New enantioselective synthesis of (10R, 11S)-(+)-juvenile hormones I and II

Article abstract of DOI:10.1002/1099-0690(200106)2001:11<2145::AID-EJOC2145>3.0.CO;2-J

The (10R,11S)-(+)-juvenile hormones I (1) and II (2) were synthesized by Sharpless asymmetric dihydroxylations of methyl (2E, 6E, 10E)-7-ethyl-3,11-dimethyl-2,6,10-tridecatrienoate (4) and methyl (2E,6E,10E)-3,7,11-trimethyl-2,6,10-tridecatrienoate (5), respectively, as the key steps.

Full text of DOI:10.1002/1099-0690(200106)2001:11<2145::AID-EJOC2145>3.0.CO;2-J

FULL PAPER
New Enantioselective Synthesis of (10R,11S)-(؉)-Juvenile Hormones I and II[‡]
Tomoko Okochi[a] and Kenji Mori*[a]
Keywords: Asymmetric synthesis / Hormones / Natural products / Terpenoids
The (10R,11S)-(+)-juvenile hormones I (1) and II (2) were syn-
thesized by Sharpless asymmetric dihydroxylations of methyl
(2E,6E,10E)-7-ethyl-3,11-dimethyl-2,6,10-tridecatrienoate (4)
and methyl (2E,6E,10E)-3,7,11-trimethyl-2,6,10-tridecatri-
enoate (5), respectively, as the key steps.
Since the isolation and identification, in the late 1960s,
The widely used asymmetric Sharpless processes Ϫ epox-
of insect juvenile hormones I [(ϩ)-JH I (1)][1] and II [(ϩ)- idation (AE) and dihydroxylation (AD) Ϫ are very versatile
JH II (2)][2] secreted by the moth Hyalophora cecropia, the and efficient reactions for utilization in the synthesis of JHs
chemistry and biology of JHs has attracted the attention of in substantial quantities. AE was employed by Prestwich
many scientists. The synthesis of enantiomerically pure (ϩ)- and Wawrzenczyk[11] to prepare (ϩ)-JH I (1, 95% ee), while
´
JH I and (ϩ)-JH II remained a difficult task, as reviewed AD was applied to the synthesis of (ϩ)-JH III (3, 92% ee)
previously.[3Ϫ6] Indeed, it was only in 1990 that (ϩ)-JH I by Crispino and Sharpless.[12] An advantage of the AD ap-
(1) was shown to be 12,000 times more active than (Ϫ)-JH proach is the introduction of the two hydroxy groups at C-
I, when bioassayed by topical application against allatecto- 10 and C-11 at a late stage in the synthesis, eliminating the
mized fourth instar larvae of the silkworm moth, Bombyx need for a cumbersome protection-deprotection of the diol
mori.[7] The enantiomers of 1 used for the bioassay were system during the course of the synthesis. To synthesize
prepared by Mori and Fujiwhara, employing yeast reduc- (ϩ)-JH I (1) and II (2) employing AD, however, triene es-
tion as the key asymmetric process.[8,9] There are two ters 4 and 5 must be prepared efficiently. Because we had
known syntheses of (ϩ)-JH II (2): one by Mori and already developed this capability, largely in the course of
Fujiwhara,[8] and the other by Kosugi et al.[10] Both of the synthesis of (ϩ)-faranal (6), the trail pheromone of the
them, however, suffer from multi-step conversion into 2 Pharaoh’s ant,[13] we started our endeavor to synthesize
after introduction of the two chiral centers into the interme- (ϩ)-JH I (1) and II (2) employing AD.
diates.
Scheme 2 summarizes our synthesis of triene esters 4 and
5, the substrates for Sharpless AD.[14] Commercially avail-
able cyclopropyl methyl ketone (7) was converted into the
known diacetate 8[15] by Julia cleavage[16] of cyclopro-
pylmethylcarbinol, followed by transformations including
selenium dioxide oxidation of a terminal methyl group.[15]
Treatment of 8 with methylmagnesium bromide in the pres-
ence of dilithium tetrachlorocuprate under Schlosser condi-
tions[17] gave the known alcohol 9.[18] Tosylation of 9 to give
10 was followed by Finkelstein reaction to convert 10 to the
known iodide 11.[19] Alkylation of acetylene as its lithium
saltϪethylenediamine complex with 11 furnished 12 in a
moderate yield of 50%. Negishi’s zirconocene-catalyzed car-
boalumination[20] of 12 with triethylaluminium in the pres-
ence of a small amount of water in dichloromethane[21] was
followed by treatment with n-butyllithium and paraformal-
dehyde to give 13a in 31% yield. The observed low yield
must have been due to the bulkiness of the ethyl group,
because the yield of the lower homologue 13b[22] was 70%
when the same process was executed employing trimethylal-
uminium. The alcohols 13a and 13b were then converted
into the corresponding bromides 14a and 14b by treatment
with phosphorus tribromide.
Scheme 1. Structures of insect juvenile hormones and related com-
pounds
[‡]
Synthesis of Compounds with Juvenile Hormone Activity,
XXXII. Ϫ Part XXXI: H. Watanabe, H. Shimizu, K. Mori,
Synthesis 1994, 1249Ϫ1254.
[a]
Department of Chemistry, Faculty of Science, Science
Further transformations leading to the triene esters 4 and
5 were executed according to the method developed by Sum
and Weiler,[23] which had been successfully used in our pre-
University of Tokyo,
Kagurazaka 1-3, Shinjuku-ku, Tokyo 162-8601, Japan
Fax: (internat.) ϩ 81-3/3235-2214
Eur. J. Org. Chem. 2001, 2145Ϫ2150
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/0611Ϫ2145 $ 17.50ϩ.50/0
2145

T. Okochi, K. Mori
FULL PAPER
Phosphorylation of 15a and 15b as their enol forms fur-
nished 16a and 16b, which were separately treated with li-
thium dimethylcuprate to afford the desired triene esters 4
and 5. The overall yields of 4 and 5 were 1.8% and 4.1%,
respectively, on the basis of 7 (15 steps).
The remaining steps to (ϩ)-JH I (1) and (ϩ)-JH II (2)
are summarized in Scheme 3. In the key AD steps, we essen-
tially followed the procedure as reported by Crispino and
Sharpless[12] in their JH III synthesis. Asymmetric dihy-
droxylation of 4 in the presence of 1,4-bis(dihydroquini-
nephthalazine) [(DHQ)2-PHAL] was achieved by using
commercially available AD-mix-α to give, after chromato-
graphic separation, the desired (10S,11S)-diol 17a (46%),
(6S,7S)-diol 18a (7%), and crystalline (6S,7S,10S,11S)-te-
trol 19a (15%). The diol 17a was shown to be of 95% ee as
estimated by the HPLC analysis of the corresponding (R)-
α-methoxy-α-trifluoromethylphenylacetate (MTPA ester,
20a). Similarly, triene ester 5 furnished 17b (27%), 18b (5%),
and crystalline 19b (38%) upon AD with AD-mix-α . In
the case of 5, the double bond at C-6 with a methyl group
at C-7 was dihydroxylated almost as rapidly as the terminal
double bond at C-10, and therefore the tetrol 19b was the
major product. The enantiomeric purity of 17b as deter-
mined by the HPLC analysis of 20b was an ee of 92%, a
value slightly lower than that for 17a.
