Enantiospecific first total synthesis of (+)-trans-α-himachalene

Article abstract of DOI:10.1016/j.tetlet.2004.07.103

An enantiospecific first total synthesis of (+)-trans-α-himachalene, one of the eight male specific sesquiterpenes isolated from the crucifer flea beetle Phyllotreta cruciferae, starting from the readily and abundantly available monoterpene, (R)-carvone,

Full text of DOI:10.1016/j.tetlet.2004.07.103

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6867–6870
Enantiospecific first total synthesis of (+)-trans-a-himachaleneq
A. Srikrishna* and P. Ravi Kumar
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
Received 4 June 2004; revised 11 July 2004; accepted 22 July 2004
Abstract—An enantiospecific first total synthesis of (+)-trans-a-himachalene, one of the eight male specific sesquiterpenes isolated
from the crucifer flea beetle Phyllotreta cruciferae, starting from the readily and abundantly available monoterpene, (R)-carvone, is
described.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Flea beetles constitute the largest subfamily of the leaf
beetle family Chrysomelidae. Adult flea beetles feed on
host plant foliage and the larvae typically feed on the
roots of the same plant. The group includes both agri-
cultural pests and beneficial species. For example, Phyllo-
treta cruciferae Goeze is a significant pest of canola and
rapeseed in the northern prairie areas of the United
States and Canada and it also attacks cabbage, horse-
radish and other crucifers in many regions. On the other
hand, Aphthona flava Guillebeau, A. czwalinae, and
A. cyparissiae are effective biocontrol agents of the leafy
spurge (Euphorbia esula L.). In an attempt to discover
the possible pheromone components of the flea beetles,
the research group of Bartelt1 investigated volatile con-
stituents from the four species P. cruciferae, A. flava, A.
czwalinae, and A. cyparissiae, which led to the isolation
of eight male specific compounds 1–8 exhibiting phero-
monal function (Fig. 1). The structure of trans-a-hima-
starting from the readily and abundantly available
monoterpene (R)-carvone 10.
The retrosynthetic analysis of trans-a-himachalene 1 is
depicted in Scheme 1. It was contemplated that the pres-
ence of the propionaldehyde and isopropenyl side chains
at the C-3 and C-4 positions of methylcyclohexene, for
example, 11, would be ideal for generating hydroxy-
himachalene 12 via a carbonyl ene reaction.5 Initially,
the Lewis acid catalyzed Mukaiyama–Michael addition
H
H
H
H
H
H
H
1
2
3
4
1
chalene (+)-1 was established by comparison of the H
11
H
H
3
NMR spectral data with that of the optical antipode
(ꢀ)-1 obtained (along with various other isomers) from
a-himachalene mono and dihydrochlorides (prepared
from cis-a-himachalene 9, a major sesquiterpene of the
essential oil from the Himalayan deodar, Cedrus deod-
ara, Loud.), by the research groups of Dev,2 de Mayo3
and Bernardini.4 Herein, we report the enantiospecific
first total synthesis of trans-a-himachalene (+)-1
1
7
9
5
O
H
OH
6 β-OH
7 α-OH
5
8
9
Figure 1.
H
H
H
H
H
OH
H
1
Keywords: Terpene synthesis; Pheromones; Carbonyl ene reaction.
q Chiral synthons from carvone, Part 66. For parts 64 and 65, see
Ref. 10.
CHO
O
12
11
10
*
Corresponding author. Tel.: +91-8022932215; fax: +91-8023
600683; e-mail: ask@orgchem.iisc.ernet.in
Scheme 1.
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.07.103

6868
A. Srikrishna, P. Ravi Kumar / Tetrahedron Letters 45 (2004) 6867–6870
mixture of the methyl ether 17 and the carboxylic acid
COOMe
H
H
17a. Esterification with an excess of ethereal diazometh-
ane transformed the acid 17a into the ester 17 in 72%
yield.11 Alkylation of the ester 17 using LDA and methyl
iodide in THF at ice temperature furnished a 4:1 epi-
meric mixture of the a-methyl esters 18 in 90% yield.
A second alkylation of the epimeric mixture 18 with
LDA and methyl iodide in THF-HMPT at ice tempera-
ture furnished the a,a-dimethylated ester 19 in 60% yield
(over two steps).11
10
X
COOMe
O
OTMS
13
14
Scheme 2.
reaction6 of TMS enol ether 13, derived from (R)-carv-
one 10, to dimethylacrylate was explored for the gener-
ation of the keto ester 14, but was unsuccessful (Scheme
2).
