Aromatic annulation on the p-menthane monoterpenes: Enantiospecific synthesis of the trans and cis isomers of calamenene and 8-hydroxycalamenene

Article abstract of DOI:10.1016/j.tetlet.2005.05.037

A new enantiospecific route to sesquiterpenes of the calamenene family is described. The synthetic pathway starts from easily available 3-oxygenated-p-menthane monoterpenes and affords the title compounds by a homologation-benzannulation sequence. The trans and cis isomers of the natural compounds calamenene and 8-hydroxycalamenene were obtained in enantiopure form starting from (-)-menthone and (+)-isomenthone, respectively.

Full text of DOI:10.1016/j.tetlet.2005.05.037

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4769–4772
Aromatic annulation on the p-menthane monoterpenes:
enantiospecific synthesis of the trans and cis isomers of
calamenene and 8-hydroxycalamenene
Stefano Serra* and Claudio Fuganti
C.N.R., Istituto di Chimica del Riconoscimento Molecolare, Sezione ÔAdolfo QuilicoÕ presso Dipartimento di Chimica,
Materiali ed Ingegneria Chimica ÔGiulio NattaÕ del Politecnico, Via Mancinelli 7, I-20133 Milano, Italy
Received 23 March 2005; revised 2 May 2005; accepted 11 May 2005
Available online 31 May 2005
Abstract—A new enantiospecific route to sesquiterpenes of the calamenene family is described. The synthetic pathway starts from
easily available 3-oxygenated-p-menthane monoterpenes and affords the title compounds by a homologation–benzannulation
sequence. The trans and cis isomers of the natural compounds calamenene and 8-hydroxycalamenene were obtained in enantiopure
form starting from (ꢀ)-menthone and (+)-isomenthone, respectively.
Ó 2005 Elsevier Ltd. All rights reserved.
The chiral substituted tetrahydronaphthalene deriva-
tives of type 1 and 2 (Fig. 1) are important natural prod-
ucts, which have attracted considerable attention
because of their remarkable properties. The sesquiter-
pene calamenene1 is widespread in plants and is a com-
ponent of a number of essential oils. The oxygenated
constituents display a wide range of biological activities.
(+)-8-Hydroxycalamenene is the active principle of the
seeds of Dysoxylum acutangulum2 that have been tradi-
tionally known as fish-poisonous plant material in Indo-
nesia. Otherwise, some serrulatane3 and pseudopterosin4
diterpenoids possess anti-mycobacterial,5 analgesic and
anti-inflammatory activities.6
Compounds with structure 1 and 2 share the difficult
accessibility by synthesis especially in enantiopure form.
Their preparation could be accomplished by two differ-
ent approaches. The first starts with a functionalised
aromatic ring and then builds up the chiral cyclohexane
ring.7 The second approach is based on the use of chiral
cyclic precursors on which the aromatic ring is created
by an annulation reaction.8 In both cases the major
problem is due to the difficulty in introducing the stereo-
centres in the benzylic position and the epimerisation of
existing stereocentres, respectively. The benzannulation
approach has received growing interest since the prepa-
ration of highly substituted compounds could be per-
formed straightforwardly in few regiospecific steps. In
this field, we have previously developed a method for
annulation that allows the construction of substituted
phenols starting from substituted 3-alkoxycarbonyl-
3,5-hexadienoic acids9 and from 3-alkoxycarbonyl-3-
en-5-ynoic acids.10 The latter process is very flexible
and can be used for the preparation of chiral tetrahydro-
naphthalenes11 and for the enantiospecific synthesis of
various natural products.12 Moreover, we have recently
shown that enantiomer-enriched 3-13 and 3,9-oxygen-
ated14 p-menthane monoterpenes are easily obtainable
by means of enzymes mediated resolution of racemic
materials. We envisaged that the combination of the
latter finding could be applicable to the preparation of
compounds 1 and 2 starting from p-menthane derivative
of type 3 (Fig. 2) through homologation to hexadienoic
acid 4 and benzannulation reaction.
Figure 1.