Finally, the diols 17a and 17b were converted into
(10R,11S)-(ϩ)-JH I (1) and (10R,11S)-(ϩ)-JH II (2), re-
spectively, via the corresponding monomesylates 21a and
21b according to the reported procedure.[8] Physical and
spectral properties of 1 and 2, including specific rotations,
were in good accord with the data previously published.[8,10]
The enantiomeric purity of 2 was about 93% ee as estimated
by HPLC analysis on Chiralcel OB-H , while that of 1
could not be estimated by HPLC analysis due to lack of
Scheme 2. Syntheses of triene esters 4 and 5; reagents: (a) MeMgBr,
Li2CuCl4, THF (83%); (b) TsCl, C5H5N, CH2Cl2; (c) NaI, Me2CO
(92%, 2 steps); (d) HCϵCLi·H2N(CH2)2NH2, DMSO (50%); (e)
Et3Al, Cp2ZrCl2, H2O, CH2Cl2 for 13a; (f) Me3Al, Cp2ZrCl2, H2O,
CH2Cl2 for 13b; (g) nBuLi, (CH2O)n, hexane, THF (31% for 13a
and 70% for 13b); (h) PBr3, Et2O; (i) MeCOCH2CO2Me, NaH,
nBuLi, THF (83% for 15a, 77% for 15b); (j) NaH, (EtO)2P(O)Cl,
THF; (k) Me2CuLi, Et2O (60% for 4 and 66% for 5, 2 steps)
vious JH synthesis.[8] Accordingly, the dianion derived from separation of its enantiomers on the same column. The en-
methyl acetoacetate was alkylated with 14a or 14b to give antiomeric purity of 1 was assumed to be about 95% ee,
β-oxo ester 15a or 15b in 83 and 77% yield, respectively. reflecting that of the starting diol 17a.
Scheme 3. Synthesis of (10R,11S)-(ϩ)-JH I (1) and (10R,11S)-(ϩ)-JH II (2); reagents: (a) AD-mix-α , MeSO2NH2, tBuOH, H2O (65%
for 17a and 35% for 17b); (b) Ms2O, Et3N, CH2Cl2; (c) K2CO3, MeOH (91% for 1 and 84% for 2, 2 steps)
2146
Eur. J. Org. Chem. 2001, 2145Ϫ2150

New Enantioselective Synthesis of (10R,11S)-(ϩ)-Juvenile Hormones I and II
FULL PAPER
(3E)-1-Iodo-4-methylhex-3-ene (11): NaI (61.6 g, 411 mmol) was
added to a stirred solution of crude 10 (62.3 g, 274 mmol) in dry
acetone (600 mL), and the mixture was stirred and refluxed for
3 h. It was cooled to room temperature, quenched with water, and
extracted with pentane. The pentane extract was washed with satur-
ated aqueous Na2S2O3 and brine, dried with MgSO4, and concen-
trated in vacuo. The residue was chromatographed on silica gel
(pentane) to give 56.6 g (92% from 9) of 11. Ϫ n2D3 ϭ 1.5169. Ϫ IR
In conclusion, the naturally occurring (ϩ)-enantiomers
of JH I (1, 95% ee) and JH II (2, 92Ϫ93% ee) were synthe-
sized by employing Sharpless asymmetric dihydroxylation
as the key step. The overall yields of 1 and 2 were 1.0% and
1.2%, respectively, from 7 (18 steps). Our previous syntheses
of 1 and 2 gave them in 0.34% and 0.13% overall yields (21
steps), respectively, from commercially available 2-methyl-
cyclohexane-1,3-dione, although enantiomerically pure 1
and 2 (ca. 100% ee) could be secured.[8] These results there-
(film): νmax ϭ 1670 cmϪ1 (w, CϭC). Ϫ 1H NMR (400 MHz,
˜
CDCl3): δ ϭ 1.00 (t, J ϭ 7.2 Hz, 3 H, 6-H), 1.61 (s, 3 H, 4-Me),
fore substantially improved the overall yields and slightly 2.00 (q, J ϭ 7.2 Hz, 2 H, 5-H), 2.58 (q, J ϭ 7.2 Hz, 2 H, 2-H), 3.11
(t, J ϭ 7.2 Hz, 2 H, 1-H), 5.09 (t, J ϭ 7.2 Hz, 1 H, 3-H). These 1H
NMR spectroscopic data are identical with those reported for
11.[19] Ϫ HR-MS [C7H13I]: calcd. 224.0062; found 224.0068.
shortened the synthetic routes. Both Kosugi[10] and
Prestwich[11] reported their works as preliminary commun-
ications, and exact overall yields of their syntheses could
not be calculated. The present synthesis, however, is still not
efficient enough, due partly to the poor regioselectivity at
(5E)-6-Methyloct-5-en-1-yne (12):
A solution of 11 (55.6 g,
248 mmol) in dry DMSO (100 mL) was added dropwise under
the key AD step, and further improvement in the efficiency argon to a stirred and cooled (10 °C) suspension of lithium
acetylideϪethylenediamine complex (27.4 g, 297 mmol) in dry
DMSO (200 mL). The mixture was stirred for 1 h at 10 °C and
quenched with water. To this was added 1  HCl, and the mixture
was extracted with pentane. The organic layer was washed with
saturated aqueous NaHCO3 and brine, dried with MgSO4, and
concentrated under atmospheric pressure with a Vigreux column.
The residue was distilled to give 15.1 g (50%) of 12; b.p. 76Ϫ79 °C/
80 Torr. Ϫ n2D8 ϭ 1.4450. Ϫ IR (film): ν˜max ϭ 3310 cmϪ1 (s,
ϵCϪH), 2120 (m, CϵC), 1670 (w, CϭC). Ϫ 1H NMR (400 MHz,
CDCl3): δ ϭ 0.99 (t, J ϭ 7.4 Hz, 3 H, 8-H), 1.62 (s, 3 H, 6-Me),
1.94 (t, J ϭ 2.6 Hz, 1 H, 1-H), 2.00 (q, J ϭ 7.4, 2 H, 7-H),
2.17Ϫ2.29 (m, 4 H, 3-, 4-H), 5.17 (m, 1 H, 5-H). Ϫ HR-MS
[C9H14]: calcd. 122.1095; found 122.1093.
of JH synthesis to provide quantities of JHs sufficient for
biological studies is still awaited.
