Stereochemical Control over Three Contiguous Stereogenic Centers in the Intramolecular Ene Reaction of Activated 1,6-Dienes. Application to the Synthesis of (±)-Methyl Cucurbate and (±)-Methyl Epijasmonate

Article abstract of DOI:10.1021/jo961739n

The influence of a protected alcohol group adjacent to the ene or enophile component on diastereoselectivity in both thermal and Lewis acid-catalyzed 5-(3,4) ene reactions of a series of 1,6-dienes 1-7 has been studied. The results indicate that its effect can be considerable, and in one example, with a gem-dimethyl group on the connecting chain and a large silyl protecting group on the hydroxyl, the diastereocontrol was almost perfect, with three stereogenic centers and one double bond geometry set up in one step, e.g., 4 → 10. This new finding was exploited in a synthesis of epijasmonoid natural products, (±)-methyl cucurbate (19) and (±)-methyl epijasmonate (18) starting from aldehyde 24, where the key step was a highly diastereocontrolled 5-(3,4) ene cyclization 23 → 22. 1 Indian Institute of Technology 2 BARC.

Full text of DOI:10.1021/jo961739n

6006
J . Org. Chem. 1997, 62, 6006-6011
Ster eoch em ica l Con tr ol over Th r ee Con tigu ou s Ster eogen ic
Cen ter s in th e In tr a m olecu la r En e Rea ction of Activa ted
1,6-Dien es. Ap p lica tion to th e Syn th esis of (()-Meth yl Cu cu r ba te
a n d (()-Meth yl Ep ija sm on a te
Tarun K. Sarkar,*,† Binay K. Ghorai,† Sandip K. Nandy,† Bireswar Mukherjee,† and
Asoke Banerji‡
Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India, and
Bio-organic Division, Modular Laboratory, BARC, Bombay 400 085, India
Received September 10, 1996 (Revised Manuscript Received May 5, 1997X)
The influence of a protected alcohol group adjacent to the ene or enophile component on
diastereoselectivity in both thermal and Lewis acid-catalyzed 5-(3,4) ene reactions of a series of
1,6-dienes 1-7 has been studied. The results indicate that its effect can be considerable, and in
one example, with a gem-dimethyl group on the connecting chain and a large silyl protecting group
on the hydroxyl, the diastereocontrol was almost perfect, with three stereogenic centers and one
double bond geometry set up in one step, e.g., 4 f 10. This new finding was exploited in a synthesis
of epijasmonoid natural products, (()-methyl cucurbate (19) and (()-methyl epijasmonate (18)
starting from aldehyde 24, where the key step was a highly diastereocontrolled 5-(3,4) ene cyclization
23 f 22.
In tr od u ction
Y
Y
X
Z
X
Z
6
4
ene
3
(1)
7
The thermal and Lewis acid-catalyzed intramolecular
Alder ene reaction has frequently been used in organic
synthesis as a tool for carbo- and heterocyclization.1 The
stereochemistry about the forming C,C bond is usually
cis for five-membered rings, especially from unactivated
or moderately activated 1,6-dienes, but 1,6-dienes con-
taining doubly activated enophiles give trans-1,2-disub-
stituted cyclopentanes almost exclusively.1,2,3a,b,4 The
relationship between the stereochemistries of substitu-
ents on the tether and the stereochemistry of C,C bond
formation is not, however, as easily predicted.2 As part
of our continuing program to explore the potential of
intramolecular ene reactions for organic synthesis,3 we
were interested in studying the topological influence (C4/
C6) over developing (C3,C7) stereogenic centers in the
ene cyclization step (eq 1).
H
H
) OR) has not been systematically investigated. Inci-
dentally, some reports on mechanistically related Diels-
Alder reactions indicate that lesser steric bulk of an
alkoxy group makes it less effective than an alkyl group
for diastereoinduction in these reactions.6 Prompted by
the occurrence of hydroxyl-bearing chiral centers in
cyclopentanoid natural products,7 we undertook a study
of this facet of 5-(3,4)1d ene cyclizations. Accordingly, a
series of hydroxylated 1,6-dienes 1-7, with different
substituents in the ene, the tether, and the enophile, were
prepared and their thermolytic/Lewis acid-catalyzed ene
reactions were investigated. In this work, suitable
protection of the hydroxyl group was deemed important
since the hydroxyl group is sterically very small when
compared to a methyl group which has been used in
previous studies of diastereoface selectivity in 5-(3,4) ene
cyclizations.1 For example, the A value for a methyl
group is 1.88 while that for a hydroxyl group is 0.59 in
nonaqueous solutions. It was hoped that a bulky silyl
protecting group would not only prevent decomposition
of ene educts but also enhance the stereoselectivity of
the ene cyclizations.
Although, a few reports have dealt with this issue (X
) CH3, Y ) O/CH2, Z ) H; X ) H, Y ) RN/CH2, Z )
CH3; X ) Ph, Y ) O, Z ) H),1,5 the influence of an oxygen
substituent in either the ene or enophilic component (X/Z
† Indian Institute of Technology.
‡ BARC.
X Abstract published in Advance ACS Abstracts, J une 15, 1997.
(1) (a) Oppolzer, W.; Snieckus, V. Angew. Chem., Int. Ed. Engl. 1978,
17, 476. (b) Taber, D. F. Intramolecular Diels-Alder and Alder Ene
Reactions; Springer-Verlag: New York, 1984. (c) Carruthers, W.
Cycloaddition Reactions in Organic Synthesis; Pergamon Press: Ox-
ford, 1990; Chapter 5. (d) Mikami, K.; Shimizu, M. Chem. Rev. 1992,
92, 1021. (e) Snider, B. B. Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1992; Vol. 5, p 1.
(2) Thomas, B. E.; Loncharich, R. J .; Houk, K. N. J . Org. Chem.
1992, 57, 1354.
The present study has revealed that three contiguous
ring stereogenic centers can be created with a very high
level of both diastereoselectivity and diastereofacial
selectivity by the influence of an oxygen substituent as
a stereodirecting resident group in the ene/enophile
component.10 Furthermore, this work has also culmi-
(3) (a) Ghosh, S. K.; Sarkar, T. K. Tetrahedron Lett. 1986, 27, 525.
(b) Sarkar, T. K.; Subba Rao, P. S. V. Synth. Commun. 1989, 19, 1281.
(c) Sarkar, T. K.; Ghosh, S. K.; Subba Rao, P. S. V.; Satapathi, T. K.
Tetrahedron Lett. 1990, 31, 3461. (d) Sarkar, T. K.; Ghosh, S. K.;
Subba Rao, P. S. V.; Mamdapur, V. R. Ibid. 1990, 31, 3465. (e) Sarkar,
T. K.; Ghosh, S. K.; Subba Rao, P. S. V.; Satapathi, T. K.; Mamdapur,
V. R. Tetrahedron 1992, 48, 6897. (f) Sarkar, T. K.; Nandy, S. K.;
Ghorai, B. K.; Mukherjee, B. Synlett 1996, 97. (g) Sarkar, T. K.;
Nandy, S. K. Tetrahedron Lett. 1996, 37, 5195. See also refs 10 and
11.
