Synthesis of the insect pheromone (2S,3S,7RS)-diprionyl acetate by diastereoselective protonation

Article abstract of DOI:10.1002/1099-0690(200110)2001:20<3831::AID-EJOC3831>3.0.CO;2-2

The insect pheromone (2S,3S,7RS)-diprionyl acetate (1) was prepared from (S,S)-2,3-dimethylcyclohexanone (2), which in turn was obtained by the 1,4-addition of lithium dimethylcuprate to (S)-(+)-carvone (3) and diastereoselective protonation of the result

Full text of DOI:10.1002/1099-0690(200110)2001:20<3831::AID-EJOC3831>3.0.CO;2-2

FULL PAPER
Synthesis of the Insect Pheromone (2S,3S,7RS)-Diprionyl Acetate by
Diastereoselective Protonation
Sophia Ebert[a] and Norbert Krause*[a]
Keywords: Cuprates / Pheromones / Protonation / Diastereoselectivity / Natural products
The insect pheromone (2S,3S,7RS)-diprionyl acetate (1) was
prepared from (S,S)-2,3-dimethylcyclohexanone (2), which in
tion. Baeyer−Villiger rearrangement of (S,S)-2 and opening
of the lactone (S,S)-8 with octyllithium provided the hydroxy
turn was obtained by the 1,4-addition of lithium dimethyl- ketone (S,S)-9, which was transformed into the target molec-
cuprate to (S)-(+)-carvone (3) and diastereoselective pro-
tonation of the resulting enolate with phenyl salicylate, fol-
lowed by removal of the isopropenyl group and hydrogena-
ule (2S,3S,7RS)-1 by carbonyl olefination with Petasis’ re-
agent, acylation and hydrogenation.
Introduction
(2RS,3RS)-configuration (Scheme 1). Thus, an efficient en-
antioselective synthesis of (2S,3S,7RS)-diprionyl acetate
should be possible following this route when starting with
(S,S)-2,3-dimethylcyclohexanone. In this paper, we describe
the realization of this synthesis, making use of the highly
diastereoselective protonation of chiral enolates with chelat-
ing proton sources developed by us.[9] The method was also
applied to the diastereoselective synthesis of (Ϯ)-methyl epi-
jasmonate and (Ϯ)-methyl dihydroepijasmonate.[10]
The sawflies (hymenoptera: Diprionidae) belong to the
most common pine pests of Northern Europe, Asia and
North America. Esters of diprionol (3,7-dimethyl-2-penta-
decanol) have been identified by Jewett et al.[1] as phero-
mones of these insects; diprionyl acetate (1) is the attractant
of the Neodiprion species whereas the corresponding propi-
onate was found in the Diprion sawflies. Among about 85
species of diprionid sawflies, the pine sawfly Neodiprion ser-
tifer has been examined with particular intensity.[2] Biolo-
gical studies have shown that (S,S,S)-3,7-dimethyl-2-penta-
decanyl acetate is the most active of the eight stereoisomers,
and this is also the only isomer to be isolated from the in-
sect.[3] (2S,3S,7R)-Diprionyl acetate is somewhat less active
whereas all other stereoisomers show no detectable phero-
mone activity. Thus, the absolute and relative configuration
at C-2 and C-3 is highly important for the biological activ-
ity whereas the configuration at C-7 is of little relevance.[4]
(S,S,S)-3,7-Dimethyl-2-pentadecanyl acetate is also the
most active isomer of Neodiprion namulus namulus, N. le-
contei and N. pinetum;[5] in contrast, (2S,3R,7R)-diprionyl
Scheme 1
Results and Discussion
One of the most efficient and selective routes to cis-2,3-
propionate was identified as most active pheromone of Di- disubstituted cycloalkanones makes use of the chelate-con-
prion similis.[6]
trolled diastereoselective protonation of chiral metal enol-
Due to the strong dependence of the pheromone activity ates with salicylates as proton source.[9] Thus, 2,3-dimethyl-
on the absolute and relative configuration, the stereoselec- cyclohexanone is accessible with a cis:trans ratio of 96:4 by
tive synthesis of diprionyl acetate is of great interest and 1,4-addition of lithium dimethylcuprate to 2-methyl-2-
should allow its use as a pest control agent in pheromone cyclohexenone and subsequent protonation with ethyl sali-
traps. Several diastereo-[7] and enantioselective[8] syntheses cylate.[9a] In the context of Magnusson’s work,[7a,7b] this al-
of the isomers of 3,7-dimethyl-2-pentadecanyl acetate have ready constitutes a formal synthesis of racemic diprionyl
already been described; the latter make use of readily avail- acetate with the desired relative configuration at C-2 and
able chiral starting materials like citronellol, tartaric acid C-3.
