Synthesis of cis-Hedione and methyl jasmonate via cascade Baylis-Hillman reaction and Claisen ortho ester rearrangement

Article abstract of DOI:10.1002/hlca.200590248

The exocyclically unsaturated conjugated keto esters 10, obtained via a Claisen ortho ester rearrangement of the allylic hydroxy ketones 9, were either directly hydrogenated or partially isomerized into the endocyclically unsaturated tetrasubstituted didehydrojasmonoid intermediates 14, prior to a more selective hydrogenation with Pd/C in cyclohexane to the disubstituted oxocyclopentaneacetates 15 (Scheme 2). The key intermediates 9 were obtained either by a four-step sequence, including acetal protection/deprotection from enone 1, in the specific case of hydroxy ketone 9a (Scheme 1), or more directly and generally by a Baylis-Hillman reaction from cyclopent-2-en-1-one (16) and the appropriate aldehydes 17 (Scheme 2). The judicious choice of these aldehydes opens versatile modifications for the stereoselective introduction of the partially cis- or epimerized trans-C(2) jasmonoid side chain, while the Baylis-Hillman reaction, catalyzed by chiral [1,1′-binaphthalene]-2, 2′-diols (BINOLs) 19 (Scheme 3), may be efficiently conducted in a one-pot cascade fashion including the ortho ester Claisen rearrangement.

Full text of DOI:10.1002/hlca.200590248

Helvetica Chimica Acta – Vol. 88 (2005)
3069
Synthesis of cis-Hedione® and Methyl Jasmonate via Cascade Baylis–
Hillman Reaction and Claisen Ortho Ester Rearrangement
by Christian Chapuis*a), George H. Büchib)1), and Hans Wüestb)2)
a) Firmenich SA, Corporate R&D Division, P. O. Box 239, CH-1211 Geneva 8
b) Department of Chemistry, Massachusetts Institute of Technology, Cambridge MA 02139 USA
Dedicated to Dr. Ferdinand Näf on the occasion of his 65th birthday
The exocyclically unsaturated conjugated keto esters 10, obtained via a Claisen ortho ester rearrangement
of the allylic hydroxy ketones 9, were either directly hydrogenated or partially isomerized into the endocycli-
cally unsaturated tetrasubstituted didehydrojasmonoid intermediates 14, prior to a more selective hydrogena-
tion with Pd/C in cyclohexane to the disubstituted oxocyclopentaneacetates 15 (Scheme 2). The key intermedi-
ates 9 were obtained either by a four-step sequence, including acetal protection/deprotection from enone 1, in
the specific case of hydroxy ketone 9a (Scheme 1), or more directly and generally by a Baylis–Hillman reaction
from cyclopent-2-en-1-one (16) and the appropriate aldehydes 17 (Scheme 2). The judicious choice of these
aldehydes opens versatile modifications for the stereoselective introduction of the partially cis- or epimerized
trans-C(2) jasmonoid side chain, while the Baylis–Hillman reaction, catalyzed by chiral [1,1’-binaphthalene]-
2,2’-diols (BINOLs) 19 (Scheme 3), may be efficiently conducted in a one-pot cascade fashion including the
ortho ester Claisen rearrangement.
Introduction. – The thermodynamically more stable methyl (ꢀ)-(1R,2R,Z)-jasmo-
nate3) was isolated and characterized in 1962 from Jasmanirus grandiflorum L. by
Demole et al. [2] and later from Rosmarinus officinalis L. by Crabalona [3]. The pre-
cious, elegant, and radiant jasmine scent associated to this molecule and its analogues4),
largely appreciated and used by the fragrance industry, as well as the biological activity
of its corresponding acid5), motivated numerous racemic, diastereo- and enantioselec-
tive syntheses, summarized in several reviews [6]. More recently, the minor methyl (+)-
(1R,2S,Z)-epijasmonate6), also known as a pheromone [8]7), was shown to be essen-
tially responsible for the floral odor, although all stereoisomers may impart synergic
effects or improve a perfume composition as fixatives or enhancers. For more than
1
)
)
)
)
)
Deceased on 28th August, 1998.
Retired since 31st July, 1994, work performed in 1992–1993.
For a recent enantioselective synthesis, see [1].
For analogues and a structure-odor relationship study, see [4].
For plant growth inhibitory activities of the acid or Me ester, see [5a–c], and for their anti-cancer and
bloodparasites cytotoxic properties, see [5d–e].
For the corresponding biologically active unstable (+)-(Z)-cis-acid, see [7]. Some of the biological activities
reported for the trans isomer are artefacts due to epimerization.
This compound additionally shows several other biological activities such as plant defence [7], plant-growth
regulation [9], induction of tubers in potato stolons [10], promotion of coiling in tendrils of climbing plants
[11], as well as signal transmission in interplant communication [12].
2
3
4
5
6
)
)
7
© 2005 Verlag Helvetica Chimica Acta AG, Zürich

3070
Helvetica Chimica Acta – Vol. 88 (2005)
30 years, Firmenich SA has commercialized under the trade name of Hedione®8) the
racemate of a 9 :1 equilibrated mixture of the structurally closely related methyl
trans-dihydrojasmonates9). More recent industrial development has allowed the com-
mercial availability of the even olfactively more active ‘rac-high-cis-Hedione’(>70%
cis) [16] as well as optically active methyl (+)-(1R,2S)-dihydroepijasmonate [17]. We
now wish to report on our efforts directed towards an alternative process, based on a
cascade Baylis–Hillman reaction/orthoester Claisen rearrangement, to construct this
jasmonoid skeleton with versatile stereocontrol as well as modifications of the C(2)
side chain.
Results and Discussion. – Our procedure to introduce the methyl acetate substitu-
ent at C(1) as well as the cis-configuration at the C(2)=C(3) bond of the side chain of
the targeted cis-Hedione or methyl epijasmonate backbones was initially based on an
orthoester Claisen rearrangement10) followed by hydrogenation. Unfortunately, direct
photo-oxidation (MeOH, AcONa, O2, Rose Bengal, hv, then Me2S [20]) of the exocy-
clic-enone 1 (Scheme 1) afforded the desired hydroxy enone in only 6% isolated yield,
along with 5,6-dioxodecanoic acid (5% yield)11). Alternatively, Payne epoxidation
(H2O2, NaOH, [21]) of enone 1 also failed to produce the corresponding a,b-epoxy
ketone 2 as a potential precursor in more than 3% yield12). Under alternative 3-chlor-
operbenzoic acid (mCPBA) oxidation conditions, enone 1 afforded the new unsatu-
rated lactone 3 in 11% yield13). We then decided to reduce enone 1 (DIBAL-H (diiso-
butylaluminium hydride), CH2Cl2, 108 [23]; 94%) to the corresponding allylic alcohol 4
[24] prior to a stereoselective epoxidation (mCPBA, CH2Cl2 [25]; 96%) in favor of the
unreported epoxy alcohol 514). Oxidation of this alcohol turned out to be difficult due
to side reactions, and the best conditions (pyridinium chlorochromate (PCC), CH2Cl2,
8
)
)
)
Methyl trans-3-oxo-2-pentylcyclopentaneacetate also possesses some biological activities [13].
Very recently, Kao Corp. seems to have re-invented [14] a more than 40 years old industrial process [15].
An analogous orthoester Claisen rearrangement of 2-(1-hydroxyethyl)cyclohex-2-en-1-one and
MeC(OEt)3 was earlier reported [18]. For a photo-Claisen rearrangement starting from 9 (R=H, Me;
Scheme 2) leading to aldehydes or ketones contrasting with our thermal orthoester Claisen procedure,
see [19].
Replacement of the sensitizer Rose Bengal by methylene blue, meso-tetraphenylporphyrine, eosine, or 9H-
fluoren-9-one proved to be even less efficient in terms of chemical yield or regioselectivity.
Oxidation of 1 failed also with the following reagents: trichloroisocyanuric acid/KOH under non-aqueous
conditions [22a] as well as NaOCl/pyridine [22b] or H2O2/NaOCl [22c]; H2O2/K2CO3 in MeOH [22d]; H2O2
in AcOH [22e]; H2O2/Bu4NF in DMSO [22f]; H2O2/Et3N in toluene [22g]; H2O2 ·urea/NaOH in MeOH
[22h]; H2O2 ·urea/DBU in THF [22i]; tBuOOH/DBU [22j]; NaBO3 ·4H2O in dioxane [22k]; dimethyldiox-
ane/acetone/CH2Cl2 [22l].
9
10
11
12
)
)
13
14
)
)
Further oxidation with an excess of mCPBA afforded the corresponding epoxy lactone in 22% yield after
column chromatography (SiO2, hexane/AcOEt 95:5): IR: 3000, 2950, 2930, 2860, 1745, 1460, 1325, 1105,
1045. H-NMR (200 MHz; J in Hz): d 0.93 (t, J=7, 3 H); 1.4 (m, 3 H); 1.55 (m, 3 H); 1.87 (m, 1 H); 1.97
(m, 1 H); 2.12 (m, 1 H); 2.2 (m, 1 H); 2.6 (td, J=7, 10, 1 H); 2.74 (td, J=7, 10, 1 H); 3.3 (t, J=7, 1 H).
When this epoxy alcohol was treated for 15 min in refluxing THF with 2.8 mol-equiv of lithium diisopro-
pylamide (LDA), the corresponding bis-allylic diol was obtained in 76% yield: IR: 3600, 3400, 3000,
2950, 2925, 2850, 1445, 1375, 1035. 1H-NMR (200 MHz; J in Hz): d 0.92 (t, J=7, 3 H); 1.39 (m, 4 H);
1.48 (m, 1 H); 1.65 (m, 1 H); 1.76 (m, 2 H); 2.3 (m, 2 H); 2.5 (m, 2 OH); 4.36 (t, J=5, 1 H); 4.85 (m, 1
H); 5.8 (br. s, 1 H).
1

Helvetica Chimica Acta – Vol. 88 (2005)
3071
[26]) led to the isolation of the desired epoxy ketone 2 in only 12% yield15)16). Alterna-
tively, in view of this drawback, we also protected enone 1 as its corresponding acetal 6
(ethylene glycol, cyclohexane, fumaric acid [36a]; 55%) before epoxidation (mCPBA,
CH2Cl2; 93%). Treatment of epoxide 7 with an excess of base (2.0 mol-equiv. of LDA,
THF, ꢀ208; 66%) afforded the allylic alcohol 8. Deprotection (HCl, H2O/THF, (43%
yield); or acetone/H2O, pyridine·TsOH, 208 [36b] (94% yield)) finally gave access to
the desired allylic alcohol 9a. Subsequent orthoester Claisen rearrangement
(MeC(OMe)3, pivalic acid, 1108), gave the unsaturated keto ester 10a as a 1:6 :3 b,g-
deconjugated/(Z)/(E) mixture in 88% yield. The (E)/(Z) ratio is not totally under
kinetic control, being also influenced by a deconjugation/conjugation process under
the acidic reaction conditions. Alternatively, this sequence was reversed, and the
Claisen rearrangement was conducted with allylic hydroxy acetal 8 (MeC(OMe)3, prop-
anonic acid, 1108) to give methyl ester 11 in 86% yield as a ca. 7:3 (Z)/(E) mixture of
stereoisomers. Further deprotection of 11 (acetone/H2O, pyridine·TsOH, 208 [36b])
gave quantitatively a 7:3 (Z)/(E) mixture of conjugated enone 10a.
Ikan and Ravid already reported in 1974 that either methyl acetate enolate addition
or Reformatzky reaction to the endocyclic-enone 12, allowed the isolation of the terti-
ary allylic hydroxy ester 13a in 84% yield [37]. After Jones oxidation, the tetrasubsti-
tuted enone 14a [38] (87% yield) was hydrogenated under basic conditions (MeOH,
NaOH, 5% Pd/C, 208) to afford methyl trans-dihydrojasmonate 15a in 43% yield.
We repeated this sequence and performed the hydrogenation under neutral conditions
(cyclohexane, 10% Pd/C, 208) to obtain Hedione® (15a) as a 38 :62 trans/cis mixture.
Similarly, hydrogenation of 10a ((Z)/(E) 7:3, MeOH, 5% Pd/C, 208) gave a 1:1
trans/cis mixture in 98% yield. An almost identical result was obtained when a 1:3 :6
b,g-deconjugated/(Z)/(E) mixture 10a (vide supra) was hydrogenated (cyclohexane,
5% Pd/C, ca. 08; 98%). We also repeated the sequence with the ethyl esters 13b
(75%) and 14b [39] (93%). It is noteworthy that treatment of any mixture 10a with
t
either 0.04 mol-equiv. of BuOK/hexane at 608 or KF/Al2O3 at 1208 [40] afforded
pure (E)-10a in 78–90% yield. Pure (E)-10a delivered quantitatively a 57:43 trans/
cis mixture 15a after hydrogenation at 1 atm. in the presence of 5% Pd/C in cyclohex-
ane at 208. The exocyclic enone 10a as the mentioned 1:3 :6 mixture could also be par-
tially isomerized in 74% yield to a 9 :53 :28 :10 mixture of b,g-deconjugated-10a/14a/
(Z)-10a/(E)-10a when heated at 1208 for 6 h with 0.028 mol-equiv. of [RuH(h5-
C8H11)2]BF4 [41]17). Hydrogenation of such a mixture gave quantitatively Hedione®
15
)
In contrast, the following oxidation conditions were inefficient: Jones reagent, Et2O; MnO2, hexane; poly(4-
vinylpyridinium dichromate), cyclohexane [27]; pyridinium dichromate (PDC), DMF [28]; PDC, CH2Cl2;
Oxone®, acetone [29]; 2,2,6,6-tetramethylpiperidin-1-yloxy (TEMPO), iodobenzene diacetate or mCPBA
[30] and Dess–Martin periodinane, CH2Cl2 [31]. The Oxone®/CF3C(O)Me conditions [32] afforded cleanly
and quantitatively the isomerized (2RS)-2-[(1SR)-1-hydroxypentyl]cyclopentanone [33] via 1,2-H-shift
with concomitant epoxide-ring opening.
Keto epoxide 2 was also obtained in 5% yield by addition of pentanal (NaOH, EtOH, [34]) to 2-chlorocy-
clopentan-1-one [35], while deprotection of 7 failed.
The isomerization to 14a was inefficient under the following conditions: 10% (w/w) of conc. HCl soln.,
MeOH, 658; 10% of RhCl3 ·nH2O, MeOH, 658; 10% (w/w) of MeONa, MeOH, 658; I2, 658. In contrast,
5% (w/w) of 10%Pd/C and decahydronaphthalene at 1808 or 5% (w/w) of Ru3(CO)12 or [RuCl2(pCym)]2
neat at 1808 gave maximally 23–25% of 14a after 6 h.
16
17
)
)

3072
Helvetica Chimica Acta – Vol. 88 (2005)
Scheme 1
a) O2, hv, Rose Bengal, then Me2S. b) H2O2, NaOH. c) DIBAL-H, 108, CH2Cl2. d) mCPBA, 08, CH2Cl2. e)
PCC, CH2Cl2. f) Ethylene glycol, cyclohexane, fumaric acid. g) LDA 2 equiv., THF, ꢀ208. h) pyridine·
TsOH, acetone/H2O. i) MeC(OMe)3, pivalic acid, 1108. j) MeC(OMe)3, propanoic acid, 1108. k) MeCO2R,
(Me3Si)2NLi, THF; or BrCH2COOR, Zn, benzene. l) Jones oxidation. m) 5–10% Pd/C, H2, cyclohexane. n)
[RuH(h5-C8H11)2]BF4, 1208. o) HIO3, DMSO, 658.
(15a) as a 47:53 trans/cis mixture (cyclohexane, 5% Pd/C, 208), prior to epimerization
(MeOH, MeONa, 98%) to a 92 :8 trans/cis mixture.