(6) (a) Tietze, L. F.; Kiedrowski, G. V. Tetrahedron Lett. 1981, 22,
219. (b) Franck, R. W.; et al. J . Am. Chem. Soc. 1982, 104, 1106. (c)
See also ref 1b, p 54.
(7) Paquette, L. A.; Doherty, A. M. Polyquinane Chemistry; Springer-
Verlag: Berlin, 1987.
(8) Allinger, N. L.; Freiberg, L. A. J . Org. Chem. 1966, 31, 804.
(9) Hirsch, J . A. In Topics Stereochemistry; Allinger, N. L., Eliel, E.
L., Eds.; Wiley-Interscience: New York, 1967; Vol. 1, p 199.
(10) For a preliminary report, see: Sarkar, T. K.; Ghorai, B. K.;
Nandy, S. K; Mukherjee, B. Tetrahedron Lett. 1994, 35, 6903.
(4) Tietze, L. F.; Beifuss, U.; Ruther, M.; Ruhlmann, A.; Antel, J .;
Sheldrick, G. M. Angew. Chem., Int. Ed. Engl. 1988, 27, 1186.
(5) Mikami, K.; Matsueda, H.; Nakai, T. Synlett 1993, 235.
S0022-3263(96)01739-2 CCC: $14.00 © 1997 American Chemical Society

Intramolecular Ene Reaction of Activated 1,6-Dienes
J . Org. Chem., Vol. 62, No. 17, 1997 6007
Ta ble 1. Ster eoch em ica l Con tr ol over Th r ee Con tigu ou s Ster eogen ic Cen ter s
runa
educt
temp/time
product/(ratiob)
combined yieldc (%)
diastereoselectivity/diastereofacial selectivity
1
2
3
4
5
6
3
1
4
5
6
7
235 °C/40 h
235 °C/40 h
235 °C/18 h
235 °C/40 h
rt/2 h
9/12 (79:21)
8/11 (88:12)
10
13/14 (88:12)
15/17 (96:4)
16
83
97
96
86
90
90
∼100% cis/79% trans
∼100% cis/88% trans
∼100% cis/100% trans
∼88% cis/100% trans
∼96% trans/100% trans
∼100% trans/100% trans
rt/3 h
a
In runs 1-4, a 5% solution of the diene in toluene was heated in a sealed Corning tube under argon. In runs 5 and 6, a 0.5 M solution
b
of the diene in CH2Cl2 was exposed to ZnBr2 (anhydrous). Capillary GC and GC-MS analyses give the diastereomeric composition of
products in these runs which is as follows: run 1 (1.8:77.7:20.5); run 2 (1.09:81.4:5.57:11.9); run 3 (96.4:1.9:0.6:1.1); run 4 (11.9:87.5:0.6);
run 5 (95.6:4.4); run 6 (single compound, based on 1H-NMR). Trace diastereomers were not properly characterized and were ignored.
c Isolated yield after chromatography.
nated in a synthesis of two jasmonoid natural products,
Table 1 reveals the following features of the present
ene reaction. In runs 1 and 2, diastereoselectivity is
uniformly high, but the diastereofacial selectivity in-
creases with increasing steric bulk of the silyl12 substitu-
ent on oxygen. The most striking result is, however,
observed in run 3 where the 1,6-diene 4 carrying a
strategically located TMS group and a gem-dimethyl
group on the tether gives the cyclopentanoid allylsilane
10 in very high yield with nearly 100% diastereoselec-
tivity and 100% diastereofacial selectivity. In runs 4 and
5 while diastereofacial selectivity is very high, diaste-
reoselectivity actually increases in the Lewis acid cata-
lyzed reactions in accordance with previous observa-
tions.3a,b,4 Similarly, in run 6, the doubly activated 1,6-
diene yielded 16 as the only product as revealed from
1H-NMR analysis.
In order to rationalize the high stereoselectivities
observed in the present ene cyclizations, the Oppolzer
model13 of transition states is invoked as the Houk model2
is inadequate in the cases of activated enophiles.
In the cases of 1, 3, and 4, only two transition states A
and B are possible due to the Z-ene geometry (Figure 1).
B, with an endo OR group, is obviously less preferred.
Thus, 8-10 are the predominant products. 5 and 6
prefer transition states C,E rather than D,F, where due
to the orientation of the OR group, the steric interactions
(OR-Me interactions vs OR-H interactions) are much
more severe compared to those in B. The 100% diaste-
reofacial selectivity in the cases of 5 and 6 can therefore
be readily explained. That thermal ene reaction of 5
gives 13 as the major product via transition state C, and
Lewis acid-catalyzed ene cyclization of 6 gives almost
exclusively 15 via the transition state E is in accord with
previous work from this laboratory.3a,b,4 The exclusive
formation of 16 from 7 can be explained via a transition
state similar to E.
e.g., (()-methyl cucurbate and (()-methyl epijasmonate.11
Resu lts a n d Discu ssion
En e Cycliza tion of 1-7. The thermolytic cyclizations
of 1-5 were carried out in toluene (5% solution) in sealed
tubes under an atmosphere of argon. Attempts to cyclize
the free alcohol 2 under this condition was thwarted as
it underwent extensive decomposition. The ene reactions
of 6 and 7 were effected at ambient temperature in CH2-
Cl2 in the presence of a Lewis acid (ZnBr2). The product
ratios (Table 1) were determined by high-field NMR,
capillary GC, and GC-MS analysis.
OR3
R1
R2
OTBDPS
R1
R2
CO2Me
R4 R4
1: R1 = R2 = Me; R3 = TBDPS; R4 = H
2: R1 = R2 = Me; R3 = R4 = H
3: R1 = R2 = Me; R3 = TBDMS; R4 = H
4: R1 = H; R2 = TMS; R3 = TBDPS; R4 = Me
5: R1 = H; R2 = CO2Me
6: R1 = R2 = CO2Et
TBDPSO
CO2Et
CO2Et
7
R1 R1
OR1
OR2
H
H
H
H
MeO2C
MeO2C
R3
R3
R4
R2
8: R1 = H; R2 = TBDPS; R3 = R4 = Me
9: R1 = H; R2 = TBDMS; R3 = R4 = Me
10: R1 = Me; R2 = TBDPS; R3 = H; R4 =TMS
11: R1 = TBDPS; R2 = R3 = Me
12: R1 = TBDMS; R2 = R3 = Me
Syn th esis of (()-Meth yl Cu cu r ba te (19) a n d (()-
Meth yl Ep ija sm on a te (18). Having thus developed a
highly stereocontrolled route to a functionalized cyclo-
pentane ring system with three contiguous stereogenic
centers and a versatile olefinic side chain, we felt well-
suited to tackle some natural product total syntheses.
The jasmonoid natural products, e.g., (()-methyl cucur-
bate (19) and (()-methyl epijasmonate (18) were chosen
as the initial targets.14 Incidentally, the rich biological
profile displayed by nearly all jasmonoids has contributed
to their popularity as targets of intense synthetic interest
in recent years.14
OTBDPS
OTBDPS
H
H
H
H
MeO2C
MeO2C
13
R2 R2
14
R3
R1
OTBDPS
H
H
H
H
EtO2C
EtO2C
EtO2C
EtO2C
Our approach to (()-methyl cucurbate (19), a plant
growth inhibitor, and thence to (()-methyl epijasmonate
(18), the queen of aroma, is summarized by the discon-
15: R1 = OTBDPS; R2 = Me; R3 =H
16: R1 = R2 = H; R3 = OTBDPS
17
(11) For a preliminary report, see: Sarkar, T. K.; Ghorai, B. K.;
Banerji, A. Tetrahedron Lett. 1994, 35, 6907.