and proline, but are rather long. A very straightforward
Our enantioselective synthesis of (2S,3S,7RS)-diprionyl
synthesis of racemic diprionyl acetate was described by acetate (1) started with the commercially available chiral en-
Magnusson[7a,7b] starting from 2,3-dimethylcyclohexanone one (S)-(ϩ)-carvone (3); Michael addition of lithium di-
(2) whereby cis-2 furnished the pheromone with
a
methylcuprate and enolate protonation with phenyl salicyl-
ate (4) provided (S,S,S)-5 with 80% chemical yield, 98% ds
and Ͼ99% ee (Scheme 2). Whereas methyl or ethyl salicyl-
ate gave similar diastereoselectivities,[9b,9c] the use of the less
volatile phenyl ester facilitated the separation of product
[a]
Lehrstuhl für Organische Chemie II, Universität Dortmund,
44221 Dortmund, Germany
Fax: (internat.) ϩ49-231/755-3884
E-mail: nkrause@pop.uni-dortmund.de
Eur. J. Org. Chem. 2001, 3831Ϫ3835
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/1020Ϫ3831 $ 17.50ϩ.50/0
3831

S. Ebert, N. Krause
FULL PAPER
Scheme 2
and proton source by simple distillation. It should be noted proceeded uneventfully. The following carbonyl olefination,
here that 5 can be obtained with up to 93% ds by using the however, turned out be difficult due to the low reactivity of
polymeric chelating proton donors developed by us;[9c] in this substrate, and we were unable to reproduce the yield of
this case, the separation is carried out by filtration.
66% obtained by Magnusson[7a,7b] with the Wittig reagent
In order to remove the isopropenyl group from ketone Ph3PϭCH2. Here, Petasis’ reagent Cp2TiMe2 [14] turned out
(S,S,S)-5, we made use of a Criegee rearrangement. Ozon- to be a useful alternative, giving the desired product (S,S)-
ation of 5 in methanol, followed by treatment of the peroxy 10 with 60% yield [with regard to (S,S)-8] and 98% ds. Fi-
ester with cupric acetate and ferric sulfate[11] gave rise to nally, acylation (95% yield) and (non-stereoselective) hydro-
the formation of the enones (S,S)-6 and (S,S)-7 with 43% genation with palladium on charcoal as catalyst (93% yield)
and 13% yield, respectively (Scheme 2). Both products were provided the target molecule (2S,3S,7RS)-diprionyl acetate
obtained with 98% ds and Ͼ98% ee and could be converted (1). The diastereomeric purity (with regard to C-2 and C-
into (S,S)-2,3-dimethylcyclohexanone (2) by catalytic hy- 3) could be determined by gas chromatography on Car-
drogenation. The use of palladium on charcoal as the hy- bowax to be 98% (no splitting of the GC peaks because of
drogenation catalyst in diethyl ether, however, caused con- the presence of two diastereomers with regard to the ste-
siderable epimerization at C-2 to give large amounts of reogenic center at C-7 was observed). The low volatility of
trans-2. This isomerization could be prevented by using the product, however, prevented the determination of the
ethyl acetate as solvent, but in this case 2,3-dimethylcyclo- enantiomeric excess with a cyclodextrin GC column. An
hexanol was formed as a side product. The catalyst of cho- enantiomeric purity of at least 95% ee was determined by
ice turned out to be rhodium on charcoal in petroleum NMR spectroscopy in the presence of Eu(hfc)3 as a chiral
ether, giving (S,S)-2 with high chemical yield, 95Ϫ96% ds shift reagent.
and Ͼ99% ee.