One carbon homologation of the ester 19 to the alde-
hyde 20 followed by intramolecular carbonyl ene reac-
tion was contemplated for the construction of the
himachalene framework. Reduction of the ester 19 with
LAH in ether at 0ꢁC furnished the corresponding alco-
hol 21 in 86% yield, which on oxidation with PCC and
sodium acetate in methylene chloride gave the aldehyde
22 in 76% yield.11 Wittig reaction of the aldehyde 22
with methoxymethylenetriphenylphosphorane in THF
furnished a 1:1 E/Z mixture of the enol ether 23 in
71% yield. Acid catalyzed hydrolysis of the enol ether
23 in 0.02M THF solution using 3N aqueous hydro-
chloric acid at room temperature generated, instead of
the aldehyde 20, a 5:1 mixture of the bicyclic alcohol
24 and the diol 25, in 66% yield, which were separated
by column chromatography on silica gel.11 The struc-
tures of the alcohols 24 and 25 were deduced from their
spectral data. Alcohols 24 and 25 were formed via the
acid catalyzed carbonyl ene reaction of the initially
formed aldehyde 20, followed by partial hydrolysis of
the allyl methoxy group in 24 (!25) under the reaction
conditions (Scheme 4). It is worth mentioning that the
reaction proceeded in a highly stereoselective manner,
and only one stereoisomer was obtained. No attempt
was made to assign the stereochemistry of the alcohol
moiety in 24 as it is deoxygenated in the next reaction
step. In order to confirm the structure of alcohol 24, it
was converted into the enone 26 via the ketone 27. Thus,
oxidation of alcohol 24 with PCC and sodium acetate in
methylene chloride furnished the b,c-unsaturated ketone
27 in 80% yield, which on isomerization with 1,8-diaza-
bicyclo[5.4.0]undec-7-ene (DBU) in methylene chloride
generated the enone 26 in 90% yield (Scheme 5).11 The
structure of the enone 26 was established from the spec-
tral data and unambiguously confirmed by single crystal
X-ray analysis (Fig. 2).11
Consequently, an alternative longer route was investi-
gated (Scheme 3). Generation of the kinetic dienolate
of (R)-carvone 10 using LDA in THF and alkylation
with methyl bromoacetate at ꢀ70ꢁC generated, exclu-
sively, the trans-keto ester 15 in 75% yield. The trans
stereoselectivity is well established in the kinetic alkyl-
ation of carvone.7 Chemo- and stereoselective reduction
of the ketoester 15 with sodium borohydride in metha-
nol at ꢀ30ꢁC furnished, exclusively, the hydroxy ester
16, in 79% yield. WilliamsonÕs etherification of the hydr-
oxy ester 16 with sodium hydride and methyl iodide in
the presence of a catalytic amount of tetrabutylammo-
nium iodide (TBAI) in refluxing THF furnished a 5:2
H
H
H
a
b
O
10
OH
COOMe
16
O
COOMe
15
c
H
H
H
g
e
COOMe
CHO
R
OMe
COOR
MeO
MeO
h
18 R = H
17 R = Me
f
22
d
19 R = Me
17a R = H
H
H
H
i
OH
OH
H
+
H
H
H
MeO
MeO
OMe
HO
23
24
( 5 : 1 )
25
j
Next, attention was turned to the conversion of the bicy-
clic alcohol 24 into trans-a-himachalene 1 via reductive
deoxygenation of the C-4 hydroxy group and reductive
cleavage of the allylic methoxy group. Since BartonÕs
deoxygenation protocol was unsuccessful, it was decided
to carry out the deoxygenation8 of the hydroxy group in
H
H
H
OMs
H
k
H
H
H
MeO
MeO
29
(+)-1
28
Scheme 3. Reagents, conditions, and yields: (a) LDA, THF, ꢀ70ꢁC,
45min; BrCH2CO2Me, 3h; rt, 6h, 75%; (b) NaBH4, MeOH, ꢀ30ꢁC,
45min, 79%; (c) NaH, MeI, TBAI, THF, reflux, 6h, 72%; (d) CH2N2,
Et2O, 0ꢁC, 90%; (e) LDA, MeI, THF, 0ꢁC!rt, 6h; (f) LDA, MeI,
THF, HMPT, 0ꢁC!rt, 6h, 60% (over two steps); (g) (i) LAH, Et2O,
0ꢁC, 2h, 86%; (ii) PCC, NaOAc, CH2Cl2, rt, 1h 76%; (h)
Ph3P+CH2OMe Clꢀ, K+ tAmOꢀ, THF, rt, 3h, 71%; (i) 3N HCl,
THF, rt, 1.5h, 66%; (j) MsCl, py, CH2Cl2, DMAP, rt, 2h, 71%; (k) Li,
liq. NH3, THF, 33ꢁC, 45min, 57%.
