Synthesis and stereochemistry of the four himachalene-type sesquiterpenes isolated from the flea beetle (Aphthona flava) as pheromone candidates

Article abstract of DOI:10.1002/ejoc.200300812

Both the (1S,2R) and (1R,2S) isomers of 2,6,6-trimethylbicyclo[5.4.0]undec- 7-en-9-one (1) were synthesized by starting from (S)- and (R)-citronellal (5), respectively. The stereochemistry of (1R,2S)-(-)-1 was established by an X-ray analysis; it exhibits a CD spectrum similar to that of cholest-4-en-3-one, in agreement with its absolute configuration. The ketones (1S,2R)- and (1R,2S)-1 were converted into the en-antiomers of three other himachalene hydrocarbons, 2,2,6-trimethyl-10-methylenebicyclo[5.4.0]undec-1(11)-ene (2), 1,1,5,8-tetramethyl-1,2,3,4,5,6,5a-hepta hydro benzo [1,2-a]-[7]annulene (3), and 1,1,5,8-tetramethyl-1,2,3,4,5-pentahydrobenzo[a][7]annulene (ar-himachalene, 4). The stereochemistry of these himachalene-type sesquiterpenes isolated from flea beetles such as Aphthona flava and Phyllotreta cruciferae as their male-pheromone components was revised to (1S,2R)-1, (6R,7S)-2,(5R,5aS)-3, and (R)-4. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200300812

FULL PAPER
Synthesis and Stereochemistry of the Four Himachalene-Type Sesquiterpenes
Isolated from the Flea Beetle (Aphthona flava) as Pheromone Candidates[‡]
Shin-etsu Muto,[a] Masahiko Bando,[b] and Kenji Mori*[a]
Keywords: Aphthona flava / Configuration determination / Himachalenes / Pheromones / Terpenoids
Both the (1S,2R) and (1R,2S) isomers of 2,6,6-trimethylbicy-
clo[5.4.0]undec-7-en-9-one (1) were synthesized by starting
from (S)- and (R)-citronellal (5), respectively. The stereo-
1,1,5,8-tetramethyl-1,2,3,4,5,6,5a-heptahydrobenzo[1,2-a]-
[7]annulene (3), and 1,1,5,8-tetramethyl-1,2,3,4,5-pentahyd-
robenzo[a][7]annulene (ar-himachalene, 4). The stereochem-
chemistry of (1R,2S)-(−)-1 was established by an X-ray ana- istry of these himachalene-type sesquiterpenes isolated from
lysis; it exhibits a CD spectrum similar to that of cholest-4-
en-3-one, in agreement with its absolute configuration. The
ketones (1S,2R)- and (1R,2S)-1 were converted into the en-
antiomers of three other himachalene hydrocarbons, 2,2,6-
flea beetles such as Aphthona flava and Phyllotreta cruci-
ferae as their male-pheromone components was revised to
(1S,2R)-1, (6R,7S)-2, (5R,5aS)-3, and (R)-4.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
trimethyl-10-methylenebicyclo[5.4.0]undec-1(11)-ene
(2),
Introduction
In 2001, Bartelt and co-workers isolated and identified
six new himachalene-type sesquiterpenes and the known ar-
himachalene as the male-specific pheromone candidates of
the flea beetle Aphthona flava.[1] The same himachalenes
were also isolated from another flea beetle, Phyllotreta cru-
ciferae.[1] Flea beetles include both agricultural pests like P.
cruciferae and beneficial species like A. flava.
Four out of the seven himachalenes identified by Bartelt
et al. are shown in Figure 1. In 2003 they reported the syn-
thesis of racemates of the six new himachalenes.[2] As for
the stereochemistry of these compounds, they proposed the
absolute configuration opposite to that shown in Fig-
ure 1.[1]
In continuation of our work on the synthesis of himach-
alenes like 3-methyl-α-himachalene, the sex pheromone of
Lutzomyia longipalpis,[3] we became interested in clarifying Figure 1. Structures of Aphthona flava himachalenes; nomenclature
is adopted according to Chemistry 4-D Draw ver. 5.0 (Chem. Inno-
vation Software, Inc.)
the stereochemistry of these new himachalenes. This paper
describes the synthesis of the enantiomers of himachalene-
type compounds 1Ϫ4, starting from the enantiomers of cit-
ronellal. The relative stereochemistry of 1 was unambigu-
ously determined by an X-ray analysis of (1R,2S)-1, and
the absolute configuration of 1 was assigned on the basis
of that of the starting citronellal. Our synthetic and stereo-
chemical studies on 1Ϫ4 resulted in a revision of the abso-
lute configuration of the naturally occurring 1Ϫ4, as shown
in Figure 1.
[‡]
Pheromone Synthesis, CCXXVI. Part CCXXV: K. Mori, T.
Ohtaki, H. Ohrui, D. R. Berkebile, D. A. Carlson, Eur. J. Org.
Chem. 2004, 1089Ϫ1096.
[a]
Insect Pheromone and Traps Division, Fuji Flavor Co., Ltd.
Results and Discussion
Midorigaoka 3-5-8, Hamura-City, Tokyo 205-8503, Japan
Fax: (internat.) ϩ 81-42-555-7920
[b]
Institute of Organic Chemistry, Otsuka Pharmaceutical Co.,
Because himachalene compounds 2Ϫ4 are derivable from
the ketone 1, its enantioselective synthesis must be planned
Ltd.
Kawauchi, Tokushima 771-0192, Japan
1946
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200300812
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Four Himachalene-Type Sesquiterpenes
FULL PAPER
first. Scheme 1 shows the retrosynthetic analysis of (1R,2S)-
1. For the construction of (1R,2S)-1, Robinson annulation
with (S)-2,2,6-trimethylcycloheptanone (A) could be per-
formed in analogy with Bartelt’s synthesis of (Ϯ)-1.[2] The
ketone A was to be prepared via β-oxo ester B by Dieck-
mann condensation of diethyl (2RS,6S)-2,6-dimethyloc-
tanedioate (C). (S)-Citronellal (5, Takasago, 97% ee) serves
as an ideal starting material for the preparation of C. This
plan was realized as detailed below.
Scheme 1. Retrosynthetic analysis of (1R,2S)-1
Scheme 2. Synthesis of 1; reagents and conditions: (a) PDC, DMF,
0 °C to room temp.; (b) K2CO3, EtI, DMF, 0 °C to room temp.
