product was chromatographed (1.7 Â 49 cm column,
silica gel (49 g), hexane/Et2O 5 : 1) to give 0.11 g of 25 (as a result of H2O elimination on silica gel) and 1.57 g
(77%) of 10 as colorless oil. After bulb-to-bulb distillation of the crude 10 at 3 ´ 10 2 Torr/1108, the yield was
86%.
Data of 10: [a]D21
ˆ
1.4 (c ˆ 4.41, CHCl3). IR: 3640 (free, OH), 3520 (br., OH), 2960, 2880, 2740 (CHO),
1715 (CˆO), 1490, 1455, 1390, 1370, 1315, 1245, 1145, 1120, 1085, 985, 940, 905. 1H-NMR (AC-300)1): 9.90
(dd, J ˆ 2.6, 1.1, H C(2')); 2.71 (dd, J ˆ 16.1, 2.6, Ha C(1')); 2.59 (dd, J ˆ 16.1, 1.1, Hb C(1')); 2.38 (s, OH);
2.20 (dt, J ˆ 13.4, 3.8, Hexo C(3)); 1.79 (t, J ˆ 4.2, H C(4)); 1.78 ± 1.67 (m, Hexo C(5)); 1.56 (d, J ˆ 13.4,
Hendo C(3)); 1.52 ± 1.22 (m, 2 H C(6)); 1.12 (s, Me(8)); 1.12 ± 0.95 (m, Hendo C(5)); 0.87 (s, Me(9)); 0.86
.
‡
‡
‡
(s, Me(10)). CI-MS: 214 (49, [M ‡ 18] ), 196 (12, M ), 179 (100, [M OH] ). Anal. calc. for C12H20O2
(196.29): C 73.43, H 10.27; found: C 73.21, H 10.19.
Data of [(1R)-1,7,7-Trimethylbicyclo[2.2.1]hept-2-ylidene]acetaldehyde (25): 1H-NMR (AC-300)1):
9.79 (d, J ˆ 7.7,
H
C(2')); 5.74 (dt, J ˆ 7.9, 2.2,
H
C(1')); 2.81 (br. d, J ˆ 18.0, Hexo C(3)); 2.39
(dd, J ˆ 18.0, 2.1, Hendo C(3)); 1.88 (t, J ˆ 4.1, H C(4)); 1.81 ± 1.65 (m, Hexo C(5), Hexo C(6)); 1.27 ±
1.14 (m, Hendo C(6)); 0.92 (s, Me(8)); 0.92 ± 0.76 (m, Hendo C(5)); 0.89 (s, Me(9)); 0.71 (s, Me(10)). EI-MS:
.
‡
‡
‡
178 (79, M ), 163 (44, [M Me] ), 135 (100, [M CH2CHO] ).
1-[(1R,2S)-2-Hydroxy-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]propan-2-one (11). Following the GP,
3
(12.21 g, 58.62 mmol) in Et2O (140 ml) was ozonized and then treated with Et3N (12 g, 118.58 mmol): 12.27 g
2
of crude 11 (pure by NMR). Bulb-to-bulb distillation at 3 ´ 10 Torr/1008 provided 10.73 g (87%) of 11.
Colorless crystals. M.p. 46.2 ± 47.58. [a]2D1
ˆ
47.0 (c ˆ 3.95, CHCl3). IR: 3500 (br., OH), 2980, 2950, 2880, 1700
(CˆO), 1490, 1455, 1390, 1365, 1330, 1300, 1240, 1165, 1120, 1080, 995. 1H-NMR (AC-300)1): 3.73 (s, OH); 2.72
(d, J ˆ 17.1, Ha C(1')); 2.54 (d, J ˆ 17.1, Hb C(1')); 2.14 (s, Me(3')); 2.09 (dt, J ˆ 13.3, 3.7, Hexo C(3)); 1.68 ±
1.58 (m, H C(4), Hexo C(5)); 1.48 ± 1.15 (m, 2 H C(6)); 1.29 (d, J ˆ 13.3, Hendo C(3)); 1.06 (s, Me(8));
‡
0.96 ± 0.84 (m, Hendo C(5)); 0.78 (s, Me(9), Me(10)). CI-MS: 193 (23, [(M OH] ), 95 (100). Anal. calc. for
C13H22O2 (210.32): C 74.24, H 10.54; found: C 74.39, H 10.54.
(S)-2-[(1R,2S)-2-Hydroxy-1,7,7-trimethylbicyclo[2.1.1]hept-2-yl]propanal (12). Following the GP,
4
(0.15 g, 0.72 mmol) in Et2O (15 ml) was ozonized and then treated with Et3N (0.16 g, 1.58 mmol): 0.15 g (quant.)
of 12. Colorless oil (pure by TLC and NMR). On standing, 12 decomposed significantly within 3 ± 4 h (hence no
elemental analysis and optical rotation). IR: 3510 (br., OH), 2960, 2880, 2740 (CHO), 1715 (CˆO), 1480, 1455,
1
1390, 1360, 1310, 1240, 1140, 1120, 1085, 980, 940, 905. H-NMR (ARX-300)1): 9.77 (d, J ˆ 1.4, H C(1')); 2.57
(q, J ˆ 7.3, H C(2')); 2.29 (s, OH); 2.27 (dt, J ˆ 13.2, 3.8, Hexo C(3)); 1.82 ± 1.71 (m, H C(4), Hexo C(5));
1.60 (d, J ˆ 13.2, Hendo C(3)); 1.56 ± 1.45 (m, Hexo C(6)); 1.39 ± 1.31 (m, Hendo C(6)); 1.20 (d, J ˆ 7.3, Me(3'));
.
‡
1.10 (s, Me(8)); 1.10 ± 1.01 (m, Hendo C(5)); 0.96 (s, Me(10)); 0.85 (s, Me(9)). EI-MS: 210 (3, M ), 192 (3,
.
‡
[M H2O] ), 153 (10), 122 (8), 110 (16), 109 (15), 108 (17), 96 (9), 95 (100), 81 (8), 69 (18), 67 (7), 55 (11),
41 (20).