Experimental Section
Boiling points and melting points: uncorrected values. Ϫ IR: Jasco
A-102. Ϫ 1H NMR: Jeol JNM-EX 90A (90 MHz), Jeol JNM-
LA400 (400 MHz), and Jeol JNM-LA500 (500 MHz) (TMS at δ ϭ
0.00 or CHCl3 at δ ϭ 7.26 as an internal standard). Ϫ 13C NMR:
Jeol JNM-LA400 (100 MHz) and Jeol JNM-LA500 (126 MHz)
(CDCl3 at δ ϭ 77.0 as an internal standard). Ϫ Optical rotation:
Jasco DIP-1000. Ϫ MS: Jeol JMS-AX505HA. Ϫ Column chroma-
tography: Merck Kieselgel 60 Art 1.07734. Ϫ TLC: 0.25 mm Merck
silica gel plates (60FϪ254). ϪMPLC: Pegasil Prepsil-5020Ϫ12B.
(2E,6E)-3-Ethyl-7-methylnona-2,6-dien-1-ol (13a): Water (443 µL,
24.6 mmol) was slowly added at Ϫ23 °C under argon, with vigor-
ous stirring, to a stirred and cooled solution of bis(cyclopentadien-
yl)zirconium dichloride (1.05 g, 3.52 mmol) and triethylaluminium
(0.92  in hexane, 53 mL, 49 mmol) in dry CH2Cl2 (20 mL). After
stirring for 30 min at Ϫ23 °C, a solution of 12 (2.00 g, 16.4 mmol)
in dry CH2Cl2 (20 mL) was added dropwise to the reaction mixture.
It was then stirred for 2 h at Ϫ23 °C and concentrated under re-
duced pressure. The organic compounds were dissolved by addition
of dry hexane (20 mL), and the hexane solution was transferred
into another flask through a cannula. To this was added n-butylli-
thium (1.60  in hexane, 10.3 mL, 16.4 mmol). After dissolving the
precipitate by addition of THF (20 mL), paraformaldehyde
(984 mg, 32.8 mmol) was added to the mixture. It was stirred for
14 h at room temperature, and quenched with MeOH. To this was
added 1  HCl, and the mixture was filtered through a pad of
Celite. The filtrate was extracted with diethyl ether, and the ether
solution was washed with saturated aqueous NaHCO3 and brine,
dried with MgSO4, and concentrated in vacuo. The residue was
chromatographed on silica gel (hexane/ethyl acetate, 10:1) to give
(3E)-4-Methylhex-3-en-1-ol (9): A solution of Li2CuCl4 (0.75  in
THF, 2.0 mL, 1.5 mmol) was added at Ϫ10 °C under argon to a
stirred and cooled solution of 8[15] (6.80 g, 34.0 mmol) in dry THF
(40 mL). To this was added dropwise a solution of MeMgBr (0.95
 in THF, 143 mL, 136 mmol). The mixture was allowed to warm
to room temperature and stirred for 1 h. A saturated aqueous
NH4Cl solution was then added. The mixture was extracted with
ethyl acetate, and the organic layer was washed with brine, dried
with MgSO4, and concentrated in vacuo. The residue was distilled
to give 3.24 g (83%) of 9; b.p. 82Ϫ84 °C/23 Torr. Ϫ n2D3 ϭ 1.4484.
Ϫ IR (film): ν˜max ϭ 3350 cmϪ1 (br. s, OϪH), 1675 (w, CϭC), 1050
1
(s, CϪO). Ϫ H NMR (90 MHz, CDCl3): δ ϭ 1.00 (t, J ϭ 7.4 Hz,
3 H, 6-H), 1.49 (s, 1 H, OϪH), 1.65 (s, 3 H, 4-Me), 1.86Ϫ2.43 (m,
4 H, 2-, 5-H), 3.62 (t, J ϭ 6.7 Hz, 2 H, 1-H), 5.12 (br. t, J ϭ 7.3 Hz,
1 H, 3-H). These data are identical with those reported for 9.[18]
(3E)-4-Methylhex-3-enyl Tosylate (10): TsCl (68.8 g, 361 mmol) was
added portionwise at 0 °C to a stirred and cooled solution of 9
(31.5 g, 274 mmol) in CH2Cl2 (300 mL) and pyridine (44 mL,
545 mmol). After stirring for 7 h at 0 °C, the mixture was quenched
with water and concentrated in vacuo to remove CH2Cl2. It was
extracted with diethyl ether, and the ether solution was washed with
1  HCl, water, and brine, dried with MgSO4, and concentrated in
vacuo to give 62.3 g (quant.) of crude 10. This was employed in the
923 mg (31%) of 13a. Ϫ n2D8 ϭ 1.4740. Ϫ IR (film): νmax ϭ 3330
˜
cmϪ1 (br. s, OϪH), 1670 (w, CϭC), 1010 (s, CϪO). Ϫ 1H NMR
(500 MHz, CDCl3): δ ϭ 0.98 (t, J ϭ 7.4 Hz, 3 H, CH2CH3), 0.99
(t, J ϭ 7.6 Hz, 3 H, CH2CH3), 1.28 (br. s, 1 H, OϪH), 1.60 (s, 3
H, 7-Me), 1.95Ϫ2.15 (m, 8 H, 4-, 5-, 8-H, 3-CH2CH3), 4.16 (d, J ϭ
7.0 Hz, 2 H, 1-H), 5.11 (br. t, J ϭ 6.7 Hz, 1 H, 6-H), 5.38 (t, J ϭ
7.0 Hz, 1 H, 2-H). Ϫ C12H22O (182.3): calcd. C 79.06, H 12.16;
found C 78.94, H 12.24.
˜
next step without further purification. Ϫ IR (film): νmax ϭ 1670
cmϪ1 (w, CϭC), 1600 (m, Ar), 1500 (w, Ar), 1360 (s, SO2), 1180 (s,
SO2). Ϫ 1H NMR (90 MHz, CDCl3): δ ϭ 0.94 (t, J ϭ 7.4 Hz, 3
H, 6-H), 1.55 (s, 3 H, 4-Me), 1.95 (q, J ϭ 7.4 Hz, 2 H, 5-H), (2E,6E)-3,7-Dimethylnona-2,6-dien-1-ol (13b): Water (773 µL,
2.15Ϫ2.50 (m, 2 H, 2-H), 2.45 (s, 3 H, Ar-CH3), 3.99 (t, J ϭ 7.1 Hz, 42.9 mmol) was slowly added at Ϫ23 °C under argon, with vigor-
2 H, 1-H), 4.96 (t, J ϭ 7.1 Hz, 1 H, 3-H), 7.33 (d, J ϭ 8.3 Hz, 2 ous stirring, to a stirred and cooled solution of bis(cyclopentadien-
H, Ar), 7.79 (d, J ϭ 8.3 Hz, 2 H, Ar).