(74%, 2 steps); (c) O3, MeOH, Ϫ78 °C; then Me2S (72%); (d) (EtO)2-
P(O)CHMeCO2Et, NaH, THF, Ϫ30 °C (96%); (e) H2, PtO2,
EtOAc, room temp. (quant.); (f) i) tBuOK, m-xylene, 150 °C; ii)
diluted HCl (79%); (g) i) NaOH, MeOH, H2O, reflux; ii) diluted
HCl (85%); (h) tBuOK, tBuOH, MeI, 0 °C to room temp. (88%
based on consumed 12); (i) LDA, TMSCl, THF, Ϫ78 °C; ii) MeLi,
CH2ϭC(TMS)COMe, THF; iii) NaOMe, MeOH, room temp.
(44% based on consumed 13)
The synthesis of the enantiomers of 1 is summarized in
Scheme 2. (S)-Citronellal (5) was oxidized with pyridinium
dichromate (PDC) to give (S)-citronellic acid (6), which was
esterified with ethyl iodide and potassium carbonate to fur-
nish ethyl ester (S)-7. Ozonolysis of (S)-7 afforded aldehyde
(S)-8, which was subjected to HornerϪWadsworthϪ
Emmons olefination to give diethyl ester (S)-9 [(E)/(Z) ϭ
1
87:13 as judged by H NMR spectroscopy]. Hydrogenation omers of 1 were nicely crystalline, we were able to carry out
of (S)-9 over Adams’s platinum oxide catalyst yielded satu- an X-ray analysis of (Ϫ)-1. Figure 2 shows the perspective
rated ester (2RS,6S)-10, the precursor C to be employed in view of (Ϫ)-1, which must be (1R,2S)-1, taking into account
the Dieckmann condensation.
the (2S) configuration of (S)-citronellal origin. This X-ray
Treatment of 10 with potassium tert-butoxide in hot m- result is in good agreement with the result of the ab initio
xylene resulted in ring closure to give the β-oxo ester calculation reported by Bartelt.[2] Further evidence
(2RS,3S,7RS)-11,[4,5] which was heated under reflux with supporting the (1R,2S) absolute configuration assigned to
sodium hydroxide in aqueous methanol to effect hydrolysis (Ϫ)-1 was provided by its CD spectrum, which is similar
and decarboxylation, furnishing the ketone (2RS,6S)-12. to that of cholest-4-en-3-one in the 300Ϫ400 nm region, as
Methylation of 12 with potassium tert-butoxide and methyl shown in Figure 3. The two enantiomers of 1 obviously
iodide in tert-butyl alcohol gave the trimethyl ketone (S)- exhibit spectra that are antipodal to each other.
13. Robinson annulation of (S)-13 with 3-trimethylsilyl-3-
Scheme 3 summarizes the conversion of the enantiomers
buten-2-one under Stork’s conditions[6Ϫ8] afforded bicyclic of ketone 1 into the enantiomers of himachalene-type hy-
ketone (1R,2S)-1 as colorless rods, m.p. 52.0Ϫ53.5 °C, drocarbons 2, 3 and 4. The crystalline ketone (1R,2S)-1 was
[α]2D2 ϭ Ϫ62 (hexane). The overall yield of (1R,2S)-1 was treated with methylenetriphenylphosphorane to give
13% based on (S)-citronellal (9 steps). Similarly, (1S,2R)-1, (6S,7R)-2, [α]2D1 ϭ Ϫ12 (hexane). The specific rotation of
m.p. 52.0Ϫ53.5 °C, [α]D22 ϭ ϩ64 (hexane), was synthesized the naturally occurring 2 was reported as [α]D ϭ ϩ1.6 (hex-
from (R)-citronellal. The specific rotation of the naturally ane).[1] Bartelt et al. prepared the naturally occurring 2 by
occurring 1 was not reported.[1]
Wittig methylenation of the naturally occurring 1.[1] The
Bartelt et al. obtained (Ϯ)-1 as an oil, and its relative naturally occurring 1 and 2 are therefore (1S,2R)-1 and
configuration (1R*,2S*) was assigned by 1H NMR spectro- (6R,7S)-2.
scopic studies coupled with an ab initio calculation of the
Treatment of (6S,7R)-2 with hot formic acid caused
lowest-energy conformation of 1.[2] Because the enanti- double-bond migration to give a mixture of (6S,7R)-2 and
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1947

S. Muto, M. Bando, K. Mori
FULL PAPER
Figure 2. X-ray structure of (1R,2S)-(Ϫ)-1
Scheme 3. Synthesis of 2, 3 and 4; reagents and conditions: (a)
Ph3PMeBr, nBuLi, THF, 0 °C to room temp. (69% based on con-
sumed 1); (b) HCO2H, MeOH, room temp. (88% based on con-
sumed 2); (c) chloranil, C6H6, 75 °C (63%)
curring 3 has an [α]D value of ϩ82 (hexane),[1] and therefore
its configuration is (5R,5aS)-3. Finally, dehydrogenation of
(6S,7R)-2 with chloranil[1] afforded (S)-ar-himachalene (4),
[α]2D6 ϭ Ϫ10 (hexane). Aphthona flava produces ar-himach-
alene with [α]D Ͻ ϩ10 (hexane),[1] which must therefore be
(R)-4. For the purpose of bioassay, the naturally occurring
enantiomers themselves were then synthesized from
(1S,2R)-1, giving (6R,7S)-2, (5R,5aS)-3 and (R)-4.
Our synthesis of (1R,2S)-(Ϫ)-1 started from (S)-(Ϫ)-cit-
ronellal (5), and the relative stereochemistry of (1R,2S)-1
was proved by its X-ray analysis. There was therefore no
room for error. Accordingly, we conclude that the himach-
alene-type pheromone candidates isolated from Aphthona
flava possess the absolute configuration as shown in Fig-
ure 1 and the lower part of Scheme 3, opposite to what has
been proposed by Bartelt.[1] This conclusion was supported
by Dr. Bartelt’s GC comparison of our synthetic enanti-
omers of 1Ϫ4 with natural 1Ϫ4 on a chiral stationary phase
(CDX-B). It was also ascertained by GC analysis that the
Figure 3. CD spectra of (a) (1R,2S)-(Ϫ)-1 (1.63 m in hexane);
(b) (1S,2R)-(ϩ)-1 (1.33 m in hexane); and (c) cholest-4-en-3-one
(1.67 m in hexane)
(5S,5aR)-3 (17:83), which could be separated by chromatog- European Silver Fir (Abies alba) produces (1R,2S)-1 and
raphy on silica gel, impregnated with silver nitrate, to fur- (6S,7R)-2, the opposite enantiomers of the insect materi-
nish (5S,5aR)-3, [α]2D1 ϭ Ϫ110 (hexane). The naturally oc- als.[1]
1948
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Four Himachalene-Type Sesquiterpenes
FULL PAPER
anol (10 mL) at Ϫ78 °C at a rate of about 150 mL/min. After stir-
ring at Ϫ78 °C for 3 h, the color of the reaction mixture changed
to pale blue. O2 was then passed through to remove the ozone for
30 min, and Me2S (0.76 mL, 10.3 mmol) was added at Ϫ78 °C. The
mixture was warmed to room temperature and then concentrated
under reduced pressure. The residue was diluted with water and
extracted with Et2O. The extract was washed with brine, dried with
MgSO4, and concentrated under reduced pressure. The residue was
purified by chromatography (hexane/Et2O, 10:1) to give (S)-8
(643 mg, 72%) as a colorless oil, n2D4 ϭ 1.4325. [α]2D2 ϭ Ϫ6.64 (c ϭ
In summary, the male-produced pheromone candidates
(1S,2R)-1, (6R,7S)-2, (5R,5aS)-3 and (R)-4 of the flea beetle
Aphthona flava were synthesized from (R)-(ϩ)-citronellal.