(R)-2-[(1R,2S)-2-Hydroxy-1,7,7-trimethylbicyclo[2.1.1]hept-2-yl]propanal (13). Following the GP,
5
(0.09 g, 0.43 mmol) in Et2O (15 ml) was ozonized and then treated with Et3N (0.10 g, 0.99 mmol): 0.09 g (quant.)
of 13. Colorless oil (pure by TLC and NMR). On standing, 13 decomposed significantly within 3 ± 4 h (hence no
elemental analysis and optical rotation). IR: 3520 (br., OH), 2960, 2880, 2740 (CHO), 1715 (CˆO), 1480, 1450,
1380, 1360, 1315, 1230, 1145, 1120, 1085, 980, 930, 905. 1H-NMR (ARX-300)1): 9.91 (d, J ˆ 2.8, H C(1')); 2.69 ±
2.60 (m, H C(2')); 1.96 (dt, J ˆ 13.2, 3.7, Hexo C(3)); 1.81 ± 1.69 (m, H C(4), Hexo C(5)); 1.55 ± 1.39 (m, 2
H
C(6)); 1.43 (d, J ˆ 13.2, Hendo C(3)); 1.18 (d, J ˆ 7.4, Me(3')); 1.12 ± 0.97 (m, Hendo C(5)); 1.08 (s, Me(8));
. .
‡ ‡
0.85 (s, Me(9)); 0.82 (s, Me(10)). EI-MS: 210 (3, M ), 192 (2, [M H2O] ), 153 (12), 151 (9), 110 (16), 109
(17), 108 (21), 107 (7), 96 (9), 95 (100), 93 (8), 81 (10), 69 (21), 55 (11), 43 (9), 41 (19).

Helvetica Chimica Acta ± Vol. 82 (1999)
1395
(1R,2R)- and (1R,2S)-2-Hydroxy-1,3,3-trimethylbicyclo[2.2.1]heptane-2-carbaldehyde (14a and 14b, resp.).
Following the GP, 6 (0.17 g, 0.94 mmol) in Et2O (15 ml) was ozonized and then treated with Et3N (0.21 g,
2.08 mmol): 0.17 g (quant.) of pure (by TLC and NMR) 14a as colorless oil (containing 5% of 14b). IR: 3520
(br., OH), 2960, 2880, 2735 (CHO), 1715 (CˆO), 1480, 1455, 1380, 1365, 1310, 1255, 1110, 1080, 1010, 990.
1H-NMR (ARX-300)1): 9.70 (s, H C(1')); 3.39 (br. s, OH); 2.11 ± 2.07 (m, Hsyn C(7)); 2.01 ± 1.92
(m, Hendo C(6)); 1.82 ± 1.71 (m, H C(4), Hendo C(5)); 1.53± 1.39 (m, Hexo C(5)); 1.36 ± 1.32 (m, Hanti C(7));
‡
1.03 ± 0.80 (m, Hexo C(6)); 0.97 (s, Me(10)); 0.86 (s, Me(8)); 0.85 (s, Me(9)). CI-MS: 183 (5, [M ‡ 1] ), 153
(17), 109 (7), 81 (100). Anal. calc. for C11H18O2 (182.26): C 72.49, H 9.95; found: C 72.57, H 9.82.
(1R,2R)- and (1R,2S)-2-Hydroxy-1,3,3-trimethylbicyclo[2.2.1]heptane-2-acetaldehyde (15a and 15b, resp.).
Following the GP, 7 (2.01 g, 10.34 mmol) in Et2O (35 ml) was ozonized and then treated with Et3N (2.10 g,
2
20.75 mmol): 1.93 g of crude 15 with satisfactory purity (by TLC and NMR). Bulb-to-bulb distillation (3 ´ 10
Torr/908) gave 1.80 g (88%) of 15a as colorless oil (containing 5% 15b). [a]2D1
ˆ
4.6 (c ˆ 3.84, CHCl3). IR:
3520 (br., OH), 2960, 2880, 2840, 2735 (CHO), 1715 (CˆO), 1475, 1465, 1390, 1375, 1310, 1270, 1240, 1115,
1085, 1060, 1010, 990. 1H-NMR (ARX-300)1): 10.03 (d, J ˆ 1.5, H C(2')); 3.36 (s, OH); 2.81 (dd, J ˆ 18.0, 1.5,
Ha C(1')); 2.52 (d, J ˆ 17.6, Hb C(1')); 2.06 ± 2.00 (m, Hendo C(6)); 1.77 ± 1.66 (m, H C(4), Hendo C(5));
1.52 ± 1.38 (m, Hexo C(5), Hsyn C(7)); 1.15 ± 0.92 (m, Hexo C(6), Hanti C(7)); 1.01 (s, Me(10)); 1.00
.
.
‡
‡
(s, Me(8)); 0.92 (s, Me(9)). EI-MS: 196 (20, M ), 181 (15), 178 (25, [M H2O] ), 153 (6), 125 (8), 114
(29), 113 (11), 83 (6), 82 (11), 81 (100), 70 (20), 69 (41), 55 (12), 41 (32). Anal. calc. for C12H20O2 (196.29):
C 73.43, H 10.27; found: C 73.15, H 10.38.
1-[(1R,2R)- and (1R,2R)-2-Hydroxy-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]propan-2-one (16a and 16b,
resp.). Following the GP, 8 (13.05 g, 62.65 mmol) in Et2O (150 ml) was ozonized and then treated with Et3N
(12.68 g, 125.30 mmol): 13.12 g of crude 16. The crude product was chromatographed (3.5 Â 100 cm column,
silica gel (310 g) hexane/Et2O 30 :1 ! 15 : 1): 0.24 g of 16b (oil), 3.24 g of mixed fractions, and 8.28 g of 16a
(oil). Total yield of 16: 11.76 g (89%).
Data of 16a: [a]D21 ˆ‡ 11.2 (c ˆ 4.04, CHCl3). IR: 3480 (br., OH), 2980, 2880, 1703 (CˆO), 1465, 1406,
1375, 1362, 1326, 1171, 1080, 995. 1H-NMR (ARX-300)1): 4.52 (s, OH); 2.82 (d, J ˆ 17.8, Ha C(1')); 2.43 (d, J ˆ
17.8, Hb C(1')); 2.21 (s, Me(3')); 2.20 ± 2.07 (m, Hendo C(6)); 1.76 ± 1.61 (m, H C(4), Hendo C(5)); 1.54 ± 1.32
(m, Hexo C(5), Hsyn C(7)); 1.11 ± 1.07 (m, Hanti C(7)); 1.02 ± 0.85 (m, Hexo C(6)); 0.99 (s, Me(10)); 0.99
.
.