Helvetica Chimica Acta – Vol. 88 (2005)
3073
At this point, we realized that allylic hydroxy ketones of type 9a would be accessible
via a Baylis–Hillman reaction18), starting from commercially available cyclopent-2-en-
1-one (16)19). Although numerous conditions have been reported for the catalyzed
Morita–Baylis–Hillman reaction20), we were attracted by the procedure of Yamada
and Ikegami [45] (1.0 mol-equiv. of 16, 1.5 mol-equiv. of 17; 0.1 mol-equiv. of rac-
[1,1’-binaphthalene]-2,2’-diol (BINOL), 0.2 mol-equiv. of Bu3P, THF, 208) and, using
pentanal (17a), could thus isolate hydroxy enone 9a in 92% yield after 3 h at 208 and
filtration through a short SiO2 column (Scheme 2).
The BINOL may be replaced by either the less expensive [biarene]-2,2’-diol or cat-
echol (=benzen-1,2-diol), albeit with a lower 50–60% chemical yield, due to the pres-
ence of by-products necessitating a careful chromatographic purification. By analogy,
starting from heptanal (17b), hydroxy enone 9b was obtained in 33% yield after
bulb-to-bulb distillation. When this freshly distilled pure alcohol was submitted to
orthoester Claisen conditions, we isolated in 98% yield an unsaturated ester 10b as
16 :52 :32 b,g-deconjugated/(Z)/(E) mixture. We noticed that both 9a,b are unstable
when neat and readily polymerize even at 208. For this reason, we performed both
the Baylis–Hillman reaction and the orthoester Claisen rearrangement in a one-pot cas-
cade procedure. This allowed us to isolate 10a in 89% overall yield as a 10 :30 :60 b,g-
deconjugated/(Z)/(E) mixture, while 10b was similarly obtained in 91% overall yield as
a 15 :29 :56 mixture of the analogous isomers. This latter mixture was either directly
hydrogenated (10% Pd/C, cyclohexane, 208; 92%) to afford 15b (53 :47 trans/cis mix-
ture) or treated with 5% Pd/Al2O3 at 1358 with 92 :8 N2/H221) to produce a 55 :45 mix-
ture of 14c/15b. Subsequent hydrogenation (MeOH, 5% Pd/C, 208) afforded quantita-
tively 15b (68 :32 trans/cis mixture).
To access the jasmonate family, we started with a ‘Diels–Alder-protected’ 6 :1 endo/
exo mixture of the cis-aldehyde 17c, easily obtained in 45% yield by thermal [4+2]-
cycloaddition of the corresponding commercially available (2Z)-pent-2-enenitrile to
cyclopentadiene22), followed by DIBAL-H reduction at 208 in 80% yield. The crude
cis-aldehyde 17c was used since purification by either column chromatography
(SiO2) or distillation resulted in extensive epimerization. Subsequent Baylis–Hillman
reaction afforded 9c (34% yield) as a complex 2 :13 :2 :10 :1:10 :14 :1 stereoisomer
18
)
Amazingly, both hydroxy enones 9a and 9b were, at this time, unreported in the literature and thus could be
patented as intermediates [42]. For known analogues of 9 with R=H or alkyl substituents (Scheme 2), see
[43] (R=H); [44] (R=Me); [45] (R=Et, Me(CH2)6); [46] (R=Pr); [47] (R=iPr, Me(CH2)4); [48]
(R=Me2CHCH2); [48b] (R=Me(CH2)5); [49] (R=Me(CH2)7); [50] (R=Ph(CH2)2).
19
20
)
)
For an easy access to 16 from cyclopentanone or cyclopentadiene, see [51a–d] and [51e], respectively.
Alternatively, the conditions of Nicolaouet al . [51a] were also applied to trans-15a, thus affording 14a in
65% yield (Scheme 1).
Nonexhaustive examples of Morita–Baylis–Hillman conditions involve Et2AlI [44], MeONa/MeOH [48b],
1H-imidazole in H2O [52]; 1H-1,2,3-triazole in H2O [53]; 1,4-diazabicyclo[2.2.2]octane (DABCO) in H2O
[54], DABCO in ionic liquids [55], N,N,N’,N’-tetramethylpropane-1,3-diamine [56]; proazaphosphatrane
sulfide [57] and air-stable trialkylphosphonium salts [58]. For reviews, see [59]; for a new interpretation
of the mechanism following studies in protic and aprotic solvents, see [60].
According to a procedure initially developed at Firmenich SA by Dr. R. Weinstein with an analogous skel-
eton and extended by Dr. F. Näf and R. Decorzant to 10a, obtained via an independent approach.
This cycloaddition was initially performed at Firmenich SA by C. Vial. Dr. R. L. Snowden and S. Linder are
acknowledged for the details of the DIBAL-H reduction.
21
22
)
)

3074
Helvetica Chimica Acta – Vol. 88 (2005)
Scheme 2
a) Aldehyde 17 (1.5 mol-equiv.), Bu3P (0.2 mol-equiv.), BINOL (0.1 mol-equiv.), THF, 208. b) MeC(OMe)3,
pivalic acid, 1108. c) 10% Pd/C, cyclohexane. d) 5% Pd/Al2O3, N2/H2 92 :8, 1358. e) [Ph3PCH2R] Br, BuLi,
toluene, ꢀ208 to 208. f) [Ph3PPr]Br, NaN(SiMe3)2, THF, 208.
mixture indicating that epimerization already occurs under the reaction conditions.
Further orthoester Claisen rearrangement led in 55% isolated yield to a 15 :15 :70 ster-
eoisomer mixture 10c. During distillation, we observed a retro-Diels–Alder reaction
generating the conjugated (E,E)-dienone derivative 10j, thus explaining the moderate
yield.
The fact that the configurational integrity of the cis-aldehyde 17c is already eroded
during the first step, and that a supplementary 1,4-hydride reduction is necessary to dis-
tinguish both unsaturations present in 10c, prompted us to abandon this approach and
to generate the desired (Z)-configuration of the jasmonate side chain via the conven-
tional Wittig procedure. Consequently, we started from glyoxal dimethyl acetal (17d)
to prepare hydroxy enone 9d in 96% yield. The subsequent rearrangement permitted
the isolation of a 2 :3 (Z)/(E) mixture of the dimethyl acetal drivative 10d in 96%

Helvetica Chimica Acta – Vol. 88 (2005)
3075
yield, which was readily isomerized (HCl, MeOH, 608; 87%)23) to the pure tetrasubsti-
tuted dimethyl acetal derivative 14d. Hydrogenation (MeOH, 5% Pd/C, 208; 60–80%)
of either 14d or the (E)/(Z) mixture 10d afforded in both cases an equilibrated 9 :1 mix-
ture 15d of the trans/cis dimethyl acetal derivatives. Deprotection (AcOH, H2O, 408) of
(E)/(Z)-10d furnished in 36% yield a 1:1:2 mixture of (Z)-10e/(E)-10e/14e, while
under the same conditions, the saturated acetal derivative 15d gave in 83% yield a
9 :1 mixture of the known trans/cis aldehyde derivative 15e [61]. Pure aldehyde deriv-
ative 14e was preferably selectively isolated in 55% yield by an identical deprotection
of pure acetal derivative 14d. A Wittig reaction ([Ph3PPr]Br, NaN(SiMe3)2, THF/DMF,
208 [62]; 44%) furnished the known didehydrojasmonate (Z)-14f [63]24), to 93% ster-
eoisomerically pure. The saturated aldehyde derivative 15e afforded, with either
(Ph3PPr)Br and BuLi in THF or toluene at ꢀ308 or ꢀ208 to 208 [61][65] (yield 57–
62%), or with (Ph3PPr)Br and NaNH2/tBuOK in THF at ꢀ708 to 208 [66] (yield
31%) the methyl jasmonate 18a as a 9 :1 trans/cis mixture of (Z)/(E) isomers 95 :5. Sim-
ilar Wittig conditions ((Ph3PBu)Br, BuLi, toluene, ꢀ308 to 208 (yield 34%) or
[Ph3P(CH2-cyclopropyl)] Br, BuLi, toluene, ꢀ308 to 208, (yield 35%)) furnished the
analogous methyl esters 18b (trans/cis 9 :1, Z/E 95 :5) and 18c (trans/cis 95 :5, Z/E
7:3)25).
Rather than an acetal derivative, we also used the commercially available aldehyde
17f with a benzyl ether protection, to obtain hydroxy enone 9f in 65% yield. Subse-
quent orthoester Claisen rearrangement furnished a 14 :29 :57 mixture 10f of b,g-
deconjugated/(Z)/(E) isomers in 68% yield. Hydrogenation with concomitant depro-
tection quantitatively afforded the (hydroxyethyl)oxo ester 15f as a 9 :1 trans/cis mix-
ture. Its oxidation (PCC, CH2Cl2, 60%) gave the corresponding aldehyde derivative
15e. As oxa analogue of methyl jasmonate, we also prepared, from the known alde-
hydes 17g,h [63][69] the Baylis–Hillman products 9g,h in 27 and 53% yield, respec-
tively. Subsequent rearrangements gave the unsaturated keto esters 10g,h in 53 and
93% yield, respectively, as 22 :39 :39 and 5 :75 :20 b,g-deconjugated/(Z)/(E) mixtures.
Hydrogenation of 10g in cyclohexane at 208 over 10% Pd/C furnished in 78% yield
ester 15g as 4 :6 trans/cis mixture, while hydrogenation of 10h in MeOH gave in 79%
yield 15h as a 9 :1 equilibrated trans/cis mixture, thus underlining again the influence
of the solvent for minimizing epimerization.
Finally, methyl 6-formylhexanoate 17i [70] was chosen to allow access to hydroxy
enone 9i (53%), which was rearranged to unsaturated keto diester 10i as a 5 :85 :10
b,g-deconjugated/(Z)/(E) mixture. Hydrogenation in cyclohexane quantitatively
afforded a 34 :66 mixture 15i of trans/cis dimethyl diesters. It is noteworthy that sub-
strate 9i, via an appropriate Carroll rearrangement, is a potential precursor of a
known intermediate of a prostaglandin PGF10 synthesis [71].
The next step was to study the asymmetric version of this process, as this was the key
point of interest which had originally attracted our attention to the Baylis–Hillman
23
)
)
These standard conditions were initially used at Firmenich SA by Dr. G. Lem on an analogous skeleton.
Compound (Z)-14f is a direct precursor in the synthesis of the corresponding natural acid, isolated from
Vicia faba L. [64].
For a potential highly (Z)-stereoselective addition of a modified allyltriarylphosphonium bromide, leading
to methyl 3,7-didehydrojasmonate [67], see [68].
24
25
)

3076
Helvetica Chimica Acta – Vol. 88 (2005)
reaction26) [45]. When the reaction between cyclopent-2-en-1-one (16) and pentanal
(17a) was catalyzed by 0.1/0.2 mol-equiv. of (+)-(R)-[1,1’-binaphthalene]-2,2’-diol
(19a)/Bu3P, we obtained hydroxy enone 9a (Scheme 3), which showed, by GC analysis
on a chiral phase, a 52 :48 enantiomer ratio. With respect to the instability of 9a (vide
supra), we decided to perform directly a cascade reaction and to determine the global
yield and optical purity by GC analysis on a chiral phase of the hydrogenated and equi-
librated trans-Hedione® (15a) as earlier reported [17b]. In the case of catalysts (+)-(R)-
19a,b almost no final induction was observed (see Table). Using commercially available
or known 3,3’-disubstituted [1,1’-binaphthalene]-2,2’-diols (+)-(R)-19c–g [73]27), as
suggested by McDougal and Schaus [78], we observed insignificant final asymmetric
inductions as indicated in the Table. The situation was unchanged when either
Ca(OiPr)2 or the bimetallic low-temperature conditions of Sasai et al. [72x] were
used with (+)-(R)-19a28). The measured final e.e.s result from both the asymmetric
Baylis–Hillman reaction and the Claisen chirality transfer. A rapid racemization of
the transient allylic alcohol under acidic conditions may be excluded29). Although ero-
sion may result from Pd/C [79], total racemization by isomerization/hydrogenation via
14a may also be excluded in view of the stringent conditions required17). This was dem-
onstrated by isolating after column chromatography SiO2 +5% AgNO3, cyclohexane/
AcOEt 93 :7 the pure stereoisomers (ꢀ)-(S,Z)-10a ([a]2D0 =ꢀ1.4, c=1.0 CHCl3; 22%
e.e.) and (+)-(R,E)-10a ([a]2D0 =+21.3, c=1.0 CHCl3; 22% e.e.) from a 8 :2 (Z)/(E)
Claisen-reaction mixture, issued from (ꢀ)-(S)-9a ([a]2D0 =ꢀ8.4, c=2.3, CHCl3; 22%
e.e.). Their independent hydrogenation with Raney-Ni in either EtOH or AcOEt
[79] afforded (+)-(1S,2S)-15a and (ꢀ)-(1R,2R)-15a in 22 and 15% e.e., respectively,
thus confirming both the nonexclusive thermodynamic origin of isomer (E)-10a
(depending on the reaction time, temperature, and acidic conditions) and the moderate
diastereoselectivity of the Claisen-reaction kinetic mixture. When hydrogenation was
performed with 10%Pd/C in cyclohexane, the optical purity was 21 and 13% e.e.,
respectively, suggesting with both catalysts a more rapid isomerization of the stereo-
isomer (E)-10a towards 14a as compared to its hydrogenation.
In view of the poor inductions in the Baylis–Hillman reaction, the thermally less
exigent Claisen rearrangement under either Ireland [80] or the less basic Fehr condi-
tions [17c] was not attempted. In the Baylis–Hillman reaction of 16 and 17a catalyzed
with (+)-(R)-19d, we increased the enantioselectivity to 31% e.e. (albeit with 15%
26
)
)
For enantioselective Baylis–Hillman reactions, see [72].
27
We initially prepared {5,6 :5’,6’-bis(ethane-1,2-diyldioxy)[1,1’-biphenyl]-2,2’-diyl}bis[diphenylphosphine]
for the enantioselective isomerization of geranyldiethylamine to citronellal (see [74], p. 105). This new
diphosphine was later independently developed [75] and exploited [76] by Genêt et al. Rather than
5,6,5’,6’-hetero-analogues of (+)-(R)-19a,b [77], dimerization of either sesamol (=1,3-benzodioxol-5-ol)
or 2,3-dihydro-1,4-benzodioxin-6-ol, afforded the corresponding 4,5,4’,5’-hetero-substituted 2,2’-diols
[77c]. The efficiency of diols (+)-(R)-19c,d as analogues of (+)-(R)-19a,b [77] as well as others possessing
induced atropisomerism derived from [1,1’-biphenyl]-2,2’,6,6’-tetrol shall be reported in due course. (+)-
(R)-19f has an [a]2D0 =+49 (c=0.7, CHCl3).
28
29
)
)
Contrasting with the structure of the catalyst reported in their publication, Japanese authors used, in their
Exper. Part, a 2:3 ratio of Ca(OiPr)2 and (+)-(R)-BINOL (19a) [45]. Even traces of exceeding free BINOL
may catalyze the reaction (see Table, Footnote d)).
Indeed, when (ꢀ)-(S)-9a was heated at 80–1108 with 0.1 mol-equiv. of pivalic acid in EtOH/toluene, no rac-
emization was observed after 8 h.