Their enantiomers were also synthesized from (S)-(Ϫ)-cit-
ronellal. These enantiomers will be bioassayed in Hungary,
´
by Dr. M. Toth, employing the crucifer flea beetle, Phyllo-
treta cruciferae, as the test insect. Finally, it must be added
that Pandey and Dev assigned the (S) configuration to (ϩ)-
ar-himachalene in 1968.[9] Our present result is in conflict
with theirs. Further investigation is being continued in co- 1.52, CHCl3). IR (film): ν˜max. ϭ 2960 (s, CϪH), 2720 (m, CHO),
1730 (s, CϭO) cmϪ1 1H NMR (300 MHz, CDCl3): δ ϭ 0.96 (d,
.
operation with Dr. R. J. Bartelt to solve this stereochem-
ical controversy.
J ϭ 6.6 Hz, 3 H, 3-Me), 1.25 (t, J ϭ 7.2 Hz, 3 H, OCH2CH3), 1.53
(dddd, J ϭ 14.1, 8.1, 8.1, 6.6 Hz, 1 H, 4-Ha), 1.70 (dddd, J ϭ 14.1,
8.7, 7.5, 5.7 Hz, 1 H, 4-Hb), 1.99 (dddt, J ϭ 7.5, 6.6, 6.3, 5.7 Hz, 1
H, 3-H), 2.16 (dd, J ϭ 15.0, 7.5 Hz, 1 H, 2-Ha), 2.28 (dd, J ϭ 15.0,
6.3 Hz, 1 H, 2-Hb), 2.46 (m, 2 H, 5-H), 4.13 (q, J ϭ 7.2 Hz, 2 H,
OCH2CH3), 9.77 (t, J ϭ 1.5 Hz, 1 H, CHO) ppm. 13C NMR
(75 MHz, CDCl3): δ ϭ 14.2, 19.4, 28.5, 29.8, 41.5, 60.3, 172.7,
202.1 ppm. This compound was employed for the next step without
further purification.
Experimental Section
General: Melting points and boiling points are uncorrected. IR:
Jasco FT/IR-410. 1H NMR: Varian Mercury-300 (300 MHz) (TMS
at δ ϭ 0.00 or CHCl3 at δ ϭ 7.26 as an internal standard). 13C
NMR: Varian Mercury-300 (75 MHz) (CDCl3 at δ ϭ 77.0 as an
internal standard). MS: Jeol JMS-SX 102A and Hitachi M-80B.
Optical rotation: Jasco DIP-1000. CD spectra: Jasco J-725 spec-
trometer. Refractive index (nD): Atago DMT-1. CC: Merck Kiesel-
gel 60 Art 1.07734. TLC: 0.25-mm Merck silica gel plates (60F-
254). Microanalyses were performed at the Center for New Materi-
als Research, Science University of Tokyo.
Ethyl (R)-3-Methyl-6-oxohexanoate [(R)-8]: In a similar manner to
that described for the preparation of (R)-8, (S)-7 (10.0 g,
46.7 mmol) gave (R)-8 (6.17 g, 69%) as a colorless oil. Its IR, 1H
NMR and 13C NMR spectra are identical to those of (S)-8. n2D3
ϭ
1.4338. [α]2D6 ϭ ϩ7.19 (c ϭ 1.05, CHCl3). This compound was em-
ployed for the next step without further purification.
Diethyl (S,E)-2,6-Dimethyloct-2-enedioate [(S)-9]: A solution of tri-
ethyl 2-phosphonopropanoate (17.6 g, 73.9 mmol) in dry THF
(60 mL) was added dropwise to a stirred suspension of NaH (60%
in oil, 2.53 g, 176 mmol) in dry THF (60 mL) at Ϫ30 °C under
argon. After stirring at Ϫ10 °C for 1 h, a solution of (S)-8 (9.08 g,
52.8 mmol) in dry THF (60 mL) was added dropwise at Ϫ30 °C,
and the mixture was stirred for 30 min. The reaction mixture was
quenched with water, and extracted with Et2O. The extract was
successively washed with water and brine, dried with MgSO4, and
concentrated under reduced pressure. The residue was purified by
chromatography (hexane/EtOAc, 20:1) to give (S)-9 (12.9 g, 96%)
as a colorless oil, n2D1 ϭ 1.4560. [α]2D2 ϭ Ϫ7.12 (c ϭ 1.58, CHCl3).
IR (film): ν˜max. ϭ 2980 (s, CϪH), 1735 (s, CϭO), 1710 (s, CϭO),
Ethyl (S)-3,7-Dimethyl-6-octenoate [(S)-7]: Pyridinium dichromate
(PDC; 100 g, 266 mmol) was added to a stirred solution of (S)-5
[α2D4 ϭ Ϫ13.4 (neat), 30.0 g, 195 mmol] in DMF (200 mL) at 0 °C.
After stirring at room temperature for 5 h, the reaction mixture
was quenched with 1  aqueous HCl and extracted with Et2O. The
extract was washed three times with 10% aqueous NaOH, the com-
bined alkaline aqueous layer was acidified with concd. HCl, and
the separated organic acid was extracted with Et2O. The extract
was washed with brine, dried with MgSO4, and concentrated under
reduced pressure. The crude product 6 (26.0 g) was dissolved in
DMF (100 mL), and treated with K2CO3 (31.6 g, 229 mmol) and
EtI (30.0 g, 192 mmol) at 0 °C. The mixture was stirred overnight
at room temperature, quenched with water, and extracted with
Et2O. The extract was successively washed with water and brine,
dried with MgSO4, and concentrated under reduced pressure. The
residue was purified by distillation (b.p. 98Ϫ99 °C/6 Torr) to give
(S)-7 (28.6 g, 74%), n2D4 ϭ 1.4400. [α]2D1 ϭ Ϫ4.84 (c ϭ 1.72, CHCl3).