‡
‡
(s, Me(8)); 0.86 (s, Me(9)). EI-MS: 210 (13, M ), 195 (12), 192 (24, [M H2O] ), 152 (9), 128 (35), 127
(10), 109 (9), 85 (24), 82 (10), 81 (100), 80 (15), 70 (9), 69 (47), 67 (9), 55 (9), 43 (39), 41 (23). Anal. calc. for
C13H22O2 (210.32): C 74.24, H 10.54; found: C 74.30, H 10.40.
Data of 16b: [a]D21
ˆ
0.7 (c ˆ 1.84, CHCl3). IR: 3720 (OH, free), 3580 (br., OH), 3070, 2980, 1750 (CˆO),
1525, 1455, 1435, 1425, 1380, 1365, 1265, 1220, 1140, 1105, 930. 1H-NMR (ARX-300)1): 4.37 (s, OH); 2.92 (d, J ˆ
18.2, Ha C(1')); 2.46 (d, J ˆ 18.2, Hb C(1')); 2.20 (s, Me(3')); 2.09 ± 2.04 (m, Hsyn C(7)); 1.61 ± 1.52
(m, H C(4), Hendo C(5)); 1.42 ± 1.18 (m, Hexo C(5), 2 H C(6)); 1.06 (s, Me(10)); 1.02 (s, Me(8)); 0.99 ±
0.96 (m, Hanti C(7)); 0.84 (s, Me(9)).
(1R,2R)-2-(Hydroxymethyl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (17). Following the GP, 1 (0.36 g,
2.00 mmol) in Et2O (15 ml) was ozonized and then treated with LiAlH4 (0.35 g, 9.22 mmol): 0.34 g of crude 17
(17/isoborneol 85 :15; by NMR). The crude product was chromatographed (1.3 Â 43 cm column, silica gel
(19 g), hexane/Et2O 2 : 1): 0.06 g of isoborneol and 0.27 g (74%) of 17 as colorless crystals.
Data of Isoborneol (ˆ(1R,2R)-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-ol): 1H-NMR (ARX-300)1): 3.55
(dd, J ˆ 6.4, 3.9, H C(2)); 1.68 ± 1.53 (m, 2 H C(3), H C(4), Hexo C(5), OH); 1.45 ± 1.39 (m, Hexo C(6));
0.96 ± 0.87 (m, Hendo C(5), Hendo C(6)); 0.95 (s, Me(8)); 0.83 (s, Me(10)); 0.75 (s, Me(9)). 13C-NMR
(75 MHz): 79.51 (C(2)); 48.76 (C(1)); 46.14 (C(7)); 44.87 (C(4)); 40.22 (C(3)); 33.82 (C(6)); 27.09 (C(5));
20.35 (Me(8)); 20.01 (Me(9)); 11.27 (Me(10)).
Data of 17: M.p. 191 ± 1928 (hexane/Et2O). [a]2D1
ˆ
3.0 (c ˆ 4.05, CHCl3). IR (CCl4): 3620 (OH, free),
3450 (br., OH), 2940, 2866, 1450, 1390, 1370, 1350, 1276, 1120, 1083, 1066, 1050, 976. H-NMR (ARX-300)1):
3.59 (dd, J ˆ 10.6, 3.5, Ha C(1')); 3.44 (dd, J ˆ 10.6, 5.6, Hb C(1')); 2.13 (s, OH); 1.87 (dt, J ˆ 13.1, 3.7,
Hexo C(3)); 1.85 (s, OH); 1.73 ± 1.61 (m, H C(4), Hexo C(5)); 1.43 ± 1.20 (m, 2 H C(6)); 1.28 (d, J ˆ 13.1,
Hendo C(3)); 1.05 (s, Me(8)); 1.00 ± 0.89 (m, Hendo C(5)); 0.86 (s, Me(10)); 0.78 (s, Me(9)). EI-MS: 184 (5,
1
.
‡
M
), 153 (47), 135 (7), 110 (16), 109 (13), 108 (18), 97 (9), 96 (9), 95 (100), 93 (13), 69 (20), 67 (7), 55 (13),
43 (10), 41 (16). Anal. calc. for C11H20O2 (184.28): C 71.70, H 10.94; found: C 71.82, H 10.87.
(1R,2S)-(2-Hydroxyethyl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (18). Following the GP,
2 (1.53 g,
7.87 mmol) in Et2O (40 ml) was ozonized and then treated with LiAlH4 (1.37 g, 36.05 mmol): 1.52 g of crude
18. Recrystallization from hexane gave 1.28 g (82%) of 18. Colorless crystals. M.p. 55.0 ± 55.28. [a]D21 ˆ‡ 10.1
(c ˆ 3.65, CHCl3). IR: 3600 (OH, free), 3440 (br., OH), 2990, 2950, 2880, 1490, 1455, 1430, 1390, 1375, 1275,

1396
Helvetica Chimica Acta ± Vol. 82 (1999)
1145, 1115, 1080, 1025, 1000, 940. 1H-NMR (ARX-300)1): 4.00 ± 3.83 (m, 2 H C(2')); 2.66 (s, OH); 2.41
(s, OH); 2.07 (dt, J ˆ 13.2, 3.7, Hexo C(3)); 1.92 ± 1.83 (m, Ha C(1')); 1.76 ± 1.61 (m, H C(4), Hexo C(5),
Hb C(1')); 1.46 (d, J ˆ 13.2, Hendo C(3)); 1.43 ± 1.37 (m, 2 H C(6)); 1.10 (s, Me(8)); 1.01 ± 0.93
.
‡
‡
(m, Hendo C(5)); 0.90 (s, Me(10)); 0.86 (s, Me(9)). CI-MS: 216 (3, [M ‡ 18] ), 198 (11, M ). 181 (100,
.
‡
[M OH] ). Anal. calc. for C12H22O2 (198.31): C 72.68, H 11.18; found: C 72.73, H 11.00.
(1R,2S)-2-[(2R)- and (2S)-2-Hydroxypropyl]-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (19a and 19b, resp.).
Following the GP, 3 (5.12 g, 24.58 mmol) in Et2O (100 ml) was ozonized and then treated with LiAlH4 (3.74 g,
98.42 mmol): 5.11 g of crude 19a/19b 3 :1 (by NMR). The crude product was chromatographed (4.2 Â 72 cm
column, silica gel (430 g), hexane/Et2O 4 : 1): 0.93 g of 19b, 1.42 g of mixed fractions, and 2.45 g of 19a. Yield of
19: 4.80 g (92%).