(12) Hwu, J . R.; Wang, N. Chem. Rev. 1989, 89, 1599.
(13) Oppolzer, W.; Robbiani, C. Helv. Chim. Acta 1980, 63, 2010.

6008 J . Org. Chem., Vol. 62, No. 17, 1997
Sarkar et al.
Sch em e 2a
Transition States
R1O
H
OH
b
OR1)) ((
OR1
CHO
H
a
THPO
THPO
R2O
(CH2)2TMS
R2
R2
H
26: R1 = H; R2 = THP
27: R1 = TBDPS; R2 = THP
28: R1 = TBDPS; R2 = H
(CH2)2TMS
c
H
H
CO2Me
24
25
d
CO2Me
H
H
A
B
OTBDPS
g
OTBDPS
OTBDPS
e,f
H
H
H
H
+
8-10
11, 12
MeO2C
MeO2C
MeO2C
OR1)) ((
TMS
TMS
R1O
H
TMS
H
H
23
22
29
R
R
OTBDPS
OR
O
H
3
2
j
h
l
1
2
1
H
H
H
H
H
H
H
H
CO2Me
CO2Me
MeO2C
MeO2C
MeO2C
C
D
R
21: R =CH2
20: R = O
i
30: R = TBDPS
19: R = H
18
k
13, 17
((
OR1))
H
H
H
H
a
R
R
(a) LiCtC(CH2)2TMS/THF/HMPA, -78 °C, 80%; (b) i-BuMgBr/
Cp2TiCl2(cat.), 65%; (c) TBDPSCl/Im/DMF, 85%; (d) PPTS/EtOH,
97%; (e) (COCl)2/DMSO, 90%; (f) (MeO)2P(O)CH(Li)CO2Me, 80%;
(g) 235 °C, 18 h, 95%; (h) HI/bz, 79%; (i) O3, 88%; (j) Ph3(Pr)PBr/
NaN(TMS)2, 50%; (k) n-Bu4NF, 89%; (l) H2CrO4/ether, 70%.
R1O
H
CO2Me
H
CO2Me
E
F
2). Thermolysis of a 5% solution of 23 in toluene under
argon in a sealed tube for 18 h gave an inseparable
mixture of 22 and 29 in a ratio of ∼9:1. Another trace
but unidentified diastereomer (0.5%) was also formed as
indicated from capillary GC and GC-MS analyses of the
crude product. Syntheses of 19 and 18 were next
pursued with the inseparable mixture 22/29. Protode-
silylation of 22 f 21 (only one diastereomer is shown
henceforth for convenience) was initially fraught with
difficulties as most of the recommended reagents includ-
ing BF3‚2AcOH16 or concd HCl were ineffective. Fortu-
nately, exposure of 22 to two-phase HI-benzene, water
mixture17 gave the desired terminal olefin 21 in 79%
yield. 21 is contaminated with ∼10% of its C3-â isomer,
CHOR signal of which resonates at δ 4.2 (1H-NMR) in
analogy with C3-â isomer of methyl cucurbate where the
same signal appears at δ 4.2.18 As expected, the CHOR
signal of the major diastereomer 21 resonates at δ 4.0
(1H-NMR) in analogy with methyl cucurbate where C3-H
also appears at δ 4.0.14b Oxidative cleavage of 21 (with
ozone) gave the jasmonoid building block 20 in 88% yield
which was next subjected to “salt-free” Wittig olefination
using n-propyltriphenylphosphorane, generated from the
corresponding phosphonium salt with NaN(TMS)2, under
the condition described by Bestmann et al.19 to provide
30 (50% yield). Desilylation (with n-Bu4NF) at room
temperature gave (()-methyl cucurbate (19) in 89% yield.
During this step, the minor C3-â isomer (∼10%) carried
over from 22/29 was eliminated presumably via lactone
formation as inferred from the appearance of a broad
singlet at δ 4.6 in the 1H-NMR spectrum of the trace
byproduct.14a The spectral properties of 19 are in agree-
ment with those reported by Kitahara et al.14b Also, 19
R = H, CO2R
14, 15
F igu r e 1.
Sch em e 1
O
OH
OTBDPS
3
3
1
2
1 2
1
2
H
H
H
H
H
H
MeO2C
MeO2C
MeO2C CHO
20
18
19
OTBDPS
TMS
OTBDPS
OTBDPS
3
2
3
2
3
1 2
1
1
H
H
H
H
MeO2C
MeO2C
MeO2C
TMS
23
22
21
nective analysis pictured in Scheme 1. Thus, formation
of the crucial C2-C1 bond (23 f 22) would generate the
appropriately functionalized cyclopentane for ready elabo-
ration to 19 and 18. In light of previous model studies,
we expected to achieve excellent induction by the resident
center C3 during the ene cyclization step.
Putting this plan into action, the known aldehyde 2415
was transformed into the activated 1,6-diene 23 (Scheme
(14) Cucurbic, acid; for synthesis, see: (a) Seto, H.; Yoshioka, H.
Chem. Lett. 1990, 1797. (b) Kitahara, T.; Miura, M.; Warita, Y.;
Takagi, Y.; Mori, K. Agric. Biol. Chem. 1987, 51, 1129. (c) Borm, C.;
Winterfeldt, E. Liebig Ann. 1996, 1209. (d) Stadmuller, H.; Knochel,
P. Synlett 1995, 463. Methyl epijasmonate; for synthesis, see: (e)
Helmchen, G.; Goeke, A.; Laner, G.; Urmann, M.; Fried, J . Angew.
chem., Int. Ed. Engl. 1990, 29, 1024. (f) Kitahara, T.; Nishi, T.; Mori,
K. Tetrahedron 1991, 47, 6999 and references cited therein. (g)
Crombie, L.; Mistry, M. K. J . Chem. Soc., Chem. Commun. 1988, 539.
(h) See also refs 14a, 14b, and 14d.
(16) Fleming, I.; Paterson, I. Synthesis 1979, 446.
(17) Saloman, R. G.; Coughlin, D. J . J . Org. Chem. 1979, 44, 3784.
(18) Montforts, F. P.; Gesing-Zibulak, I.; Grammenos, W.; Schneider,
M.; Lanman, K. Helv. Chim. Acta 1989, 72, 1852.
(19) (a) Bestmann, H. J .; Stransky, W.; Vostrowsky, O. Chem. Ber.
1976, 109, 1694. (b) Ibid. 1976, 109, 3375.
(15) Bestmann, H. J .; Gunawardena, N. E. Synthesis 1992, 1239.