1
1650 (m, CϭC) cmϪ1. H NMR (300 MHz, CDCl3): δ ϭ 0.96 (d,
J ϭ 6.6 Hz, 3 H, 6-Me), 1.25 (t, J ϭ 7.2 Hz, 3 H, OCH2CH3), 1.28
(t, J ϭ 7.2 Hz, OCH2CH3), 1.33 (m, 1 H, 5-Ha), 1.48 (m, 1 H, 5-
Hb), 1.83 (tq, J ϭ 1.5, 0.9 Hz, 3 H, 2-Me), 1.98 (m, 1 H, 6-H), 2.13
(dd, J ϭ 14.7, 7.8 Hz, 1 H, 7-Ha), 2.18 (m, 2 H, 4-H), 2.30 (dd,
J ϭ 14.7, 6.3 Hz, 1 H, 7-Hb), 4.12 (q, J ϭ 7.2 Hz, 2 H, OCH2CH3),
4.18 (q, J ϭ 7.2 Hz, 2 H, OCH2CH3), 6.73 (tq, J ϭ 7.5, 1.5 Hz, 1
H, 3-H) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 12.3, 14.25, 14.28,
19.5, 26.1, 30.1, 35.3, 41.7, 60.2, 60.4, 128.0, 141.7, 168.2,
172.9 ppm. C14H24O4 (256.3): calcd. C 65.60, H 9.44; found C
65.73, H 9.58.
1
IR (film): ν˜max. ϭ 2965 (s, CϪH), 1735 (s, CϭO) cmϪ1. H NMR
(300 MHz, CDCl3): δ ϭ 0.94 (d, J ϭ 6.6 Hz, 3 H, 3-H), 1.25 (t,
J ϭ 7.2 Hz, 3 H, OCH2CH3), 1.30 (m, 2 H, 4-H), 1.60 (s, 3 H, 7-
Me), 1.68 (d, J ϭ 1.2 Hz, 3 H, 7-Me), 1.98 (m, 3 H, 3, 5-H), 2.10
(dd, J ϭ 14.4, 7.8 Hz, 1 H, 1-Ha), 2.30 (dd, J ϭ 14.4, 6.0 Hz, 1 H,
1-Hb), 4.12 (q, J ϭ 7.2 Hz, 2 H, OCH2CH3), 5.09 (tq, J ϭ 7.2,
1.2 Hz, 1 H, 6-H) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 14.3,
17.6, 19.6, 25.4, 25.7, 30.0, 36.8, 41.9, 60.1, 124.3, 131.5, 173.3 ppm.
C12H22O2 (198.3): calcd. C 72.68, H 11.18; found C 72.41, H 11.30.
Diethyl (R,E)-2,6-Dimethyloct-2-enedioate [(R)-9]: In a similar
manner to that described for the preparation of (S)-9, (R)-8 (2.42 g,
14.1 mmol) gave (R)-9 (3.38 g, 91%) as a colorless oil. Its IR, 1H
Ethyl (R)-3,7-Dimethyl-6-octenoate [(R)-7]: In a similar manner to
that described for the preparation of (S)-7, (R)-5 [α2D4 ϭ ϩ10.6
(neat), 22.1 g, 144 mmol] gave (R)-7 (16.0 g, 56%) as a colorless oil.
Its IR, 1H NMR and 13C NMR spectra are identical to those of
(S)-7. n2D3 ϭ 1.4400. [α]2D3 ϭ ϩ3.42 (c ϭ 1.30, CHCl3). HRMS (EI)
[Mϩ] (C12H22O2): calcd. 198.1620; found 198.1628.
NMR and 13C NMR spectra are identical to those of (S)-9. n2D6
ϭ
1.4540. [α]2D6 ϭ ϩ7.44 (c ϭ 1.04, CHCl3). HRMS (EI) [Mϩ]
(C14H24O4): calcd. 256.1675; found 256.1665.
Diethyl (2RS,6S)-2,6-Dimethyloctanedioate [(S)-10]: A solution of
(S)-9 (4.22 g, 16.5 mmol) in EtOAc (10 mL) was added to a stirred
suspension of PtO2 (100 mg) in EtOAc (20 mL) at 0 °C under H2.
After stirring at room temperature for 3 h, the mixture was filtered
Ethyl (S)-3-Methyl-6-oxohexanoate [(S)-8]: Ozone was passed
through a stirred solution of (S)-7 (1.03 g, 5.20 mmol) in dry meth-
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1949

S. Muto, M. Bando, K. Mori
FULL PAPER
through Celite and the filtrate was concentrated under reduced (m, 2 H), 1.59 (m, 1 H), 1.81 (m, 3 H), 2.30Ϫ2.60 (m, 3 H, 2, 7-
pressure. The residue was purified by chromatography (hexane/ H) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 16.5, 18.0, 22.6, 23.2,
EtOAc, 20:1) to give (S)-10 (4.28 g, quant.) as a colorless oil. A 23.9, 28.0, 31.70, 31.78, 31.80, 33.5, 38.4, 38.9, 46.4, 47.4, 49.8,
portion of it was further purified by chromatography to afford an 50.2, 215.4, 216.3 ppm. HRMS (EI) [Mϩ] (C9H16O): calcd.
analytical sample. n2D1 ϭ 1.4330. [α]D21 ϭ Ϫ5.26 (c ϭ 1.85, CHCl3). 140.1201; found 140.1208.
1
IR (film): ν˜max. ϭ 2935 (s, CϪH), 1735 (s, CϭO) cmϪ1. H NMR
(2RS,6R)-2,6-Dimethylcycloheptanone [(R)-12]: In a similar manner
(300 MHz, CDCl3): δ ϭ 0.92 (d, J ϭ 6.6 Hz, 3 H, 6-Me), 1.13 (d,
to that described for the preparation of (S)-12, (R)-11 (2.73 g,
J ϭ 6.9 Hz, 3 H, 2-Me), 1.25 (t, J ϭ 7.2 Hz, 6 H, OCH2CH3),
1.08Ϫ1.23 (m, 5 H, 3-Ha, 4, 5-H), 1.64 (m, 1 H, 3-Hb), 1.95 (m, 1
1
12.9 mmol) gave (R)-12 (1.29 g, 72%) as a colorless oil. Its IR, H
NMR and 13C NMR spectra are identical to those of (S)-12. n2D3
ϭ
H, 6-H), 2.09 (dd, J ϭ 14.4, 8.1 Hz, 1 H, 7-Ha), 2.27 (dd, J ϭ 14.4,
6.3 Hz, 1 H, 7-Hb), 2.40 (tq, J ϭ 7.2, 6.9 Hz, 1 H, 2-H), 4.12 (q,
J ϭ 6.9 Hz, 4 H, OCH2CH3) ppm. 13C NMR (75 MHz, CDCl3):
δ ϭ 14.3, 17.0, 17.1, 19.59, 19.61, 24.5, 30.17, 30.20, 33.81, 33.82,
36.47, 36.49, 39.5, 41.84, 41.87, 60.1, 173.2, 176.79, 176.81 ppm.