Keywords: Annulation; Terpenes; Calamenene; Enantiospecific;
Tetralins.
*
Corresponding author. Tel.: +39 2 2399 3076; fax: +39 2 2399
3080; e-mail: stefano.serra@polimi.it
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.037

4770
S. Serra, C. Fuganti / Tetrahedron Letters 46 (2005) 4769–4772
Figure 2. Retrosynthesis of 1 and 2.
Herein we communicate a preliminary accomplishment
of this synthetic plan. We used (ꢀ)-menthone 5 and
(+)-isomenthone15 6 as starting materials for the prepa-
ration of sesquiterpenes of the calamenene family. The
latter compounds are the most simple p-menthane deriv-
atives of type 3 (R = H) and are easily available in high
enantiomeric purity. According to our retrosynthetic
analysis, we needed hexadienoic acid 4, which was pre-
pared from 3 by stepwise C1–C4 homologation. The
regioselective introduction of the double bond at the
C2(3) carbon was performed by the Shapiro reaction
(Scheme 1).16
Scheme 2. Reagents and conditions: (i) 11, CH2Cl2, reflux, 48 h; (ii) 12,
t
tBuOH, BuOK, 50 °C 4 h; (iii) 13 (1.1 equiv), ꢀ60 °C, 1 h; (iv) LDA
(1 equiv), ꢀ60 °C 10 min, 1 h at rt then NH4Cl aq.
In order to avoid epimerisation at C(4) of the p-men-
thane framework, the tosylhydrazones of ketones 5
and 6 were prepared following the careful conditions de-
scribed by Garner et al.17 The lithium derivatives 7 and 8
were treated with DMF to give the isomerically pure
aldehydes 918 and 10,19 respectively. An essential aspect
of our approach is the regioselective conversion of the
latter compounds into the corresponding mono esters
mono acids of type 4. In our previous work this kind
of transformation has been achieved straightforwardly
by Wittig reaction20 or by Stobbe condensation21 of
the starting a,b-unsaturated aldehydes with triphenyl-
(a-ethoxy-carbonyl-b-carboxyethyl)phosphonium ylide
11 or with dimethyl succinate 12, respectively. Unfortu-
nately, the application of the latter procedures on alde-
hydes 9 and 10 was disappointing since no reaction took
place under the usual conditions (Scheme 2). This
behaviour is probably due to the steric hindrance of
the isopropyl group. Therefore, we settled on the more
nucleophilic lithium enolate 13 to accomplish this
homologation step.
to give 4. Therefore the reaction mixtures were treated
with an equimolar amount of LDA at low temperature
followed by warming to 0 °C. When employed the above
condensation protocol, 9 and 10 afforded the homolo-
gated dienoic acids in satisfactory yields (70–75%)
although as a mixture of isomers. In effect, the analysis
of the reaction mixture23 revealed that even if acids of
type 4 were the major components (74–77%), their 3-
(Z) isomers (18–19%) and the 2,5-hexadienoic acids
(5–8%) were also formed. Since the isomers were not
separable by chromatography and only 3-(E)-hexadi-
enoic acids are able to give benzannulation reactions,
the whole isomeric mixtures were used in the next step.
Hence, the impure acids 15 and 16 were obtained from
aldehydes 9 and 10, respectively (Scheme 3). They were
treated at 0 °C with trifluoroacetic anhydride as activat-
ing agent, in the presence of an excess of triethylamine.9
After a short reaction time at rt (1 h), work up and
chromatographic separation afforded annulated phenols
1724 and 1825 as nicely crystalline compounds and as
single isomers. Some polymeric tar materials were also
observed. The latter are conceivably derived from the
isomeric dienoic acids as confirmed by the yield of the
annulated products, corresponding to a quantitative
conversion of 15 and 16.
According to this finding, aldehydes 9 and 10 reacted
with 13 at low temperature (ꢀ60 °C) to afford the corre-
sponding bicyclic condensation product of type 14.22
The latter intermediates do not rearrange spontaneously
Reduction of the ester group to a methyl substituent was
accomplished in two steps in nearly quantitative yield.