Helvetica Chimica Acta – Vol. 88 (2005)
3077
Scheme 3
a) 17 (1.5 mol-equiv.), (+)-(R)-19 (0.1 mol-equiv.), Bu3P (0.2 mol-equiv.), THF, 208. b) MeC(OMe)3, pivalic
acid, 1108. c) 10% Pd/C, cyclohexane, then MeONa, MeOH.
Table. Global Inductions and Yields of (+)-trans-Hedione 15a in the Presence of (+)-(R)-BINOL Analogues
19a–g for the Asymmetric Baylis–Hillman Reaction of 16 and 17a Followed by Acidic Orthoester Claisen
Rearrangement, Hydrogenation, and Epimerization
Reaction time [h] for B.-H. reaction at 208
(ꢀ)-(S)-9a
(+)-(1S,2S)-15a
e.e. [%]
e.e. [%]
global yield [%]
(+)-(R)-19a
(+)-(R)-19b
(+)-(R)-19c
(+)-(R)-19d
(+)-(R)-19ed)
(+)-(R)-19f
(+)-(R)-19g
3, 15a), 144b)
3
48
15, 96c)
15
4, 5a), 18b)
6
2, 2a), 8b)
1
82, 20a), 8b)
54
81
68, 22c)
93
5
2
22, 10c)
12, 4c)
2.5
1
1
15
15
2
1.5
68
71
a)With 0.1 mol-equiv. of Ca(OiPr)2 /19a 2 :3. b) With 0.16 mol-equiv. of
mol-equiv. of
-Selectride/19d 1:1. d) With 0.01 mol-equiv of 19e.
L
-Selectride/19a 1 :1 at ꢀ228. c) With 0.16
L
yield) when Bu3P was replaced by (ꢀ)-1,1’-(ethane-1,2-diyl)bis[(2S,5S)-2,5-dimethyl-
phospholane], while the antipode (+)-(R)-9a was obtained after 18 h at 208 with 8%
e.e., when the mismatching (+)-1,1’-(ethane-1,2-diyl)bis[(2R,5R)-2,5-dimethylphos-
pholane] was used30).
30
)
The following sterically more crowded or less basic bis[phosphines] were inactive: (+)-1,1’-(ethane-1,2-
diyl)bis[(2R,5R)-2,5-diethylphospholane]; (ꢀ)-1,1’-(1,2-phenylene)bis[(2R,5R)-2,5-dimethylphospholane];
(+)-(S)-{1-[(1R)-2-(dicyclohexylphosphino)ferrocen-1-yl]ethyl}dicyclohexylphosphine, and (ꢀ)-(R)-{1-
[(1S)-2-(diphenylphosphino)ferrocen-1-yl]ethyl}dicyclohexylphosphine.

3078
Helvetica Chimica Acta – Vol. 88 (2005)
Conclusions. – Our one-pot, two-step cascade sequence is formally a short cut cor-
responding to a Michael addition of dimethyl malonate to cyclopent-2-en-1-one with
concomitant trapping of the resulting enolate with an appropriate aldehyde followed
by mesylation/elimination of the aldol product and final de(methoxycarbonyl)ation.
The resulting exocyclic unsaturation allows by hydrogenation over Pd/C in cyclohexane
to partially control the trans/cis configuration at C(2) (ꢁ50%). A better stereoselectiv-
ity is obtained by isomerization of the exocyclic C=C bond into the tetrasubstituted
endocyclic position prior to hydrogenation (ꢁ62% for pure 14a). By versatile modifi-
cation of the aldehyde, this procedure allows to modify the substitution at C(2). The
asymmetric version gave almost no global inductions, due to poor enantioselectivity
during the Baylis–Hillman reaction associated with the only partial diastereoselectivity
during the ortho ester Claisen acidic rearrangement as well as partial isomerization of
the exocyclic to the endocyclic position of the resulting C=C bond during hydrogena-
tion. None of the presented jasmonoid analogues 10, 14, 15, and 18, exhibits better
olfactory properties than the natural products.
We thank Mrs C. Cantatore, Mr. H. Pamingle, and K. Saidi for their valuable experimental skill. Dr. J.
McKew is acknowledged for the preparation of (+)-(R)-19e.
Experimental Part
General. See [81]. Chiral GC separations. Chirasil-Dex-CB column (25 m, 0.25 mm); He flow 2.5 ml/min, at
1508 for 20 min; tR [min] (ꢀ)-(S)-9a, 6.93; (+)-(R)-9a, 7.44; (+)-(R,Z)-10a, 11.31; (ꢀ)-(S,Z)-10a, 11.54; (+)-
(R,E)-10a, 12.93; (ꢀ)-(S,E)-10a, 14.11; (ꢀ)-(1R,2R)-15a, 9.92; (+)-(1S,2S)-15a, 10.58; (+)-(1R,2S)-15a, 11.46;
(ꢀ)-(1S,2R)-15a, 12.00.
General Procedure A: Baylis–Hillman Reaction. A soln. of cyclopent-2-en-1-one (16; 1.0 mol-equiv.), the
appropriate aldehyde 17 (1.5 mol-equiv.), [1,1’-binaphthalene]-2,2’-diol (0.1 mol-equiv.), and Bu3P (0.2 mol-
equiv.) in THF (800 ml/mol) was stirred at 208 under Ar for 3–15 h. The crude mixture was evaporated and
the residue passed through a short column of SiO2 (cyclohexane/Et2O 7 :3) to separate the desired product
from the apolar aldehyde, Bu3P, and the polar [1,1’-binaphthalene]-2,2’-diol.
General Procedure B: Claisen Reaction. A mixture of hydroxy ketone 9 (1.0 mol-equiv.), trimethyl ortho-
acetate (1770 ml/mol), and pivalic acid (0.17 mol-equiv.) was heated at 1108 for 3 h with distillation of MeOH.
The mixture was evaporated and the residue bulb-to-bulb distilled to afford 10 as a (E)/(Z) mixture contami-
nated by traces of b,g-deconjugated (E)-isomers.
(2RS,3RS)-2-Butyl-1-oxaspiro[2.4]heptan-4-one (2). A soln. of hydroxy epoxide 5 (0.85 g, 5 mmol) in
CH2Cl2 (5 ml) was added to a suspension of PCC (1.6 g, 7.5 mmol) and anh. AcONa (123 mg, 1.5 mmol) in CH2
Cl2 (5 ml). After 2 h at 208, Et2O was added, and the mixture was filtered. The filtrate was washed with H2O,
dried (Na2SO4), and evaporated and the residue purified by CC (15 g SiO2, hexane/AcOEt 95 :5 ! 9 :1): 2
(12%).
Alternatively, 2N NaOH (2.5 ml, 5 mmol) was added at 108 over 20 min to a soln. of enone 1 (1.64 g, 10
mmol) and 30% H2O2 soln. (3 ml, 30 mmol) in MeOH (15 ml). After 4 h at 208, the mixture was poured into
H2O, extracted with Et2O, washed with H2O, dried (Na2SO4), and evaporated and the residue purified by CC
(40 g SiO2, hexane/AcOEt 95 :5 ! 8 :2): 2 (3%). IR: 3000, 2950, 2930, 2860, 1740, 1460, 1400, 1100, 995, 910.
1H-NMR (200 MHz): 0.92 (t, J=7, 3 H); 1.4 (m, 4 H); 1.54 (m, 3 H); 1.97 (m, 1 H); 2.11 (m, 2 H); 2.2 (m, 1
H); 2.42 (dd, J=7, 9, 1 H); 3.18 (t, J=5, 1 H).
(5E)-Dec-5-eno-5-lactone (3). A soln. of 70% mCPBA (7.4 g, 30 mmol) in CH2Cl2 (25 ml) was added at 208
to a soln. of enone 1 (10 g, 26 mmol) and NaHCO3 (2.7 g, 32 mmol) in CH2Cl2 (75 ml) and H2O (10 ml). After 5 h
and 20% of conversion, the mixture was poured into brine, washed with H2O to neutral, dried (Na2SO4), and
evaporated, and the residue purified by CC (SiO2, cyclohexane/Et2O 85 :15): pure 3 (11%). IR: 3000, 2930,
2859, 1760, 1694, 1345, 1238, 1198, 1140, 1049, 968. 1H-NMR: 0.9 (t, J=7, 3 H); 1.32 (m, 4 H); 1.86 (quint.,

Helvetica Chimica Acta – Vol. 88 (2005)
3079
J=7, 2 H); 1.98 (q, J=7, 2 H); 2.5 (t, J=5, 2 H); 2.6 (t, J=5, 2 H); 5.18 (t, J=7, 1 H). 13C-NMR: 13.9 (q); 18.4
(t); 22.2 (t); 22.4 (t); 25.3 (t); 30.7 (t); 31.8 (t); 110.0 (d); 148.2 (s); 169.0 (s). MS: 168 (23, M+C), 125 (42), 112 (22),
97 (97), 83 (45), 55 (100), 42 (18).
(2E)-2-Pentylidenecyclopentan-1-ol (4). At 08, 1
wise to a soln. of enone 1 (14.4 g, 95 mmol) in CH2Cl2 (50 ml). After 4 h at 208, MeOH (25 ml) was added at 08
followed by 2 H2SO4 and H2O. The org. layer was washed with H2O and 5% NaHCO3 soln., dried (Na2SO4), and
M DIBAL-H in CH2Cl2 (100 ml, 100 mmol) was added drop-
N
evaporated, and the residue distilled: 4 (86%). B.p. 688/0.8 Torr. IR: 3580, 3000, 2950, 2910, 2850, 1450, 1375,
1035, 920. 1H-NMR: 0.89 (t, J=7, 3 H); 1.3 (m, 4 H); 1.6 (m, 2 H); 1.81 (m, 2 H); 1.99 (q, J=7, 2 H); 2.17
(m, 1 H); 2.34 (m, 1 H); 2.6 (br. s, OH); 4.38 (br. s, 1 H); 5.52 (t, J=5, 1 H). 13C-NMR: 14.0 (q); 22.1 (t); 22.5
(t); 27.0 (t); 29.1 (t); 31.6 (t); 35.6 (t); 75.5 (d); 124.3 (d); 145.6 (s). MS: 154 (10, M+C), 111 (32), 97 (100), 93
(10), 83 (14), 79 (19), 55 (25), 41 (19). Unpleasant, dirty, dusty, floral.
(2RS,3RS)-2-Butyl-1-oxaspiro[2.4]heptan-4-ol (5). At 08, 80% mCPBA (17.6 g, 82 mmol) was added por-
tionwise to a soln. of 4 (12.6 g, 81.8 mmol) in CH2Cl2 (200 ml). After 2 h at 08, the mixture was diluted with hex-
ane, washed with 10% Na2CO3 soln. and brine, dried (Na2CO3), and evaporated, and the residue distilled: 5
(96%). B.p. 588/0.05 Torr. IR: 3459, 2957, 2930, 2872, 1466, 1457, 1400, 1379, 1316, 1295, 1240, 1153, 1099,
1032, 988, 950, 932, 909, 857. 1H-NMR: 0.95 (t, J=7, 3 H); 1.4 (m, 4 H); 1.55 (m, 3 H); 1.64 (m, 2 H); 1.75
(m, 1 H); 1.92 (m, 2 H); 2.0 (m, 1 H); 3.02 (t, J=5, 1 H); 3.92 (t, J=7, 1 H). 13C-NMR: 14.0 (q); 19.6 (t); 22.5
(t); 26.4 (t); 28.5 (t); 29.5 (t); 33.9 (t); 60.9 (d); 69.3 (s); 71.9 (d). MS: 170 (0, M+C), 84 (100), 71 (20), 55 (36),
41 (20).
(6E)-6-Pentylidene-1,4-dioxaspiro[4.4]nonane (6). A mixture of enone 1 (30.4 g, 0.2 mol), ethylene glycol
(80 ml, 1.84 mol), and fumaric acid (2.0 g, 17.2 mmol) in cyclohexane (200 ml) was heated under reflux for 4
days with H2O separation. The cold mixture was washed with sat. NaHCO3 soln. and brine to neutral, dried
(Na2SO4), and evaporated, and the residue distilled through a Vigreux column: pure 6 (55%). B.p. 1208/10
1
Torr. IR: 2956, 2926, 2873, 1650, 1465, 1437, 1309, 1202, 1145, 1114, 1043, 1002, 944, 924, 852, 825. H-NMR:
0.9 (t, J=7, 3 H); 1.35 (m, 4 H); 1.75 (q, J=7, 2 H); 1.81 (m, 2 H); 2.02 (q, J=7, 2 H); 2.34 (m, 2 H); 3.95
(m, 2 H); 4.05 (m, 2 H); 5.61 (m, 1 H). 13C-NMR: 14.0 (q); 20.8 (t); 22.5 (t); 26.3 (t); 28.9 (t); 31.3 (t); 36.5
(t); 64.5 (2t); 114.2 (s); 125.0 (d); 140.6 (s). MS: 196 (18, M+C), 167 (38), 139 (100), 99 (40), 67 (20), 55 (18),
41 (18).
2-Butyl-1,5,8-trioxadispiro[2.0.4.3]undecane (7). To a soln. of 6 (10.9 g, 56 mmol) in CH2Cl2 (100 ml) at 08
was added 80% mCPBA (12 g, 56 mmol), and the mixture was stirred for 1 h. The cold mixture was diluted with
hexane, washed with cold 5% Na2CO3 soln. and H2O, dried (Na2SO4), and evaporated, and the residue distilled:
1
7 (93%). B.p.: 758/0.8 Torr. IR: 2957, 2931, 2873, 1649, 1467, 1435, 1325, 1191, 1096, 1070, 1036, 948, 868. H-
NMR: 0.91 (t, J=7, 3 H); 1.49 (m, 2 H); 1.51 (m, 2 H); 1.7–1.95 (m, 8 H); 3.09 (t, J=5, 1 H); 3.91 (m, 2 H);
4.05 (m, 2 H). 13C-NMR: 14.0 (q); 18.7 (t); 22.5 (t); 24.9 (t); 28.5 (t); 29.1 (t); 34.3 (t); 60.0 (d); 65.4 (2t); 68.7
(s); 113.1 (s). MS: 212 (0, M+C), 169 (8), 99 (100), 86 (11), 55 (18), 42 (8).
1-(1,4-Dioxaspiro[4.4]non-6-en-6-yl)pentan-1-ol (8). At ꢀ208, 2.5
M BuLi in hexane (6 ml, 15 mmol) was
added to a soln. of diisopropylamine (2.7 ml, 20 mmol) in hexane (20 ml). Then a soln. of 7 (1.06 g, 5 mmol)
in THF (5 ml) was added dropwise at ꢀ208, and after 2 h at ꢀ208, the mixture was poured into NH4Cl soln.
and extracted with Et2O, the extract washed with H2O, dried (Na2SO4), and evaporated, and the residue distil-
led: 8 (66%). B.p. 908/0.8 Torr. IR: 3434, 2955, 2930, 2872, 2859, 1648, 1465, 1453, 1377, 1338, 1316, 1209, 1135,
1042, 1016, 948, 918, 857. 1H-NMR: 0.92 (t, J=7, 3 H); 1.1–1.55 (m, 6 H); 1.7 (q, J=5, 2 H); 2.07 (t, J=7, 1 H);
2.38 (m, 1 H); 3.7 (s, OH); 3.96 (m, 2 H); 4.06 (m, 2 H); 4.24 (t, J=7, 1 H); 6.02 (br. s, 1 H). 13C-NMR: 14.1 (q);
22.7 (t); 27.8 (t); 28.1 (t); 35.1 (t); 35.9 (t); 64.7 (t); 64.9 (t); 67.6 (d); 120.6 (s); 133.4 (d); 143.5 (s). MS: 212 (0,
M+C), 183 (20), 170 (19), 155 (100), 111 (64), 87 (17), 83 (18).
2-(1-Hydroxypentyl)cyclopent-2-en-1-one (9a). In a Pyrex vessel, a soln. of enone 1 (7.2 g, 47.4 mmol), Rose
Bengal (0.1 g, 0.1 mmol), and AcONa (0.1 g, 1.2 mmol) in MeOH (95 ml) and H2O (5 ml) was irradiated with a
Philips-HPK125W Hg lamp while O2 was bubbled through the soln. After 3 h, 1.5–2 l of O2 was absorbed, and
Me2S (15 ml) was added. After 1 h at 208, the mixture was evaporated, the residue diluted with Et2O (50 ml), the
soln. washed with brine (3×20 ml), dried (Na2SO4), and evaporated and the residue purified by CC (SiO2, cy-
clohexane/AcOEt 35 :65): 9a (6%) and 5,6-dioxodecanoic acid (5%).
Alternatively, a mixture of 8 (1.5 g, 7 mmol) and 10% HCl soln. (1 ml) in THF (15 ml) was stirred at 208 for
2 h. Then the mixture was washed with sat. NaHCO3 soln. and brine, dried (Na2SO4), and evaporated, and the
residue bulb-to-bulb distilled: 9a (43%).
Hydroxy ketone 9a was also obtained in 94% yield according to the procedure used for the deprotection of
(Z)-10a or in 92% yield according to Procedure A.