C14H26O4 (258.3): calcd. C 65.09, H 10.14; found C 65.27, H 10.36.
1.4548. [α]2D3 ϭ ϩ59.5 (c ϭ 1.15, CHCl3). HRMS (EI) [Mϩ]
(C9H16O): calcd. 140.1201; found 140.1204.
(S)-2,2,6-Trimethylcycloheptanone [(S)-13]: A solution of (S)-12
(1.41 g, 10.0 mmol) in tBuOH (5.0 mL) was added to a stirred solu-
tion of tBuOK (3.36 g, 29.9 mmol) in tBuOH (15 mL) at room tem-
perature. After stirring for 30 min, MeI (3.0 mL, 48.2 mmol) was
added at 0 °C. The mixture was warmed to room temperature over
2 h, filtered through Celite, and the filtrate was concentrated under
reduced pressure. The residue was diluted with water, and extracted
with Et2O. The extract was washed with brine, dried with MgSO4,
and concentrated carefully under reduced pressure in order not to
lose the low-boiling product. The residue was purified by chroma-
Diethyl (2RS,6R)-2,6-Dimethyloctanedioate [(R)-10]: In a similar
manner to that described for the preparation of (S)-10, (R)-9
(2.92 g, 11.4 mmol) gave (R)-10 (3.02 g, quant.) as a colorless oil.
Its IR, 1H NMR and 13C NMR spectra are identical to those of
(S)-10. n2D3 ϭ 1.4320. [α]2D6 ϭ ϩ4.19 (c ϭ 1.06, CHCl3). HRMS (EI)
[Mϩ] (C14H26O4): calcd. 258.1831; found 258.1822.
(2RS,3S,7RS)-2-Ethoxycarbonyl-3,7-dimethylcycloheptanone [(S)- tography (hexane/Et2O, 50:1) to give (S)-13 [994 mg, 88% based on
11]: A solution of (S)-10 (7.55 g, 29.3 mmol) in m-xylene (80 mL) consumed (S)-12] as a colorless oil, n2D4 ϭ 1.4546. [α]2D4 ϭ Ϫ51.7
was added dropwise to a stirred solution of tBuOK (6.60 g, (c ϭ 1.03, CHCl3). IR (film): ν˜max. ϭ 2925 (s, CϪH), 1700 (s, Cϭ
1
58.8 mmol) in m-xylene (100 mL) over 2 h at 150 °C. After stirring O) cmϪ1. H NMR (300 MHz, CDCl3): δ ϭ 0.99 (d, J ϭ 6.6 Hz,
at 150 °C for 1 h, the reaction mixture was cooled to room tempera- 3 H, 6-Me), 1.07 (s, 6 H, 2-Me), 1.20 (m, 2 H), 1.72 (m, 5 H), 2.23
ture, diluted with 1  aqueous HCl, and extracted with Et2O. The (ddd, J ϭ 10.8, 2.1, 1.5 Hz, 1 H, 7-Ha), 2.63 (dd, J ϭ 11.1, 10.8 Hz,
extract was successively washed with water and brine, dried with 1 H, 7-Hb) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 23.4, 23.5, 23.8,
MgSO4, and concentrated under reduced pressure. The residue was 27.4, 33.5, 39.4, 39.5, 47.61, 47.64, 217.3 ppm. HRMS (EI) [Mϩ]
purified by chromatography (hexane/EtOAc, 20:1) to give (S)-11 (C10H18O): calcd. 154.1358; found 154.1359.
(4.89 g, 79%) as a colorless oil, n2D4 ϭ 1.4589. [α]2D4 ϭ ϩ43.1 (c ϭ
(R)-2,2,6-Trimethylcycloheptanone [(R)-13]: In a similar manner to
1.96, CHCl3). IR (film): ν˜max. ϭ 2930 (s, CϪH), 1745 (s, CϭO),
that described for the preparation of (S)-13, (R)-12 (1.28 g,
9.14 mmol) gave (R)-13 [636 mg, 55% based on the consumed (R)-
1705 (s, CϭO) cmϪ1. 1H NMR (300 MHz, CDCl3): δ ϭ 1.01, 1.03,
1.09 and 1.14 (each d, J ϭ 7.2, J ϭ 6.6, J ϭ 6.9 Hz and J ϭ 7.2 Hz,
total 3 H, 3-Me), 1.23 and 1.25 (each t, each J ϭ 6.9 Hz, total 3
H, OCH2CH3), 1.44 (d, J ϭ 4.8 Hz, 3 H, 7-Me), 1.36Ϫ1.95 (m, 5
H), 2.25 (m, 1 H), 2.44 (m, 1 H, 3-H), 2.73 (m, 1 H, 7-H), 3.33,
3.44, 3.75 and 3.84 (each d, J ϭ 9.3, J ϭ 9.9, J ϭ 2.4 Hz and J ϭ
2.1 Hz, total 1 H, 2-H), 4.14 and 4.18 (each q, each J ϭ 6.9 Hz,
total 2 H, OCH2CH3) ppm. HRMS (EI) [Mϩ] (C12H20O3): calcd.
212.1412; found 212.1410.
1
12] as a colorless oil. Its IR, H NMR and 13C NMR spectra are
identical to those of (S)-13. n2D3 ϭ 1.4520. [α]2D3 ϭ ϩ45.6 (c ϭ 1.21,
CHCl3). HRMS (EI) [Mϩ] (C10H18O): calcd. 154.1358; found
154.1357.