Reduction of 17 and 18 with LiAlH4 gave the corre-
sponding benzyl alcohols that were further reduced to
phenols 1926 and 2027 by hydrogenation in the presence
of Pd/C as catalyst. The latter (ꢀ)-trans- and (+)-cis-8-
hydroxycalamenene showed identical NMR spectral
data to those reported for the natural compounds
isolated from D. acutangulum,2 Leminda millecra,28a
Dysoxylum schiffner28b and Bazzania trilobata,29 respec-
tively. The comparison of the optical rotation data
showed that 19 had identical value and opposite sign
to that reported for the natural product.2,28 Moreover,
20 showed the same sign and superior optical rotation
Scheme 1. Reagents and conditions: (i) TsNHNH2, CH2Cl2, 0 °C, 2 h;
(ii) BuLi (5 equiv), hexane/TMEDA, ꢀ78 °C 10 min then 1 h at rt; (iii)
DMF (10 equiv), ꢀ78 °C 10 min, 10 min at rt then NH4Cl aq.
20
20
D
value (½aꢁ +67.9, c 1, CHCl3) to that reported29a (½aꢁ
D

S. Serra, C. Fuganti / Tetrahedron Letters 46 (2005) 4769–4772
4771
Scheme 3. Reagents and conditions: (i) 13 (1.1 equiv), ꢀ60 °C 1 h, LDA (1 equiv) ꢀ60 °C 10 min, 1 h at rt then NH4Cl aq; (ii) (CF3CO)2O
(1.9 equiv), THF, Et3N (4 equiv), 0 °C 10 min then 1 h at rt; (iii) LiAlH4 (1 equiv), Et2O, 0 °C 30 min; (iv) H2 (1 equiv), 10% Pd/C (cat.), MeOH; (v)
NaH (1.2 equiv), THF, (EtO)2POCl (1.1 equiv), 2 h at rt then NH4Cl aq; (vi) Li (1.5 equiv), NH3 liq., ꢀ60 °C 1 h then NH4Cl dry.
4. Look, S. A.; Fenical, W. Tetrahedron 1987, 43, 3363–
3370.
5. Rodriguez, A. D.; Ramirez, C. J. Nat. Prod. 2001, 64,
100–102.
+31, c 4.2, CHCl3). These results confirm their previous
assigned absolute and relative stereochemistries and
show that cis-8-hydroxycalamenene isolated from nat-
ure is not enantiomerically pure. The next step was the
deoxygenation of the phenol functionality to the corre-
sponding aromatic hydrocarbon. This transformation
was accomplished by conversion of phenols 19 and 20
to their corresponding diethyl phosphate esters.30
Reductive cleavage by mean of lithium in liquid ammo-
nia smoothly afforded the (ꢀ)-trans- and (+)-cis-calam-
enene 2131 and 22,32 respectively. The spectral and
optical rotation data of the latter compounds were in
good accord with those of earlier studies that assigned
unambiguously their absolute stereochemistry.8a,33
6. Roussis, V.; Wu, Z.; Fenical, W.; Strobel, S. A.; Van
Duyne, G. D.; Clardy, J. J. Org. Chem. 1990, 55, 4916–
4922.
7. (a) Brenna, E.; Dei Negri, C.; Fuganti, C.; Gatti, F. G.;
Serra, S. Tetrahedron: Asymmetry 2004, 15, 335–340; (b)
Cesati, R. R.; De Armas, J.; Hoveyda, A. H. J. Am. Chem.
Soc. 2004, 126, 96–101; (c) Tanaka, K.; Qiao, S.; Tobisu,
M.; Lo, M. M.-C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122,
9870–9871; (d) Majdalani, A.; Schmalz, H.-G. Synlett
1997, 1303–1305.