yl)zirconium dichloride (1.84 g, 6.17 mmol) and trimethylalu-
Eur. J. Org. Chem. 2001, 2145Ϫ2150
2147

T. Okochi, K. Mori
FULL PAPER
minium (1.0  in hexane, 86 mL, 86 mmol) in dry CH2Cl2 (50 mL). (t, J ϭ 7.6 Hz, 3 H, CH2CH3), 0.97 (t, J ϭ 7.4 Hz, 3 H, CH2CH3),
After stirring for 30 min at Ϫ23 °C, a solution of 12 (3.50 g, 1.59 (s, 3 H, 11-Me), 1.93Ϫ2.09 (m, 8 H, 8-, 9-, 12-H, 7-CH2CH3),
28.6 mmol) in dry CH2Cl2 (30 mL) was added dropwise to the reac- 2.30 (q like, J ϭ 7.4 Hz, 2 H, 5-H), 2.56 (t, J ϭ 7.4 Hz, 2 H, 4-H),
tion mixture. It was then stirred for 30 min at Ϫ23 °C and concen-
trated under reduced pressure. The organic compounds were dis-
3.45 (s, 2 H, 2-H), 3.74 (s, 3 H, CO2Me), 5.02 (t, J ϭ 7.2 Hz, 1 H,
6-H), 5.08 (br. t, J ϭ 6.7 Hz, 1 H, 10-H). Some peaks considered
solved by addition of dry hexane (30 mL), and the hexane solution to belong to the enol form could also be observed [δ ϭ 12.01 (s,
was transferred into another flask through a cannula. To this was 0.07 H, OϪH), 3.72 (s, 0.21 H, CO2Me)]. Ϫ C17H28O3 (280.4):
added n-butyllithium (1.60  in hexane, 17.9 mL, 28.6 mmol). After calcd. C 72.82, H 10.06; found C 72.85, H 10.34.
dissolving the precipitate by addition of THF (30 mL), paraformal-
Methyl (6E,10E)-7,11-Dimethyl-3-oxotrideca-6,10-dienoate (15b):
In the same manner as described above, 14b (4.60 g, 19.7 mmol)
was converted into 15b (4.37 g, 83% from 13b). Ϫ n2D4 ϭ 1.4745. Ϫ
dehyde (1.71 g, 57.2 mmol) was added to the mixture. It was stirred
for 1 h at room temperature, and quenched with MeOH. To this
was added 1  HCl, and the mixture was concentrated in vacuo.
The residue was extracted with diethyl ether. The ether solution
was washed with saturated aqueous NaHCO3 and brine, dried with
MgSO4, and concentrated in vacuo. The residue was chromato-
graphed on silica gel (hexane/ethyl acetate, 10:1) to give 3.35 g
IR (film): νmax ϭ 1760 cmϪ1 (s, CϭO), 1725 (s, CϭO), 1660 (w,
˜
1
CϭO), 1640 (m, CϭC). Ϫ H NMR (500 MHz, CDCl3): δ ϭ 0.97
(t, J ϭ 7.5 Hz, 3 H, 13-H), 1.59 (s, 3 H, 11-Me), 1.61 (s, 3 H, 7-
Me), 1.94Ϫ2.01 (m, 4 H, two of 8-, 9-, 12-H), 2.03Ϫ2.09 (m, 2 H,
one of 8-, 9-, 12-H), 2.29 (q like, J ϭ 7.3 Hz, 2 H, 5-H), 2.56 (t,
J ϭ 7.3 Hz, 2 H, 4-H), 3.44 (s, 2 H, 2-H), 3.74 (s, 3 H, CO2Me),
5.07 (br. t, J ϭ 7.3 Hz, 2 H, 6, 10-H). Some peaks considered to
belong to the enol form could also be observed [δ ϭ 12.01 (s, 0.06
H, OϪH), 3.72 (s, 0.18 H, CO2Me)]. Ϫ C16H26O3 (266.4): calcd. C
72.14, H 9.84; found C 72.17, H 10.10.
(70%) of 13b. Ϫ n2D6 ϭ 1.4710. Ϫ IR (film): νmax ϭ 3350 cmϪ1 (br.
˜
1
s, OϪH), 1670 (w, CϭC), 1000 (s, CϪO). Ϫ H NMR (500 MHz,
CDCl3): δ ϭ 0.98 (t, J ϭ 7.5 Hz, 3 H, 9-H), 1.30 (br. s, 1 H, OϪH),
1.60 (s, 3 H, 7-Me), 1.68 (s, 3 H, 3-Me), 1.98 (q, J ϭ 7.5 Hz, 2 H,
8-H), 2.04 (br. t, J ϭ 7.4 Hz, 2 H, 4-H), 2.12 (q like, J ϭ 7.0 Hz, 2
H, 5-H), 4.15 (d, J ϭ 7.1 Hz, 2 H, 1-H), 5.09 (br. t, 1 H, 6-H), 5.42
(t, J ϭ 7.1 Hz, 1 H, 2-H). These IR and 1H NMR spectroscopic
data are identical with those reported for 13b.[22] Ϫ C11H20O
(168.2): calcd. C 78.51, H 11.98; found C 78.51, H 12.05.
Methyl (2E,6E,10E)-7-Ethyl-3,11-dimethyltrideca-2,6,10-trienoate
(4): A solution of 15a (2.07 g, 7.38 mmol) in dry THF (20 mL) was
added dropwise at 0 °C under argon to a stirred and cooled suspen-
sion of NaH (60% dispersion in mineral oil, 429 mg, 11.1 mmol) in
dry THF (8 mL). The mixture was stirred at 0 °C for 15 min, and
(EtO)2P(O)Cl (1.60 mL, 1.92 g, 11.1 mmol) was added dropwise at
0 °C. After stirring for 1.5 h, the mixture was quenched with satur-
ated aqueous NH4Cl and extracted with diethyl ether. The ether
solution was washed with saturated aqueous NaHCO3 and brine,
dried with Na2SO4, and concentrated in vacuo to give 3.16 g of
crude phosphoric ester 16a. This was dissolved in dry diethyl ether
(30 mL), and this ethereal solution was added dropwise to a solu-
tion of Me2CuLi (0.50 , 43 mL, 22 mmol), prepared according to
the reported procedure,[23] at Ϫ70 °C under argon. After stirring
for 2 h at Ϫ70 °C, the reaction mixture was quenched with satur-
ated aqueous NH4Cl. The stirring was continued for an additional
5 min, and the mixture was filtered through a pad of Celite. The
filtrate was extracted with diethyl ether, and the ether solution was
washed with saturated aqueous NaHCO3 and brine, dried with
MgSO4, and concentrated in vacuo. The residue was chromato-
graphed on silica gel (hexane/ethyl acetate, 100:1) to give 1.71 g
(83% from 15a) of 4. Further purification was curried out by
MPLC (hexane/ethyl acetate, 100:1) to give pure 4 (1.24 g, 60%
(2E,6E)-1-Bromo-3-ethyl-7-methylnona-2,6-diene (14a): Phosphorus
tribromide (765 µL, 4.20 mmol) was added to a stirred and cooled
solution of 13a (2.19 g, 12.0 mmol) in dry diethyl ether (25 mL) at
Ϫ40 °C under argon. The mixture was allowed to warm to Ϫ30
°C, stirring for 20 min, and quenched with MeOH. It was diluted
with water and extracted with diethyl ether. The ether solution was
washed with saturated aqueous NaHCO3 and brine, dried with
Na2SO4, and concentrated in vacuo to give 2.68 g (91%) of crude
14a. It was employed in the next step without further purification.