(1R,2S)-2,6,6-Trimethylbicyclo[5.4.0]undec-7-en-9-one [(1R,2S)-1]:
nBuLi (1.58  in hexane, 2.26 mL, 3.57 mmol) was added to a
stirred solution of diisopropylamine (0.60 mL, 4.28 mmol) in THF
(8.0 mL) at 0 °C under argon. After stirring for 30 min, a solution
of (S)-13 (500 mg, 3.25 mmol) in THF (3.0 mL) was added at Ϫ78
°C. The mixture was stirred at Ϫ78 °C for 30 min, and TMSCl
(0.80 mL, 6.48 mmol) was added dropwise at Ϫ78 °C. After stirring
at Ϫ78 °C for 1 h, the mixture was diluted with hexane and satu-
rated aqueous NH4Cl, and extracted with Et2O. The extract was
washed with water, saturated aqueous NaHCO3 and brine, dried
(2RS,3R,7RS)-2-Ethoxycarbonyl-3,7-dimethylcycloheptanone [(R)-
11]: In a similar manner to that described for the preparation of
(S)-11, (R)-10 (2.63 g, 10.2 mmol) gave (R)-11 (1.88 g, 87%) as a
1
colorless oil. Its IR and H NMR spectra are identical to those of
(S)-11. n2D5 ϭ 1.4580. [α]2D5 ϭ Ϫ40.3 (c ϭ 0.55, CHCl3). HRMS (EI)
[Mϩ] (C12H20O3): calcd. 212.1412; found 212.1413.
(2RS,6S)-2,6-Dimethylcycloheptanone [(S)-12]:
A
solution of with K2CO3, and concentrated under reduced pressure. The residue
NaOH (0.50 g, 12.5 mmol) in water (10 mL) was added to a stirred was diluted with THF (10 mL), and MeLi (2.2  in Et2O, 1.47 mL,
solution of (S)-11 (1.09 g, 5.14 mmol) in MeOH (2.0 mL) at room 3.23 mmol) was added at 0 °C under argon. The mixture was stirred
temperature. After refluxing for 4 h, the reaction mixture was co- and refluxed for 1 h, and then cooled to Ϫ78 °C. A solution of 2-
oled to room temperature, diluted with 1  aqueous HCl, and ex- trimethylsilyl-1-buten-3-one (500 mg, 3.52 mmol) in THF (3.0 mL)
tracted with Et2O. The extract was successively washed with water was added, and the mixture was warmed to room temperature.
and brine, dried with MgSO4, and concentrated carefully under After stirring overnight, the reaction was quenched with water, and
reduced pressure in order not to lose the low-boiling product. The extracted with Et2O. The extract was washed with brine, dried with
residue was purified by chromatography (hexane/Et2O, 30:1) to give K2CO3, and concentrated under reduced pressure. A solution of
(S)-12 (612 mg, 85%) as a colorless oil, n2D4 ϭ 1.4540. [α]2D4 ϭ Ϫ54.2 10% NaOMe in methanol (10 mL) was added at room temperature
(c ϭ 1.10, CHCl3). IR (film): ν˜max. ϭ 2925 (s, CϪH), 1700 (s, Cϭ to a solution of the crude residue in MeOH (4.0 mL). After re-
1
O) cmϪ1. H NMR (300 MHz, CDCl3): δ ϭ 0.98 and 0.99 ppm(e- fluxing for 6 h, the mixture was diluted with 1  aqueous HCl, and
ach d, each J ϭ 6.6 Hz, total 3 H, 6-Me), 1.05 and 1.07 (each d, extracted with Et2O. The extract was washed with water, saturated
J ϭ 7.2 Hz and J ϭ 6.9 Hz, total 3 H, 2-Me), 1.18 (m, 1 H), 1.36 aqueous NaHCO3 and brine, dried with MgSO4, and concentrated
1950
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 1946Ϫ1952

Four Himachalene-Type Sesquiterpenes
FULL PAPER
under reduced pressure. The residue was purified by chromatogra-
(5S,5aR)-1,1,5,8-Tetramethyl-1,2,3,4,5,6,5a-heptahydrobenzo[1,2-a][7]-
phy (hexane/Et2O, 10:1) to give (1R,2S)-1 [294 mg, 44% based on annulene [(5S,5aR)-3]: Formic acid (0.15 mL, 3.98 mmol) was ad-
consumed (S)-13] as colorless prisms, m.p. 52.0Ϫ53.5 °C. [α]2D2
Ϫ62 (c ϭ 0.51, hexane). CD (c ϭ 0.00163, hexane): ∆ε ϭ ϩ12.3
ϭ
ded to a stirred solution of (6S,7R)-2 (33 mg, 0.16 mmol) in MeOH
(1 mL) at room temperature. The mixture was stirred at room tem-
(232 mm), Ϫ2.43 (331), Ϫ3.46 (345), Ϫ3.14 (360), Ϫ1.33 (377). IR perature overnight, diluted with water, and extracted with hexane.
(KBr): ν˜max. ϭ 2925 (s, CϪH), 1670 (s, CϭO), 1610 (CϭC), 1455 The extract was washed with brine, dried with MgSO4, and concen-
(m), 1340 (m), 1255 (m) cmϪ1 1H NMR (300 MHz, C6D6): δ ϭ trated under reduced pressure. The residue was purified by chroma-
.
0.71 (d, J ϭ 6.6 Hz, 3 H, 2-Me), 0.80 (s, 3 H, 6-Me), 0.93 (s, 3 H,
tography (20% AgNO3, SiO2; hexane) to give (5S,5aR)-3 [22 mg,
6-Me), 0.81Ϫ1.11 (m, 2 H), 1.15Ϫ1.58 (m, 6 H), 1.63 (m, 1 H), 88% based on consumed (6S,7R)-2] as a colorless oil, n2D4 ϭ 1.5010.
1.79 (ddd, J ϭ 9.6, 3.9, 2.7 Hz, 1 H, 1-H), 2.24 (ddd, J ϭ 17.4, 7.2, [α]2D1 ϭ Ϫ110 (c ϭ 0.85, hexane). IR (film): ν˜max. ϭ 2925 (s, CϪH),
3.0 Hz, 1 H, 10-Ha), 2.30 (ddd, J ϭ 17.4, 12.6, 4.8 Hz, 1 H, 10- 1655 (w, CϭC), 1455 (m), 1365 (m), 1200 (m), 785 (m) cmϪ1. H
1
Hb), 6.05 (s, 1 H, 8-H) ppm. 13C NMR (75 MHz, C6D6): δ ϭ 20.7, NMR (300 MHz, C6D6): δ ϭ 0.85 (d, J ϭ 6.6 Hz, 3 H, 5-Me),
22.4, 26.0, 27.7, 30.9, 32.7, 36.0, 37.6, 39.6, 39.7, 40.0, 123.6, 176.2,
197.9 ppm. EI MS (70 eV): m/z (%) ϭ 206 (39) [Mϩ], 191 (18), 178 (m, 4 H), 1.72 (m, 2 H), 1.73 (m, 3 H, 8-Me), 2.09 (dddt, J ϭ 16.8,
(50), 163 (53), 150 (71), 135 (100), 121 (41), 109 (46), 93 (52), 79 6.2, 3.0, 3.0 Hz, 1 H, 6-Ha), 2.27 (ddd, J ϭ 16.8, 6.3, 1.2 Hz, 1 H,
0.90Ϫ1.20 (m, 2 H), 1.06 (s, 3 H, 1-Me), 1.11 (s, 3 H, 1-Me), 1.53
(40), 67 (29), 55 (38), 41 (67). These spectroscopic data are identical 6-Hb), 5.25 (m, 1 H, 9-H), 5.57 (s, 1 H, 7-H) ppm. 13C NMR
with those reported for (Ϯ)-1.[2] C14H22O (206.3): calcd. C 81.50,
H 10.75; found C 81.28, H 10.60.