Intramolecular Ene Reaction of Activated 1,6-Dienes
J . Org. Chem., Vol. 62, No. 17, 1997 6009
Meth yl (1RS,2SR,3SR)-2-[2-[(E)-3-Meth yl-1-bu ten yl]-3-
[(ter t-bu tyld ip h en ylsilyl)oxy]cyclop en tyl]a ceta te (8) a n d
Met h yl (1RS,2SR,3RS)-2-[2-[(E)-3-Met h yl-1-b u t en yl]-3-
[(ter t-bu tyld ip h en ylsilyl)oxy]cyclop en tyl]a ceta te (11). A
solution of 1 (1.5 g, 3.23 mmol) in dry toluene (30 mL) was
taken in seven corning tubes (30 cm long, 2 cm diameter),
purged with argon, and sealed. These sample tubes were
heated at 235 °C ((2 °C) for 40 h in a constant temperature
oven. After the samples were to room temperature, the solvent
was removed in vacuo and the residue passed through a plug
of silica gel and eluted with ethyl acetate-petroleum ether
(60-80 °C) (2.5:97.5) to give 8 and 11 (1.40 g, 97%) as a
colorless thick oil: IR 3422, 3050, 2945, 1732, 1444 cm-1; 1H-
NMR for major isomer 8 (CDCl3) δ 0.86 (d, 3H, J ) 6.7 Hz),
0.87 (d, 3H, J ) 6.7 Hz), 1.04 (s, 9H), 1.58-1.66 (m, 1H), 1.79-
1.84 (m, 1H), 1.93-1.98 (m, 1H), 2.1 (dd, 1H, J ) 15.7, 8.8
Hz), 2.26 (dd, 1H, J ) 15.6, 6.8 Hz), 2.49-2.59 (m, 1H), 2.69-
2.74 (m, 1H), 3.63 (s, 3H), 3.97-4.0 (m, 1H), 4.85 (dd, 1H, J )
15.2, 10.1 Hz), 5.15 (dd, 1H, J ) 15.2, 6.7 Hz), 7.32-7.42 (m,
6H), 7.61-7.65 (m, 4H); 1H-NMR for other minor diastereomer
11 (partial) δ 0.99 (d, 6H, J ) 6.76 Hz), 1.03 (s, 9H), 4.18-
4.22 (m, 1H), 5.36 (dd, 1H, J ) 15.2, 9.8 Hz), 5.48 (dd, 1H, J
) 15.2, 6.6 Hz); 13C-NMR for major isomer 8 (CDCl3) δ 173.402
(s), 140.556 (d), 135.934 (d), 135.805 (d), 134.632 (s), 134.377
(s), 129.465 (d), 127.504 (d), 124.174 (d), 79.971 (d), 54.996 (d),
51.152 (q), 37.062 (d), 36.348 (t), 33.697 (t), 31.205 (d), 28.811
(t), 27.099 (q), 22.683 (q), 22.510 (q), 19.190 (s); 13C-NMR for
minor diastereomer 11 (partial) δ 140.960 (d), 123.394 (d),
77.198 (d), 51.646 (d), 37.379 (d), 37.235 (t), 32.851 (t), 31.454
(d), 28.161 (t), 22.876 (q), 19.302 (s); GC-MS (COL SGE-BP-5,
0.32 mm/25 m, isothermal 260 °C); one major peak 8 tR ) 16.36
min (81.44%); m/z (relative intensity) no M+, 433 (45), 407 (M
- Me3C, 100), 333 (18), 213 (20), 199 (56), 177 (9), 153 (7),
135 (28), 119 (4), 105 (4), 93 (4), 79 (4), 69 (9); for minor
diastereomer 11 tR ) 19.01 min (11.9%); m/z (relative intensity)
no M+, 407 (M - Me3C, 100), 213 (21), 199 (30), 181 (9), 169
(9), 135 (20), 119 (12), 69 (25). Anal. Calcd for C29H40O3Si: C,
74.95; H, 8.67. Found: C, 74.99; H, 8.61.
Meth yl (1RS,2SR,3SR)-2-[2-[(E)-3-m eth yl-1-bu ten yl]-3-
[(ter t-bu tyld im eth ylsilyl)oxy]cyclop en tyl]a ceta te (9) a n d
m et h yl (1RS,2SR,3RS)-2-[2-[(E)-3-m et h yl-1-b u t en yl]-3-
[(ter t-bu tyld im eth ylsilyl)oxy]cyclop en tyl]a ceta te (12):
1H-NMR for major isomer 9 (CDCl3) δ 0.02 (d, 6H, J ) 6.6
Hz), 0.86 (s, 9H), 0.96 (d, 6H, J ) 6.5 Hz), 1.1-1.4 (m, 1H),
1.45-1.85 (m, 2H), 1.8-2.12 (m, 2H), 2.2-2.4 (m, 2H), 2.34-
2.5 (m, 1H), 2.5-2.7 (m, 1H), 3.64 (s, 3H), 3.88-3.93 (m, 1H),
4.85 (dd, 1H, J ) 15.2, 10.1 Hz), 5.15 (dd, 1H, J ) 15.2, 6.74
Hz), 7.32-7.41 (m, 6H), 7.61-7.65 (m, 4H); 1H-NMR for other
minor diastereomer 12 (partial) 3.72 (s, 3H), 4.08-4.18 (m,
1H), 5.6-5.9 (m, 2H); GLC (column 3%, OV-17, 0.25 mm × 50
m, N2 40 mL/min, 180 °C isothermal), tR for major diastere-
omer 9, 15.9 min (77.7%), for minor diastereomer 12, 17.3 min
(20.5%). Anal. Calcd for C19H36O3Si: C, 67.01; H, 10.65.
Found: C, 67.07; H, 10.69.
is free from any E-isomer as confirmed from capillary GC
as well as 13C-NMR analysis. This is the first synthesis
of methyl cucurbate (19) wherein three chiral centers on
the cyclopentane ring have been created in proper ster-
eochemical relationship in a single operation. The previ-
ous syntheses were either nonstereoselective14b or re-
quired an inversion14a of hydroxyl stereochemistry.
Finally, two-phase oxidation of (()-methyl cucurbate (19)
with chromic acid under Brown’s condition20 gave (()-
methyl epijasmonate (18) in 70% isolated yield. The
synthetic (()-methyl epijasmonate (18) has a very in-
1
tense, typical “jasmonate fragrance”. The H- and 13C-
NMR of our synthetic (()-18 agreed nicely with those
supplied by Prof. G. Helmchen.14e However, close ex-
amination of the 13C-NMR spectrum of our synthetic (()-
methyl epijasmonate (18) shows the presence of traces
(∼7-10%) of the C2 epimer, popularly known as methyl
jasmonate (from the appearance of signals at
δ
134.06(d), 53.99(d), 38.79(t), 38.01(d), 37.71(t)). This was
further confirmed by actual epimerization of synthetic
(()-18 under acidic conditions to give the C2 epimer
(methyl jasmonate) containing 5% of (()-18. Note that
the C2 proton in (()-methyl jasmonate (C2 epimer of (()-
18) appears as a one-proton multiplet at δ 2.6-2.8
whereas the C2 proton in (()-18 appears as one-proton
multiplet at δ 2.72-2.97. In addition, in the 13C-NMR
spectrum of (()-methyl jasmonate (C2 epimer of (()-18),
C2 (δ 53.91) and C1 (δ 37.94) carbons of the cyclopen-
tane ring lie downward relative to those in (()-methyl
epijasmonate (18) by δ ∼1.24 and 2.4, respectively, due
to γ-gauche upfield shift.21
Finally, the jasmonoid building block 20 should prove
valuable for the synthesis of other jasmonoid natural
products, namely, methyl tuberonate and congeners.22 In
addition, while 10 should serve as a key intermediate
for coriolin23 and also chloriolin A,24 9/12 may be tailored
into oreodaphnenol25 via intramolecular keto-carbeniod
addition across the π-bond, and work in these directions
is currently underway in this laboratory.