8. (a) Davidson, J. P.; Corey, E. J. J. Am. Chem. Soc. 2003,
125, 13486–13489; (b) Nakashima, K.; Imoto, M.; Sono,
M.; Tori, M.; Nagashima, F.; Asakawa, Y. Molecules
2002, 7, 517–527; (c) Kocienski, P. J.; Pontiroli, A.; Qun,
L. J. Chem. Soc., Perkin Trans. 1 2001, 2356–2366; (d)
Corey, E. J.; Lazerwith, S. E. J. Am. Chem. Soc. 1998, 120,
12777–12782; (e) Corey, E. J.; Palani, A. Tetrahedron Lett.
1997, 38, 2397–2400; (f) Dieter, R. K.; Lin, Y. J.
Tetrahedron Lett. 1985, 26, 39–42.
9. Serra, S.; Fuganti, C.; Moro, A. J. Org. Chem. 2001, 66,
7883–7888, and references cited therein.
10. Serra, S.; Fuganti, C. Synlett 2005, 809–812, and refer-
ences cited therein.
11. Brenna, E.; Fuganti, C.; Serra, S. Synlett 1998, 365–
366.
12. Serra, S. Synlett 2000, 890–892, and references cited
therein.
In summary, we have demonstrated that the benzannu-
lation approach on the 3-oxygenated-p-menthane
framework allows the straightforward construction of
substituted calamenene sesquiterpenes in stereospecific
fashion. The trans and cis isomers of the natural
compounds calamenene and 8-hydroxycalamenene were
synthesised in enantiopure form starting from (ꢀ)-
menthone and (+)-isomenthone, respectively. Since
(+)-menthone and (ꢀ)-isomenthone are easily available
by synthesis,34 the preparation of their enantiomeric
forms is also possible. Our synthetic path compares
favourably with those reported previously both in terms
of selectivity, length and overall yield. Further applica-
tion of this methodology for the preparation of seco-
pseudopterosin and related diterpenes are underway.
13. Serra, S.; Brenna, E.; Fuganti, C.; Maggioni, F. Tetrahe-
dron: Asymmetry 2003, 14, 3313–3319.
14. Serra, S.; Fuganti, C. Helv. Chim. Acta 2002, 85, 2489–
2502.
15. (+)-isomenthone was obtained by oxidation of commer-
cially available (+)-isomenthol according to the procedure
described by: Lombardo, L. Org. Synth. 1987, 65, 81–89.
16. Chamberlin, A. R.; Bloom, S. H. Org. React. 1990, 39, 1–
83.
Acknowledgements
The authors thank COFIN for partial financial support.
17. Garner, C. M.; Mossman, B. C.; Prince, M. E. Tetrahe-
dron Lett. 1993, 34, 4273–4276.
References and notes
20
18. Aldehyde 9: ½aꢁD +103.1 (c 3, CHCl3). Anal. Calcd for
1. Bordoloi, M.; Shukla, V. S.; Nath, S. C.; Sharma, R. P.
Phytochemistry 1989, 28, 2007–2037.
2. Nishizawa, M.; Inoue, A.; Sastrapradja, S.; Hayashi, Y.
Phytochemistry 1983, 22, 2083–2085.
3. (a) Hall, S. R.; Raston, C. L.; Skelton, B. W.; White, A. H.
J. Chem. Soc., Perkin Trans. 2 1981, 1467–1472; (b) Croft,
K. D.; Ghisalberti, E. L.; Jefferies, P. R.; Raston, C. L.;
White, A. H. Tetrahedron 1977, 33, 1475–1480.
C11H18O: C, 79.46; H, 10.91. Found: C, 79.55; H, 10.90;
1H NMR (400 MHz, CDCl3) d 9.39 (s, 1H), 6.65 (br s,
1H), 2.58–2.23 (m, 3H), 1.98–1.80 (m, 1H), 1.76–1.59 (m,
1H), 1.55–1.36 (m, 1H), 1.20–1.04 (m, 1H), 1.10 (d,
J = 7.3 Hz, 3H), 0.91 (d, J = 6.9 Hz, 3H), 0.69 (d,
J = 6.9 Hz, 3H); 13C NMR (400 MHz, CDCl3) d 194.4,
158.3, 143.8, 37.6, 31.4, 28.7, 27.9, 20.6, 20.6, 20.5, 17.0;
EI-MS m/z 166 (61), 151 (11), 137 (12), 123 (100), 109 (49),

4772
S. Serra, C. Fuganti / Tetrahedron Letters 46 (2005) 4769–4772
95 (74), 81 (36), 67 (23); IR (neat) cmꢀ1 1690, 1628, 1460,
1368, 1162, 705.