(75 MHz, C6D6): δ ϭ 21.2, 22.4, 23.1, 26.7, 28.1, 32.6, 34.3, 37.6,
38.6, 39.9, 41.0, 116.1, 119.7, 132.7, 153.6 ppm. EI MS (70 eV):
m/z (%) ϭ 204 (57) [Mϩ], 189 (16), 161 (27), 147 (8), 133 (100), 119
(72), 105 (54), 91 (21), 77 (11), 69 (13), 55 (17), 41 (19). HRMS
(EI) [Mϩ] (C15H24): calcd. 204.1878; found 204.1876.
(1S,2R)-2,6,6-Trimethylbicyclo[5.4.0]undec-7-en-9-one [(1S,2R)-1]:
In a similar manner to that described for the preparation of
(1R,2S)-1, (R)-13 (400 mg, 2.60 mmol) gave (1S,2R)-1 [182 mg,
44% based on consumed (R)-13] as colorless prisms. m.p.
52.0Ϫ53.5 °C. Its IR, 1H NMR and 13C NMR spectra are identical
to those of (1R,2S)-1. [α]2D3 ϭ ϩ64 (c ϭ 0.79, hexane). CD (c ϭ
0.00133, hexane): ∆ε ϭ Ϫ12.1 (232 mm), ϩ2.07 (331), ϩ3.09 (344),
ϩ2.79 (359), ϩ1.27 (377). C14H22O (206.3): calcd. C 81.50, H
10.75; found C 81.34, H 10.85.
(5R,5aS)-1,1,5,8-Tetramethyl-1,2,3,4,5,6,5a-heptahydrobenzo[1,2-a]-
[7]annulene [(5R,5aS)-3]: In a similar manner to that described for
the preparation of (5S,5aR)-3, (6R,7S)-2 (25 mg, 0.12 mmol) gave
(5R,5aS)-3 [20 mg, 95% based on consumed (6R,7S)-2] as a color-
1
less oil. Its IR, MS, H NMR and 13C NMR spectra are identical
to those of (5S,5aR)-3. n2D5 ϭ 1.5059. [α]2D5 ϭ ϩ115 (c ϭ 0.55, hex-
ane). HRMS (EI) [Mϩ] (C15H24): calcd. 204.1878; found 204.1873.
(6S,7R)-2,2,6-Trimethyl-10-methylenebicyclo[5.4.0]undec-1(11)-ene
[(6S,7R)-2]: nBuLi (1.58  in hexane, 0.17 mL, 0.27 mmol) was ad-
ded to a stirred suspension of methyltriphenylphosphonium bro-
mide (104 mg, 0.291 mmol) in dry THF (5 mL) at 0 °C under argon
and the mixture was then warmed to room temperature. After stir-
ring for 3 h, a solution of (1R,2S)-1 (49 mg, 0.24 mmol) in dry THF
(1 mL) was added to the resulting mixture at 0 °C. The mixture
was stirred at room temperature for 1.5 h, diluted with water, and
extracted with Et2O. The extract was washed with brine, dried with
MgSO4, and concentrated under reduced pressure. The residue was
purified by chromatography (20% AgNO3, SiO2; hexane/Et2O,
50:1) to give (6S,7R)-2 [13 mg, 69% based on consumed (1R,2S)-1]
as a colorless oil, n2D4 ϭ 1.5200. [α]2D3 ϭ Ϫ12 (c ϭ 0.85, hexane). IR
(film): ν˜max. ϭ 2925 (s, CϪH), 1625 (m, CϭC), 1455 (s), 1360 (m),
(S)-1,1,5,8-Tetramethyl-1,2,3,4,5-pentahydrobenzo[a][7]annulene
[(S)-4, (S)-ar-Himachalene]: Chloranil (60 mg, 0.24 mmol) was ad-
ded to a stirred solution of (6S,7R)-2 (24 mg, 0.12 mmol) in dry
benzene (2 mL) at room temperature. After stirring at 75 °C for
5 h, the mixture was cooled to room temperature, diluted with
water, and extracted with hexane. The extract was successively
washed with water and brine, dried with MgSO4, and concentrated
under reduced pressure. The residue was purified by chromatogra-
phy (hexane) to give (S)-4 (15 mg, 63%) as a colorless oil, n2D4
1.5272. [α]2D6 ϭ Ϫ10 (c ϭ 0.65, hexane). IR (film): ν˜max. ϭ 2925 (s,
CϪH), 1610 (w, CϭC), 1460 (m), 1360 (m), 810 (m) cmϪ1 1H
ϭ
.
NMR (300 MHz, C6D6): δ ϭ 1.31 (d, J ϭ 6.6 Hz, 3 H, 5-Me), 1.34
(s, 3 H, 1-Me), 1.42 (s, 3 H, 1-Me), 1.28Ϫ1.78 (m, 6 H, 2, 3, 4-H),
2.27 (d, J ϭ 0.6 Hz, 3 H, 8-Me), 3.26 (m, 1 H, 5-H), 7.03 (ddt, J ϭ
7.8, 1.5, 0.6 Hz, 1 H, 7-H), 7.21 (d, J ϭ 7.8 Hz, 1 H, 6-H), 7.31 (d,
J ϭ 1.5 Hz, 1 H, 9-H) ppm. 13C NMR (75 MHz, C6D6): δ ϭ 21.1,
21.3, 24.2, 34.1, 36.8, 39.5, 41.3, 125.8, 126.9, 135.1, 141.1,
147.6 ppm. EI MS (70 eV): m/z (%) ϭ 202 (53%) [Mϩ], 187 (100),
159 (15), 145 (56), 131 (31), 119 (10), 105 (10), 91 (7), 41 (7).
HRMS (EI) [Mϩ] (C15H22): calcd. 202.1721; found 202.1730.
1200 (w) cmϪ1 1H NMR (300 MHz, C6D6): δ ϭ 0.87 (d, J ϭ
.