3080
Helvetica Chimica Acta – Vol. 88 (2005)
Data of 9a: B.p. 1208/0.3 Torr. IR: 3412, 2925, 2858, 1682, 1630, 1439, 1335, 1251, 1193, 1041, 1000, 923, 885.
1H-NMR: 0.88 (t, J=7, 3 H); 1.32 (m, 4 H); 1.68 (m, 2 H); 2.47 (dd, J=5, 7, 2 H); 2.6 (br. s, 2 H); 3.3 (br. s, OH);
4.44 (t, J=5, 1 H); 7.49 (s, 1 H). 13C-NMR: 14.0 (q); 22.6 (t); 26.6 (t); 27.6 (t); 35.3 (t); 35.6 (t); 67.7 (d); 148.0 (s);
158.1 (d); 210.1 (s). MS : 168 (0, M+C), 150 (18), 135 (6), 121 (9), 111 (100), 83 (15), 55 (11).
2-(1-Hydroxyheptyl)cyclopent-2-en-1-one (9b). According to Procedure A: 9b (33%). IR: 3410, 2940, 1690,
1040. 1H-NMR: 0.87 (t, J=7, 3 H); 1.2–1.4 (m, 8 H); 1.64 (m, 2 H); 2.43 (m, 2 H); 2.6 (m, 2 H); 3.23 (s, OH); 4.45
(t, J=7, 1 H); 7.5 (s, 1 H). 13C-NMR: 14.1 (q); 22.6 (t); 25.4 (t); 26.6 (t); 29.2 (t); 31.8 (t); 35.3 (t); 36.0 (t); 67.4
(d); 148.4 (s); 158.2 (d); 209.9 (s). MS: 196 (0.5, M+C), 178 (10), 135 (7), 121 (8), 111 (100), 83 (13), 55 (11).
2-[(3-Ethylbicyclo[2.2.1]hept-5-en-2-yl)hydroxymethyl]cyclopent-2-en-1-one (9c). According to Procedure
A: 9c (34%) as a 2 :13 :2 :10 :1 :10 :14 :1 stereoisomer mixture. IR: 3400, 2960, 1695, 1000. 1H-NMR (character-
istic signals from the mixture): 0.79 (t, J=7, 3 H); 3.1 (br. s, 1 OH); 4.19 (d, J=7, 1 H); 5.92 (m, 1 H); 6.12 (m, 1
H); 7.45 (d, J=7, 1 H). MS: 232 (0.5, M+C), 167 (8), 149 (100), 137 (12), 111 (18), 66 (44).
2-(1-Hydroxy-2,2-dimethoxyethyl)cyclopent-2-en-1-one (9d). According to Procedure A: 9d (96%). IR:
3430, 2922, 2830, 1690, 1632, 1440, 1344, 1248, 1189, 1125, 1040, 972. 1H-NMR: 2.47 (m, 2 H); 2.67 (m, 2 H);
3.3 (br. s, OH); 3.42 (s, 3 H); 3.45 (s, 3 H); 4.53 (s, 2 H); 7.68 (br. s, 1 H). 13C-NMR: 27.0 (t); 35.1 (t); 55.3
(q); 55.5 (q); 67.6 (d); 104.9 (d); 143.7 (s); 161.2 (d); 209.2 (s). MS: 186 (0, M+C), 123 (11), 75 (100), 47 (12).
2-[2-(Benzyloxy)-1-hydroxyethyl]cyclopent-2-en-1-one (9f). According to Procedure A: 9f (65%). IR: 3442,
2855, 1690, 1632, 1452, 1327, 1249, 1193, 1098, 1027, 999. 1H-NMR: 2.42 (m, 2 H); 2.6 (m, 2 H); 3.15 (br. s, OH);
3.48 (dd, J=7, 9, 1 H); 3.71 (dd, J=4, 7, 1 H); 4.59 (q, J=7, 2 H); 4.69 (m, 1 H); 7.3 (m, 5 H); 7.6 (br. s, 1 H). 13C-
NMR: 26.8 (t); 35.2 (t); 66.9 (d); 72.7 (t); 73.3 (t); 127.8 (3d); 128.5 (2d); 137.8 (s); 144.9 (s); 160.0 (d); 208.8 (s).
MS: 232 (0, M+C), 111 (66), 108 (21), 91 (100), 65 (15).
2-(2-Ethoxy-1-hydroxyethyl)cyclopent-2-en-1-one (9g). According to Procedure A: 9g (27%). IR: 3429,
2972, 2865, 1739, 1690, 1632, 1439, 1347, 1248, 1111, 1063, 1030, 1000, 885. 1H-NMR: 1.2 (t, J=7, 3 H); 2.44
(m, 2 H); 2.62 (m, 2 H); 3.4 (dd, J=7, 8, 1 H); 3.54 (m, OH); 3.55 (m, 1 H); 3.66 (dd, J=4, 7, 1 H); 3.74 (m,
1 H); 4.65 (m, 1 H); 7.68 (br. s, 1 H). 13C-NMR: 15.1 (q); 26.8 (t); 35.2 (t); 66.7 (t); 66.8 (d); 72.9 (t); 145.1
(s); 159.9 (d); 208.9 (s). MS: 170 (0.5, M+C), 152 (21), 123(11), 111 (100), 95 (19), 79 (18), 59 (17).
2-(1-Hydroxy-3-methoxypropyl)cyclopent-2-en-1-one (9h). According to Procedure A: 9h (53%). IR: 3418,
2920, 2871, 1690, 1630, 1440, 1333, 1250, 1191, 1111, 1000, 923, 788. 1H-NMR: 1.84 (m, 1 H); 2.04 (m, 1 H); 2.46
(m, 2 H); 2.62 (m, 2 H); 3.37 (s, 3 H); 3.6 (t, J=7, 2 H); 3.75 (d, J=5, OH); 4.64 (m, 1 H); 7.59 (br. s, 1 H). 13C-
NMR: 26.6 (t); 35.0 (t); 35.4 (t); 58.9 (q); 67.4 (d); 71.2 (t); 148.0 (s); 158.4 (d); 209.1 (s). MS: 170 (0.5, M+C), 152
(28), 138 (32), 111 (100), 109 (30), 82 (31), 45 (27).
Methyl 7-hydroxy-7-(5-oxocyclopent-1-en-1-yl)heptanoate (9i). According to Procedure A: 9i (53%). IR:
3437, 2928, 2857, 1732, 1691, 1630, 1436, 1334, 1250, 1194, 1171, 1087, 1038, 1000, 788. 1H-NMR: 1.38 (m, 3
H); 1.48 (m, 1 H); 1.67 (m, 4 H); 2.31 (t, J=7, 2 H); 2.46 (m, 2 H); 2.61 (m, 2 H); 2.88 (br. s, OH); 3.68 (s, 3
H); 4.43 (br. t, J=7, 1 H); 7.46 (br. s, 1 H). 13C-NMR: 24.8 (t); 25.1 (t); 26.6 (t); 28.9 (t); 34.0 (t); 35.3 (t);
35.6 (t); 51.5 (q); 67.7 (d); 147.8 (s); 157.9 (d); 174.2 (s); 210.0 (s). MS: 240 (0.5, M+C), 222 (3), 190 (21), 130
(8), 111 (100), 87 (21), 55 (13).
Methyl (2Z)-3-Oxo-2-pentylidenecyclopentaneacetate ((Z)-10a). A mixture of 11 (250 mg, 0.93 mmol) and
pyridine·TsOH (50 mg) in acetone/H2O 9 :1 (10 ml) was stirred at 208 for 1 h and then evaporated. The residue
was dissolved in hexane and the soln. washed with 5% NaHCO3 soln. and H2O, dried (Na2SO4), and evaporated:
10a (98%) as 3 :7 (E)/(Z) mixture.
Alternatively, according to Procedure B: b,g-deconjugated-10a/(Z)-10a/(E)-10a 11:61:28 (88%).
Alternatively, by a one-pot cascade procedure from cyclopentenone 16: b,g-deconjugated-10a/(Z)-10a/(E)-
10a 10 :30 :60 (89% overall).
Data of (Z)-10a: IR: 3000, 2950, 2925, 2850, 1710, 1630, 1430, 1360, 1260, 1165, 1110. 1H-NMR: 0.9 (t, J=7,
3 H); 1.38 (m, 4 H); 1.58 (m, 1 H); 2.2 (m, 1 H); 2.3 (m, 2 H); 2.38 (dd, J=9, 14, 1 H); 2.6 (dd, J=7, 15, 1 H); 2.7
(m, 2 H); 3.15 (m, 1 H); 3.7 (s, 3 H); 5.9 (dt, J=2, 7, 1 H). 13C-NMR: 13.9 (q); 22.4 (t); 26.7 (t); 27.5 (t); 31.5 (t);
38.2 (t); 38.7 (d); 39.4 (t); 51.7 (q); 137.8 (s); 141.7 (d); 172.6 (s); 207.7 (s). MS: 224 (58, M+C), 195 (10), 167 (20),
151 (100), 135 (28), 121 (41), 109 (68), 93 (52), 79 (59), 67 (30).
Methyl (2E)-3-Oxo-2-pentylidenecyclopentaneacetate ((E)-10a). CC purification (SiO2, cyclohexane/
AcOEt 7:3) of the above mixture for anal. purposes gave (E)-10a (54%). IR: 3000, 2950, 2925, 2850, 1710,
1
1630, 1430, 1360, 1260, 1160, 1110. H-NMR: 0.92 (t, J=7, 3 H); 1.37 (m, 2 H); 1.46 (m, 2 H); 1.88 (m, 1 H);
2.05 (m, 1 H); 2.19 (q, J=7, 2 H); 2.3–2.5 (m, 4 H); 3.42 (m, 1 H); 3.7 (s, 3 H); 6.6 (dt, J=2, 7, 1 H). 13C-
NMR: 13.9 (q); 22.5 (t); 25.2 (t); 29.0 (t); 30.8 (t); 35.0 (d); 35.8 (t); 38.6 (t); 51.8 (q); 138.4 (d); 139.8 (s);
172.4 (s); 206.3 (s). MS: 224 (57), 195 (9), 167 (15), 151 (100), 121 (32), 109 (62), 93 (48), 79 (60), 67 (31), 55
(30), 41 (41).