MS m/z 218 (29), 203 (2), 175 (100), 160 (13), 147 (12), 141
(4), 128 (4), 121 (5), 115 (6), 105 (2), 91 (4); IR (neat) cmꢀ1
3460, 1619, 1579, 1464, 1287, 1239, 1164, 1029, 974, 841.
20
19. Aldehyde 10: ½aꢁD ꢀ12.8 (c 3, CHCl3). Anal. Calcd for
C11H18O: C, 79.46; H, 10.91. Found: C, 79.60; H, 10.90;
1H NMR (400 MHz, CDCl3) d 9.41 (s, 1H), 6.63 (d,
J = 3.4 Hz, 1H), 2.48–2.33 (m, 2H), 2.00–1.88 (m, 1H),
1.86–1.78 (m, 1H), 1.77–1.69 (m, 1H), 1.50–1.33 (m, 2H),
1.14 (d, J = 7.2 Hz, 3H), 0.89 (d, J = 6.8 Hz, 3H), 0.84 (d,
J = 6.8 Hz, 3H); 13C NMR (400 MHz, CDCl3) d 194.5,
157.2, 144.1, 36.5, 31.9, 29.9, 27.5, 22.5, 21.3, 20.1, 19.6;
EI-MS m/z 166 (76), 151 (19), 137 (23), 123 (100), 109 (68),
95 (90), 81 (48), 67 (27); IR (neat) cmꢀ1 1687, 1633, 1458,
1171, 695.
20. Ro¨der, E.; Krauss, H. Liebig Ann. Chem. 1992, 177–181.
21. (a) Johnson, W. S.; Daub, G. H. Org. React. 1951, 6, 1–73;
for a more recent procedure on aliphatic aldehydes see: (b)
Burk, M. J.; Bienewald, F.; Harris, M.; Zanotti-Gerosa,
A. Angew. Chem., Int. Ed. 1998, 37, 1931–1933.
20
27. (+)-cis-8-Hydroxycalamenene 20: mp 71–73 °C; ½aꢁD
+67.9 (c 1, CHCl3). Anal. Calcd for C15H22O: C, 82.52;
H, 10.16. Found: C, 82.65; H, 10.15; 1H NMR (400 MHz,
CDCl3) d 6.71 (s, 1H), 6.42 (s, 1H), 4.52 (s, 1H), 3.12–3.02
(m, 1H), 2.74–2.66 (m, 1H), 2.45–2.32 (m, 1H), 2.25 (s,
3H), 1.82–1.56 (m, 4H), 1.23 (d, J = 7.1 Hz, 3H), 1.05 (d,
J = 6.9 Hz, 3H), 0.71 (d, J = 6.9 Hz, 3H); 13C NMR
(400 MHz, CDCl3) d 153.0, 141.3, 135.7, 126.7, 120.9,
112.8, 43.3, 30.9, 28.8, 26.5, 21.1, 21.1, 20.5, 17.4, 16.4; EI-
MS m/z 218 (15), 203 (2), 175 (100), 160 (11), 147 (12), 141
(4), 128 (5), 121 (6), 115 (9), 105 (4), 91 (7); IR (nujol)
cmꢀ1 3405, 1619, 1583, 1459, 1377, 1271, 1170, 839.
28. (a) McPhail, K. L.; Davies-Coleman, M. T.; Starmer, J. J.
Nat. Prod. 2001, 64, 1183–1190; (b) Mulholland, D. A.;
Iourine, S.; Taylor, D. A. H. Phytochemistry 1998, 47,
1421–1422.
22. The compounds of type 14 were identified by quenching
the reaction at low temperature followed by GC–MS
analysis of the crude reaction mixture.