6.6 Hz, 3 H, 6-Me), 0.99 (s, 3 H, 2-Me), 1.06 (m, 2 H), 1.16 (s, 3
H, 2-Me), 1.30 (m, 2 H), 1.49 (m, 3 H), 1.72 (m, 2 H), 1.96 (m, 1
H, 7-H), 2.26 (m, 1 H, 9-Ha), 2.45 (m, 1 H, 9-Hb), 4.88 (s, 1 H, 10-
CHaHb), 4.97 (s, 1 H, 10-CHaHb), 6.20 (s, 1 H, 11-H) ppm. 13C
NMR (75 MHz, C6D6): δ ϭ 20.0, 22.6, 25.3, 26.8, 27.8, 31.8, 36.4,
37.2, 38.8, 39.3, 40.7, 109.4, 122.8, 143.9, 154.5 ppm. EI MS
(70 eV): m/z (%) ϭ 204 (100) [Mϩ], 189 (63), 175 (8), 161 (72), 147
(37), 133 (89), 119 (72), 105 (70), 91 (68), 79 (31), 69 (26), 55 (36),
41 (46). HRMS (EI) [Mϩ] (C15H24): calcd. 204.1878; found
204.1884.
(R)-1,1,5,8-Tetramethyl-1,2,3,4,5-pentahydrobenzo[a][7]annulene
[(R)-4, (R)-ar-Himachalene]: In a similar manner to that described
for the preparation of (S)-4, (6R,7S)-2 (25 mg, 0.12 mmol) gave
(R)-4 (18 mg, 72%) as a colorless oil. Its IR, MS, 1H NMR and
13C NMR spectra are identical to those of (S)-4. n2D5 ϭ 1.5288.
[α]2D5 ϭ ϩ7.8 (c ϭ 0.45, hexane). HRMS (EI) [Mϩ] (C15H22): calcd.
202.1721; found 202.1713.
(6R,7S)-2,2,6-Trimethyl-10-methylenebicyclo[5.4.0]undec-1(11)-ene
[(6R,7S)-2]: In a similar manner to that described for the prep-
aration of (6S,7R)-2, (1S,2R)-1 (100 mg, 0.485 mmol) gave (6R,7S)-
2 [77 mg, 82% based on consumed (1S,2R)-1] as a colorless oil. Its X-ray Analysis of (1R,2S)-1: Crystal Data: C14H22O, M ϭ 206.33,
1
IR, MS, H NMR and 13C NMR spectra are identical to those of
(6S,7R)-2. n2D6 ϭ 1.5222. [α]2D6 ϭ ϩ6.0 (c ϭ 0.90, hexane). HRMS
(EI) [Mϩ] (C15H24): calcd. 204.1878; found 204.1872.
orthorhombic, space group P212121, a ϭ 10.86(1) A, b ϭ 12.056(7)
˚
A, c ϭ 9.634(7) A, V ϭ 1261(2) A , Z ϭ 4, Dcalcd. ϭ 1.087 Mg·mϪ3
,
3
˚
˚
˚
F(000) ϭ 456, µ(Mo-Kα) ϭ 0.660 cmϪ1. The crystal used for data
Eur. J. Org. Chem. 2004, 1946Ϫ1952
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1951

S. Muto, M. Bando, K. Mori
FULL PAPER
collection was a colorless prism with the approximate dimensions
0.80 ϫ 0.50 ϫ 0.50 mm. All data were obtained with a Rigaku
AFC-5S automated four-circle diffractometer with graphite-mon-
ochromated Mo-Kα radiation. Unit cell parameters were deter-
mined by least-squares refinement of the optimized setting angles
of 25 reflections in the range 13.2° Ͻ θ Ͻ 14.8°. The intensities
were measured using the ω/2θ scan technique up to 55°. Three
standard reflections were monitored every 150 measurements. The
data were corrected for Lorentz and polarization factors. An ab-
Acknowledgments
We thank Dr. R. J. Bartelt (U. S. Department of Agriculture,
National Center for Agricultural Utilization Research, Peoria, IL)
for discussion and gas chromatographic analysis of the final prod-
ucts. S. M. and K. M. are grateful to Mr. M. Hagihara, Drs. T.
Chuman and M. Chiba (Fuji Flavor Co.) for their support.
[1]
sorption correction (ψ-scan,[10] transmission factor
ϭ
R. J. Bartelt, A. A. Cosse, B. W. Zilkowski, D. Weisleder, F. A.
´
Momany, J. Chem. Ecol. 2001, 27, 2397Ϫ2423.
R. J. Bartelt, D. Weisleder, F. A. Momany, Synthesis 2003,
117Ϫ123.
T. Tashiro, M. Bando, K. Mori, Synthesis 2000, 1852Ϫ1862.
O. S. Bhanot, Indian J. Chem. 1967, 5, 127Ϫ128.
N. J. Leonard, C. W. Schimelpfenig, Jr., J. Org. Chem. 1958,
23, 1708Ϫ1710.
G. Stork, B. Ganem, J. Am. Chem. Soc. 1973, 95, 6152Ϫ6153.
A. Ottolenghi, M. Friedkin, A. Zilkha, Can. J. Chem. 1963,
41, 2977Ϫ2982.
0.945Ϫ0.999), but no decay correction, was applied. Of the 1617
independent reflections collected, all reflections were used for
structure determination and refinement. The structure was solved
by direct methods using the TEXSAN crystallographic software
package.[11] All non-H atoms were found in the Fourier map. The
refinement of the atomic parameters were carried out by the full-
matrix least-squares refinement, using anisotropic temperature fac-
tors for all non-H atoms. All H-atoms were located geometrically
and not refined. The final refinement converged with R ϭ 0.058
and Rw ϭ 0.134 {R1 ϭ 0.044 and RW1 ϭ 0.120 calculated by 965
reflections with I Ͼ [2σ(I)] for 138 parameters}. Atomic scattering
factors were taken from ‘‘International Tables for X-ray Crystallo-
graphy’’.[12] CCDC-218493 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
Cambridge Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB2 1EZ, UK; Fax: (internat.) ϩ 44-1223/336-033; E-mail:
deposit@ccdc.cam.ac.uk].
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
R. E. Gawley, Synthesis 1976, 777Ϫ794.
R. C. Pandey, S. Dev, Tetrahedron 1968, 24, 3829Ϫ3839.
A. C. T. North, D. C. Phillips, F. S. Mathews, Acta Crystallogr.,
Sect. A 1968, 24, 351Ϫ359.
[10]
[11]
[12]
Molecular Structure Corporation, teXsan, Single Crystal Struc-
ture Analysis Software, version 1.7, MSC, 3200 Reseach Forest
Drive, The Woodlands, TX 77381, USA, 1995.
International Tables for X-ray Crystallography, vol. C, Kynoch
Press, Birmingham, UK, 1992.
Received December 30, 2003
1952
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 1946Ϫ1952