Data of 19a: Colorless crystals from hexane/Et2O. M.p. 104.0 ± 104.58. [a]2D1
ˆ
0.8 (c ˆ 3.92, CHCl3). IR:
3600 (OH, free), 3460 (br., OH), 2960, 2880, 1490, 1455, 1430, 1390, 1375, 1295, 1240, 1150, 1115, 1085, 940, 910.
1H-NMR (ARX-300)1): 4.28 ± 4.17 (m, H C(2')); 3.03 (s, OH); 2.51 (s, OH); 2.01 (dt, J ˆ 13.2, 3.8,
Hexo C(3)); 1.78 ± 1.57 (m, H C(4), Hexo C(5), 2 H C(1')); 1.49 ± 1.26 (m, Hendo C(3), 2 H C(6)); 1.18
(d, J ˆ 6.2, Me(3')); 1.07 (s, Me(8)); 1.03 ± 0.95 (m, Hendo C(5)); 0.98 (s, Me(10)); 0.83 (s, Me(9)). CI-MS: 230
.
‡
‡
‡
(48, [M ‡ 18] ), 212 (88, M ), 195 (100, [M OH) ). Anal. calc. for C13H24O2 (212.33): C 73.54, H 11.39;
found: C 73.81, H 11.31.
Data of 19b: Colorless crystals from hexane/Et2O. M.p. 57.2 ± 57.88. [a]D21 ˆ‡ 16.2 (c ˆ 4.02, CHCl3).
1H-NMR (ARX-300)1): 4.19 ± 4.10 (m, H C(2')); 3.72 (s, OH); 2.81 (s, OH); 2.06 (dt, J ˆ 13.3, 3.3,
Hexo C(3)); 1.75 ± 1.56 (m, H C(4), Hexo C(5), Ha C(1')); 1.46 ± 1.33 (m, Hendo C(3), 2 H C(6),
Hb C(1')); 1.18 (d, J ˆ 6.2, Me(3')); 1.08 (s, Me(8)); 0.98 ± 0.87 (m, Hendo C(5)); 0.83 (s, Me(9), Me(10)).
(1R,2S)-2-[(1R)-2-Hydroxy-1-methylethyl]-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (20). Following the
GP, 4 (0.21 g, 1.01 mmol) in Et2O (15 ml) was ozonized and then treated with LiAlH4 (0.16 g, 4.21 mmol).
The crude product was chromatographed (1.3 Â 22 cm column, silica gel (8 g), hexane/Et2O 5 : 1): 0.15 g (71%)
of 20. Colorless solid. M.p. 59 ± 618 (hexane/Et2O). [a]2D1
ˆ
1.4 (c ˆ 4.00, CHCl3). IR: 3626 (OH, free), 3466
1
(br., OH); 2940, 2873, 1480, 1450, 1383, 1150, 1106, 1073, 980, 960. H-NMR (DRX-250)1): 4.05 (dd, J ˆ 11.0,
3.3, Ha C(1')); 3.65 (dd, J ˆ 11.0, 3.5, Hb C(1')); 2.57 (br. s,OH); 2.35 (s, OH); 2.14 (dt, J ˆ 13.2, 3.8,
Hexo C(3)); 1.77 ± 1.57 (m, H C(4), Hexo C(5),
H
C(2')); 1.54 (d, J ˆ 13.2, Hendo C(3)); 1.48 ± 1.41
(m, 2 H C(6)); 1.15 (d, J ˆ 7.0, Me(3')); 1.07 (s, Me(8)); 1.07 ± 0.98 (m, Hendo C(5)); 0.96 (s, Me(10)); 0.83
.
.
‡
‡
(s, Me(9)). EI-MS: 212 (3, M ), 194 (0.6, [M H2O] ), 180 (3), 171 (4), 153 (12), 121 (10), 110 (16), 109
(24), 108 (41), 96 (10), 95 (100), 93 (12), 83 (12), 81 (15), 69 (33), 67 (12), 59 (11), 55 (17), 43 (13), 41 (28).
Anal. calc. for C13H24O2 (212.33): C 73.54, H 11.39; found: C 73.69, H 11.18.
(1R,2S)-2-[(1S)-2-Hydroxy-1-methylethyl]-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (21). Following the GP,
5 (0.18 g, 0.86 mmol) in Et2O (15 ml) was ozonized and then treated with LiAlH4 (0.13 g, 3.42 mmol). The crude
product was chromatographed (1.3 Â 22 cm column, silica gel (8 g), hexane/Et2O 5 : 1): 0.12 g (67%) of 21.
Colorless solid. M.p. 89 ± 908 (hexane/Et2O). [a]D21 ˆ‡ 24.0 (c ˆ 4.00, CHCl3). IR: 3627 (OH, free), 3463 (br.,
OH), 2933, 2876, 1480, 1450, 1390, 1366, 1106, 1076, 963. 1H-NMR (DRX-250)1): 4.13 (dt, J ˆ 10.6, 3.4,
Ha C(1')); 3.63 (ddd, J ˆ 10.6, 5.3, 2.3, Hb C(1')); 2.72 (s, OH C(2)); 2.22 (dd, J ˆ 5.3, 4.1, OH C(1')); 1.89
(dt, J ˆ 13.2, 4.2, Hexo C(3)); 1.80 ± 1.64 (m, H C(4), Hexo C(5), H C(2')); 1.54 ± 1.37 (m, 2 H C(6)); 1.42
(d, J ˆ 13.2, Hendo C(3)); 1.17 (d, J ˆ 7.0, Me(3')); 1.06 (s, Me(8)); 1.03 (s, Me(10)); 1.04 ± 0.95
.
.
‡
‡
(m, Hendo C(5)); 0.84 (s, Me(9)). EI-MS: 212 (8, M ), 194 (2, [M H2O] ), 153 (17), 110 (15), 109 (17),
108 (43), 102 (9), 96 (8), 95 (100), 93 (12), 83 (9), 81 (11), 69 (20), 67 (9), 55 (14), 43 (12), 41 (23). Anal. calc.
for C13H24O2 (212.33): C 73.54, H 11.39; found: C 73.68, H 11.22.
(1R,2R)- and (1R,2S)-2-(Hydroxymethyl)-1,3,3-trimethylbicyclo[2.2.1]heptan-2-ol (22a and 22b, resp.).