1
Ϫ IR (film): νmax ϭ 1640 cmϪ1 (w, CϭC), 1200 (m). Ϫ H NMR
˜
(90 MHz, CDCl3): δ ϭ 0.98 (t, J ϭ 7.7 Hz, 3 H, 9-H), 1.04 (t, J ϭ
7.6 Hz, 3 H, 3-CH2CH3), 1.60 (s, 3 H, 7-Me), 1.80Ϫ2.33 (m, 8 H,
4-, 5-, 8-H, 3-CH2CH3), 4.04 (d, J ϭ 8.6 Hz, 2 H, 1-H), 5.09 (m, 1
H, 6-H), 5.49 (t, J ϭ 8.6 Hz, 1 H, 2-H).
(2E,6E)-1-Bromo-3,7-dimethylnona-2,6-diene (14b): In the same
manner as described above, 13b (3.32 g, 19.7 mmol) was converted
into 14b (4.60 g, quant.). Ϫ IR (film): νmax ϭ 1660 cmϪ1 (m, Cϭ
˜
C), 1200 (m). Ϫ 1H NMR (90 MHz, CDCl3): δ ϭ 0.98 (t, J ϭ
7.4 Hz, 3 H, 9-H), 1.60 (s, 3 H, 7-Me), 1.72 (s, 3 H, 3-Me)
1.80Ϫ2.20 (m, 6 H, 4-, 5-, 8-H), 4.02 (d, J ϭ 8.4 Hz, 2 H, 1-H),
5.09 (br. s, 1 H, 6-H), 5.53 (br. t, J ϭ 8.4 Hz, 1 H, 2-H).
from 15a). Ϫ n2D7 ϭ 1.4821. Ϫ IR (film): νmax ϭ 1720 cmϪ1 (s, Cϭ
˜
1
O), 1645 (m, CϭC). Ϫ H NMR (500 MHz, CDCl3): δ ϭ 0.96 (t,
Methyl
(6E,10E)-7-Ethyl-11-methyl-3-oxotrideca-6,10-dienoate
J ϭ 7.6 Hz, 3 H, CH2CH3), 0.98 (t, J ϭ 7.4 Hz, 3 H, CH2CH3),
1.59 (s, 3 H, 11-Me), 1.94Ϫ2.09 (m, 8 H, four of 4-, 5-, 8-, 9-, 12-
H and 7-CH2CH3), 2.17 (d, J ϭ 1.3 Hz, 3 H, 3-Me), 2.13Ϫ2.22 (m,
4 H, two of 4-, 5-, 8-, 9-, 12-H and 7-CH2CH3), 3.68 (s, 3 H,
CO2Me), 5.05 (br. t, J ϭ 6.3 Hz, 1 H, 6-H or 10-H), 5.09 (br. t,
J ϭ 6.8 Hz, 1 H, 6-H or 10-H), 5.67 (br. s, 1 H, 2-H). Ϫ C18H30O2
(278.4): calcd. C 77.65, H 10.86; found C 77.67, H 11.13.
(15a): A solution of methyl acetoacetate (1.81 g, 15.6 mmol) in dry
THF (15 mL) was added dropwise at 0 °C under argon to a stirred
and cooled suspension of NaH (60% dispersion in mineral oil,
686 mg, 17.1 mmol) in dry THF (20 mL). The mixture was stirred
for 15 min at 0 °C, and n-butyllithium (1.59  in hexane, 9.81 mL,
15.6 mmol) was added to it. After stirring for 40 min, a solution
of 14a (2.68 g, 10.9 mmol) in dry THF (15 mL) was added drop-
wise, and the mixture was stirred for 1 h at 0 °C. The reaction Methyl (2E,6E,10E)-3,7,11-Trimethyltrideca-2,6,10-trienoate (5): In
mixture was then quenched with saturated aqueous NH4Cl and
the same manner as described above, 15b (660 mg, 2.48 mmol) was
extracted with diethyl ether. The ether solution was washed with converted into 5 (434 mg, 66% from 15b). Ϫ n2D6 ϭ 1.4825. Ϫ IR
1
water and brine, dried with MgSO4, and concentrated in vacuo.
The residue was chromatographed on silica gel (hexane/ethyl acet-
(film): ν˜max ϭ 1720 cmϪ1 (s, CϭO), 1650 (m, CϭC). Ϫ H NMR
(500 MHz, CDCl3): δ ϭ 0.97 (t, J ϭ 7.5 Hz, 3 H, 13-H), 1.59 (s, 3
ate, 30:1) to give 2.60 g (77% from 13a) of 15a. Ϫ n2D7 ϭ 1.4704. Ϫ H, 7-Me or 11-Me), 1.60 (s, 3 H, 7-Me or 11-Me), 1.94Ϫ2.10 (m,
IR (film): ν˜max ϭ 1760 cmϪ1 (s, CϭO), 1720 (s, CϭO), 1660 (m,
6 H, three of 4-, 5-, 8-, 9-, 12-H), 2.16 (d, J ϭ 1.2 Hz, 3 H, 3-Me),
1
CϭO), 1640 (m, CϭC). Ϫ H NMR (400 MHz, CDCl3): δ ϭ 0.95 2.13Ϫ2.20 (m, 4 H, two of 4-, 5-, 8-, 9-, 12-H), 3.68 (s, 3 H,
2148
Eur. J. Org. Chem. 2001, 2145Ϫ2150

New Enantioselective Synthesis of (10R,11S)-(ϩ)-Juvenile Hormones I and II
FULL PAPER
CO2Me), 5.06Ϫ5.11 (m, 2 H, 6-, 10-H), 5.67 (br. s, 1 H, 2-H). Ϫ (s, CϭC). These IR data are identical with those reported for 17b.[8]
1
C17H28O2 (264.4): calcd. C 77.22, H 10.67; found C 77.21, H 10.96. Ϫ H NMR (500 MHz, CDCl3): δ ϭ 0.92 (t, J ϭ 7.5 Hz, 3 H, 13-
H), 1.08 (s, 3 H, 11-Me), 1.35Ϫ1.58 (m, 4 H, 9-, 12-H), 1.61, (s, 3
Methyl (2E,6E,10S,11S)-7-Ethyl-10,11-dihydroxy-3,11-dimethyltri-
H, 7-Me), 1.99 (br. s, 2 H, OϪH), 2.15 (d, J ϭ 0.9 Hz, 3 H, 3-Me),
2.03Ϫ2.27 (m, 6 H, 4-, 5-, 8-H), 3.37 (dd, J ϭ 10.7, 1.8 Hz, 1 H,
10-H), 3.67 (s, 3 H, CO2Me), 5.14 (br. s, 1 H, 6-H), 5.66 (s, 1 H,
2-H). Ϫ C17H30O4 (298.4): calcd. C 68.42, H 10.13; found C 68.63,
H 10.34. Ϫ 18b: n2D6 ϭ 1.4920. Ϫ [α]2D5 ϭ Ϫ25 (c ϭ 0.40, MeOH).