For the remaining steps from (S,S)-2 to the target molec-
ule (2S,3S,7RS)-diprionyl acetate (1) we intended to follow
Magnusson’s The regioselective
synthesis.[7a,7b]
BaeyerϪVilliger oxidation of (S,S)-2 to the lactone (S,S)-
Conclusion
In this paper, we describe the diastereo- and enantioselec-
8[12] (74% yield) and the subsequent ring opening with oc- tive synthesis of the insect pheromone (2S,3S,7RS)-di-
tyllithium (prepared from 1-iodooctane by halogen-metal prionyl acetate (1) from (S,S)-2,3-dimethylcyclohexanone
exchange with tBuLi[13]) to give the hydroxy ketone (S,S)-9 (2), which was obtained by 1,4-addition of lithium di-
3832
Eur. J. Org. Chem. 2001, 3831Ϫ3835

Synthesis of the Insect Pheromone (2S,3S,7RS)-Diprionyl Acetate
FULL PAPER
2-Me), 0.97 (d, J ϭ 6.9 Hz, 3-Me), 1.45 (m, 2 H), 1.48 (s, 3 H, 3Ј-
H), 1.80Ϫ1.92 (m, 2 H), 2.09 (m, 1 H), 2.36 (m, 2 H), 4.65 (s, 1 H,
1Ј-H), 4.71 (s, 1 H, 1Ј-H). Ϫ 13C NMR (C6D6): δ ϭ 12.3 (ϩ, 2-
Me), 13.9 (ϩ, 3-Me), 20.5 (ϩ, C-3Ј), 36.2 (ϩ, C-3), 37.8 (Ϫ, C-4),
methylcuprate to (S)-(ϩ)-carvone (3) and diastereoselective
protonation of the resulting enolate with phenyl salicylate,
followed by removal of the isopropenyl group and hydro-
genation. BaeyerϪVilliger rearrangement of (S,S)-2 and
opening of the lactone (S,S)-8 with octyllithium provided
the hydroxy ketone (S,S)-9, which was transformed into the
target molecule (2S,3S)-1 by carbonyl olefination with Pet-
asis’ reagent, acylation and hydrogenation. The sequence is
not selective with regard to the stereogenic center at C-7;
however, this is of no practical consequence since the phero-
mone activity is hardly affected by the configuration at
this position.
41.1 (ϩ, C-5), 46.7 (Ϫ, C-6), 48.1 (ϩ, C-2), 109.8 (Ϫ, C-1Ј), 147.8
Ϫ1
˜
(x, C-2Ј), 209.9 (x, C-1). Ϫ IR (neat): ν ϭ 3082 cm (s), 2989 (s,
CϪH), 1711 (s, CϭO), 1453 (s). Ϫ MS: m/z (%) ϭ 166 (75) [Mϩ],
151 (10) [M Ϫ Me], 95 (50), 69 (100). Ϫ HRMS calcd. for C11H18O
166.1366; found 166.1362.
(S,S)-5,6-Dimethyl-2-cyclohexenone (6) and (S,S)-5,6-Dimethyl-3-
cyclohexenone (7): Ozone was passed through a solution of (S,S,S)-
5 (6.62 g, 39.8 mmol) in 100 mL of dry methanol for 1.5 h whilst
cooling between Ϫ10° and Ϫ40 °C. The slightly blue solution was
then purged with argon for 10 min., and Cu(OAc)2·H2O (16.0 g,
80.0 mmol) was added whilst stirring at Ϫ20 °C. After 15 min.,
FeSO4·7H2O (13.3 g, 48.0 mmol) was added, and the mixture was
Our enantioselective synthesis of diprionyl acetate by dia-
stereomeric protonation is competitive with, if not super-
ior to, previous enantioselective preparations of this phero-
mone,[8] because it starts from a cheap, commercially avail- warmed slowly to room temperature. After stirring for 18 h, water
was added and the mixture was washed five times with diethyl
ether. The combined organic phases were washed with a satd.