H
23
24
25
CHO
MeO
20
Scheme 4.

A. Srikrishna, P. Ravi Kumar / Tetrahedron Letters 45 (2004) 6867–6870
6869
3. Challand, B. D.; Hikino, H.; Kornis, G.; Lange, G.;
de Mayo, P. J. Org. Chem. 1969, 34, 794.
4. Harref, A. B.; Bernardini, A.; Fkih-Tetouani, S.; Jacquier,
R.; Viallefont, P. J. Chem. Res. (S), 1981, 372 J. Chem.
Res. (M), 1981, 4329.
DBU
H
H
PCC
CH2Cl2
NaOAc
O
O
24
90%
CH2Cl2
80%
H
H
MeO
MeO
27
26
5. (a) Oppolzer, W.; Snieckus, V. Angew. Chem., Int. Ed.
Engl. 1978, 17, 476; (b) Taber, D. F. Intramolecular Diels–
Alder and Alder Ene Reactions; Springer: Berlin, 1984; (c)
Snider B. B., Trost, B. M., Fleming, I., Eds.; Comprehen-
sive Organic Synthesis; Pergamon: Oxford, 1992; Vol. 5,
p 1.
Scheme 5.
6. Narasaka, K.; Soai, K.; Aikawa, Y.; Mukaiyama, T. Bull.
Chem. Soc. Jpn. 1976, 49, 779.
7. Gesson, J. P.; Jacquesy, J.-C.; Renoux, B. Tetrahedron
1989, 45, 5853.
8. Turos, E.; Audia, J. E.; Danishefsky, S. J. J. Am. Chem.
Soc. 1989, 111, 8231.
9. It is worth mentioning that the reaction did not produce
any significant amount of the isomeric himachalene (6,6,9-
trimethyl-2-methylenebicyclo[5.4.0]undec-9-ene).2,3
10. Part 64: Srikrishna, A.; Satyanarayana, G. Org. Lett.
2004, 6, 2337; Part 65: Srikrishna, A.; Viswajanani, R.;
Dinesh, C. Ind. J. Chem. Sec. B 2004, 43, 1265.
Figure 2. X-ray structure of the enone 26.
11. All the compounds exhibited spectral data (IR, 1H and 13
C
NMR, mass and HRMS) consistent with their structures.
Selected spectral data for the ester 17: ½aŠ2D3: +66.6 (c 3.5,
24 via the sulphonate ester 28. Thus, reaction of alcohol
24 with methanesulfonyl chloride, pyridine, and a cata-
lytic amount of DMAP in methylene chloride furnished
the mesylate 28 in 71% yield. Reaction of 28 with lith-
1
CHCl3). IR (neat): mmax/cmꢀ1 1739, 1640, 887. H NMR
(300MHz, CDCl3 + CCl4): d 5.51 (1H, br s, H-40), 4.74
(2H, s, C@CH2), 3.82–3.72 (1H, m, CH-OMe), 3.61 (3H, s,
COOCH3), 3.17 (3H, s, O–CH3), 2.39 (1H, d, J = 14.1Hz),
2.30–1.80 (5H, m), 1.66 (6H, s, 2 · olefinic CH3). 13C
NMR (75MHz, CDCl3 + CCl4, DEPT): d 173.1 (C, O–
C@O), 146.3 (C, C@CH2), 134.6 (C, C-30), 125.4 (CH, C-
40), 113.5 (CH2, C@CH2), 83.2 (CH, CH-OMe), 54.0
(CH3, O–CH3), 51.2 (CH3, COOCH3), 46.7 (CH, C-60),
37.5 (CH, C-10), 36.1 (CH2), 30.8 (CH2), 19.5 (CH3) and
18.3 (CH3) [2 · olefinic CH3]. Mass: m/z 238 (M+, 12%),
164 (33), 149 (35), 133 (50), 123 (25), 105 (47), 98 (100), 91
(35). HRMS: m/z calcd for C14H22O3Na (M+Na):
261.1467. Found: 261.1450. For the ester 19:
ium in liquid ammonia and THF at ꢀ33ꢁC generated di-
25
D
rectly, trans-a-himachalene11 1, ½aŠ +67 (c 1.4, hexane),
{lit.1 [a]D +50 (c 0.008, hexane)}, instead of the methyl
ether 29, via simultaneous reductive demesylation and
demethoxylation reactions, in a regioselective manner.9
Synthetic trans-a-himachalene (+)-1 exhibited 1H
NMR spectral data identical to those of the natural
sample isolated1 from the flea beetles, and the 13C
NMR data reported4 for the optical antipode (ꢀ)-1 by
Bernardini and co-workers.