Helvetica Chimica Acta – Vol. 88 (2005)
3081
Methyl (2Z)-2-Heptylidene-3-oxocyclopentaneacetate ((Z)-10b). According to Procedure B: b,g-deconju-
gated-10b/(Z)-10b/(E)-10b 16 :58 :32 (98%).
Alternatively, by a one-pot cascade procedure from cyclopentenone 16: b,g-deconjugated-10b/(Z)-10b/(E)-
10b 15 :29 :56 (91% overall).
Data of (Z)-10b: IR: 3000, 2950, 2925, 2850, 1705, 1630, 1430, 1360, 1260, 1160, 1111. 1H-NMR: 0.89 (t, J=7,
3 H); 1.29 (m, 6 H); 1.58 (m, 2 H); 1.89 (m, 1 H); 2.05 (m, 1 H); 2.2 (m, 1 H); 2.3 (m, 2 H); 2.65 (m, 3 H); 3.15 (m,
1 H); 3.71 (s, 3 H); 5.91 (dt, J=2, 7, 1 H). MS: 252 (52, M+C), 195 (13), 179 (100), 167 (16), 161 (20), 135 (28), 121
(35), 109 (36), 79 (37). Floral, green, soapy, jasmine, very weak.
Methyl (2E)-2-Heptylidene-3-oxocyclopentaneacetate ((E)-10b). CC (SiO2, cyclohexane/AcOEt 7:3) for
anal. purposes gave (E)-10b (50%). IR: 3000, 2950, 2925, 2850, 1705, 1630, 1430, 1362, 1260, 1160, 1110. 1H-
NMR: 0.9 (t, J=7, 3 H); 1.3 (m, 6 H); 1.48 (quint., J=7, 2 H); 1.89 (m, 1 H); 2.06 (m, 1 H); 2.2 (q, J=7, 1
H); 2.3–2.5 (m, 5 H); 3.45 (m, 1 H); 3.71 (s, 3 H); 6.59 (t, J=7, 1 H). 13C-NMR: 14.1 (q); 22.6 (t); 25.2 (t);
28.6 (t); 29.1 (t); 29.2 (t); 31.6 (t); 35.0 (d); 35.8 (t); 38.6 (t); 51.8 (q); 138.4 (d); 139.8 (s); 172.4 (s); 206.3 (s).
MS: 252 (47, M+C), 195 (11), 179 (100), 135 (22), 121 (31), 109 (39), 79 (4).
Methyl 2-[(3-Ethylbicyclo[2.2.1]hept-5-en-2-yl)methylene]-3-oxocyclopentaneacetate (10c). According to
Procedure B: 10c (55%) as a 15 :15 :70 stereoisomer mixture. Main stereoisomer: IR: 3391, 2955, 2930, 2870,
1
1736, 1702, 1629, 1460, 1435, 1407, 1377, 1306, 1260, 1230, 1170, 1093, 1051, 1002, 892. H-NMR: 0.92 (t, J=7,
3 H); 1.42 (sext., J=7, 2 H); 1.57 (m, 2 H); 1.68 (m, 2 H); 1.89 (m, 1 H); 2.0–2.57 (m, 6 H); 2.61 (m, 1 H);
3.28 (m, 1 H); 3.7 (s, 3 H); 6.09 (m, 1 H); 6.25 (m, 2 H). MS: 288 (0, M+C), 222 (8), 193 (100), 149 (15), 133
(10), 119 (12), 107 (10), 105 (12), 91 (23), 79 (14).
Methyl [2-(2,2-Dimethoxyethylidene)-3-oxocyclopentaneacetate (10d). According to Procedure B: 10d
1
(96%) as a 2 :3 (Z)/(E) mixture. IR: 3418, 2920, 2871, 1690, 1630, 1440, 1333, 1250, 1191, 1111, 1000, 923. H-
NMR (main (E)-isomer in the mixture): 2.05 (m, 1 H); 2.4 (m, 4 H); 2.64 (m, 2 H); 3.32 (s, 3 H); 3.34 (s, 3
H); 3.7 (s, 3 H); 5.12 (d, J=6, 1 H); 6.47 (d, J=6, 1 H). MS: (Z)-10d: 242 (7, M+C), 210 (65), 195 (27), 178
(40), 169 (100), 151 (72), 137 (52), 119 (71), 109 (47), 91 (66), 79 (33); (E)-10d: 242 (21, M+C), 211 (72), 169
(92), 151 (100), 137 (30), 123 (32), 109 (59), 91 (34), 75 (68).
Methyl 3-Oxo-2-(2-oxoethylidene)cyclopentaneacetate (10e). A soln. of acetal 10d (2.0 g, 8.26 mmol) in
AcOH (10 ml) and H2O (10 ml) was heated at 408 for 3 h. The aq. phase was saturated with NaCl, and the mix-
ture was extracted with Et2O. The org. phase was washed with brine, dried (Na2SO4), and evaporated, and the
residue bulb-to-bulb distilled: (Z)-10e/(E)-10e/14e 1:1 :2 (36%). GC/IR: 3420, 2952, 1720, 1697, 1435, 1406,
1353, 1257, 1169, 1118, 1065, 1000. MS: (Z)-10e: 196 (3, M+C), 168 (100), 165 (20), 137 (11), 109 (100), 79
(39), 77 (19). (E)-10e: 196 (3, M+C), 168 (100), 165 (21), 122 (27), 109 (99), 95 (35), 79 (45), 57 (25).
Methyl 2-[2-(Benzyloxy)ethylidene]-3-oxocyclopentaneacetate (10f). According to Procedure B: b,g-decon-
jugated-10f/(Z)-10f/(E)-10f 14 :29 :57 (68%). IR ((E)-10f in mixture): 3647, 2949, 1730, 1649, 1454, 1435, 1362,
1
1158, 1079, 1000. H-NMR (E-10f in mixture): 1.5–2.5 (m, 5 H); 2.6 (m, 2 H); 3.68 (s, 3 H); 4.2–2.8 (m, 4 H);
6.64 (t, J=5, 1 H); 7.3 (m, 5 H). MS: (E)-10f: 288 (0.5, M+C), 197 (25), 165 (8), 91(100), 65 (8).
Methyl 2-(2-Ethoxyethylidene)-3-oxocyclopentaneacetate (10g). According to Procedure B: b,g-deconju-
gated-10g/(Z)-10g/(E)-10g 22 :39 :39 (53%). ((Z)-10g in the mixture): IR: 2972, 1730, 1649, 1436, 1352, 1261,
1
1166, 1103, 1002, 932, 753. H-NMR: 1.22 (t, J=7, 3 H); 1.5–2.5 (m, 4 H); 2.68 (m, 2 H); 3.19 (m, 1 H); 3.51
(q, J=7, 2 H); 3.71 (s, 3 H); 4.2 (m, 1 H); 4.58 (m, 1 H); 6.01 (t, J=5, 1 H). MS: 226 (58, M+C), 197 (40), 180
(22), 170 (27), 165 (42), 153 (99), 137 (27), 125 (100), 121 (39), 111 (59), 79 (54).
Methyl (2Z)-2-(3-Methoxypropylidene)-3-oxocyclopentaneacetate (10h). According to Procedure B: b,g-
deconjugated-10h/(Z)-10h/(E)-10h. 5 :75 :20 (93%). IR ((Z)-10h in mixture): 2949, 2876, 1733, 1712, 1637,
1435, 1366, 1261, 1166, 1111, 1037, 999, 877. 1H-NMR ((Z)-10h in mixture): 1.6–2.5 (m, 4 H); 2.65 (m, 2 H);
2.97 (m, 2 H); 3.18 (m, 1 H); 3.33 (s, 3 H); 3.48 (t, J=7, 2 H); 3.71 (s, 3 H); 5.99 (t, J=5, 1 H). 13C-NMR
((Z)-10h in mixture): 26.6 (t); 28.2 (t); 38.2 (t); 38.7 (d); 39.2 (t); 51.7 (q); 58.5 (q); 71.7 (t); 137.3 (d); 139.1
(s); 172.5 (s); 207.6 (s). MS: (Z)-10h: 226 (2, M+C), 194 (82), 163 (10), 153 (17), 135 (30), 121 (100), 107 (12),
91 (29), 79 (57), 45 (90); (E)-10h: 226 (2, M+C), 194 (78), 153 (14), 135 (27), 121 (88), 91 (25), 79 (48), 45
(100). Without character.
Methyl (7E)-7-[2-(2-Methoxy-2-oxoethyl)-5-oxocyclopentylidene]heptanoate ((E)-10i). According to Pro-
cedure B: b,g-deconjugated-10i/(Z)-10i/(E)-10i 5 :10 :85 (96%). ((E)-10i in the mixture): IR: 2947, 2857,
1730, 1644, 1435, 1362, 1309, 1260, 1165, 1191, 1002, 978. 1H-NMR: 1.38 (m, 3 H); 1.5 (m, 2 H); 1.65 (m, 3
H); 1.88 (m, 1 H); 2.06 (m, 1 H); 2.2 (q, J=7, 2 H); 2.32 (t, J=7, 2 H); 2.42 (m, 2 H); 3.42 (m, 1 H); 3.68 (s, 3
H); 3.70 (s, 3 H); 6.58 (t, J=5, 1 H). 13C-NMR: 24.7 (t); 25.2 (t); 28.3 (t); 28.9 (t); 29.0 (t); 33.9 (t); 35.0 (d);
35.8 (d); 38.6 (t); 51.5 (q); 51.8 (q); 137.8 (d); 140.0 (s); 172.3 (s); 174.0 (s); 206.3 (s). MS: 296 (13, M+C), 264
(19), 246 (12), 191 (100), 163 (40), 121 (20), 79 (35).

3082
Helvetica Chimica Acta – Vol. 88 (2005)
Methyl (2E)-3-Oxo-2-[(2E)-pent-2-enylidene]cyclopentaneacetate ((E)-10j). During the distillation of 10c,
(E)-10j (33%) was obtained. IR: 2958, 2873, 1730, 1630, 1436, 1261, 1165, 1000, 893. 1H-NMR: 1.07 (t, J=7,
3 H); 1.89 (m, 1 H); 2.09 (m, 1 H); 2.27 (m, 2 H); 2.4 (m, 2 H); 2.51 (m, 2 H); 3.57 (m, 1 H); 3.7 (s, 3 H); 6.28
(m, 2 H); 6.94 (d, J=9, 1 H). 13C-NMR: 13.0 (q); 25.4 (t); 26.6 (t); 35.4 (d); 35.8 (t); 39.0 (t); 51.8 (q); 124.9
(d); 133.5 (d); 137.1 (s); 149.2 (d); 172.4 (s); 206.8 (s). MS: 222 (6, M+C), 193 (100), 149 (12), 133 (9), 119
(12), 105 (13), 91 (22). Hedione, green, mastic.
Methyl (6Z)-6-Pentylidene-1,4-dioxaspiro[4.4]nonane-7-acetate (11). A mixture of 8 (246 mg, 1.16 mmol),
propanoic acid (10 ml) and trimethyl orthoacetate (2 ml) was heated under reflux for 75 min and then evapo-
rated. The residue was distilled: 11 (86%) as a 7:3 (Z)/(E) mixture. IR: 2954, 2929, 2872, 1735, 1650, 1457,
1435, 1377, 1303, 1266, 1245, 1063, 999, 945, 891. 1H-NMR: 0.9 (t, J=7, 3 H); 1.2–1.47 (m, 6 H); 1.7 (m, 1
H); 1.91 (m, 1 H); 2.2 (m, 1 H); 2.3 (dd, J=9, 14, 1 H); 2.59 (dd, J=5, 15, 1 H); 2.9 (m, 1 H); 3.29 (d, J=14,
2 H); 3.66 (s, 3 H); 3.93 (m, 2 H); 4.07 (m, 2 H); 5.50 (dt, J=4, 8, 1 H). 13C-NMR: 14.0 (q); 22.5 (t); 27.1 (t);
28.4 (t); 31.9 (t); 36.2 (t); 39.2 (d); 39.7 (t); 51.5 (q); 64.1 (t); 64.2 (t); 114.7 (s); 130.5 (d); 141.0 (s); 173.2 (s).
MS: 268 (18), 237 (17), 211 (100), 195 (55), 137 (33), 99 (24), 79 (15).
Methyl 1-Hydroxy-2-pentylcyclopent-2-eneacetate (13a). According to [37]: 13a (80%) 13C-NMR: 14.1 (q);
22.6 (t); 26.0 (t); 27.6 (t); 28.8 (t); 32.0 (t); 38.8 (t); 42.4 (t); 51.8 (q); 83.7 (s); 126.4 (d); 147.1 (s); 173.5 (s). For
other analyses, see [37]. Jasmine, buttery, floral, rancid, dirty, vomit.
Ethyl 1-Hydroxy-2-pentylcyclopent-2-ene-1-acetate (13b). A mixture of enone 12 (2.28 g, 15 mmol), ethyl
bromoacetate (2.2 ml, 20 mmol), and granular activated Zn (washed with diluted HCl, H2O, and MeOH,
dried at 1008/0.1 Torr) in benzene (40 ml) was heated under reflux. The reaction started after ca. 30 min; heating
under reflux was continued for 45 min. The cold mixture was diluted with Et2O, washed with sat. NH4Cl soln.,
dried, and evaporated. The remaining oil (4.8 g) was purified by CC (SiO2 (60 g), hexane/AcOEt 95 :5 ! 9 :1):
1
13b (84%). IR: 3000, 2950, 2920, 2850, 1720, 1690, 1625, 1460, 1365, 1020. H-NMR: 0.9 (t, J=7, 3 H); 1.3 (t,
J=7, 3 H); 1.34 (m, 3 H); 1.51 (m, 1 H); 1.95 (m, 2 H); 2.15 (m, 3 H); 2.39 (m, 2 H); 2.42 (d, J=16, 1 H);
2.72 (d, J=16, 1 H); 3.6 (br. s, 1 OH); 4.19 (q, J=7, 2 H); 5.5 (br. s, 1 H). 13C-NMR: 14.1 (q); 14.2 (q); 22.6
(t); 26.0 (t); 27.6 (t); 28.8 (t); 32.0 (t); 38.8 (t); 42.6 (t); 60.7 (t); 83.8 (s); 126.3 (d); 147.1 (s); 173.1 (s). MS:
240 (0, M+C), 222 (52), 193 (18), 166 (50), 134 (64), 119 (38), 105 (53), 93 (72), 92 (68), 91 (100), 79 (51).
Methyl 3-Oxo-2-pentylcyclopent-1-ene-1-acetate (14a). Under Ar, b,g-deconjugated-10a/(Z)-10a/(E)-10a
10 :30 :60 (650 mg, 2.9 mmol) was heated at 1208 for 6 h in the presence of [RuH(h5-C8H11)2]BF4 (32.5 mg,
0.08 mmol). Bulb-to-bulb distillation afforded b,g-deconjugated-10a/14a/(Z)-10a/(E)-10a 9 :53 :28 :10 (74%).
For analyses, see [37].
Alternatively, pure 14a (84%) was obtained according to [37].
Alternatively, a soln. of HIO3 (2.64 g, 15 mmol) in DMSO (15 ml) protected from light was heated at 808 for
1 hour. Then a soln. of Hedione® trans/cis (9 :1; 15a; 2.26 g, 10 mmol) in DMSO (10 ml) was added at 658. After
18 h at 658, the cold soln. was extracted with Et2O and H2O. The org. phase was dried (Na2SO4) and evaporated
and the residues purified by CC (SiO2, cyclohexane/AcOEt 9 :1): 14a (65%). Floral, jasmine, very weak, vague.
Ethyl 3-Oxo-2-pentylcyclopent-1-ene-1-acetate (14b). To a soln. of 13b (0.96 g, 4 mmol) in Et2O (40 ml) was
added 2.5M Jones reagent (2 ml, 5 mmol) at 08. The cooling bath was removed, and stirring was continued for 10
min. The org. layer was washed with H2O, 5% NaHCO3 soln., dried (Na2SO4), and evaporated. The residue was
distilled: 14b (93%). B.p. 1208/0.9 Torr. IR: 2955, 2930, 2850, 1725, 1690, 1640, 1460, 1440, 1365, 1300, 1180, 1110,
1022. 1H-NMR: 0.87 (t, J=7, 3 H); 1.28 (m, 4 H); 1.28 (t, J=7, 3 H); 1.37 (m, 2 H); 2.19 (t, J=7, 2 H); 2.4 (m, 2
H); 2.61 (m, 2 H); 3.46 (s, 2 H); 4.19 (q, J=7, 2 H). 13C-NMR: 14.0 (q); 14.2 (q); 22.5 (t); 23.2 (t); 28.0 (t); 29.7
(t); 31.8 (t); 34.3 (t); 37.0 (t); 61.3 (t); 143.2 (s); 163.8 (s); 169.2 (s); 209.2 (s). MS: 238 (2, M+C), 220 (6), 182 (10),
165 (5), 151 (100), 135 (10), 121 (10), 109 (33), 79 (12).
Methyl 2-Heptyl-3-oxocyclopent-1-ene-1-acetate (14c). Formier gas (N2/H2 92 :8) was bubbled (10 bubbles/
min) through a stirred suspension of 10b (2.52 g, 10 mmol) in the presence of 5% Pd/Al2O3 (20 mg) at 1358 for
8 h. After filtration and purification by CC (5%AgNO3/SiO2, cyclohexane/AcOEt 97:3), 14c was isolated in
45% yield from the totally saturated material. IR: 2960, 2930, 2850, 1725, 1690, 1640, 1460, 1440, 1365, 1300,
1
1180, 1110, 1020. H-NMR: 0.89 (t, J=7, 3 H); 1.26 (m, 8 H); 1.36 (m, 2 H); 2.18 (t, J=7, 2 H); 2.4 (m, 2 H);
2.6 (m, 2 H); 3.46 (s, 2 H); 3.73 (s, 3 H). 13C-NMR: 14.1 (q); 22.6 (t); 23.3 (t); 28.4 (t); 29.1 (t); 29.7 (t); 29.6
(t); 31.8 (t); 34.4 (t); 36.6 (t); 52.3 (q); 143.3 (s); 163.5 (s); 169.6 (s); 209.2 (s). MS: 252 (2, M+C), 179 (100),
168 (19), 135 (12), 109 (35), 79 (22), 41 (18). Cocoa butter, fatty-lard, milky, buttery.
Methyl 2-(2,2-Dimethoxyethyl)-3-oxocyclopent-1-ene-1-acetate (14d). A soln. of acetal 10d (800 mg, 3.3
mmol) in MeOH (5 ml) and a trace amount of conc. HCl was heated for 3 h at 608. A trace of NaHCO3 was
added to the cold mixture. The filtrate was evaporated and the residue bulb-to-bulb distilled: 14d (87%). B.p.
1508/0.1 mbar. IR: 2930, 2832, 1736, 1696, 1649, 1434, 1352, 1255, 1192, 1170, 1117, 1080, 1049, 1010, 971.