NaHCO3 solution, brine, and water and dried with MgSO4. After
removal of the solvent in vacuo the crude product was purified by
column chromatography (SiO2, petroleum ether/tert-butyl methyl
ether, 10:1), providing 2.11 g (43%) of (S,S)-6 and 0.62 g (13%) of
(S,S)-7 as colorless liquids. GC analysis with Lipodex E revealed
diastereomeric ratios of 98:2 and enantiomeric excesses of Ͼ 98%
ee for both products.
able terpene and does not require any other chiral reagent
or building block. The method can also be applied to the
synthesis of other stereoisomers of 1 since carvone (3) is
readily available in both enantiomeric forms; likewise, insect
pheromones with branched or shorter chains[15] are access-
ible by reacting lactone (S,S)-8 with the appropriate orga-
nolithium reagent.
(S,S)-6: 1H NMR (C6D6): δ ϭ 0.59 (d, J ϭ 6.9 Hz, 3 H, 6-Me),
0.92 (d, J ϭ 7.1 Hz, 3 H, 5-Me), 1.52Ϫ1.76 (m, 3 H, 4-H, 5-H),
2.22 (dq, J ϭ 4.2/7.1 Hz, 1 H, 6-H), 5.90 (dt, J ϭ 14.3/2.0 Hz, 1
H, 2-H), 6.13 (m, 1 H, 3-H). Ϫ 13C NMR (C6D6): δ ϭ 11.0 (ϩ, 6-
Me), 15.2 (ϩ, 5-Me), 31.9 (Ϫ, C-4), 33.6 (ϩ, C-5), 46.4 (ϩ, C-6),
Experimental Section
General Information: NMR spectra were recorded with a Bruker
WM 400 spectrometer at 400 MHz (1H) and 100.6 MHz (13C) in
CDCl3 as solvent and internal standard (δ ϭ 7.27 for 1H, δ ϭ 77.05
for 13C). The signals of a major component of a product mixture
are marked with an asterisk (*). IR spectra were obtained with a
PerkinϪElmer 1600 FT-IR spectrometer, and mass spectra with
A.E.I. MS-30 and MS-50 spectrometers (EI, 70 eV). GC-MS spec-
tra were recorded with a Hewlett Packard HP 5850 Series II spec-
trometer. GC analyses were carried out with a Dani 86.10 or a
Carlo Erba GC 8000 gas chromatograph with hydrogen as carrier
gas and an OV-1701 capillary column. Elemental analyses were ob-
tained with PerkinϪElmer CHN 240 A and B analyzers. The reac-
tions were carried out in thoroughly dried glassware under argon.
Diethyl ether was distilled from LiAlH4 prior to use. MeLi, and
tBuLi were titrated with diphenylacetic acid according to the pro-
cedure of Kofron and Baclawski.[16]
˜
129.0 (ϩ, C-2), 146.7 (ϩ, C-3), 201.2 (x, C-1). Ϫ IR (neat): ν ϭ
3030 cmϪ1 (s), 2970 (s, CϪH), 1683 (s, CϭO). Ϫ MS: m/z (%) ϭ
124 (15) [Mϩ], 96 (20), 68 (100).
(S,S)-7: 1H NMR (C6D6): δ ϭ 0.64 (d, J ϭ 7.1 Hz, 3 H, 6-Me),
0.95 (d, J ϭ 6.9 Hz, 3 H, 5-Me), 2.17 Ϫ2.53 (m, 4 H, 2-H, 5-H, 6-
H), 5.28 (m, 1 H, 3-H), 5.55 (m, 1 H, 4-H). Ϫ 13C NMR (C6D6):
δ ϭ 11.0 (ϩ, 6-Me), 15.2 (ϩ, 5-Me), 37.9 (ϩ, C-5), 40.2 (Ϫ, C-2),
47.0 (ϩ, C-6), 123.4 (ϩ, C-3), 133.6 (ϩ, C-4), 208.9 (x, C-1). Ϫ IR
(neat): ν˜ ϭ 3029 cmϪ1 (s), 2970 (s, CϪH), 1715 (s, CϭO). Ϫ MS:
m/z (%) ϭ 124 (35) [Mϩ], 96 (35), 68 (100). Ϫ HRMS calcd. for
C8H12O 124.0884; found 124.0886.