½aŠ25: +94.2 (c 6.4, CHCl3). IR (neat): mmax/cmꢀ1 1732,
D
887. 1H NMR (300MHz, CDCl3 + CCl4): d 5.73 (1H, br s,
H-40), 4.70 (2H, br s, C@CH2), 3.60 (3H, s, CO2CH3), 3.52
(1H, s, CH–OMe), 3.20 (3H, s, OCH3), 2.45 (1H, dd,
J = 6.9 and 2.7Hz), 2.40–2.00 (2H, m), 2.00–1.85 (1H, m),
1.74 (3H, s) and 1.72 (3H, s) [2 · olefinic CH3], 1.18
(3H, s) and 1.11 (3H, s) [2 · CH3]. 13C NMR (75MHz,
CDCl3 + CCl4, DEPT): d 177.7 (C, OC@O), 148.8 (C,
C@CH2) 134.5 (C, C-30), 126.6 (CH, C-40), 111.7 (CH2,
C@CH2), 78.6 (CH, C-20), 54.5 (CH3, OCH3), 51.3 (CH3,
CO2CH3), 46.1 (CH), 45.4 (C, C-2), 42.7 (CH), 29.5 (CH2,
C-50), 23.4 (CH3), 23.0 (CH3), 21.7(CH3), 19.9 (CH3).
Mass: m/z 207 (MꢀCO2CH3, 8%), 165 (Mꢀ[Me2C–
CO2CH3], 30), 149 (45), 133 (90), 123 (50), 114 (45), 109
(50), 102 (100), 98 (90), 93 (40), 91 (40). HRMS: m/z calcd
for C16H26O3 Na (M+Na): 289.1780. Found: 289.1797.
In conclusion, we have accomplished the enantiospecific
first total synthesis of the natural enantiomer of trans-a-
himachalene (+)-1 starting from the readily and abun-
dantly available (R)-carvone in 11 steps employing an
intramolecular carbonyl ene reaction as the key step.
The present sequence in addition to confirming the stereo-
structure, also established the absolute configuration of
the natural product.
Acknowledgements
We thank Professor Bartelt, National Center for Agri-
cultural Utilization Research, Peoria, for sending copies
of the 1H and mass spectra of natural trans-a-himachal-
ene (+)-1; and the Council of Scientific and Industrial
Research, New Delhi for the award of a research fellow-
ship to P.R.K.
For the aldehyde 22: ½aŠ24: +88.0 (c 7.0, CHCl3). IR (neat):
D
m
max/cmꢀ1 2711, 1722, 1643, 890. 1H NMR (300MHz,
CDCl3 + CCl4): d 9.27 (1H, s, O@C–H), 5.63 (1H, s, H-
40), 4.78 (1H, s) and 4.73 (1H, s) [C@CH2], 3.55 (1H, d,
J = 5.1Hz, H-20), 3.14 (3H, s, OCH3), 2.40–2.00 (3H, m),
1.90–1.60 (1H, m), 1.71 (3H, s) and 1.68 (3H, s) [2 · olef-
inic CH3], 1.02 (6H, s) [2 · CH3]. 13C NMR (75MHz,
CDCl3 + CCl4, DEPT): d 202.4 (CH, O@C–H), 148.6 (C,
C@CH2), 134.9 (C, C-30), 125.9 (CH, C-40), 113.1 (CH2,
C@CH2), 79.2 (CH, C-20), 54.7 (CH3,OCH3), 49.0 (C, C-
2), 46.0 (CH), 43.3 (CH), 30.3 (CH2, C-50), 20.7 (CH3),
20.3 (CH3), 20.2 (CH3), 18.2 (CH3). Mass: m/z 236 (M+,
10%), 195 (20), 187 (20), 165 (20), 149 (70), 135 (90), 123
References and notes
1. Bartelt, R. J.; Cosse, A. A.; Zilkowski, B. W.; Weisleder,
D.; Momany, F. A. J. Chem. Ecol. 2001, 27, 2397.