Following the GP, 6 (0.30 g, 1.66 mmol) in Et2O (15 ml) was ozonized and then treated with LiAlH4 (0.30 g;
7.89 mmol): 0.31 g of crude 22/endo-fenchol 85 :15 (by NMR). The crude product was chromatographed (1.3 Â
43 cm column, silica gel (25 g), hexane/Et2O 2 : 1): 0.05 g of endo-fenchol and 0.23 g (74%) of 22a as colorless
crystals (containing 8% of the exo-OH isomer 22b). Recrystallization from hexane gave 0.07 g of pure endo-OH
isomer 22a.
Data of endo-Fenchol (ˆ(1R,2R)-1,3,3-Trimethylbicyclo[2.2.1]heptan-2-ol): 1H-NMR (300 MHz)1): 3.27
(s, Hexo C(2)); 1.70 ± 1.60 (m, H C(4), Hendo C(6), OH); 1.49 ± 1.37 (m, 2 H C(5), Hsyn C(7)); 1.15 ± 1.07
(m, Hanti C(7)); 1.09 (s, Me(10)); 1.05 ± 0.98 (m, Hexo C(6)); 0.99 (s, Me(8)); 0.86 (s, Me(9)). 13C-NMR
(75 MHz): 84.98 (C(2)); 49.05 (C(1)); 47.85 (C(4)); 40.90 (C(7)); 38.98 (C(3)); 30.61 (Me(8)); 25.99 (C(6));
25.01 (C(5)); 20.07 (Me(9)); 19.35 (Me(10)).
Data of 22a: M.p. 99 ± 1008 (hexane). [a]2D1
ˆ
14.7 (c ˆ 4.01, CHCl3). IR (CCl4): 3626 (OH, free), 3450
(br., OH), 2943, 2863, 1466, 1450, 1383, 1363, 1116, 1083, 1050, 970. 1H-NMR (DRX-250)1): 3.71 (dd, J ˆ 10.8,

Helvetica Chimica Acta ± Vol. 82 (1999)
1397
5.4, Ha C(1')); 3.61 (dd, J ˆ 10.8, 4.6, Hb C(1')); 2.38 (br. s, OH); 2.11 (br. s, OH); 2.05 ± 1.93
(m, Hendo C(6)); 1.78 ± 1.67 (m, Hendo C(5)); 1.63 ± 1.57 (m, H C(4), Hsyn C(7)); 1.48 ± 1.36 (m, Hexo C(5));
1.15 ± 0.94 (m, Hexo C(6), Hanti C(7)); 1.09 (s, Me(10)); 1.02 (s, Me(8)); 0.97 (s, Me(9)). CI-MS: 202 (9, [M ‡
.
‡
‡
‡
18] ), 184 (10, M ), 167 (42, [M OH] ), 153 (25), 81 (100). Anal. calc. for C11H20O2 (184.28): C 71.70,
H 10.94; found: C 71.66, H 10.86.
(1R,2R)-2-(2-Hydroxyethyl)-1,3,3-trimethylbicyclo[2.2.1]heptan-2-ol (23). Following the GP, 7 (1.12 g;
5.76 mmol) in Et2O (40 ml) was ozonized and then treated with LiAlH4 (0.88 g; 23.16 mmol). Recrystallization
(hexane) of the crude product gave 1.02 g (89%) of 23. Colorless crystals. M.p. 70.6 ± 71.38. [a]2D1
ˆ
23.5 (c ˆ
4.20, CHCl3). IR: 3620 (OH, free), 3440 (br., OH), 2950, 2880, 1465, 1415, 1390, 1370, 1245, 1165, 1115, 1060,
1020, 850. 1H-NMR (AC-300)1): 3.89 ± 3.84 (m, 2 H C(2')); 2.58 (br. s, OH); 2.39 (br. s, OH); 1.93 ± 1.78
(m, 2 H C(1'), Hendo C(6)); 1.74 ± 1.62 (m, H C(4), Hendo C(5)); 1.57 ± 1.52 (m, Hsyn C(7)); 1.48 ± 1.37
(m, Hexo C(5)); 1.11 ± 1.00 (m, Hexo C(6), Hanti C(7)); 1.04 (s, Me(10)); 1.02 (s, Me(8)); 1.00 (s, Me(9)). CI-
.
‡
‡
‡
MS: 216 (3, [M ‡ 18] ), 198 (38, M ), 181 (100, [M OH] ). Anal. calc. for C12H22O2 (198.31): C 72.68,
H 11.18; found: C 72.71, H 11.14.
(1R,2R)-2-[(2S)-2-Hydroxypropyl]-1,3,3-trimethylbicyclo[2.2.1]heptan-2-ol (24). Following the GP,
8
(7.00 g, 33.61 mmol) in Et2O (130 ml) was ozonized and then treated with LiAlH4 (5.15g, 135.53 mmol). The
crude product was chromatographed (4.2 Â 83 cm column, silica gel (500 g), hexane/Et2O 2 : 1): 0.18 g of endo-
fenchol and 5.60 g (79%) of 24 as colorless crystals. M.p. 68.8 ± 69.98 (hexane). [a]D21 ˆ‡ 5.8 (c ˆ 4.00, CHCl3).
IR: 3610 (OH, free), 3460 (br., OH), 2960, 2880, 1465, 1415, 1375, 1290, 1165, 1120, 1105, 1085, 1070, 995, 930,
840. 1H-NMR (DRX-250)1): 4.19 (m, H C(2')); 2.77 (s, 2 OH); 1.93 ± 1.52 (m, H C(4), Hendo C(5),
Hendo C(6), Hsyn C(7)); 1.82 (dd, J ˆ 15.1, 9.3, Ha C(1')); 1.62 (dd, J ˆ 15.2, 1.3, Hb C(1')); 1.50 ± 1.36
(m, Hexo C(5)); 1.20 ± 0.91 (m, Hexo C(6), Hanti C(7)); 1.17 (d, J ˆ 6.2, Me(3')); 1.07 (s, Me(10)); 0.98
.
‡
‡
‡
(s, Me(8)); 0.91 (s, Me(9)). CI-MS: 230 (46, [M ‡ 18] ), 212 (100, M ), 195 (82, [M OH] ). Anal. calc. for
C13H24O2 (212.33): C 73.54, H 11.39; found: C 73.35, H 11.19.