(S,S)-2,3-Dimethylcyclohexanone (2):[7a,7b] A solution of (S,S)-6
(621 mg, 5.0 mmol) in 50 mL of petroleum ether was treated with
60 mg of rhodium on charcoal (5%) and hydrogenated at ambient
pressure for 3 h. The catalyst was filtered off and the solvent was
removed in vacuo, giving 570 mg (90%) of (S,S)-2 as a colorless
liquid. GC analysis with Lipodex E showed a cis:trans ratio of 96:4
and an enantiomeric excess of Ͼ99% ee for the trans isomer. The
analogous reaction of 124 mg (1.0 mmol) of (S,S)-7 provided
101 mg (80%) of (S,S)-2 with cis:trans ϭ 95:5 and Ͼ 99% ee. Ϫ
[α]2D4 ϭ ϩ28.3 (c ϭ 3.39, chloroform).
(S,S,S)-2,3-Dimethyl-5-(2-propen-2-yl)-cyclohexanone (5): MeLi
(1.6  solution in diethyl ether; 94 mL, 0.15 mol) was added drop-
wise at Ϫ20 °C to a suspension of CuI (14.3 g, 75.0 mmol) in
300 mL of diethyl ether. The resulting clear cuprate solution was
stirred at Ϫ20 °C for 5 min., cooled to Ϫ80 °C, and (S)-carvone
(3; 7.51 g, 50.0 mmol) in 100 mL of diethyl ether was added drop-
wise. The mixture was warmed to Ϫ30 °C within 1 h and then again
cooled to Ϫ80 °C. It was then transferred through a Teflon tube (S,S)-6,7-Dimethyl-2-oxepanone (8):[7a,7b] A solution of MCPBA
into a solution of phenyl salicylate (4; 42.8 g, 0.2 mol) in 300 mL
of diethyl ether which was also kept at Ϫ80 °C. The mixture was
(2.40 g, 11.8 mmol) (85%) in 40 mL of dichloromethane was added
dropwise at room temperature to (S,S)-2 (1.03 g, 8.2 mmol) in
warmed to room temperature, and 11.5 mL (0.2 mol) of acetic acid 30 mL of dichloromethane. The mixture was stirred for 16 h, the
was added. After filtration through Celite the filtrate was washed
twice with a satd. NaHCO3 solution and dried with MgSO4. Re-
precipitate was filtered off, and the filtrate was washed twice with
a satd. NaHCO3 solution and dried with MgSO4. Purification of
moval of the solvent in vacuo was followed by distillation of the the crude product obtained after removal of the solvent in vacuo
crude product, furnishing 6.62 g (80%) of (S,S,S)-5 as a colorless by column chromatography (SiO2, cyclohexane/diethyl ether, 3:2)
liquid (bp13 ϭ 110 °C). The diastereomeric purity was determined gave 860 mg (74%) of (S,S)-8 as a colorless liquid. GC analysis
1
1
by GC to be 98%. Ϫ H NMR (C6D6): δ ϭ 0.61 (d, J ϭ 7.1 Hz,
revealed a cis:trans ratio of Ն96:4. Ϫ H NMR (CDCl3): δ ϭ 0.95
Eur. J. Org. Chem. 2001, 3831Ϫ3835
3833

S. Ebert, N. Krause
(d, J ϭ 7.4 Hz, 3 H, 6-Me), 1.34 (d, J ϭ 6.6 Hz, 3 H, 7-Me), 1.75 C-4, C-5, C-2Ј, C-3Ј, C-4Ј, C-5Ј, C-6Ј, C-7Ј), 36.0, 36.2, (2-, C-6,
FULL PAPER
(m, 4 H), 1.95 (m, 1 H), 2.55Ϫ2.65 (m, 2 H), 4.60 (q, J ϭ 6.6 Hz,
1 H, 7-H). Ϫ 13C NMR (CDCl3): δ ϭ 10.4 (ϩ, 6-Me), 17.9 (Ϫ, C-
4), 20.1 (ϩ, 7-Me), 34.7, 35.1 (2-, C-3, C-5), 36.1 (ϩ, C-6), 78.3
(ϩ, C-7), 175.5 (x, C-2).