Exp er im en ta l Section
Gen er a l Deta ils. All reactions were carried out under a
dry nitrogen or argon atmosphere in flame-dried flasks.
Solvents were dried by distillation from drying agents as
follows: diethyl ether, THF, DME, toluene, and benzene
(sodium benzophenone ketyl), dichloromethane (P2O5), DMSO,
HMPA, Et3N, and pyridine (CaH2). Column chromatography
and TLC were carried out on silica gel. 1H-NMR spectra of
CDCl3 solutions were recorded at 200, 300, and 400 MHz and
that of CCl4 solutions at 90 MHz.
Met h yl (1RS,2SR,3RS)-2-[2-[(E)-3-(t r im et h ylsilyl)-1-
p r op en yl]-3-[(ter t-bu tyld ip h en ylsilyl)oxy]-4,4-d im eth yl-
cyclop en tyl]a ceta te (10): IR 2954, 2861, 1741, 1661, 1249,
1
1162, 1110, 847, 700 cm-1; H-NMR (CDCl3) δ -0.14 (s, 9H),
0.83 (s, 3H), 0.93-1.15 (m, 15H), 1.56-1.63 (m, 1H), 1.87 (dd,
1H, J ) 15.1, 9.5 Hz), 2.19 (dd, 1H, J ) 15.1, 5.1 Hz), 2.53-
2.62 (m, 2H), 3.44 (d, 1H, J ) 5.86 Hz), 3.57 (s, 3H), 4.52 (dd,
1H, J ) 15.1, 9.5 Hz), 4.85 (ddd, 1H, J ) 15.1, 9.4, 6.0 Hz),
7.28-7.42 (m, 6H), 7.61-7.66 (m, 4H); 13C-NMR (CDCl3) δ
173.892 (s), 136.240 (d), 134.827 (s), 134.060 (s), 130.208 (d),
129.285 (d), 127.242 (d), 127.112 (d), 87.429 (d), 52.604 (d),
51.245 (q), 45.073 (t), 41.626 (s), 37.275 (t), 34.544 (d), 28.050
(q), 27.169 (q), 22.939 (t), 22.481 (q), 19.547 (s), -1.88 (q); EIMS
m/z (relative intensity) no M+, 479 (M - Me3C, 28), 459 (2),
405 (3), 375 (8), 345 (3), 329 (8), 297 (7), 249 (12), 213 (16),
199 (39), 159 (24), 135 (52), 73 (100, Me3Si). Anal. Calcd for
C32H48O3Si2: C, 71.53; H, 9.02. Found: C, 71.59; H, 9.01.
Meth yl (1RS,2SR,3RS)-2-[2-isop r op en yl-3-[(ter t-bu tyl-
d ip h en ylsilyl)oxy]-4,4-d im eth ylcyclop en tyl]a ceta te (13)
a n d Meth yl (1SR,2SR,3RS)-2-[2-isop r op en yl-3-[(ter t-bu -
t yld ip h en ylsilyl)oxy]-4,4-d im et h ylcyclop en t yl]a cet a t e
(14): 1H-NMR (CDCl3) δ 0.87 (s, 3H), 0.99 (s, 9H), 1.1 (s, 3H),
(20) Brown, H. C.; Garg, C. P.; Liu, K. T. J . Org. Chem. 1971, 36,
387.
(21) (a) Schneider, H.-J .; Nguyen-ba, N.; Thomas, F. Tetrahedron
1982, 38, 2327. (b) Whitesell, J . K.; Minton, M. A. J . Am. Chem. Soc.
1987, 109, 225. (c) Rajanbabu, T. V.; Fukunaga, T.; Reddy, G. S. J .
Am. Chem. Soc. 1989, 111, 1759. (d) Yadav et al. Can. J . Chem. 1991,
69, 779
(22) (a) Koda, Y.; Omer, E. S. A.; Yoshihara, T.; Shibata, H.;
Sakamura, S.; Okazawa, Y. Plant Cell Physiol. 1988, 29, 1047. (b)
Yoshihara, T.; Omer, E. S. A.; Koshino, H.; Sakamura, S.; Kikutu, Y.;
Koda, Y. Agric. Biol. Chem. 1989, 53, 2835. (c) Yoshihara, T.;
Matsuura, H.; Ichihara, A.; Kikuta, Y.; Koda, Y. In Progress in Plant
Growth Regulation; Karssen, C. M., Van Loon, L. C.; Vreugdenhil, D.,
Eds.; Academic Publishers: Netherlands, 1992; p 286. (d) Matsuura,
H.; Yoshihara, T.; Ichihara, A.; Kukuta, Y.; Koda, Y. Biosci. Biotech.
Biochem. 1993, 57, 1253.
(23) Oppolzer, W.; Ando, A. Chemia 1992, 46, 122.
(24) Cheng, X.-C.; Varoglu, M.; Abrell, L.; Crews, P.; Lobkovvsky,
E.; Clardy, J . J . Org. Chem. 1994, 59, 6344.
(25) Weyerstahl, P.; Marschall-Weyerstahl, H.; Wahlburg, H.-C.
Liebigs Ann. Chem. 1989, 307.

6010 J . Org. Chem., Vol. 62, No. 17, 1997
Sarkar et al.
1.22 (s, 3H), 1.52-1.68 (m, 2H), 1.87 (dd, 1H, J ) 15.4, 9.3
Hz), 2.14 (dd, 1H, J ) 15.5, 5.8 Hz), 2.63-2.73 (m, 1H), 2.79
(dd, 1H, J ) 11.1, 8.0 Hz), 3.56 (s, 3H), 3.72 (dd, 1H, J ) 8.3
Hz), 4.18 (s, 1H), 4.50 (singlet with allylic fine spliting, 1H),
7.28-7.40 (m, 6H), 7.60-7.68 (m, 4H); 1H-NMR for minor
diastereomer 14 (partial) δ 0.75 (s, 3H), 2.23-2.38 (m, 2H),
3.57 (s, 3H), 4.54-4.56 (m, 2H); 13C-NMR (CDCl3) δ 173.919
(s), 142.859 (d), 136.286 (d), 134.240 (s), 134.008 (s), 129.459
(d), 129.254 (d), 128.305 (s), 127.253 (d), 126.987 (d) 114.246
(t), 84.073 (d), 54.257 (d), 51.259 (q), 45.246 (t), 41.291 (s),
37.131 (t), 32.824 (d), 27.085 (q), 23.532 (q), 21.408 (q), 19.519
(s); 13C-NMR for minor diastereomer 14 (partial) δ 115.247 (t),
83.400 (d), 61.778 (d), 44.883 (t), 39.385 (t), 33.735 (d), 28.633
(q), 27.293 (q), 25.314 (q), 17.639 (q); GC [OV-17 (fused silica),
0.25 mm × 50 m 250 °C isothermal]; minor isomer tR 17.158
min (11.89%); major isomer tR 18.112 min (87.5%); HRMS for
(C33H40O3Si) EI (M - C4H9) calcd 407.2042, found 407.2032.