Helvetica Chimica Acta – Vol. 88 (2005)
3083
1H-NMR: 2.43 (m, 2 H); 2.53 (d, J=7, 2 H); 2.67 (m, 2 H); 3.33 (s, 6 H); 3.54 (s, 2 H); 3.73 (s, 3 H); 4.39 (t, J=7, 1
H). 13C-NMR: 27.7 (t); 30.1 (t); 34.2 (t); 36.8 (t); 52.2 (q); 54.2 (2q); 103.4 (d); 138.2 (s); 167.1 (s); 169.6 (s); 208.9
(s). MS: 242 (0.5, M+C), 210 (47), 195 (8), 151 (36), 123 (17), 109 (16), 91 (17), 75 (100).
Methyl 3-Oxo-2-(2-oxoethyl)cyclopent-1-ene-1-acetate (14e). A soln. of acetal 14d (330 mg, 1.36 mmol) in
H2O (8 ml) and AcOH (8 ml) was stirred at 608 for 2 h. The cold mixture was evaporated, the residue diluted
with Et2O, the soln. extracted with brine, washed with sat. aq. NaHCO3 soln. and brine to neutral, dried
(Na2SO4), and evaporated, and the residue bulb-to-bulb distilled: 14e (55%). B.p. 1708/0.1 mbar. IR: 2952,
2839, 1722, 1694, 1648, 1435, 1352, 1255, 1192, 1171, 1118, 1062, 1010. 1H-NMR: 2.5 (m, 2 H); 2.76 (m, 2 H);
3.39 (s, 2 H); 3.45 (s, 2 H); 3.7 (s, 3 H); 9.65 (s, 1 H). 13C-NMR: 30.7 (t); 34.1 (t); 37.0 (t); 38.2 (t); 52.5 (q);
134.9 (s); 168.0 (s); 168.9 (s); 197.0 (d); 207.8 (s). MS: 196 (3, M+C), 168 (85), 137 (12), 109 (100), 79 (43), 53 (17).
Methyl (2Z)-3-Oxo-2-(pent-2-enyl)cyclopent-1-ene-1-acetate (14f). At 208, 1
M sodium bis(trimethylsilyl)-
amide in THF (0.74 ml, 0.74 mmol) was added dropwise to a soln. of triphenylpropylphosphonium bromide
(0.29 g, 0.74 mmol) in THF (1 ml). After 1 h, DMF (0.25 ml) and a soln. of keto aldehyde 14e (40 mg, 0.2
mmol) in THF (0.3 ml) were added. After 2 h at 208, the mixture was poured onto ice, and extracted with Et2O.
The org. phase was washed with brine to neutrality, dried (Na2SO4), and evaporated and the residue purified by
CC (SiO2, Et2O/cyclohexane 2 :3): (Z)-14f (44%) contaminated by 7% of (E)-isomer. IR: 2969, 2926, 1739, 1698,
1644, 1437, 1354, 1259, 1172, 1119, 1087, 1048, 879. 1H-NMR: 0.99 (t, J=7, 3 H); 2.15 (q, J=7, 2 H); 2.42 (m, 2
H); 2.61 (m, 2 H); 2.97 (d, J=7, 2 H); 3.48 (s, 2 H); 3.72 (s, 3 H); 5.2 (m, 1 H); 5.41 (m, 2 H). 13C-NMR: 14.1 (q);
20.6 (t); 21.3 (t); 29.9 (t); 34.2 (t); 36.6 (t); 52.3 (q); 124.4 (d); 133.0 (d); 141.8 (s); 164.0 (s); 169.5 (s); 208.6 (s).
MS: 222 (21, M+C), 193 (100), 149 (72), 133 (51), 105 (48), 91 (69), 79 (57), 77 (44), 55 (39). Jasmine, floral.
Methyl trans-3-Oxo-2-pentylcyclopentaneacetate (trans-15a). A soln. of 10a (3.01 g, 13.1 mmol: b,g-decon-
jugated/(Z)/(E)-10a 10 :30 :60) in cyclohexane (30 ml) was hydrogenated at 08 under 1 atm of H2 over 5% Pd/C
(300 mg). After 18 h, the mixture was filtered and evaporated, and the residue bulb-to-bulb distilled: 15a (98%)
as a 52 :48 trans/cis mixture.
A soln. of enone 14a (1.0 g, 4.1 mmol) in cyclohexane (10 ml) was hydrogenated at 208 under 1 atm. of H2
over 10% Pd/C (50 mg). After 1.5 h, the mixture was evaporated and the residue bulb-to-bulb distilled: 15a,
(98%) as a 38 :62 trans/cis mixture. Epimerization with a trace of MeONa/MeOH afforded quantitatively 15a
as a 92 :8 trans/cis mixture. For analyses, see [17]. Jasmine, floral, somewhat rancid, weak.
Methyl trans-3-Oxo-2-heptylcyclopentaneacetate (trans-15b). A soln. of 10b (3.0 g, 11.9 mmol; b,g-deconju-
gated/(Z)(E)-10b 15 :29 :56) in cyclohexane (30 ml) was hydrogenated at 1 atm H2 over 10% Pd/C (100 mg).
After 18 h, the mixture was evaporated and the residue bulb-to-bulb distilled: 15b (92%) as a 53 :47 trans/cis
mixture. Epimerization with a trace of MeONa/MeOH afforded quantitatively 15b as a 9 :1 trans/cis mixture
for analyses. B.p. 1608/0.1 mbar. IR: 2923, 2853, 1733, 1435, 1167, 1014, 721. 1H-NMR: 0.87 (t, J=7, 3 H);
1.24 (m, 10 H); 1.38 (m, 1 H); 1.54 (m, 2 H); 1.8 (m, 1 H); 2.12 (m, 1 H); 2.24 (m, 1 H); 2.35 (m, 3 H); 2.64
(m, 1 H); 3.72 (s, 3 H). 13C-NMR: 14.1 (q); 23.7 (t); 27.2 (t); 27.5 (t); 27.9 (t); 29.1 (t); 29.9 (t); 31.8 (t); 37.7
(t); 38.1 (t); 39.0 (d); 51.7 (d); 54.2 (q); 172.7 (s); 219.7 (s). MS: 254 (3, M+C), 181 (22), 156 (39), 83 (100), 55
(17). MS: cis-15b: 254 (5, M+C), 181 (28), 156 (32), 83 (100), 55 (21). Fruity, floral, velvety, veloutone, peach,
very weak.
Methyl trans-2-(2,2-Dimethoxyethyl)-3-oxocyclopentaneacetate (trans-15d). A soln. of 10d (1.0 g, 4.13
mmol; (Z)-/(E)-10d 2 :3) in MeOH (10 ml) was hydrogenated at 1 atm H2 over 10% Pd/C (100 mg). After 2
h, the mixture was evaporated and the residue bulb-to-bulb distilled: 15d (60%) as a 9 :1 trans/cis mixture.
1
IR: 3000, 1730, 1715, 1170, 720. H-NMR: 1.51 (m, 1 H); 1.78 (m, 1 H); 1.89 (m, 2 H); 2.18 (m, 1 H); 2.35 (m,
4 H); 2.72 (m, 1 H); 3.32 (s, 3 H); 3.34 (s, 3 H); 3.71 (s, 3 H); 4.62 (dd, J=7, 9, 1 H). 13C-NMR: 27.4 (t); 31.2
(t); 37.3 (t); 38.5 (t); 38.9 (d); 50.3 (d); 51.6 (q); 53.1 (q); 53.4 (q); 102.7 (d); 172.7 (s); 218.9 (s). MS: 244 (0,
M+C), 212 (8), 181 (23), 139 (27), 89 (37), 75 (100). MS: cis-15d: 244 (0, M+C), 213 (12), 181 (13), 139 (21), 89
(35), 75 (100). Without character.
Methyl trans-3-Oxo-2-(2-oxoethyl)cyclopentaneacetate (trans-15e). A mixture of 15d (0.43 g, 1.76 mmol),
H2O (8 ml), and AcOH (8 ml) was stirred for 3 h at 408. The cold mixture was evaporated, the residue diluted
with Et2O, the soln. washed with brine, sat. aq. NaHCO3 soln., and brine to neutral, dried (Na2SO4), and evapo-
rated, and the residue bulb-to-bulb distilled: 15e (83%) as a 9 :1 trans/cis mixture.
Alternatively, a suspension of 15f (85 mg, 0.425 mmol), PCC (140 mg, 0.65 mmol), and SiO2 (100 mg) in
CH2Cl2 (2 ml) was stirred for 15 min at 208. Et2O (2 ml) and Celite (100 mg) were added, and the mixture
was passed through a short column of SiO2 (Et2O). The filtrate was evaporated and the residue bulb-to-bulb
distilled: 15e (60%, 9 :1 trans/cis). IR: 2955, 2930, 2869, 1737, 1701, 1464, 1408, 1378, 1229, 1170, 1087, 1003,
968, 901, 800. 1H-NMR: 1.59 (m, 1 H); 2.25–2.4 (m, 5 H); 2.43 (m, 1 H); 2.57 (m, 1 H); 2.71 (dd, J=7, 16, 1