2. Joseph, T. C.; Dev, S. Tetrahedron 1968, 24, 3853.

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A. Srikrishna, P. Ravi Kumar / Tetrahedron Letters 45 (2004) 6867–6870
(55), 119 (65), 109 (45), 99 (70), 98 (C6H10O, retro DA
fragment, 100), 91 (50). HRMS: m/z calcd for
CH3), 1.90–1.75 (1H, m), 1.13 (3H, s) and 0.77 (3H, s)
[2 · CH3]. 13C NMR (75MHz, CDCl3 + CCl4, DEPT):
199.9 (C, C@O), 165.8 (C, C-2), 137.9 (C, C-9), 131.7 (CH,
C-3), 127.6 (CH, C-10), 79.6 (CH, C-8), 58.9 (CH3,OCH3),
57.2 (CH2, C-5), 55.9 (CH), 39.9 (CH), 34.4 (C, C-6), 27.3
(CH3), 25.7 (CH2, C-8), 24.2 (CH3), 23.6 (CH3), 22.6
(CH3). HRMS: m/z calcd for C16H25O2 (M+1): 249.1854.
Found: 249.1857. For trans-a-himachalene 1: ½aŠ2D3: +67
(c 1.4, hexane). lit.1 [a]D: +50.0 (c 0.008, hexane) lit.2 for
(ꢀ)-1 [a]D: ꢀ39.5. IR (neat): mmax/cmꢀ1 1636, 884. 1H
NMR (500MHz, CDCl3): d 5.28 (1H, br s, H-8), 4.76 (1H,
s) and 4.68 (1H, s) [C@CH2], 2.35–2.20 (2H, m), 2.10–1.95
(2H, m), 1.90–1.75 (2H, m), 1.67 (3H, s, olefinic CH3),
1.75–1.50 (3H, m), 1.50–1.40 (1H, m), 1.37–1.20 (2H, m),
0.96 (3H, s) and 0.70 (3H, s) [2 · CH3]. 13C NMR
(75MHz, CDCl3 + CCl4, DEPT): d 155.9 (C, C-2), 134.1
(C, C-9), 124.0 (CH, C-8), 109.9 (CH2, C@CH2), 50.7
(CH, C-7), 40.83 (CH, C-1), 40.77 (CH2), 36.6 (C, C-6),
34.9 (CH2), 31.9 (CH2), 31.1 (CH2), 29.9 (CH3), 24.3
(CH3), 23.3 (CH3), 20.5 (CH2, C-4). [lit.4 data: (25MHz,
CDCl3): d 156.3, 134.8, 123.7, 109.3, 50.6, 40.7, 40.6, 36.3,
34.7, 31.8, 30.9, 29.6, 23.8, 22.8, 20.4]. Mass: (C15H24) m/z
204 (M+, 5%), 203 (MꢀH, 25), 189 (MꢀMe, 12), 175 (10),
161 (15), 149 (30), 135 (40), 133 (35), 121 (45), 119 (40),
109 (70), 105 (60), 91 (60), 69 (100).
C15H24O2Na (M+Na): 259.1674. Found: 259.1660. For
the alcohol 24: ½aŠ24: +64.3 (c 3.0, CHCl3). IR (neat): mmax
/
D
cmꢀ1 3393 (OH), 2926, 1637, 1466, 1444, 1389, 1368, 1188,
1089, 1068, 1032, 931, 889. 1H NMR (300MHz,
CDCl3 + CCl4): d 5.77 (1H, d, J = 6.6Hz, H-10), 4.90
(1H, s) and 4.80 (1H, s) [C@CH2], 3.96 (1H, br s, H-4),
3.87 (1H, d, J = 6.3Hz, H-8), 3.09 (3H, s, OCH3), 2.68
(1H, dd, J = 13.2 and 3.9Hz), 2.35–2.00 (3H, m), 1.90–
1.70 (3H, m), 1.70 (3H, s, olefinic CH3), 1.70–1.40 (2H, m),
1.16 (3H, s) and 0.89 (3H, s) [2 · CH3]. 13C NMR
(75MHz, CDCl3 + CCl4, DEPT): d 150.5 (C, C-2), 134.8
(C, C-9), 127.9 (CH, C-10), 113.0 (CH2,C@CH2), 78.8
(CH, C-8), 66.7 (CH, C-4), 52.4 (CH2), 51.0 (CH3, OCH3),
47.3 (CH), 43.4 (CH), 42.8 (CH2), 35.8 (C, C-6), 33.2
(CH2), 31.0 (CH3), 24.5 (CH3), 21.0 (CH3). Mass: m/z 250
(M+, 12%), 218 (10), 147 (18), 133 (20), 119 (32), 105
(30), 99 (20), 91 (35), 49 (100). HRMS: m/z calcd
for C16H26O2Na (M+Na): 273.1830. Found: 273.1841.