Dieth yl (1SR,2SR,3RS)-2-[2-Isop r op en yl-3-[(ter t-bu tyl-
d ip h en ylsilyl)oxy]-4,4-d im eth ylcyclop en tyl]p r op a n e-1,3-
d ioa te (15). To a stirred suspension of dry ZnBr2 (457 mg,
1.99 mmol) in dry dichloromethane (3 mL) was added 6 (1.045
g, 1.9 mmol) dropwise over a period of 10 min under argon.
After 3 h the reaction mixture was quenched with saturated
aqueous ammonium chloride and extracted with ether (3 ×
10 mL). The ether layer was washed with brine, dried
(MgSO4), and concentrated to give a colorless oil, 15 (940 mg,
(t), 19.146 (s), -1.958 (q); 13C-NMR (CDCl3) for other minor
diastereomer 29 δ 124.863 (d), 77.210 (d), 51.954, 37.459,
37.251, 32.485 (t), 29.696, 27.861, -1.812 (q); GC-MS (COL
SGE-BP-5, 0.32 mm/25 m, isothermal 260 °C) one major peak
22 tR ) 23.22 min (89.5%); m/z (relative intensity) no M+, 493
(M - Me, 41), 486 (4), 477 (54), 451 (M - Me3C, 100) 419 (1.5),
377 (4), 347 (3), 335 (3), 303 (4), 273 (3), 271 (26), 221 (4), 213
(23), 199 (44), 181 (5), 153 (5), 135 (21), 119 (5), 105 (12), 91
(4), 79 (5), 73 (38); trace diastereomer tR ) 23.40 min (0.8%);
m/z (relative intensity) no M+, 451 (M - Me3C, 100), 441 (4),
417 (5), 395 (4), 380 (8), 349 (7), 319 (6), 281 (36), 269 (36),
257 (12), 252 (13), 243 (28), 231 (12), 219 (40), 199 (68), 181
(20), 155 (14), 135 (18), 119 (75), 107 (14), 92 (12), 73 (24), 69
(84); minor diastereomer 29 tR ) 25.55 min (9.7%); m/z
(relative intensity) no M+, 451 (M - Me3C, 100), 431 (2), 419
(3), 393 (9), 348 (9), 335 (17), 301 (7), 281 (5), 271 (20), 263
(5), 225 (14), 213 (25), 199 (40), 183 (10), 166 (5), 135 (28), 105
(12), 73 (68). Anal. Calcd for C30H44O3Si2: C, 70.71; H, 8.74.
Found: C, 70.82; H, 8.71.
Meth yl 2-[2-(2-P r op en yl)-3-[(ter t-bu tyld ip h en ylsilyl)-
oxy]cyclop en tyl]a ceta te (21). To a stirred solution of 22/
29 (450 mg, 0.89 mmol) in dry benzene (12 mL) was added
57% aqueous hydrogen iodide (0.113 mL), and the mixture was
stirred for 12 h at room temperature. The organic layer was
washed with water (2 × 15 mL) and brine, dried (Na2SO4),
and concentrated. Preparative layer chromatography [silica
gel 2% ethyl acetate-petroleum ether (60-80 °C) as develop-
ing solvent] of the residue gave 21 (305 mg, 79%) as a colorless
thick oil: IR 3056, 2942, 1736, 1642, 1444, 1362, 1268, 1174,
90%): IR 949, 2868, 1734, 1654, 1248, 1161, 892 cm-1 1H-
;
NMR (CDCl3) δ 0.79 (s, 3H), 1.01 (s, 9H), 1.03 (s, 3H), 1.07 (s,
3H), 1.18 (t, 3H, J ) 7.2 Hz), 1.26 (t, 3H, J ) 7.2 Hz), 1.36-
1.47 (m, 1H), 1.59-1.71 (m, 1H), 2.25-2.43 (m, 1H), 2.57 (dd,
1H, J ) 10.6, 8.5 Hz), 3.26 (d, 1H, J ) 8.4 Hz), 3.71 (d, 1H, J
) 8.5 Hz), 4.05 (q, 2H, J ) 7.2 Hz), 4.17 (q, 2H, J ) 7.2 Hz),
4.57-4.58 (m, 2H), 7.30-7.44 (m, 6H), 7.65-7.71 (m, 4H); 13C-
NMR (CDCl3) δ 168.592 (s), 168.504 (s), 142.586 (s), 136.426
(d), 134.260 (s), 134.088 (s), 129.440 (d), 129.327 (d), 127.272
(d), 127.036 (d), 116.027 (t), 83.453 (d), 61.103 (t), 60.893 (t),
59.155 (d), 56.210 (d), 42.129 (t), 40.529 (s), 35.921 (d), 28.351
(q), 27.161 (q), 24.763 (q), 19.625 (s), 17.418 (q), 14.088 (q),
13.823 (q); HRMS for (C33H46O5Si) EI (M - C4H9) calcd for
493.2410, found 493.2403. 15 is contaminated with 17 (4%)
as confirmed by conversion of the malonate side chain to
methyl acetate and comparison of the products with 13/14 by
1H-NMR and capillary GC.
Dieth yl (1SR,2RS,5RS)-2-[5-isop r op en yl-2-[(ter t-bu tyl-
d ip h en ylsilyl)oxy]cyclop en t yl]p r op a n e-1,3-d ioa t e (16):
1H-NMR (CDCl3) δ 1.05 (s, 9H), 1.17 (t, 3H, J ) 7.2 Hz), 1.18
(t, 3H, J ) 7.2 Hz), 1.42-1.75 (m, 6H), 1.76 (s, 3H), 2.58-2.64
(m, 2 H), 3.30 (d, 1H), 3.96-4.10 (m, 5H), 4.68-4.71 (m, 2H),
7.26-7.42 (m, 6H), 7.60-7.69 (m, 4H); 13C-NMR (CDCl3) δ
168.65 (s), 168.38 (s), 146.95 (s), 135.92 (d), 135.80 (d), 134.67
(s), 133.96 (s), 129.55 (d), 129.49 (d), 127.53 (d), 127.46 (d),
111.01 (t), 78.13 (d), 60.93 (t), 60.86 (t), 52.84 (d), 50.94 (d),
48.31 (d), 34.18 (t), 29.37 (t), 26.97 (q), 19.17 (s), 18.80 (q), 13.91
(q); HRMS for (C31H42O5Si) EI (M - C4H9) calcd for 465.2096,
found 465.2097.