(1R,2S)-2-(2,2-Dimethoxyethyl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (31). According to a modified GP,
2 (1.00 g, 5.15 mmol) in MeOH/CH2Cl2 1:1 (30 ml) was ozonized and then treated with Me2S (0.64 g,
10.30 mmol). Then the mixture was washed with H2O and evaporated and the crude product chromatographed
(2.3  36 cm column, silica gel (55 g), hexane/Et2O 10 : 1): 0.81 g (65%) of 31. Colorless oil. [a]D21 ˆ‡ 0.7 (c ˆ
4.10, CHCl3). IR: 3480 (br., OH), 2990, 2940, 2870, 2830, 1485, 1455, 1385, 1370, 1290, 1240, 1190, 1115, 1100,
1075, 1040, 990. 1H-NMR (AC-300)1): 4.69 (t, J ˆ 5.7, H C(2')); 3.61 (s, OH); 3.35 (s, 2 MeO); 2.03 (dt, J ˆ
13.0, 3.7, Hexo C(3)); 1.87 (dd, J ˆ 14.3, 5.9, Ha C(1')); 1.80 (dd, J ˆ 14.3, 5.5, Hb C(1')); 1.73 ± 1.63
(m, H C(4), Hexo C(5)); 1.45 ± 1.25 (m, 2 H C(6)); 1.36 (d, J ˆ 13.0, Hendo C(3)); 1.06 (s, Me(8)); 1.01 ±
.
‡
‡
0.90 (m, Hendo C(5)); 0.83 (s, Me(10)); 0.82 (s, Me(9)). EI-MS: 242 (6, M ), 225 (0.7, [M OH] ), 211 (26),
210 (100), 195 (98), 179 (29), 167 (25), 153 (16), 151 (21), 123 (9), 95 (21), 81 (18), 75 (58), 69 (24), 67 (20),
‡
59 (14), 58 (34), 55 (41). CI-MS: 225 (3, [M OH] ), 210 (22), 196 (80), 193 (100), 170 (91). ESI-MS: 507
‡
‡
([2M ‡ Na] ), 265 ([M ‡ Na] ). Anal. calc. for C14H26O3 (242.36): C 69.38, H 10.81; found: C 69.15,
H 10.71.
Ozonolysis of 2 and Reduction with NaBH4: Mixture of 2,2'-Oxybis[(1R,2S)-1,7,7-trimethylspiro[bicy-
clo[2.2.1]heptane-2,4'-[1,3,2]dioxaborinane] (32) and (1R,2S)-2'-Hydroxy-1,7,7-trimethylspiro[bicyclo[2.2.1]-
heptane-2,4'-[1,3,2]dioxaborinane] (33). According to a modified GP, 2 (1.00 g, 5.15 mmol) in Et2O (40 ml) was
ozonized and then treated with NaBH4 (0.68 g, 17.98 mmol). The mixture was allowed to warm to r.t., stirred for
1.5 h at r.t., then hydrolyzed (2n aq. HCl), washed with 5% aq. NaHCO3 soln. and H2O, dried (MgSO4), and
evaporated: 1.15 g of 32/33 1:2 (by 1H-NMR). Colorless crystalline solid. 1H-NMR (DRX-250, C6D6; only
1
some important signals are given) ) 3.86, 3.78 (2m, CH2O); 2.13, 2.03 (2dt, Hexo C(3) 1.42, 1.34 (2s, Me(8));
1.03, 0.95 (2s, Me(10)); 0.95, 0.92 (2s, Me(9)). 13C-NMR (AM-400, C6D6)1): 82.63, 82.38 (C(2)); 60.32, 60.28
(CH2CH2O); 52.34 (C(1)); 49.62 (C(7)); 46.34, 46.23 (C(3)); 45.45, 45.43 (C(4)); 33.75, 33.66 (CH2CH2O); 30.16
.
‡
(C(6)); 27.06, 27.02 (C(5)); 21.61 (Me(9)); 21.22, 21.18 (Me(8)); 10.49 (Me(10)). EI-MS: 430 (36, M of 32),
‡
‡
‡
223 (57, [M 1] of 33). CI-MS: 448 (60, [M ‡ 18] of 32), 242 (100, [M ‡ 18] of 33). ESI-MS: 499 ([M ‡
‡
‡
3 Na] of 32), 247 ([M ‡ Na] of 33).
Hydrolysis of Products 32/33. To a stirred soln. of 32/33 (0.70 g) in Et2O (30 ml), conc. aq. HCl soln. (10 ml)
was introduced. The mixture was vigorously stirred for 1.5 h and diluted with H2O (30 ml). After separation, the
aq. layer was extracted with Et2O (2 Â 20 ml), the combined Et2O phase washed with 5% aq. NaHCO3 soln. and
H2O, dried (MgSO4), and evaporated, and the crude product (0.57 g) chromatographed (2 Â 40 cm column,
silica gel (36 g), hexane/Et2O 10 : 1): 0.33 g of 35 and 0.12 g of 36 as colorless oils.
Data of 2-(1,7,7-Trimethylbicyclo[2.2.1]hept-2-ylidene)ethanol (35). H-NMR (AC-300)1): 5.25 (tt, J ˆ 7.9,
1
2.4, H C(1')); 4.03 (dd, J ˆ 10.9, 8.1, Ha C(2')); 3.97 (dd, J ˆ 10.9, 7.8, Hb C(2')); 2.37 (dq, J ˆ 16.5, 3.0,

1398
Helvetica Chimica Acta ± Vol. 82 (1999)
Hexo C(3)); 1.85 (dd, J ˆ 16.5, 2.1, Hendo C(3)); 1.76 ± 1.62 (m, H C(4), Hexo C(5)); 1.60 ± 1.53
(m, Hendo C(5)); 1.22-1.06 (m, 2 H C(6)); 0.86 (s, Me(10)); 0.83 (s, Me(9)); 0.66 (s, Me(8)). 13C-NMR
1
(XL-200; tentative assignments are marked with asterisks) ): 157.30 (C(2)); 112.45 (C(1')); 51.47 (C(1)); 47.69
(C(7)); 44.40 (C(4)); 42.29 (C(2')); 34.50* (C(3)); 33.91* (C(6)); 27.76 (C(5)); 19.51* (Me(8)); 18.79*
.
‡
‡
(Me(9)); 12.53 (Me(10)). CI-MS: 180 (8, M ), 163 (100, [M OH] ). Anal. calc. for C12H20O (180.29):
C 79.94, H 11.18; found: C 79.99, H 11.24.