3084
Helvetica Chimica Acta – Vol. 88 (2005)
H); 2.9 (dd, J=7, 16, 1 H); 3.69 (s, 3 H); 9.77 (s, 1 H). 13C-NMR: 27.6 (t); 37.0 (t); 38.4 (d); 38.6 (t); 42.4 (t); 49.2
(d); 51.7 (q); 172.5 (s); 199.8 (d); 217.7 (s). MS: 198 (3, M+C), 167 (20), 156 (35), 125 (17), 97 (100), 83 (46), 55
(29). MS: cis-15e: 193 (3, M+C), 167 (19), 156 (34), 125 (15), 97 (100), 83 (49), 55 (33). Without character.
Methyl trans-2-(2-Hydroxyethyl)-3-oxocyclopentaneacetate (trans-15f). A soln. of 10f (1.15 g, 4.0 mmol;
b,g-deconjugated/(Z)/(E)-10f 14 :29 :57) in MeOH (10 ml) was hydrogenated at 1 atm H2 over 10% Pd/C
(100 mg). After 18 h, the mixture was filtered and evaporated and the residue bulb-to-bulb distilled: 15f
(98%) as a 9 :1 trans/cis mixture. IR: 2949, 1730, 1436, 1163, 1041. 1H-NMR: 1.57 (m, 1 H); 1.78 (m, 2 H);
1.98 (m, 1 H); 2.2 (m, 1 H); 2.25–2.45 (m, 4 H); 2.66 (m, 1 H); 2.89 (br. s, OH); 3.71 (s, 3 H); 3.76 (m, 2 H).
13C-NMR: 27.5 (t); 30.7 (t); 37.4 (t); 38.4 (t); 38.6 (d); 51.8 (q); 53.0 (d); 61.0 (t); 172.7 (s); 221.2 (s). MS: 200
(0, M+C), 182 (18), 168 (19), 156 (27), 140 (18), 125 (20), 109 (78), 83 (100), 55 (53).
Methyl trans-2-(2-Ethoxyethyl)-3-oxocyclopentaneacetate (trans-15g). As described for 15b: 15g (78%) as
40 :60 trans/cis mixture, which spontaneously epimerized in CDCl3 to a 95 :5 trans/cis mixture. IR: 2950,
2862, 1730, 1435, 1377, 1256, 1194, 1160, 1105, 997. 1H-NMR: 1.16 (t, J=7, 3 H); 1.49 (m, 1 H); 1.84 (sext.,
J=7, 2 H); 1.9 (m, 1 H); 2.2 (m, 2 H); 2.25–2.4 (m, 3 H); 2.72 (m, 1 H); 3.44 (m, 2 H); 3.51 (t, J=7, 2 H);
3.71 (s, 3 H). 13C-NMR: 15.2 (q); 27.4 (t); 27.8 (t); 37.5 (t); 38.2 (d); 38.7 (t); 51.6 (d); 51.6 (q); 66.0 (t); 67.6
(t); 172.7 (s); 219.2 (s). MS: 228 (0, M+C), 156 (40), 109 (17), 83 (100), 73 (40). MS: cis-15g: 228 (0, M+C), 156
(40), 109 (12), 83 (100), 73 (40). Cheese, curdled milk.
Methyl trans-2-(3-Methoxypropyl)-3-oxocyclopentaneacetate (trans-15h). As described for 15d: 15h (79%)
as a 9 :1 trans/cis mixture. B.p. 1808/0.1 mbar. IR: 2928, 2867, 1730, 1436, 1408, 1380, 1334, 1256, 1193, 1159, 1112,
1
1016. H-NMR: 1.45–1.77 (m, 4 H); 1.83 (m, 1 H); 2.11 (m, 2 H); 2.24 (m, 2 H); 2.34 (m, 2 H); 2.64 (m, 1 H);
3.31 (s, 3 H); 3.37 (t, J=7, 2 H); 3.7 (s, 3 H). 13C-NMR: 24.4 (t); 26.6 (t); 27.2 (t); 37.6 (t); 38.1 (d); 38.8 (t);
51.6 (q); 53.8 (d); 58.5 (q); 72.7 (t); 172.6 (s); 219.4 (s). MS: 228 (0.5, M+C), 196 (9), 155 (37), 123 (100), 45
(15). MS: cis-15h: 228 (0.5, M+C), 196 (9), 155 (37), 123 (100), 45 (15). Vaguely mushroom, hedione, weak.
Methyl trans-2-(2-Methoxy-2-oxoethyl)-5-oxocyclopentaneheptanoate (trans-15i). As described for 15b: 15i
1
(96%) as a 66 :34 trans/cis mixture. IR: 2929, 2855, 1735, 1435, 1193, 1166, 1013. H-NMR: 1.32 (m, 5 H); 1.43
(m, 1 H); 1.54 (m, 2 H); 1.62 (m, 2 H); 1.8 (m, 2 H); 2.2 (m, 2 H); 2.25–2.4 (m, 5 H); 2.63 (m, 1 H); 3.66 (s, 3 H);
3.71 (s, 3 H). 13C-NMR: 24.9 (t); 26.5 (t); 27.2 (t); 27.8 (t); 28.9 (t); 29.5 (t); 34.0 (t); 37.7 (t); 38.1 (d); 38.9 (t); 51.5
(q); 51.7 (q); 54.2 (d); 172.6 (s); 174.2 (s); 219.6 (s). MS: 298 (2, M+C), 235 (12), 193 (20), 156 (75), 83 (100), 55
(16). MS: cis-15i: 298 (2, M+C), 235 (12), 193 (18), 156 (80), 83 (100), 55 (18).
3-endo-Ethylbicyclo[2.2.1]hept-5-ene-2-endo-carbaldehyde (cis-endo-17c). Cyclopentadiene dimer (54.36
g, 0.412 mol) and 70% (2Z)-pent-2-enenitrile (95.16 g, 0.82 mol; Fluka) were heated at 1808 for 23 h in a 500-
ml Berghof autoclave. After cooling, the mixture was distilled through a Vigreux column, and the fraction
33–518/0.06 mbar (69.9 g, 83% pure) was redistilled over a Widmer column: 3-exo/endo-ethylbicyclo[2.2.1]-
hept-5-ene-2-exo/endo-carbonitrile 1 :2 (45%), separated by prep. GC for analyses. 3-endo-Ethylbicyclo[2.2.1]-
hept-5-ene-2-endo-carbonitrile: IR: 2960, 2945, 2890, 2250, 1460, 1385, 1345, 1255, 1160. 1H-NMR: 0.98 (t, J=7,
3 H); 1.2 (m, 1 H); 1.29 (d, J=7, 1 H); 1.46 (m, 1 H); 1.57 (d, J=7, 1 H); 2.2 (m, 1 H); 2.98 (br. s, 1 H); 3.02 (dd,
J=3.5, 9, 1 H); 3.19 (br. s, 1 H); 6.22 (m, 1 H); 6.28 (m, 1 H). 13C-NMR: 12.8 (q); 24.6 (t); 33.2 (d); 44.4 (d); 45.3
(d); 46.8 (d); 48.4 (t); 120.9 (s); 134.6 (d); 136.1 (d). MS: 147 (1, M+C); 105 (5); 66 (100); 39 (8). Pinanol, cam-
phoraceous, pinene.
At 208, 1.0M DIBAL-H in hexane (66 ml, 0.066 mol) was added dropwise to a soln. of a distilled enriched
fraction of cis-endo/cis-exo carbonitrile 6 :1 (4.86 g, 0.33 mol) in THF (60 ml). After 2 h, the mixture was poured
onto 10% H2SO4 soln. at 08. After extraction with Et2O, the org. phase was washed with brine to neutral, dried
(Na2SO4) and evaporated and the crude residue (>80%) used as such for the next reaction. A sample was puri-
fied by CC (SiO2, cyclohexane/AcOEt 97:3) for anal. purpose: cis-endo-17c. IR: 3070, 2976, 2944, 2884, 2823,
1
2727, 1730, 1461. H-NMR: 0.98 (t, J=7, 3 H); 1.01 (m, 1 H); 1.38 (d, J=7, 1 H); 1.43 (sept., J=5, 1 H); 1.56
(d, J=7, 1 H); 2.43 (m, 1 H); 2.88 (m, 1 H); 3.0 (s, 1 H); 3.07 (s, 1 H); 6.23 (m, 1 H); 6.33 (m, 1 H); 9.36 (d,
J=4, 1 H). 13C-NMR: 13.4 (q); 23.4(t); 45.4 (d); 46.0 (d); 47.5 (d); 49.4 (t); 55.7 (d); 135.0 (d); 135.7 (d);
207.6 (d). MS: 150 (2, M+C), 85(9), 66 (100), 39 (10).
3-exo-Ethylbicyclo[2.2.1]hept-5-ene-2-exo-carbaldehyde (cis-exo-17c). During the purification of the main
cis-endo stereoisomer; the intermediate 3-exo-ethylbicyclo[2.2.1]hept-5-ene-2-exo-carbonitrile was isolated. IR:
2960, 2940, 2880, 2350, 1460, 1380, 1335. 1H-NMR: 1.06 (t, J=7, 3 H); 1.5 (m, 2 H); 1.51 (d, J=7, 1 H); 1.68 (d,
J=7, 1 H); 1.8 (sext., J=7, 1 H); 2.42 (d, J=8, 1 H); 2.72 (br. s, 1 H); 3.18 (br. s, 1 H); 6.04 (m, 1 H); 6.23 (m, 1
H). 13C-NMR: 13.4 (q); 26.3 (t); 33.7 (d); 43.5 (d); 44.3 (t); 45.7 (d); 48.0 (d); 121.7 (s); 134.3 (d); 139.6 (d). MS:
147 (0.5, M+C), 118 (4), 105 (5), 91 (5), 66 (100), 39 (10).
During the purification of the main cis-endo stereoisomer, the cis-exo-17c was isolated. IR: 3071, 2977,
2888, 2818, 2717, 1731, 1460. 1H-NMR: 0.98 (t, J=7, 3 H); 1.21 (m, 1 H); 1.45 (d, J=7, 1 H); 1.61 (m, 1 H);

Helvetica Chimica Acta – Vol. 88 (2005)
3085
1.69 (d, J=7, 1 H); 1.75 (m, 1 H); 2.24 (m, 1 H); 2.72 (br. s, 1 H); 2.98 (br. s, 1 H); 6.09 (m, 1 H); 6.22 (m, 1 H);
9.77 (d, J=4, 1 H). 13C-NMR: 13.9 (q); 24.6 (t); 43.5 (t); 44.0 (d); 45.0 (d); 45.8 (d); 53.2 (d); 135.7 (d); 139.1 (d);
206.9 (d). MS: 150 (1, M+C), 85 (12), 66 (100), 39 (6).
Methyl trans-3-Oxo-2[(2Z)-pent-2-enyl]cyclopentaneacetate (18a). Triphenylpropylphosphonium bromide
(1430 mg, 3.7 mmol) was added to a suspension of NaNH2 (272 mg, 3.4 mmol) in THF (7 ml). After 5 min at
208, tBuOK (34 mg, 0.3 mmol) was added and after 1 h at 208, the temp. was cooled down to ꢀ708. A soln.
of 15e (730 mg, 3.68 mmol) in THF (3 ml) was added dropwise, then the temp. was raised gradually to 208.
The mixture was poured onto ice and diluted with Et2O, the org. phase washed with brine to neutrality, dried
(Na2SO4), and evaporated, and the residue bulb-to-bulb distilled: methyl jasmonate (Z)-18a (31%) as a 9 :1
trans/cis mixture.
Alternatively, 1.6M BuLi in hexane (0.85 ml, 1.35 mmol) was added dropwise at 08 to a suspension of triphe-
nylpropylphosphonium bromide (540 mg, 1.4 mmol) in toluene (3 ml). After 1 h at 208, the mixture was cooled
down to ꢀ208, and a soln. of 15e (250 mg, 1.26 mmol) in toluene (4 ml) was added dropwise in 1 h. After 2 h at
ꢀ208 and 1 h at 208, H2O and then hexane were added. The mixture was filtered and evaporated and the residue
bulb-to-bulb distilled: (Z)-18a (62%) as a 9 :1 trans/cis mixture of (Z)/(E)-isomers 95 :5. B.p. 1758/0.1 mbar. IR:
1
2961, 1725, 1436, 1408, 1375, 1335, 1258, 1229, 1194, 1162, 1069, 985. H-NMR: 0.95 (t, J=7, 3 H); 1.5 (quint.,
J=7, 1 H); 1.9 (m, 1 H); 2.07 (quint., J=7, 2 H); 2.1–2.4 (m, 7 H); 2.7 (m, 1 H); 3.7 (s, 3 H); 5.25 (m, 1 H);
5.45 (m, 1 H). 13C-NMR: 14.2 (q); 20.6 (t); 25.5 (t); 27.3 (t); 37.6 (t); 38.1 (d); 38.7 (t); 51.3 (q); 53.9 (d);
125.6 (d); 133.7 (d); 172.3 (s); 217.9 (s). MS: 224 (30, M+C), 193 (12), 156 (22), 151 (39), 109 (27), 95 (32), 83
(100), 79 (29), 67 (28), 55 (27), 41 (40). Jasmine, mushroom, humus, delphone.
Methyl trans-2-[(2Z)Hex-2-enyl]-3-oxocyclopentaneacetate (18b). As described for 18a (BuLi at ꢀ308): 18b
(34%) as a 9 :1 trans/cis mixture of (Z)/(E)-isomers 95 :5. IR: 2956, 2872, 1730, 1436, 1408, 1377, 1335, 1259,
1229, 1193, 1162, 983. 1H-NMR: 0.91 (t, J=7, 3 H); 1.38 (sext., J=7, 2 H); 1.5 (m, 1 H); 1.89 (m, 1 H); 2.02
(sext., J=7, 2 H); 2.11 (m, 1 H); 2.2–2.4 (m, 6 H); 2.71 (m, 1 H); 3.70 (s, 3 H); 5.3 (m, 1 H); 5.48 (m, 1 H).
13C-NMR: 13.8 (q); 22.7 (t); 25.7 (t); 27.2 (t); 29.4 (t); 37.7 (t); 38.1 (d); 38.8 (t); 51.6 (q); 54.0 (d); 125.8 (d);
132.3 (d); 172.5 (s); 218.9 (s). MS: 238 (25, M+C), 207 (8), 165 (35), 156 (28), 147 (15), 135 (18), 109 (21), 95
(29), 83 (100), 79 (29), 67 (27), 55 (33), 41 (29). Methyl jasmonate, vitamins.
Methyl trans-2-(3-Cyclopropylprop-2-enyl)-3-oxocyclopentaneacetate (18c). As described for 18a (BuLi at
ꢀ308): 18c (35%) as a 95 :5 trans/cis mixture of 7:3 (Z)/(E)-isomers. IR: 2990, 1730, 1720, 1040. 1H-NMR: 0.31
(m, 3 H); 0.72 (m, 2 H); 1.52 (m, 2 H); 1.94 (m, 1 H); 2.12 (m, 1 H); 2.2–2.4 (m, 3 H); 2.5 (m, 2 H); 2.78 (m, 1 H);
3.70 (s, 3 H); 4.82 (t, J=7, 1 H); 5.23 (m, 1 H). 13C-NMR: 6.9 (t); 7.0 (t); 9.7 (d); 25.9 (t); 27.3 (t); 37.8 (t); 38.0
(d); 38.8 (t); 51.6 (q); 54.2 (d); 123.9 (d); 136.4 (d); 172.6 (s); 219.0 (s). MS: 236 (6, M+C), 218 (5), 193 (10), 163
(69), 121 (28), 91 (45), 83 (100), 81 (62), 79 (87), 77 (33), 67 (35), 55 (35), 41 (39).
REFERENCES
[1] K. Suzuki, K. Inomata, Y. Endo, Org. Lett. 2004, 6, 409.
[2] E. Demole, E. Lederer, D. Mercier, Helv. Chim. Acta 1962, 45, 675.
[3] L. Crabalona, C. R. Acad. Sci. (Paris), Ser. C 1967, 264, 2074.
[4] W. Giersch, I. Farris, Helv. Chim. Acta 2004, 87, 1601; H. Kiyota, T. Koike, E. Higashi, T. Oritani, Flav.
Fragr. J. 2002, 17, 267; K. J. Rossiter, Chem. Rev. 1996, 96, 3201; M. Lenfant, R. E. Wolf, Bull. Soc.
Chim. Fr. 1963, 6, 1210.
[5] a) D. C. Aldridge, S. Galt, D. Giles, W. D. Turner, J. Chem. Soc., C, 1971, 1623; b) A. B. Ivanova, A. Y.
Yarin, L. L. Antsygina, A. N. Grechkin, Tsitologiya 2002, 44, 369 (Chem. Abstr. 2003, 137, 181080); c)
M. Saniewski, H. Urbanek, Biotechnologia 2003, 3, 75 (Chem. Abstr. 2004, 139, 304498); d) O. Fingrut,
E. Flescher, Leukemia, 2002, 16, 608; e) D. Gold, I. Pankova-Kholmyansky, O. Fingrut, E. Flescher, J. Para-
sitol. 2003, 89, 1242.
[6] E. P. Demole, in ‘Fragrance Chemistry’, Ed. E. T. Theimer, Academic Press, Orlando, 1982, p. 349; G.
Fràter, J. A. Bajgrowicz, P. Kraft, Tetrahedron 1998, 54, 7633; T. K. Sarkar, B. K. Ghorai, J. Ind. Chem.
Soc. 1999, 76, 693; H. C. Hailes, Adv. Flavours Fragr. 2002, 277, 127; H.-Y. Qiu, Y. Lin, Hecheng Huaxue
2003, 11, 486; (Chem. Abstr. 2004, 140, 406645u).
[7] F. Schröder, Angew. Chem. 1998, 110, 1271; Angew. Chem., Int. Ed. 1998, 37, 1213; M. H. Beale, J. L. Ward,
Nat. Prod. Rep. 1998, 433; G. Sembdner, P. Parthier, Annu. Rev. Plant. Physiol. Plant Mol. Biol. 1993, 44,
569; M. Hamberg, H. W. Gardner, Biochem. Biophys. Acta 1992, 1165, 1; W. Boland, J. Hopke, J. Donath, J.
Nüske, F. Bublitz, Angew. Chem. 1995, 107, 1715; Angew. Chem., Int. Ed. 1995, 34, 1600.
[8] T. C. Baker, R. Nishida, W. L. Roelofs, Science (Washington, D.C.) 1981, 214, 1359.