1090, 914, 826, 706 cm-1 1H-NMR (CDCl3) δ 1.07 (s, 9H),
;
1.14-1.33 (m, 1H), 1.55-2.1 (m, 6H), 2.17 (dd, 1H, J ) 15.09
and 9.4 Hz), 2.39 (dd, 1H, J ) 15.09 and 6.4 Hz), 2.7-2.92 (m,
1H), 3.67 (s, 3H), 3.98-4.08 (m, 1H), 4.75-4.90 (m, 2H), 5.27-
5.52 (m, 1H), 7.32-7.48 (m, 6H), 7.62-7.75 (m, 4H); 1H-NMR
for other minor diastereomer δ 2.52-2.62 (m, 1H), 4.18-4.28
(m, 1H); 13C-NMR (CDCl3) δ 173.787 (s), 137.083 (d), 135.855
(d), 134.622 (s), 134.380 (s), 129.455 (d), 127.476 (d), 115.484
(t), 78.186 (d), 51.421 (q), 50.056 (d), 36.158 (d), 35.422 (t),
32.513 (t), 31.470 (t), 28.182 (t), 27.019 (q), 19.131 (s); EIMS
m/z (relative intensity) 435 (M - 1, 0.7), 405 (2), 379 (M -
Me3C, 64), 347 (5), 305 (18), 259 (18), 213 (25), 199 (100), 181
(20), 149 (14), 135 (22), 107 (25), 79 (23). Anal. Calcd for
C27H36O3Si: C, 73.98; H, 8.32. Found: C, 74.27; H, 8.30.
Meth yl 2-[2-(2-Oxoeth yl)-3-[(ter t-bu tyld ip h en ylsilyl)-
oxy]cyclop en tyl]a ceta te (20). Ozone was bubbled through
a solution of 21 (265 mg, 0.61 mmol) in methanol (25 mL) at
-78 °C till the blue color persisted for more than 10 min. The
excess ozone was removed by allowing nitrogen gas to bubble
through the solution at -78 °C. Dimethyl sulfide (3.2 mL)
was added dropwise at the same temperature. The mixture
was allowed to attain room temperature and stirred for 2 h.
Excess dimethyl sulfide was removed by bubbling nitrogen gas
through the solution, and solvent was removed in vacuo.
Preparative layer chromatography [silica gel 5% ethyl acetate-
petroleum ether (60-80 °C) as developing solvent] of the
residue gave 20 (237 mg, 88%): IR 2932, 2720 (w), 1728, 1444,
Met h yl (1RS,2SR,3SR)-2-[2-[(E)-3-(t r im et h ylsilyl)-1-
p r op en yl]-3-[(ter t-b u t yld ip h en ylsilyl)oxy]cyclop en t yl]-
a ceta te (22) a n d m eth yl (1RS,2SR,3RS)-2-[2-[(E)-3-(tr i-
m e t h ylsilyl)-1-p r op e n yl]-3-[(t er t -b u t yld ip h e n ylsilyl)-
oxy]cyclop en tyl]a ceta te (29): IR 3050, 2942, 1738, 1624,
1
1268, 1178, 1098, 824, 708 cm-1; H-NMR (CDCl3) δ 1.06 (s,
9H), 1.12-1.27 (m, 1H), 1.55-2.58 (m, 9H), 2.72-2.95 (m, 1H),
3.65 (s, 3H), 3.88-3.98 (m, 1H), 7.33-7.48 (m, 6H), 7.6-7.7
(m, 4H), 9.28 (unresolved triplet 1H); 1H-NMR (partial) for
other minor diastereomer δ 4.25-4.42 (m, 1H).
1440, 1258, 1168, 1092, 842, 704 cm-1 1H-NMR for major
;
isomer 22 (CDCl3) δ -0.10 (s, 9H), 1.04 (s, 9H), 1.17-1.25 (m,
1H), 1.29 (d, 2H, J ) 8.0 Hz), 1.59-1.66 (m, 1H), 1.78-1.86
(m, 1H), 1.93-2.0 (m, 1H), 2.15 (dd, 1H, J ) 15.5 and 8.7 Hz),
2.30 (dd, 1H, J ) 15.5 and 6.7 Hz), 2.52 (t, 1H, J ) 8 Hz),
2.69-2.80 (m, 1H), 3.636 (s, 3H), 3.98-4.00 (m, 1H), 4.73 (dd,
1H, J ) 15 and 10 Hz), 5.13 (dt, 1H, J ) 15 and 8 Hz), 7.32-
7.41 (m, 6H), 7.60-7.65 (m, 4H). Irradiation at δ 2.75 results
in collapse of two four-line signals at δ 2.14 and 2.3 (due to
CH2CO2Me) into a two two-line signals: 1H-NMR for other
minor diastereomer 29 (partial) δ 0.01 (s, 9H), 1.03 (s, 9H),
2.35-2.48 (m, 2H), 3.61 (s, 3H), 4.15-4.21 (m, 1H), 5.34-5.36
(m, 2H); 13C-NMR for major isomer 22 δ 173.923 (s), 135.889
(d), 135.799 (d), 134.729 (s), 134.526 (s), 129.414 (d), 129.228
(d), 127.464 (d), 125.504 (d), 80.376 (d), 55.520 (d), 51.262 (q),
37.032 (d), 36.400 (t), 33.347 (t), 28.481 (t), 27.024 (q), 23.103
Met h yl 2-[2-[(Z)-2-P en t en yl]-3-[(ter t-b u t yld ip h en yl-
silyl)oxy]cyclop en t yl]a cet a t e (30). To a mixture of tri-
phenylpropylphosphonium bromide (810 mg, 2.1 mmol) and
NaN(TMS)2 (365 mg, 2.0 mmol) was added tetrahydrofuran
under argon atmosphere. The mixture was stirred for 1 h at
room temperature. During this period the mixture developed
a bright orange color, indicating the formation of the ylide.
To a solution of 20 (220 mg, 0.5 mmol) in tetrahydrofuran (8
mL) was added the solution of the ylide at -78 °C during 30
min. The mixture was stirred for 1.5 h at -78 °C, 1 h at -50
°C, 1 h at -30 °C, and 1.5 h at 0 °C and then the mixture
allowed to attain room temperature and stirred overnight
whereby the orange color disappeared and a whitish suspen-
sion formed. This was diluted with petroleum ether (60-80
°C) and the precipitated triphenylphosphine oxide separated

Intramolecular Ene Reaction of Activated 1,6-Dienes
J . Org. Chem., Vol. 62, No. 17, 1997 6011
by filtration. The filtrate was concentrated and the residue
passed through a bed of silica gel. The crude oil thereby
obtained was chromatographed over silica gel and eluted with
ethyl acetate-petroleum ether (60-80 °C) (3:97) to give 30 as
a colorless thick oil (116 mg, 50% yield): IR 2924, 2856, 1744,
The mixture was stirred for 20 min, and to this were added
excess 2-propanol and then sodium bicarbonate. The mixture
was filtered and extracted with ether. The combined ether
extracts were washed with water and brine, dried (Na2SO4),
and concentrated in vacuo. The residue was chromatographed
over silica gel and eluted with ethyl acetate-petroleum ether
(60-80 °C) (1:9) to give 18 (23 mg, 70%): IR 2960, 1737, 1642,
1611, 1248, 1158, 1098, 1053, 841, 698, 611 cm-1 1H-NMR
;
(CDCl3) δ 0.85 (t, 3H, J ) 7.5 Hz), 1.05 (s, 9H), 1.15-1.38 (m,
1H), 1.55-2.1 (m, 8H), 2.17 (dd, 1H, J ) 15 and 9.4 Hz), 2.38
(dd, 1H, J ) 15 and 6.4 Hz), 2.70-2.91 (m, 1H), 3.67 (s, 3H),
3.96-4.05 (m, 1H), 4.85-5.0 (m, 1H), 5.12-5.35 (m, 1H), 7.3-
7.48 (m, 6H), 7.58-7.7 (m, 4H); 1H-NMR for other minor
diastereomer (partial) δ 0.955 (t, 3H, J ) 7.5 Hz), 2.45-2.6
(m, 1H), 4.15-4.25 (m, 1H); 13C-NMR (CDCl3) δ 173.768 (s),
135.776 (d), 134.456 (s), 134.325 (s), 132.268 (d), 129.358 (d),
127.394 (d), 127.010 (d), 78.296 (d), 51.332 (q), 50.772 (d),
36.196 (d), 35.423 (t), 32.570 (t), 28.113 (t), 26.949 (q), 24.390
(t), 20.402 (t), 19.056 (s), 14.010 (q); 13C-NMR for other minor
diastereomer (partial) δ 128.219 (d), 48.459, 33.149, 28.741,
22.880. Anal. Calcd for C29H40O3Si: C, 74.78; H, 8.70;
Found: C, 74.96; H, 8.67.