[14]
deca-2,6-dienoate (17a): AD-mix-α
(4.53 g) and MeSO2NH2
(307 mg, 3.23 mmol) were added to a stirred and cooled solution
of 4 (900 mg, 3.23 mmol) in tBuOH (22.5 mL) and water (22.5
mL). After stirring for 24 h at 0° C, Na2S2O3·5H2O (4.5 g,
18 mmol) was added to the mixture, which was allowed to warm
to room temperature, with stirring, over 1 h. The mixture was ex-
tracted with ethyl acetate, and the organic layer was washed with
1  KOH and brine, dried with MgSO4, and concentrated in vacuo.
The residue was chromatographed on silica gel (hexane/ethyl acet-
ate, 1:1) to give recovered 4 (267 mg, 30%) and a mixture of 17a
and 18a (540 mg, 54%). Further elution with ethyl acetate gave
165 mg (15%) of tetrol 19a. The mixture of 17a and 18a was rechro-
matographed on silica gel (hexane/ethyl acetate, 1:1) to give pure
17a [467 mg, 46% (65% based on the consumed 4)] and 70 mg (7%)
of 6,7-diol 18a. The tetrol 19a was recrystallized from benzene to
give 142 mg (12%) of colorless fluffy crystals. Ϫ 17a: n2D8 ϭ 1.4875.
Ϫ [α]2D7 ϭ Ϫ17.2 (c ϭ 1.00, MeOH) {ref.[8] [α]2D5 ϭ Ϫ17 (c ϭ 0.99,
Ϫ IR (film): νmax ϭ 3500 cmϪ1 (br. s, OϪH), 1730 (s, CϭO), 1660
˜
(s, CϭC). Ϫ 1H NMR (500 MHz, CDCl3): δ ϭ 0.97 (t, J ϭ 7.5 Hz,
3 H, 13-H), 1.12, (s, 3 H, 7-Me), 1.61 (s, 3 H, 11-Me), 1.43Ϫ1.68,
(m, 4 H, 5-, 8-H), 2.03 (br. s, 2 H, OϪH), 1.95Ϫ2.23 (m, 5 H, 4-,
9-, 12-H), 2.17 (s, 3 H, 3-Me), 2.42Ϫ2.48 (m, 1 H, 4-H), 3.38 (dd,
J ϭ 10.7, 1.8 Hz, 1 H, 6-H), 3.68 (s, 3 H, CO2Me), 5.11 (t, J ϭ
6.1 Hz, 1 H, 10-H), 5.71 (s, 1 H, 2-H). Ϫ C17H30O4 (298.4): calcd.
C 68.42, H 10.13; found C 68.08, H 10.05. Ϫ 19b: m.p. 102Ϫ103
°C. Ϫ [α]2D8 ϭ Ϫ49.0 (c ϭ 1.02, MeOH). Ϫ IR (film): νmax ϭ 3330
˜
1
cmϪ1 (br. s, OϪH), 1720 (s, CϭO), 1650 (m, CϭC). Ϫ H NMR
(500 MHz, CDCl3): δ ϭ 0.94 (t, J ϭ 7.5 Hz, 3 H, 13-H), 1.11, (s,
3 H, 7-Me or 11-Me), 1.12, (s, 3 H, 7-Me or 11-Me), 1.43Ϫ1.75
(m, 12 H, 5-, 8-, 9-, 12-H, OϪH), 2.18 (d, J ϭ 1.2 Hz, 3 H, 3-Me),
2.17Ϫ2.26 (m, 1 H, 4-H), 2.42Ϫ2.49 (m, 1 H, 4-H), 3.37 (dd, J ϭ
10.7, 1.8 Hz, 1 H, 6-H or 10-H), 3.41 (dd, J ϭ 10.4, 1.8 Hz, 1 H,
6-H or 10-H), 3.69 (s, 3 H, CO2Me), 5.72 (s, 1 H, 2-H). Ϫ C17H32O6
(332.4): calcd. C 61.42, H 9.70; found C 61.37, H 9.87.
MeOH)}. Ϫ IR (film): νmax ϭ 3450 cmϪ1 (br. s, OϪH), 1720 (s,
˜
CϭO), 1645 (s, CϭC). These IR data are identical with those re-
1
ported for 17a.[8] Ϫ H NMR (500 MHz, CDCl3): δ ϭ 0.93 (t, J ϭ
7.6 Hz, 3 H, 13-H), 0.97 (t, J ϭ 7.6 Hz, 3 H, 7-CH2CH3), 1.08 (s,
3 H, 11-Me), 1.35Ϫ1.58 (m, 4 H, 9-, 12-H), 1.75 (br. s, 2 H, OϪH),
1.95Ϫ2.10 (m, 4 H, two of 4-, 5-, 8-H and 7-CH2CH3), 2.16 (d, Determination of the Enantiomeric Purities of 17a and 17b: The ee
J ϭ 1.0 Hz, 3 H, 3-Me), 2.13Ϫ2.32 (m, 4 H, two of 4-, 5-, 8-H and values of 17a and 17b were determined by HPLC analysis of the
7-CH2CH2), 3.39 (dd, J ϭ 10.4, 1.8 Hz, 1 H, 10-H), 3.69 (s, 3 H,
corresponding (R)-MTPA esters 20a and 20b (column: Pegasil Sil-
CO2Me), 5.09 (br. t, J ϭ 7.0 Hz, 1 H, 6-H), 5.67 (s, 1 H, 2-H). Ϫ ica 60Ϫ5, 4.6 mm ϫ 25 cm; solvent: hexane/THF, 7:1; flow rate:
C18H32O4 (312.4): calcd. C 69.19, H 10.32; found C 69.17, H 10.61. 1.0 mL/min; detection: 254 nm). Ϫ17a: 95% ee; (10S,11S)-20a:
Ϫ 18a: n2D6 ϭ 1.4929. Ϫ [α]2D7 ϭ Ϫ21.1 (c ϭ 1.00, MeOH). Ϫ IR
tR ϭ 11.1 min (2.3%); (10R,11R)-20a: tR ϭ 12.6 min (97.7%). Ϫ
(film): νmax ϭ 3480 cmϪ1 (br. s, OϪH), 1720 (s, CϭO), 1640 (s, 17b: 92% ee; (10S,11S)-20b: tR ϭ 12.4 min (3.9%); (10R,11R)-20b:
CϭC). Ϫ 1H NMR (500 MHz, CDCl3): δ ϭ 0.90 (t, J ϭ 7.6 Hz, 3 tR ϭ 14.1 min (96.1%).