Hexahydro-7,7,7a-trimethyl-3a,6-methano-3H-[1]benzofuran (36). 1H-NMR (AC-300): 4.00 ± 3.86
(m, 2 H C(2)); 1.97 ± 1.76 (m, 2 H C(3), Hsyn C(8)); 1.69 ± 1.25 (m, H C(6), 2 H C(4), 2 H C(5)); 1.01
(s, Me C(7a)); 0.97 overlapped (d, Hanti C(8)); 0.95 (s, Meb C(7)); 0.94 (s, 3 Mea C(7)). 13C-NMR (XL-
200): 90.68 (C(7a)); 66.37 (C(2)); 58.96 (C(3a)); 49.70 (C(6)); 44.87 (C(7)); 39.23 (C(8)); 28.68 (C(4)); 25.82
.
‡
(C(3)); 24.81 (Meb C(7)); 23.92 (C(5)); 23.19 (Mea C(7)); 17.03 (Me C(7a)). CI-MS: 180 (21, M ), 163
‡
(100, [M OH] ). Anal. calc. for C12H20O (180.29): C 79.94, H 11.18; found: C 80.01, H 11.23.
(1R,2S)-1,7,7-Trimethyl-2-[(1,2,4-trioxolan-3-yl)methyl]bicyclo[2.2.1]heptan-2-ol (37a/b; diastereoisomer
mixture). Following the GP, 2 (2.50 g, 12.87 mmol) in Et2O (40 ml) was ozonized. The mixture was warmed to
r.t., washed with 5% aq. NaHCO3 soln. and H2O, dried (MgSO4), and evaporated. The crude product
(diastereoisomer mixture 37a/37b 71:29 by NMR; it may contain up to 4% of aldehyde 10) was chromato-
graphed (3.2 Â 76 cm column, silica gel (250 g), hexane/Et2O 5 : 1): 1.66 g of 37a, 0.41 g of mixed fractions, and
0.26 g of 37b as colorless oils. Total yield of 37: 2.33 g (75%). IR (Film): 3540 (br., OH), 2960, 2880, 1490, 1455,
.
‡
‡
‡
1430, 1390, 1370, 1080. CI-MS: 260 (15, [M ‡ 18] ), 242 (10, M ), 225 (74, [M OH] ), 179 (100). ESI-MS:
‡
‡
281 ([M ‡ K] ), 265 ([M ‡ Na] ).
Data of 37a: [a]D21 ˆ‡ 19.0 (c ˆ 4.63, CHCl3). H-NMR (AC-300; tentative assignments are marked with
asterisks)1): 5.43 (t, J ˆ 5.2, H C(3')); 5.18 (s, Ha C(5')); 5.08 (s, Hb C(5')); 2.08 (s, OH); 2.07 (dt, J ˆ 13.4,
3.7, Hexo C(3)); 2.02 (dd, J ˆ 14.4, 4.8, Ha C(6')); 1.92 (dd, J ˆ 14.4, 5.6, Hb C(6')); 1.77 ± 1.68 (m, H C(4),
Hexo C(5)); 1.52 (d, J ˆ 13.4, Hendo C(3)); 1.47 ± 1.40* (m, Hendo C(6)); 1.35 ± 1.25* (m, Hexo C(6)); 1.09
(s, Me(8)); 1.09 ± 0.98 (m, Hendo C(5)); 0.88 (s, Me(10)); 0.86 (s, Me(9)).
1
Data of 37b: 1H-NMR (AC-300)1): 5.40 (t, J ˆ 4.9, H C(3')); 5.22 (s, Ha C(5')); 5.06 (s, Hb C(5')); 2.06
(dt, J ˆ 13.2, 3.7, Hexo C(3)); 1.99 (s, OH); 2.00 ± 1.87 (m, 2 H C(6')); 1.78 ± 1.66 (m, H C(4), Hexo C(5));
1.49 (d, J ˆ 13.2, Hendo C(3)); 1.51 ± 1.25 (m, 2 H C(6)); 1.10 (s, Me(8)); 1.06 ± 0.96 (m, Hendo C(5)); 0.88
(s, Me(10)); 0.86 (s, Me(9)).
(1R,2S)-1,7,7-Trimethyl-2-[(3-methyl-1,2,4-trioxolan-3-yl)methyl]bicyclo[2.2.1]heptan-2-ol (38a/b; diaste-
reoisomer mixture). Following the GP, 3 (0.53 g, 2.54 mmol) in Et2O (20 ml) was ozonized. The mixture was
warmed to r.t., washed with 5% aq. NaHCO3 soln. and H2O, dried (MgSO4), and evaporated. The crude product
(diastereoisomer mixture 38a/38b 3 :1 by 1H-NMR) was chromatographed (2 Â 45 cm column, silica gel (52 g),
hexane/Et2O 10 : 1): 0.45 g (69%) of pure 38 (diastereoisomer mixture). IR (Film): 3580 (br., OH), 2960, 2880,
1485, 1450, 1390, 1380, 1335, 1220, 1195, 1105, 1085, 1060, 970. 1H-NMR (ARX-300)1): 5.13 (s, Ha C(5'), 38a);
5.09 (s, Ha C(5'), 38b); 5.08 (s, Hb C(5'), 38a); 5.03 (s, Hb C(5'), 38b); 2.75 (s, OH, 38a); 2.39 (s, OH, 38b);
2.10± 1.94 (m, Hexo C(3)); 2.03 (d, J ˆ 14.3, Ha C(6')); 1.88 (d, J ˆ 14.3, Hb C(6')); 1.69 ± 1.55 (m, Hendo C(3),
H
C(4), Hexo C(5)); 1.53 (s, Me(7')); 1.34 ± 1.24 (m, 2 H C(6)); 1.05 (s, Me(8)); 0.99 ± 0.88 (m, Hendo C(5));
0.80 (s, Me(10)); 0.79 (s, Me(9)). 17O-NMR (81 MHz): 305.5, 271.8 (O(1), O(2)); 103.4 (O(4)); 45.8 (OH).
‡
‡
ESI-MS: 535 ([2M ‡ Na] ), 279 ([M ‡ Na] ). Anal. calc. for C14H24O4 (256.34): C 65.60, H 9.44; found:
C 65.90, H 9.47.