1442, 1311, 1259, 1168, 1021, 807, 696, 616 cm-1 1H-NMR
;
(CDCl3) δ 0.91 (t, 3H, J ) 7.5 Hz), 1.62-2.44 (m, 11H), 2.72-
2.97 (m, 1H), 3.64 (s, 3H), 5.2-5.5 (m, 2H); 13C-NMR (CDCl3)
δ 218.768 (s), 172.855 (s), 133.479 (d), 125.460 (d), 52.672 (d),
51.671 (q), 35.590 (d), 35.247 (t), 33.739 (t), 25.668 (t), 22.949
(t), 20.626 (t), 14.016 (q); 13C-NMR of the trace (7-10%) C2
epimer of (()-18 (partial) δ 134.069, 53.999, 38.795, 38.015,
37.712.
Met h yl (1RS,2RS)-2-[2-[(Z)-2-P en t en yl]-3-oxocyclo-
p en tyl]a ceta te (Meth yl J a sm on a te, C2 Ep im er of (()-18).
A drop of 1.5 N HCl was added to a solution of 18 (12 mg) in
benzene. The solution was stirred for 1.5 h. The crude product
was passed through a short silica gel column, and elution with
10% ethyl acetate-petroleum ether (60-80 °C) and concentra-
tion of the solvent gave the C2 epimer of (()-18 (10 mg) as an
Met h yl
(1RS,2SR,3SR)-2-[2-[(Z)-2-P en t en yl]-3-h y-
d r oxycyclop en tyl]a ceta te (Meth yl Cu cu r ba te, 19). To a
solution of 30 (145 mg, 0.312 mmol) in tetrahydrofuran (5 mL)
was added tetrabutylammonium fluoride trihydrate (198 mg,
0.63 mmol) under an argon atmosphere. After being stirred
for 24 h at room temperature, the mixture was partitioned
between ether and saturated aqueous sodium chloride, and
the aqueous layer was extracted with ether (3 × 15 mL). The
combined ether extracts were dried (MgSO4) and concentrated
in vacuo. Preparative layer chromatography [silica gel 15%
ethyl acetate-petroleum ether (60-80 °C) as developing
solvent] of the residue afforded a first fraction (∼3 mg) [1H
NMR δ 0.97 (t), 4.6 (bs), 5.35-5.45 (m)] and a second fraction,
19 (63 mg, 89%), as a colorless oil: IR 3420, 2924, 2857, 1730,
1631, 1454, 1250, 1162, 1054, 689, 615 cm-1; 1H-NMR (CDCl3)
δ 0.94 (t, 3H, J ) 7.5 Hz), 1.19-1.36 (m, 1H), 1.42-1.64 (m,
2H), 1.78-2.11 (m, 7H), 2.17 (dd, 1H, J ) 15.1 and 9.3 Hz),
2.39 (dd, 1H, J ) 15.1 and 6.3 Hz), 2.53-2.75 (m, 1H), 3.64 (s,
3H), 3.83-4.06 (m, 1H), 5.22-5.50 (m, 2H); 13C-NMR (CDCl3)
δ 173.699 (s), 133.014 (d), 127.079 (d), 77.412 (d), 51.474 (q),
50.559 (d), 36.661 (d), 35.264 (t), 32.472 (t), 28.289 (t), 25.249
(t), 20.607 (t), 14.115 (q); GLC (column 3% OV-17, N2 40 mL/
min, 210 °C isothermal) tR ) 9.77 min; EIMS m/z (relative
intensity) 226 (M+, 0.6), 208 (M - 18, 5), 195 (2), 165 (7), 153
(85), 134 (37), 119 (17), 109 (20), 97 (35), 83 (100), 79 (64), 67
(45), 55 (49), 41 (74), 29 (30).
oil: IR 2925, 1860, 1739, 1447, 1245, 1162 cm-1
;
1H-NMR
(CDCl3) δ 0.93 (t, 3H, J ) 7.5 Hz), 1.4-1.6 (m, 1H), 1.72-1.92
(m, 1H), 1.94-2.45 (m, 10H), 2.6-2.8 (m, 1H), 3.67 (s, 3H),
5.18-5.37 (m, 1H), 5.38-5.05 (m, 1H); 13C-NMR (CDCl3) δ
219.0 (s), 172.43 (s), 134.0 (d), 124.87 (d), 53.91 (d), 51.51 (q),
38.72 (t), 37.94 (d), 37.64 (t), 27.13 (t), 25.42 (t), 20.52 (t), 14.0
(q); 13C-NMR of the minor epimer 18 (partial) δ 125.37, 52.6,
35.52, 35.18, 33.65, 22.87; GC [OV-17 (fused silica) 10.25 mm
× 50 m, 80-220 °C, 4 °C min] tR ) 25.16 min (95%) and tR
)
25.97 min (5%).
Ackn owledgm en t. We thank CSIR [2(323)/91-EMR-
II] and DST (SP/SI/G76/90), Government of India, for
funding of this work. The CSIR, New Delhi, is also
thanked for the award of Senior Research Fellowship
to B.K.G., S.K.N., and B.M. We are thankful to Prof.
G. Helmchen and Prof. T. Kitahara for providing
comparison spectra of authentic methyl epijasmonate.
Dr. C. Fehr (Firmenich, Geveva), Mr. P. Pradhan
(BARC, Bombay), and Dr. S. K. Ghosh (BARC, Bombay)
are thanked for their help.
Su p p or tin g In for m a tion Ava ila ble: Complete experi-
mental procedure for 1-7 and 23 and spectroscopic/chemical
characterization of 8-17 and 22 (20 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
Met h yl (1RS,2SR)-2-[2-[(Z)-2-P en t en yl]-3-oxocyclo-
p en tyl]a ceta te (Meth yl Ep ija sm on a te, 18). A chromic acid
solution was prepared from sodium dichromate (5.0 g, 16.8
mmol) and 95% sulfuric acid (6.93 g, 54.2 mmol) and diluted
with water to make up 25 mL of total volume. To a solution
of 19 (33 mg, 0.146 mmol) in ether (2.5 mL) was added chromic
acid solution (0.29 mL of the stock solution) with ice cooling.
J O961739N