C-1Ј), 37.5 (ϩ, C-3), 74.1 (ϩ, C-2), 108.6 (Ϫ, C-8), 150.0 (x, C-7),
170.8 (x, MeCO).
(2S,3S)-3,7-Dimethyl-2-pentadecanyl acetate (1):[7,8] A solution of
(S,S)-3-methyl-7-octyl-7-octen-2-yl acetate (60 mg, 0.20 mmol) in
15 mL of diethyl ether was treated with 10 mg of palladium on
charcoal (10%) and hydrogenated at ambient pressure for 3 h. The
catalyst was filtered off and the solvent was removed in vacuo, giv-
ing 56 mg (93%) of (2S,3S)-1 as a colorless liquid. GC analysis
revealed a diastereomeric purity of 98%, and the enantiomeric ex-
cess was determined by 1H NMR spectroscopy with Eu(hfc)3 as
Ͼ95% ee. Ϫ 1H NMR (CDCl3): δ ϭ 0.80 (m, 9 H, 3-Me, 7-Me,
15-H), 1.00 (m, 3 H), 1.10 (d, J ϭ 6.4 Hz, 3 H, 1-H), 1.15Ϫ1.30
(m, 18 H), 1.52 (m, 1 H), 1.96 (s, 3 H, MeCO), 4.76 (m, 1 H, 2-
H). Ϫ 13C NMR (CDCl3): δ ϭ 14.1, 14.8 (2ϩ, 3-Me, C-15), 16.9
(ϩ, C-1), 19.6 (ϩ, 7-Me), 21.4 (ϩ, MeCO), 22.7, 24.5, 27.1, 29.4,
29.7, 30.0, 31.9, 32.7 (8-, C-4, C-5, C-9, C-10, C-11, C-12, C-13,
C-14), 37.2, 37.3, (2-, C-6, C-8), 37.6, 37.6 (2ϩ, C-3, C-7), 74.1 (ϩ,
C-2), 170.9 (x, MeCO).
(S,S)-2-Hydroxy-3-methyl-7-pentadecanone (9):[7a,7b] tBuLi (1.6 
solution in pentane; 7.2 mL, 11.5 mmol) was added dropwise at
Ϫ80 °C to a solution of 1-iodootane (1.26 g, 5.2 mmol) in 30 mL
of diethyl ether, and the mixture was stirred for 1 h at Ϫ80 °C and
a further hour at room temperature. The solution was again cooled
to Ϫ80 °C and added via a Teflon tubing to a solution of (S,S)-8
(711 mg, 5.0 mmol) in 10 mL of diethyl ether which was also kept
at Ϫ80 °C. The mixture was warmed to Ϫ20 °C and hydrolyzed
with 1  HCl. The organic layer was removed, and the aqueous
layer was washed three times with diethyl ether. The combined or-
ganic phases were washed with a satd. NaHCO3 solution and dried
with MgSO4. The solvent was removed, and the crude product was
used without purification in the next reaction. GC analysis showed
a diastereomeric purity of 98%. Ϫ 1H NMR (CDCl3): δ ϭ 0.82 (m,
6 H, 3-Me, 15-H), 1.07 (d, J ϭ 6.4 Hz, 3 H, 1-H), 1.20 (m, 12 H),
1.32Ϫ1.60 (m, 7 H), 2.32 (m, 3 H), 3.67 (dq, J ϭ 4.4/6.4 Hz, 1 H,
2-H). Ϫ 13C NMR (CDCl3): δ ϭ 14.0, 14.1 (2ϩ, 3-Me, C-15), 20.2
(ϩ, C-1), 21.5, 22.7, 23.9, 29.2, 29.3, 29.4, 31.8, 32.2 (8-, C-4, C-5,
C-9, C-10, C-11, C-12, C-13, C-14), 39.6 (ϩ, C-3), 42.9, 42.9 (2-,
C-6, C-8), 71.0 (ϩ, C-2), 211.7 (x, C-7).