For the diol 25: ½aŠ23: +25.5 (c 2.0, CHCl3). IR (neat):
D
m
max/cmꢀ1 3353, 1636, 890. 1H NMR (300MHz,
CDCl3 + CCl4): d 5.39 (1H, s, H-10), 4.93 (1H, s) and
4.84 (1H, s) [C@CH2], 4.00–3.85 (1H, m, H-4), 3.83 (1H, s,
H-8), 2.79 (1H, dd, J = 14.1 and 6.6Hz), 2.41 (1H, br t,
J = 11.8Hz), 2.17 (1H, d, J = 14.4Hz), 1.91 (1H, d,
J = 11.7Hz), 1.79 (3H, s, olefinic CH3), 1.80–1.60 (3H,
m), 1.50–1.05 (3H, m), 1.08 (3H, s) and 0.76 (3H, s)
[2 · CH3]. 13C NMR (75MHz, CDCl3 + CCl4, DEPT): d
149.9 (C, C-2), 134.7 (C, C-9), 126.9 (CH, C-10), 112.6
(CH2, C@CH2), 67.7 (CH), 66.2 (CH), 49.5 (CH2), 46.6
(CH), 42.8 (CH2), 41.5 (CH2), 34.5 (CH), 34.2 (C, C-6),
28.1 (CH3), 25.3 (CH3), 21.3 (CH3). Mass: m/z 236 (M+,
15%), 185 (20), 175 (20), 161 (30), 147 (75), 135 (43), 133
(45), 121 (46), 119 (75), 109 (80), 105 (70), 91 (100), 73
(75), 69 (70), 49 (90). HRMS: m/z calcd for C15H24O2Na
(M+Na): 259.1674. Found: 259.1696. For the enone 26:
X-ray data for the enone 26: X-ray data were collected
at 293K on a SMART CCD-BRUKER diffractometer
with graphite monochromated Mo-Ka radiation (k =
˚
0.7107A). The structure was solved by direct methods
(SIR92). Refinement was done by full-matrix least-squares
procedures on F2 using SHELX-97. The nonhydrogen atoms
were refined anisotropically whereas hydrogen atoms
were refined isotropically. C16H24O2, MW = 248.37, col-
orless crystal, Crystal system: orthorhombic, space group:
˚
P2(1)2(1)2(1), cell parameters: a = 8.186 (4)A, b = 10.769
3
˚
˚
˚
(6)A, c = 16.594 (9)A, V = 1462.95A , Z = 4, Dc =
1.128gcmꢀ3, F(000) = 544.0, l = 0.07mm. Total number
of l.s. parameters = 168, R1 = 0.0773 for 1293 Fo>4r(Fo)
and 0.1797 for all 2652 data. WR2 = 0.1093,
GOF = 0.886, Restrained GOF = 0.886 for all data.
ORTEP diagram is given in Figure 2. Crystallographic
data have been deposited with the Cambridge Crystallo-
graphic Data Centre (CCDC 236133).
½aŠ23: +296.1 (c 1.8, CHCl3). IR (neat): mmax/cmꢀ1 1656,
D
1
1614. H NMR (300MHz, CDCl3 + CCl4): d 5.97 (1H, s,
H-3), 5.91 (1H, d, J = 6.6Hz, H-10), 3.47 (1H, s, H-8),
3.20 (3H, s, OCH3), 2.65–2.50 (1H, m), 2.55 and 2.20 (2H,
2 · d, J = 11.7Hz, H-5), 2.36 (1H, tt, J = 13.8 and 2.7Hz),
2.35–2.15 (1H, m), 2.02 (3H, s, C2–CH3), 1.84 (3H, s, C9–