H, 7-CH2CH3), 0.97 (t, J ϭ 7.5 Hz, 3 H, 13-H), 1.37Ϫ1.45 (m, 1
˜
Methyl (2E,6E,10R,11S)-10,11-Epoxy-7-ethyl-3,11-dimethyltrideca-
2,6-dienoate (1): Ms2O (167 mg, 0.96 mmol) was added at 0° C to
a stirred and cooled solution of 17a (250 mg, 0.80 mmol) in dry
CH2Cl2 (3 mL) and Et3N (246 µL, 1.76 mmol). After having been
stirred for 2 h at 0 ° C, the mixture was quenched with water and
extracted with ethyl acetate. The organic layer was washed with
saturated aqueous NaHCO3 and brine, and concentrated in vacuo
to give 287 mg of crude 21a. This was dissolved in MeOH (15 mL),
and K2CO3 (166 mg, 1.20 mmol) was added to it at room temper-
ature. After stirring for 30 min, the mixture was quenched with
water and concentrated to remove MeOH. The residue was ex-
tracted with ethyl acetate, and the extract was washed with brine
and concentrated in vacuo. The residue was chromatographed on
silica gel (hexane/ethyl acetate, 10:1) to give 175 mg (91% based on
the consumed 17a) of 1. Further elution (hexane/ethyl acetate, 1:1)
H, one proton of 5-, 8-H or 7-CH2CH3), 1.61 (s, 3 H, 11-Me),
1.48Ϫ1.68, (m, 5 H, five protons of 5-, 8-H and 7-CH2CH3), 1.86
(br. s, 2 H, OϪH), 1.95Ϫ2.10 (m, 4 H, 9-, 12-H), 2.18 (d, J ϭ
1.2 Hz, 3 H, 3-Me), 2.14Ϫ2.24 (m, 1 H, 4-H), 2.42Ϫ2.49 (m, 1 H,
4-H), 3.48 (dd, J ϭ 10.6, 2.0 Hz, 1 H, 6-H), 3.68 (s, 3 H, CO2Me),
5.11 (br. t, J ϭ 7.0 Hz, 1 H, 10-H), 5.72 (br. s, 1 H, 2-H). Ϫ
C18H32O4 (312.4): calcd. C 69.19, H 10.32; found C 68.86, H 10.34.
Ϫ 19a: m.p. 123Ϫ124 °C. Ϫ [α]2D7 ϭ Ϫ44.6 (c ϭ 1.01, MeOH). Ϫ
IR (film): ν˜max ϭ 3330 cmϪ1 (br. s, OϪH), 1730 (s, CϭO), 1650 (s,
CϭC). Ϫ 1H NMR (500 MHz, CDCl3): δ ϭ 0.88 (t, J ϭ 7.5 Hz, 3
H, 7-CH2CH3), 0.94 (t, J ϭ 7.6 Hz, 3 H, 13-H), 1.10, (s, 3 H, 11-
Me), 1.34Ϫ1.83 (m, 10 H, 5-, 8-, 9-, 12-H, 7-CH2CH3), 2.18 (d,
J ϭ 1.0 Hz, 3 H, 3-Me), 2.19 (br. s, 4 H, OϪH), 2.14Ϫ2.26 (m, 1
H, 4-H), 2.41Ϫ2.48 (m, 1 H, 4-H), 3.41 (dd, J ϭ 10.5, 2.0 Hz, 1
H, 10-H), 3.45 (dd, J ϭ 10.5, 2.0 Hz, 1 H, 6-H), 3.69 (s, 3 H,
CO2Me), 5.72 (br. s, 1 H, 2-H). Ϫ C18H34O6 (346.5): calcd. C 62.40,
H 9.89; found C 62.39, H 10.18.
afforded 39 mg of the recovered 17a. Ϫ 1: n2D6 ϭ 1.4769. Ϫ [α]2D7
ϭ
ϩ12.7 (c ϭ 1.01, MeOH) {ref.[8] [α]2D2.5 ϭ ϩ14.5 (c ϭ 0.78,
MeOH)}. Ϫ IR (film): νmax ϭ 3000 cmϪ1 (s, CϪH), 2900 (m,
˜
Methyl (2E,6E,10S,11S)-10,11-Dihydroxy-3,7,11-trimethyltrideca-
2,6-dienoate (17b): In the same manner as described above, reco-
CϪH), 1720 (s, CϭO), 1650 (m, CϭC), 1435 (m), 1380 (m), 1360
(m), 1280 (w), 1220 (s, CϪOϪC), 1150 (s, CϪOϪC), 1060 (w),
vered 5 (143 mg, 24%), a mixture of 17b and 18b (252 mg, 35%) 1030 (w), 880 (m). Ϫ 1H NMR (400 MHz, CDCl3): δ ϭ 0.96 (t,
and tetraol 19b (286 mg, 38%) were obtained from 588 mg
(2.22 mmol) of 5. The mixture of 17b and 18b was rechromato-
J ϭ 7.6 Hz, 3 H, CH2CH3), 1.00 (t, J ϭ 7.6 Hz, 3 H, CH2CH3),
1.27, (s, 3 H, 11-Me), 1.42Ϫ1.69, (m, 4 H, 9, 12-H), 2.16 (d, J ϭ
graphed on silica gel (hexane/ethyl acetate, 1:1) to give pure 17b 1.0 Hz, 3 H, 3-Me), 1.99Ϫ2.23 (m, 8 H, 4-, 5-, 8-H, 7-CH2CH3),
[176 mg, 27% (35% based on the consumed 5)] and 35 mg (5%) of 2.71 (dd, J ϭ 6.7, 5.5 Hz, 1 H, 10-H), 3.68 (s, 3 H, CO2Me), 5.08
6,7-diol 18b. Recrystallization of 19b from benzene gave 217 mg (br. t, J ϭ 5.9 Hz, 1 H, 6-H), 5.66 (s, 1 H, 2-H). Ϫ 13C NMR
(29%) of colorless fluffy crystals. Ϫ 17b: n2D6 ϭ 1.4919. Ϫ [α]2D8
Ϫ21.9 (c ϭ 1.00, MeOH) {ref.[8] [α]2D4 ϭ Ϫ20 (c ϭ 0.96, MeOH)}.
ϭ
(126 MHz, CDCl3): δ ϭ 9.7, 13.2, 18.9, 21.6, 23.1, 25.6, 25.8, 27.3,
33.3, 41.2, 50.8, 61.8, 64.7, 115.3, 122.9, 141.3, 160.0, 167.2. These
Ϫ IR (film): νmax ϭ 3450 cmϪ1 (br. s, OϪH), 1720 (s, CϭO), 1650 1H and 13C NMR spectroscopic data are identical with those re-
˜
Eur. J. Org. Chem. 2001, 2145Ϫ2150
2149

T. Okochi, K. Mori
FULL PAPER
[2]
[3]
ported for 1.[8] Ϫ C18H30O3 (294.4): calcd. C 73.43, H 10.27; found
C 73.41, H 10.37. Ϫ The enantiomeric excess of 1 was assumed to
be the same as that of 17a, although the HPLC analysis of 1, em-
ploying a variety of chiral stationary phases, afforded only one
peak.