ˇ ´
ˇ ˇ
´
´
29. (a) Konecny, K.; Streibl, M.; Vasickova, S.; Budesinsky,
˘ˇ
M.; Saman, D.; Ubik, K.; Herout, V. Collect. Czech.
ˇ
23. Acids of type 4; their 3-(Z) isomers and the 2,5-hexadi-
enoic acids were identified by NMR and GC–MS analysis
of the purified mixture of dienoic acids.
Chem. Commun. 1985, 50, 80–93; (b) Nagashima, F.;
Momosaki, S.; Watanabe, Y.; Takaoka, S.; Huneck, S.;
Asakawa, Y. Phytochemistry 1996, 42, 1361–1366.
30. Rossi, R. A.; Bunnett, J. F. J. Org. Chem. 1973, 38, 2314–
2318.
20
24. Hydroxy-ester 17: mp 129–130 °C; ½aꢁD ꢀ71.9 (c 1,
CHCl3). Anal. Calcd for C16H22O3: C, 73.25; H, 8.45.
20
1
Found: C, 73.15; H, 8.45; H NMR (400 MHz, CDCl3) d
31. (ꢀ)-trans Calamenene 21: ½aꢁD ꢀ75.2 (c 1, CHCl3). Anal.
7.46 (d, J = 1.5 Hz, 1H), 7.32 (d, J = 1.5 Hz, 1H), 5.28 (s,
1H), 3.89 (s, 3H), 3.24–3.14 (ddq, J = 2.3, 6.6, 7 Hz, 1H),
2.59–2.53 (ddd, J = 2.7, 5.5, 5.9 Hz, 1H), 2.10–1.92 (m,
2H), 1.91–1.75 (m, 2H), 1.54 (dm, J = 13.3 Hz, 1H), 1.21
(d, J = 7 Hz, 3H), 0.98 (d, J = 6.9 Hz, 3H), 0.82 (d,
J = 6.9 Hz, 3H); 13C NMR (400 MHz, CDCl3) d 168.0,
153.7, 141.5, 135.7, 126.9, 123.3, 113.2, 52.1, 43.1, 33.2,
27.2, 26.8, 21.9, 20.8, 19.4, 19.0; EI-MS m/z 262 (24), 231
(8), 219 (100), 187 (40), 160 (10), 145 (11), 131 (4), 115 (7),
105 (2), 91 (3); IR (nujol) cmꢀ1 3420, 1698, 1582, 1438,
1421, 1294, 1239, 1029, 767.
Calcd for C15H22: C, 89.04; H, 10.96. Found: C, 89.15; H,
1
11.00; H NMR (400 MHz, CDCl3) d 7.11 (d, J = 7.9 Hz,
1H), 7.01 (s, 1H), 6.93 (d, J = 7.9 Hz, 1H), 2.81–2.70 (m,
1H), 2.72–2.64 (m, 1H), 2.29 (s, 3H), 2.28–2.16 (m, 1H),
2.00–1.91 (m, 1H), 1.88–1.78 (m, 1H), 1.65–1.54 (m, 1H),
1.39–1.27 (m, 1H), 1.26 (d, J = 7 Hz, 3H), 0.99 (d,
J = 6.8 Hz, 3H), 0.72 (d, J = 6.8 Hz, 3H); 13C NMR
(400 MHz, CDCl3) d 140.1, 139.9, 134.4, 128.8, 126.8,
126.3, 44.1, 32.6, 32.1, 30.9, 22.3, 21.7, 21.3, 21.1, 17.6; EI-
MS m/z 202 (10), 159 (100), 144 (9), 128 (16), 115 (9), 105
(7), 91 (6); IR (neat) cmꢀ1 1614, 1497, 1463, 1384, 1366,
1319, 880, 814.
20
25. Hydroxy-ester 18: mp 122–123 °C; ½aꢁD +85 (c 2, CHCl3).
20
Anal. Calcd for C16H22O3: C, 73.25; H, 8.45. Found: C,
32. (+)-cis-Calamenene 22: ½aꢁD +42.6 (c 1, CHCl3). Anal.