Acknowledgments
We thank the Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen Industrie for financial support of this work.
(S,S)-3-Methyl-7-octyl-7-octen-2-ol (10):[7a,7b] Cp2TiMe2 (0.45  so-
lution in toluene; 2.7 mL, 1.2 mmol) was added to a solution of
(S,S)-9 (103 mg, 0.40 mmol) in 30 mL of toluene, and the mixture
was heated to 65 °C for 8 h. After addition of another 1.8 mL
(0.8 mmol) of the Cp2TiMe2 solution, the mixture was heated fur-
ther to 65 °C for 8 h. After cooling to room temperature, 60 mL of
petroleum ether was added, and the precipitate was filtered off. The
solvent was removed from the filtrate in vacuo, and the product
was again treated with petroleum ether and filtered. Removal of
the solvent from the filtrate in vacuo furnished a yellow oil which
was purified by column chromatography (SiO2, petroleum ether/
tert-butyl methyl ether, 10:1), providing 61 mg (60%) of (S,S)-10 as
a colorless oil with a diastereomeric purity of 98% (GC analysis).
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6.4 Hz, 3 H, 1-H), 1.22 (m, 12 H), 1.30Ϫ1.45 (m, 6 H), 1.93 (m, 4
H), 3.65 (m, 1 H, 2-H), 4.64 (s, 2 H, 8-H). Ϫ 13C NMR (CDCl3):
δ ϭ 14.1, 14.2 (2ϩ, 3-Me, C-8Ј), 20.3 (ϩ, C-1), 22.7, 25.5, 27.8,
29.3, 29.5, 29.6, 31.9, 32.4 (8-, C-4, C-5, C-2Ј, C-3Ј, C-4Ј, C-5Ј, C-
6Ј, C-7Ј), 36.1, 36.3 (2-, C-6, C-1Ј), 39.7 (ϩ, C-3), 71.4 (ϩ, C-2),
108.6 (Ϫ, C-8), 150.2 (x, C-7).
[5]
[6]
T. Kikukawa, F. Matsumura, M. Kraemer, H. C. Coppel, A.
Tai, J. Chem. Ecol. 1982, 8, 301Ϫ314.
[7] [7a]
[7b]
G. Magnusson, Tetrahedron Lett. 1977, 2713Ϫ2716. Ϫ
[7c]
(S,S)-3-Methyl-7-octyl-7-octen-2-yl acetate:[7a,7b]
A mixture of
G. Magnusson, Tetrahedron 1978, 34, 1385Ϫ1388. Ϫ
P. J.
Kocienski, J. M. Ansell, J. Org. Chem. 1977, 42, 1102Ϫ1103.
(S,S)-10 (76 mg, 0.30 mmol), acetic anhydride (0.2 mL, 2.0 mmol),
Et3N (0.3 mL, 2.0 mmol), and DMAP (49 mg, 0.4 mmol) in 20 mL
of diethyl ether was stirred for 5 h at room temperature. The mix-
ture was then diluted with water, the organic layer was separated,
and the aqueous layer was washed three times with diethyl ether.
The combined organic phases were dried with MgSO4, the solvent
was removed in vacuo, and the crude product was purified by col-
umn chromatography (SiO2, petroleum ether/tert-butyl methyl
ether, 20:1), yielding 84 mg (95%) of (S,S)-3-methyl-7-octyl-7-
octen-2-yl acetate as a colorless oil with a diastereomeric purity of
Ϫ [7d] J. Gore, P. Place, M.-L. Roumestant, J. Org. Chem. 1978,
´
[7e]
43, 1001. Ϫ
Chem. Ecol. 1978, 4, 277Ϫ287. Ϫ
Oda, H. Watanabe, Chem. Lett. 1978, 61Ϫ64. Ϫ
D. Jewett, F. Matsumura, H. C. Coppel, J.
[7f]
A. Tai, M. Imaida, T.
[7g]
F. Matsu-
mura, A. Tai, H. C. Coppel, M. Imaida, J. Chem. Ecol. 1979,
5, 237Ϫ249.