A. S. Meyer, H. A. Schneiderman, E. Hanzmann, J. H. Ko,
Proc. Natl. Acad. Sci. USA 1968, 60, 853Ϫ860.
K. Mori, in: Recent Developments in the Chemistry of Natural
´
´
Carbon Compounds (Eds.: R. Bognar, V. Bruckner, Cs. Szan-
´
´
tay), Akademiai Kiado, Budapest, 1979, vol. 9, pp. 9Ϫ209.
K. Mori, in: Advances in Asymmetric Synthesis (Ed.: A.
Hassner), JAI Press, Greenwich, Connecticut, 1995, vol. 1,
pp. 211Ϫ221.
[4]
Methyl (2E,6E,10R,11S)-10,11-Epoxy-3,7,11-trimethyltrideca-2,6-
dienoate (2): In the same manner as described above, compound 2
(104 mg, 84% based on consumed 17b) and recovered 17b (81 mg)
were obtained from 17b (213 mg, 0.71 mmol). Ϫ 2: n2D4 ϭ 1.4782.
Ϫ [α]2D8 ϭ ϩ14.2 (c ϭ 1.01, MeOH) {ref.[8] [α]2D4.5 ϭ ϩ17.6 (c ϭ
0.590, MeOH), ref.[10] [α]2D3 ϭ ϩ15.1 (c ϭ 1.47, MeOH)}. Ϫ IR
[5]
[6]
K. Mori, in: Chirality in Agrochemicals (Eds.: N. Kurihara, J.
Miyamoto), Wiley, Chichester, 1998, pp. 199Ϫ234.
E. D. Morgan, I. D. Wilsom, in: Comprehensive Natural Prod-
ucts Chemistry, vol. 8 (‘‘Miscellaneous Natural Products In-
cluding Marine Natural Products, Pheromones, Plant Hor-
mones, and Aspect of Ecology’’) (Ed.: K. Mori), Elsevier, Ox-
ford, 1999, pp. 265Ϫ279.
(film): νmax ϭ 3000 cmϪ1 (s, CϪH), 2900 (s, CϪH), 1725 (s, Cϭ
˜
O), 1650 (m, CϭC), 1440 (s), 1380 (m), 1360 (m), 1220 (s,
CϪOϪC), 1160 (s, CϪOϪC), 880 (m), 870 (m). Ϫ 1H NMR
(400 MHz, CDCl3): δ ϭ 0.99 (t, J ϭ 7.6 Hz, 3 H, 13-H) 1.26, (s, 3
H, 11-Me), 1.41Ϫ1.70, (m, 4 H, 9-, 12-H), 1.62, (s, 3 H, 7-Me),
2.16 (d, J ϭ 1.2 Hz, 3 H, 3-Me), 2.03Ϫ2.22 (m, 6 H, 4-, 5-, 8-H),
2.70 (dd, J ϭ 6.8, 5.6 Hz, 1 H, 10-H), 3.68 (s, 3 H, CO2Me), 5.13
[7]
S. Sakurai, T. Ohtaki, H. Mori, M. Fujiwhara, K. Mori, Exper-
ientia 1990, 46, 220Ϫ221.
[8]
[9]
K. Mori, M. Fujiwhara, Tetrahedron 1988, 44, 343Ϫ354.
K. Mori, M. Fujiwhara, Liebigs Ann. Chem. 1990, 369Ϫ372.
H. Kosugi, O. Kanno, H. Uda, Tetrahedron: Asymmetry 1994,
5, 1139Ϫ1142.
[10]
1
[11]
(br. s, 1 H, 6-H), 5.66 (br. s, 1 H, 2-H). These H NMR spectro-
´
G. D. Prestwich, C. Wawrzenczyk, Proc. Natl. Acad. Sci. USA
scopic data are identical with those reported for 2.[8,10]
Ϫ
13C NMR
1985, 82, 5290Ϫ5294.
[12]
[13]
[14]
(100 MHz, CDCl3): δ ϭ 9.6, 16.0, 18.7, 21.5, 25.7, 25.8, 27.0, 36.4,
40.8, 50.7, 61.7, 64.5, 115.2, 123.4, 135.3, 159.9, 167.2. These 13C
NMR spectroscopic data are identical with those reported for 2.[8]
Ϫ C17H28O3 (280.4): calcd. C 72.82, H 10.06; found C 72.72, H
10.12.
G. A. Crispino, K. B. Sharpless, Synthesis 1993, 777Ϫ779.
K. Mori, N. Murata, Liebigs Ann. 1995, 2089Ϫ2092.
H. C. Kolb, M. S. VanNieuwenhze, K. B. Sharpless, Chem. Rev.
1994, 94, 2483Ϫ2547.
[15]
[16]
K. Mori, Y. Funaki, Tetrahedron 1985, 41, 2369Ϫ2377.
´
M. Julia, S. Julia, R. Guegan, Bull. Soc. Chim. Fr. 1960,
1072Ϫ1079.
Determination of the Enantiomeric Purity of 2: The ee value of 2
was determined as 93% by HPLC analysis (column: Chiralcel OB-
H , 4.6 mm ϫ 25 cm; solvent: hexane/iPrOH, 120:1; flow rate:
0.3 mL/min; detection: 230 nm); (ϩ)-2: tR ϭ 28.1 min (96.6%);
(Ϫ)-2: tR ϭ 30.3 min (3.4%).
[17]
[18]
[19]
[20]
[21]
[22]
[23]
C. Fouquet, M. Schlosser, Angew. Chem. Int. Ed. Engl. 1974,
13, 82Ϫ83.
L. Crombie, R.D. Wyvill, J. Chem. Soc., Perkin Trans. 1 1985,
1983Ϫ1995.
J. P. Kutney, M. J. Megrath, R. N. Young, B. R. Worth, Can.
J. Chem. 1979, 57, 3145Ϫ3154.
E. Negishi, D. E. V. Horn, O. King, N. Okukado, Synthesis
1979, 501Ϫ502.
P. Wipf, S. Lim, Angew. Chem. Int. Ed. Engl. 1993, 32,
1068Ϫ1071.
P. K. Freeman, L. Siggel, P. H. Chamberlain, G. E. Clapp,
Tetrahedron 1988, 44, 5051Ϫ5064.
F.-W. Sum, L. Weiler, Can. J. Chem. 1979, 57, 1431Ϫ1441.
Received November 23, 2000
Acknowledgments
We thank Dr. H. Takikawa for his kind technical cooperation. This
work was financially supported by Mitsubishi Rayon Co. and
Takasago International Corporation.
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