(1R,2R)-1,3,3-Trimethyl-2-[(1,2,4-trioxolan-3-yl)methyl]bicyclo[2.2.1]heptan-2-ol (39a/b diastereoisomer
mixture). Following the GP, 7 (2.00 g, 10.29 mmol) in Et2O (40 ml) was ozonized. The mixture was warmed to
r.t., washed with 5% aq. NaHCO3 soln. and H2O, dried (MgSO4), and evaporated. The crude product
(diastereoisomer mixture 39a/39b 47:53; it may contain up to 10% of aldehyde 15) was chromatographed
(3.2 Â 76 cm column, silica gel (235 g), hexane/Et2O 5 : 1): 0.32 g of 39a, 0.97 g of mixed fractions, and 0.43 g of
39b as colorless oils. Total yield of 39: 1.72 g (69%). IR (Film): 3520 (br., OH), 2950, 2880, 1465, 1425, 1390,
‡
1375, 1115, 1090, 1065, 1015, 965. ESI-MS: 281 ([M ‡ K] ).
Data of 39a: [a]D21 ˆ‡ 3.0 (c ˆ 4.37, CHCl3). IR: 3590 (br., OH), 2960, 2880, 1465, 1430, 1390, 1380, 1240,
1165, 1135, 1115, 1095, 1065, 1015, 960. 1H-NMR (AC-300)1): 5.40 (dd, J ˆ 5.0, 3.6,
H C(3')); 5.17
(s, Ha C(5')); 5.06 (s, Hb C(5')); 2.16 (dd, J ˆ 15.4, 3.6, Ha C(6')); 1.95 (dd, J ˆ 15.4, 5.0, Hb C(6')); 2.01 ±
1.91 (m, Hendo C(6)); 1.76 ± 1.65 (m, H C(4), Hendo C(5)); 1.71 (s, OH); 1.58 ± 1.54 (m, Hsyn C(7)); 1.49 ±
1.37 (m, Hexo C(5)); 1.15 ± 0.98 (m, Hexo C(6), Hanti C(7)); 1.05 (s, Me(10)); 1.03 (s, Me(8)); 0.98 (s, Me(9)).
Data of 39b: [a]D21
ˆ
4.0 (c ˆ 4.47, CHCl3). 1H-NMR (AC-300)1): 5.44 (dd, J ˆ 6.0, 3.1, H C(3')); 5.22
(s, Ha C(5')); 5.06 (s, Hb C(5')); 2.21 (s, OH); 2.09 (dd, J ˆ 15.0, 3.1, Ha C(6')); 2.06 ± 1.93 (m, Hendo C(6));

Helvetica Chimica Acta ± Vol. 82 (1999)
1399
1.92 (dd, J ˆ 15.0, 6.0, Hb C(6')); 1.76 ± 1.65 (m, H C(4), Hendo C(5)); 1.58 ± 1.54 (m, Hsyn C(7)); 1.48 ± 1.37
(m, Hexo C(5)); 1.15 ± 0.98 (m, Hexo C(6), Hanti C(7)); 1.04 (s, Me(10)); 1.03 (s, Me(8)); 0.98 (s, Me(9)).
(1R,2R)- and (1R,2S)-1,3,3-Trimethyl-2-[(3-methyl-1,2,4-trioxolan-3-yl)methyl]bicyclo[2.2.1]heptan-2-ol
(40a/b and 40c/d diastereoisomer mixtures). Following the GP, 8 (0.62 g, 2.98 mmol) in Et2O (20 ml) was
ozonized. The mixture was warmed to r.t., washed with 5% aq. NaHCO3 soln. and H2O, dried (MgSO4), and
evaporated. The crude product was chromatographed (2.0 Â 45 cm column, silica gel (52 g), hexane/Et2O 15 : 1):
0.06 g (8%) of 40b/40c 66 : 34 (by NMR), 0.06 g (8%) of 40b/40c/40d 29 : 11 : 60 (by NMR), 0.12 g (16%) of
40a (single diastereoisomer), 0.03 g (5%) of 16b, and 0.18 g (29%) of 16a.
Data of 40a: 1H-NMR (ARX-300)1): 5.17 (s, Ha C(5')); 5.15 (s, Hb C(5')); 2.60 (s, OH); 2.32 (d, J ˆ 15.2,
Ha C(6')); 2.18 ± 2.08 (m, Hendo C(6)); 2.11 (d, J ˆ 15.2, Hb C(6')); 1.75 ± 1.63 (m, H C(4), Hendo C(5));
1.55 (s, Me(7')); 1.48 ± 1.34 (m, Hexo C(5), Hsyn C(7)); 1.11 ± 0.94 (m, Hexo C(6), Hanti C(7)); 1.07
.
‡
(s, Me(10)); 1.02 (s, Me(8)); 0.99 (s, Me(9)). EI-MS: 210 (5, [M CH2OO] ), 192 (10), 128 (35), 81 (100),
‡
69 (48), ESI-MS: 279 ([M ‡ Na] ).
1
Data of 40b/40c. 1H-NMR (ARX-300, selected signals) ): 5.27 (s, Ha C(5'), 40b); 5.24 (s, Ha C(5'), 40c);
5.17 (s, Hb C(5'), 40b); 5.16 (s, Hb C(5'), 40c); 1.55 (s, Me(7'), 40c); 1.52 (s, Me(7'), 40b); 1.11, 1.06, 1.04, 1.02,
‡
0.99 (overlapped s, Me(8), Me(9), Me(10), 40b/40c). ESI-MS: 279 ([M ‡ Na] ).
1
Data of 40b/40c/40d: H-NMR (ARX-300; selected signals)1): 5.27 (s, Ha C(5'), 40b); 5.24 (s, Ha C(5'),
40c); 5.18 (s, Ha C(5'), 40d); 5.17 (s, Hb C(5'), 40b); 5.16 (s, Hb C(5'), 40c); 5.11 (s, Hb C(5'), 40d); 1.58
(s, Me(7'), 40d); 1.54 (s, Me(7'), 40c); 1.52 (s, Me(7'), 40b); 1.10, 1.05, 1.03, 1.01, 0.99, 0.98 (overlapped s, Me(8),
‡
‡
Me(9), Me(10), 40b/40c/40d). ESI-MS: 535 ([2M ‡ Na] ), 279 ([M ‡ Na] ).
REFERENCES
[1] D. G. Lee, T. Chen, in ꢀComprehensive Organic Chemistryꢁ, Eds. B. M. Trost and I. Fleming, Pergamon
Press, Oxford, 1991, Vol. 7, p. 541.
[2] J. F. Callahan, K. A. Newlander, H. G. Bryan, W. F. Huffman, M. L. Moore, N. C. F. Yim, J. Org. Chem.
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Received June 3, 1999