1
73.30; H, 8.40; H NMR (400 MHz, CDCl3) d 7.57 (br s,
Calcd for C15H22: C, 89.04; H, 10.96. Found: C, 89.20; H,
1
1H), 7.31 (br s, 1H), 5.32 (s, 1H), 3.89 (s, 3H), 3.24–3.12
(m, 1H), 2.81–2.72 (m, 1H), 2.51–2.38 (m, 1H), 1.80–1.60
(m, 4H), 1.24 (d, J = 7 Hz, 3H), 1.06 (d, J = 6.9 Hz, 3H),
0.68 (d, J = 6.9 Hz, 3H); 13C NMR (400 MHz, CDCl3)
168.0, 153.6, 141.7, 136.2, 127.6, 121.5, 112.8, 52.1, 43.4,
30.9, 28.4, 27.2, 20.9, 20.0, 17.2, 16.3; EI-MS m/z 262 (22),
231 (10), 219 (100), 187 (69), 160 (24), 145 (44), 131 (20),
115 (39), 105 (6), 91 (20); IR (nujol) cmꢀ1 3400, 1698,
1584, 1438, 1349, 1273, 1245, 1032, 773.
11.05; H NMR (400 MHz, CDCl3) d 7.03 (d, J = 7.8 Hz,
1H), 7.01 (s, 1H), 6.92 (d, J = 7.8 Hz, 1H), 2.90–2.80 (m,
1H), 2.63–2.51 (m, 1H), 2.29 (s, 3H), 2.31–2.20 (m, 1H),
1.87–1.55 (m, 4H), 1.25 (d, J = 7 Hz, 3H), 1.03 (d,
J = 6.8 Hz, 3H), 0.77 (d, J = 6.8 Hz, 3H); 13C NMR
(400 MHz, CDCl3) d 139.9, 139.7, 134.4, 128.7, 128.4,
126.3, 43.8, 32.6, 31.2, 28.9, 23.2, 21.4, 21.1, 20.1, 17.7; EI-
MS m/z 202 (10), 159 (100), 144 (9), 128 (15), 115 (9), 105
(7), 91 (5); IR (neat) cmꢀ1 1614, 1499, 1464, 1384, 1261,
1038, 880, 814.
20
26. (ꢀ)-trans-8-Hydroxycalamenene 19: ½aꢁD ꢀ37.9 (c 2,
CHCl3). Anal. Calcd for C15H22O: C, 82.52; H, 10.16.
Found: C, 82.60; H, 10.20; 1H NMR (400 MHz, CDCl3) d
6.59 (s, 1H), 6.44 (s, 1H), 4.54 (s, 1H), 3.08 (ddq, J = 2.1,
7, 6.7 Hz, 1H), 2.48 (ddd, J = 2.9, 5.8, 5.8 Hz, 1H), 2.25 (s,
3H), 2.07–1.94 (m, 2H), 1.91–1.73 (m, 2H), 1.52 (dm,
J = 13.4 Hz, 1H), 1.21 (d, J = 7.1 Hz, 3H), 0.99 (d,
J = 6.7 Hz, 3H), 0.84 (d, J = 6.7 Hz, 3H); 13C NMR
(400 MHz, CDCl3) d 153.1, 141.1, 135.0, 126.2, 122.9,
113.5, 43.2, 33.1, 27.4, 26.7, 22.0, 21.2, 21.0, 19.6, 19.4; EI-
33. (a) Bunko, J. D.; Ghisalberti, E. L.; Jefferies, P. R. Aust. J.
Chem. 1981, 34, 2237–2242; (b) Croft, K. D.; Ghisalberti,
E. L.; Hocart, C. H.; Jefferies, P. R.; Raston, C. L.; White,
A. H. J. Chem. Soc., Perkin Trans. 1 1978, 2, 1267–1270.
34. (+)-Menthone are available by oxidation of commercially
available (+)-menthol according to the procedure
described in Ref. 15. (ꢀ)-Isomenthone is available by
hydrogenation of (+)-piperitone; see for instance: Wagner,
H. Chem. Ber. 1941, 74, 657–660.