[8] [8a]
K. Mori, S. Tamada, Tetrahedron 1979, 35, 1279Ϫ1284. Ϫ
[8b]
H.-E. Högberg, S. Byström, T. Norin, Tetrahedron 1981,
[8c]
37, 2249Ϫ2254. Ϫ
H.-E. Högberg, E. Hedenström, A.-B.
Wassgren, M. Hjalmarsson, G. Bergström, J. Lövqvist, T. No-
rin, Tetrahedron 1990, 46, 3007Ϫ3018.
1
98% (GC analysis). Ϫ H NMR (CDCl3): δ ϭ 0.83 (m, 6 H, 3-Me,
[9] [9a]
N. Krause, Angew. Chem. 1994, 106, 1845Ϫ1847; Angew.
Chem. Int. Ed. Engl. 1994, 33, 1764Ϫ1765. Ϫ [9b] N. Krause, S.
Ebert, A. Haubrich, Liebigs Ann./Recueil 1997, 2409Ϫ2418. Ϫ
8Ј-H), 1.10 (d, J ϭ 6.4 Hz, 3 H, 1-H), 1.22 (m, 11 H), 1.30Ϫ1.45
(m, 5 H), 1.53 (m, 1 H), 1.93 (m, 4 H), 1.97 (s, 3 H, MeCO), 4.65
(d, J ϭ 3.7 Hz, 2 H, 8-H), 4.76 (dq, J ϭ 4.9/6.4 Hz, 1 H, 2-H). Ϫ
13C NMR (CDCl3): δ ϭ 14.1, 14.8 (2ϩ, 3-Me, C-8Ј), 16.9 (ϩ, C-
1), 21.4 (ϩ, MeCO), 22.7, 25.2, 27.8, 29.3, 29.4, 29.5, 31.9, 32.1 (8-,
[9c]
N. Krause, M. Mackenstedt, Tetrahedron Lett. 1998, 39,
9649Ϫ9650.
[10]
N. Krause, S. Ebert, following paper in this issue.
3834
Eur. J. Org. Chem. 2001, 3831Ϫ3835

Synthesis of the Insect Pheromone (2S,3S,7RS)-Diprionyl Acetate
FULL PAPER
[11]
[14] [14a]
S. L. Schreiber, J. Am. Chem. Soc. 1980, 102, 6163Ϫ6165.
N. A. Petasis, S.-P. Lu, Tetrahedron Lett. 1995, 36,
[12]
[14b]
Lactone (S,S)-8 can also be obtained from racemic ketone cis-
2393Ϫ2396. Ϫ
N. A. Petasis, S. P. Lu, E. I. Bzowej, D. K.
2 by enzymatic BaeyerϪVilliger oxidation with cyclohexanone
monooxygenase/formate dehydrogenase (M. Vogel, Universität
Leipzig, personal communication; cf. U. Schwarz-Linek, A.
Krödel, F.-A. Ludwig, A. Schulze, S. Rissom, U. Kragl, V. I.
Tishkov, M. Vogel, Synthesis 2001, 947Ϫ951).
Fu, J. P. Staszewski, I. Akritopoulouzanze, M. A. Patane, Y.
H. Hu, Pure Appl. Chem. 1996, 68, 667Ϫ670.
M. Larsson, B.-V. Nguyen, H.-E. Högberg, E. Hedenström,
Eur. J. Org. Chem. 2001, 353Ϫ363.
W. G. Kofron, L. M. Baclawski, J. Org. Chem. 1976, 41,
1879Ϫ1880.
[15]
[16]
[13] [13a]
W. F. Bailey, E. R. Punzalan, J. Org. Chem. 1990, 55,
[13b]
5404Ϫ5406. Ϫ
E. Negishi, D. R. Swanson, C. J. Rousset,
Received March 1, 2001
J. Org. Chem. 1990, 55, 5406Ϫ5409.
[O01099]
Eur. J. Org. Chem. 2001, 3831Ϫ3835
3835