3086
Helvetica Chimica Acta – Vol. 88 (2005)
[9] B. Parthier, Bot. Acta 1991, 104, 446.
[10] Y. Koda, Intl. Rev. Cytol. 1992, 135, 155.
[11] E. W. Weiler, Bio. Acta 1993, 106, 2.
[12] E. F. Farmer, C. A. Ryan, Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 7713.
[13] P. Werkhoff, G. Krammer, S. Brennecke, M. Roloff, H.-J. Bertram, Food. Rev. Intl. 2002, 18, 103; O.
Miersch, R. Kramell, B. Parthier, C. Wasternack, Phytochemistry 1999, 50, 353; M. C. S. Cano, E. G.
Plaza, R. G. Munoz, A. G. Benavente, J. Essent. Oil Res. 1998, 10, 67; A. S. C. Sing, J. Barbier, J. Smadja,
J. Nat. 1997, 9, 8; G. Buchbauer, L. Jirovetz, V. K. Kaul, J. Essent. Oil Res. 1995, 7, 5; O. Miersch, A. Preiss,
G. Sembdner, K. Schreiber, Phytochemistry 1987, 26, 1037; W. Renold, R. Näf-Müller, U. Keller, B. Will-
halm, G. Ohloff, Helv. Chim. Acta 1974, 57, 1301.
[14] M. Koji, F. Kimikazu to Kao Corp., EP 1433773A1, 23.12.2003 (Chem. Abstr. 2004, 141, 88872z).
[15] A. Firmenich, R. Firmenich, G. Firmenich, R. E. Firmenich to Firmenich SA, GB907431, 03.10.1962,
(Chem. Abstr. 1963, 58, 458f); G. Fràter, D. Lamparsky, ‘Perfumes, Arts, Sciences and Technology’, Eds.
P. M. Müller and D. Lamparsky, Elsevier, London, 1991, p. 407 and 596; G. Fràter, J. A. Bajgrowicz, P.
Kraft, Tetrahedron 1998, 54, 7633; X. Sun, S. Zhang, H. Zhou, Z. Jiang, Xiangliao Xiangjing Huazhuangpin
2002, 11, 21 (Chem. Abstr. 2003, 138, 273279n).
[16] T. Yamada, H. Fujisawa, H. Tanaka to Nippon Zeon, EP 399788, 23.5.1989 (Chem. Abstr. 1991, 114,
163600g); N. Krause, S. Ebert, Eur. J. Org. Chem. 2001, 20, 3837.
[17] a) H. Inoue, M. Ashida, T. Ohta, I. Furukawa, Sci. Engineering Rev. Doshisha Univ. 2002, 43, 114, (Chem.
Abstr. 2004, 138, 4455t); b) D. A. Dobbs, K. P. M. Vanhessche, E. Brazi, V. Rautenstrauch, J.-Y. Lenoir, J.-P.
Genêt, J. Wiles, S. H. Bergens, Angew. Chem. 2000, 112, 2080; Angew. Chem., Int. Ed. 2000, 39, 1992; c) C.
Fehr, J. Galindo, Angew. Chem. 2000, 112, 581; Angew. Chem., Int. Ed. 2000, 39, 569; d) V. Rautenstrauch,
J.-J. Riedhauser, to Firmenich SA, WO 9600206, 04.01.1996 (Chem. Abstr. 1996, 124, 232126c); e) A. Porta,
G. Vidari, G. Zanoni, J. Org. Chem. 2005, 70, 4876.
[18] A. Itoh, S. Ozawa, K. Oshima, H. Nozaki, Bull. Chem. Soc. Jpn. 1981, 54, 274.
[19] A. R. Matlin, T. C. Leckta, D. J. Mc Garvey, P. W. Jacob, H. A. Picken, Tetrahedron Lett. 1987, 28, 5083.
[20] A. M. Braun, M.-T. Maurette, E. Oliveros, ‘Photochemical Technology’, J. Wiley, Chichester, 1991, p. 458;
J. J. M. Lamberts, D. C. Neckers, Tetrahedron 1985, 41, 2183; C. Chapuis, M. Barthe, B. L. Muller, K. H.
Schulte-Elte, Helv. Chim. Acta 1998, 81, 153.
[21] J. R. Hanson, D. Baldwin, J. Chem. Soc. Perkin Trans. 1 1972, 2051.
[22] a) J. Ye, Y. Wang, J. Chen, X. Liang, Adv. Synth. Catal. 2004, 346, 691; b) S. Marmor, J. Org. Chem. 1963, 28,
250; c) C. S. Foote, S. Wexler, J. Am. Chem. Soc. 1964, 86, 3879; d) W. J. Adams, D. N. Kirk, D. J. Patel, V.
Petrow, I. A. Stuart-Webb, J. Chem. Soc. 1955, 870; e) R. E. Marker, E. M. Jones, E. L. Wittbecker, J. Am.
Chem. Soc. 1942, 64, 468; f) T. Suzuki, A. Yoshikoshi, M. Miyashita, Chem. Lett. 1987, 285; g) P. A. Jacobi,
T. A. Craig, D. G. Walker, B. A. Arrick, R. F. Frechette, J. Am. Chem. Soc. 1984, 106, 5585; h) M. S.
Cooper, H. Heaney, A. J. Newbold, W. R. Sanderson, Synlett 1990, 533; i) P. A. Bentley, S. Bergeron, M.
W. Cappi, D. E. Hibbs, M. B. Hursthouse, T. C. Nugent, R. Pulido, S. M. Roberts, L. E. Wu, Chem. Com-
mun. 1997, 739; j) A. A. Devreese, M. Demuynck, P. J. De Clercq, M. Vandewalle, Tetrahedron 1983, 39,
3039; k) K. L. Reed, J. T. Gupton, T. L. Solarz, Synth. Commun. 1989, 19, 3579; l) W. Adam, L. Hadjiara-
poglou, B. Nestler, Tetrahedron Lett. 1990, 31, 331.
[23] K. E. Wilson, R. T. Seidner, S. Masamune, J. Chem. Soc., Chem. Commun. 1970, 213.
[24] E. Oblinger, J. Montgomery, J. Am. Chem. Soc. 1997, 119, 9065; T. Kitahara, K. Hamaguchi, Y. Warita, Y.
Takagi, K. Mori, Agric. Biol. Chem. 1986, 50, 1867.
[25] C. Maignan, F. Rouessac, Bull. Soc. Chim. Fr. 1976, 550.
[26] E. J. Corey, J. W. Suggs, Tetrahedron Lett. 1975, 2647.
[27] J. M. J. Fréchet, P. Darling, M. J. Farrall, J. Org. Chem. 1981, 46, 1728.
[28] E. J. Corey, G. Schmidt, Tetrahedron Lett. 1979, 399.
[29] R. W. Murray, R. Jeyaraman, J. Org. Chem. 1985, 50, 2847; C. Xiao-Ping, Tetrahedron 2002, 58, 1301.
[30] S. D. Rychnovsky, R. Vaidyanathan, J. Org. Chem. 1999, 64, 310.
[31] D. B. Dess, J. C. Martin, J. Org. Chem. 1983, 48, 4155.
[32] L. D’Accolti, C. Fusco, C. Annese, M. R. Rella, J. S. Turteltaub, P. W. Willard, R. Curci, J. Org. Chem. 2004,
69, 8510.
[33] G. Lardelli, V. Lamberti, W. T. Weller, A. P. De Jonge, Recl. Trav. Chim. Pays-Bas 1967, 86, 481.
[34] H. H. Wassermann, N. E. Aubrey, J. Org. Chem. 1955, 77, 590; C. N. O’Callaghan, W. N. Wassef, M. M. El
Barky, J. Chem. Res. (S) 1990, 402.

Helvetica Chimica Acta – Vol. 88 (2005)
3087
[35] G. A. Olah, Y. D. Vankar, M. Arvanaghi, Tetrahedron Lett. 1979, 3653; G. A. Olah, L. Ohannessian, M.
Arvanaghi, G. K. Surya Prakash, J. Org. Chem. 1984, 49, 2032; J. G. Lee, D. S. Ha, Tetrahedron Lett.
1989, 30, 193.
[36] a) J. W. De Leeuw, E. R. De Waard, T. Beetz, H. O. Huisman, Recl. Trav. Chim. Pays-Bas 1973, 92, 1047; b)
R. Sterzycki, Synthesis 1979, 724.
[37] U. Ravid, R. Ikan, J. Org. Chem. 1974, 39, 2637; U. Ravid, R. Ikan, R. M. Sachs, J. Agr. Food Chem. 1975,
23, 835.
[38] P. Dubs, R. Stüssi, Helv. Chim. Acta 1978, 61, 998; T. Shono, M. Okawa, I. Nishiguchi, J. Am. Chem. Soc.
1975, 97, 6144; T. Shono, N. Kise, T. Fujimoto, N. Tominaga, H. Morita, J. Org. Chem. 1992, 57, 7175; T.
Shono, N. Kise, Tetrahedron Lett. 1990, 31, 1303; K. Shishido, S. Kurozumi, K. Uchimoto, to Takasago
Ltd., JP7000862, 11.03.1967, (Chem. Abstr. 1970, 72, 78526g); P. Oberhaensli, to Givaudan SA,
DE2008878, 24.09.1970 (Chem. Abstr. 1970, 73, 109363d); K. Crawford, V. Rautenstrauch, A. Uijttewaal,
Synlett 2001, 7, 1127.
[39] To Naarden, NL7002279, 20.08.1971, (Chem. Abstr. 1972, 76, 3462g).
[40] A. S. Radhakrishna, S. K. Suri, K. R. K. Prasad Rao, K. Sivaprakash, B. Singh, Synth. Commun. 1990, 20,
345.
[41] F. Bouachir, B. Chaudret, F. Dahan, F. Agbossou, I. Tkatchenko, Organometallics 1991, 10, 455; D. Jacoby,
B. Neffah, C. Chapuis, to Firmenrich SA, WO 2005/061426, 07.07.2005 (Chem. Abstr. 2005, 143, 115303)
[42] C. Chapuis, H. Wüest, to Firmenich SA, WO 2004043895, 27.03.2004, (Chem. Abstr. 2004, 141, 6855j).
[43] M. A. Guaciaro, P. M. Wovkulich, A. B. Smith III, Tetrahedron Lett. 1978, 19, 4661; A. B. Smith III, N. N.
Pilla, Tetrahedron Lett. 1980, 21, 4691; K. Y. Lee, S. G. Sankar, J. N. Kim, N. Jae, Tetrahedron Lett. 2004, 45,
5485; B. A. Wexler, B. H. Toder, G. Minaskanian, A. B. Smith III, J. Org. Chem. 1982, 47, 3333.
[44] M. Bailey, I. Staton, P. R. Ashton, I. E. Marko, W. D. Ollis, Tetrahedron: Asym. 1991, 2, 495.
[45] Y. M. A. Yamada, S. Ikegami, Tetrahedron Lett. 2000, 41, 2165.
[46] K. Sasaki, Y. Aso, T. Otsubo, F. Ogura, Chem. Lett. 1989, 607.
[47] S. Katsuda, Y. Ueno, T. Toru, Bull Chem. Soc. Jpn. 1993, 66, 2720.
[48] a) S. Luo, P. G. Wang, J.-P. Cheng, J. Org. Chem. 2004, 69, 555; b) S. Luo, X. Mi, H. Xu, P. G. Wang, J.-P.
Cheng, J. Org. Chem. 2004, 69, 8413.
[49] A. Itoh, S. Ozawa, K. Oshima, H. Nazaki, Tetrahedron Lett. 1980, 361.
[50] M. R. Netherton, G. C. Fu, Org. Lett. 2001, 3, 4295.
[51] a) K. C. Nicolaou, T. Montagnon, P. S. Baran, Angew. Chem. 2002, 114, 1444; Angew. Chem., Int. Ed. 2002,
41, 1386; b) Y. Shvo, A. H. I. Arisha, J. Org. Chem. 1998, 63, 5640; c) T. T. Wenzel, J. Chem. Soc., Chem.
Commun. 1989, 932; d) J.-Q. Yu, H.-C. Wu, E. J. Corey, Org. Lett. 2005, 7, 1415; e) M. Korach, D. R. Niel-
sen, W. H. Rideout, Org. Synth. Coll. Vol. V 1973, 414.
[52] S. Luo, B. Zhang, J. He, A. Janczuk, P. G. Wang, J.-W. Cheng, Tetrahedron Lett. 2002, 43, 7369; R. Gatri, M.
Moncef El Gaïed, Tetrahedron Lett. 2002, 43, 7835.
[53] S. Z. Luo, X. L. Mi, P. G. Wang, J. P. Cheng, Tetrahedron Lett. 2004, 45, 5171
[54] C. Yu, B. Liu, L. Hu, J. Org. Chem. 2001, 66, 5413.
[55] J.-C. Hsu, Y.-H. Yen, Y.-H. Chu, Tetrahedron Lett. 2004, 45, 4673; X. Mi, S. Luo, J.-P. Cheng, J. Org. Chem.
2005, 70, 2338.
[56] K. Y. Lee, S. Gowrisankar, J. N. Kim, Tetrahedron Lett. 2004, 45, 5485.
[57] J. You, J. Xu, J. G. Verkade, Angew. Chem. 2003, 115, 5208; Angew. Chem., Int. Ed. 2003, 42, 5054.
[58] M. R. Netherton, G. C. Fu, Org. Lett. 2001, 3, 4295.
[59] D. Basavaiah, P. D. Rao, R. S. Hyma, Tetrahedron 1996, 52, 8001; E. Ciganek, ‘The Morita–Baylis–Hillman
Reaction’, in ‘Organic Reaction’, Vol. 51, Ed. L. A. Paquette, J. Wiley, New York, 1997, p. 201; P. Langer,
Angew. Chem. 2000, 112, 3177; Angew. Chem., Int. Ed. 2000, 39, 3049; D. Basavaiah, A. J. Rao, T. Satya-
narayana, Chem. Rev. 2003, 103, 811.
[60] V. K. Aggarwal, S. Y. Fulford, G. C. Lloyd-Jones, Angew. Chem. 2005, 117, 1734; Angew. Chem., Int. Ed.
2005, 44, 2; K. E. Price, S. J. Broadwater, H. M. Jung, D. T. Mc Quade, Org. Lett. 2005, 7, 147; V. K. Aggar-
wal, I. Emme, S. Y. Fulford, J. Org. Chem. 2003, 68, 692.
[61] H. Tanaka, S. Torii, J. Org. Chem. 1975, 40, 462; T. Kitahara, M. Iwamoto, Y. Takagi, K. Mori, M. Matsui,
Agric. Biol. Chem. 1984, 1731.
[62] T. Ainai, M. Matsuumi, Y. Kobayashi, J. Org. Chem. 2003, 68, 7825.
[63] C. D. Hurd, J. L. Abernethy, J. Am. Chem. Soc. 1941, 63, 1966; T. G. Clarke, N. A. Hampson, J. B. Lee, J. R.
Morley, B. Scanlon, Can. J. Chem. 1969, 47, 1649; J. J. Havel, K. H. Chan, J. Org. Chem. 1976, 41, 513; J. L.
Ward, P. Gaskin, M. H. Beale, R. Sessions, Y. Koda, C. Wasternack, Tetrahedron 1997, 53, 8181.

3088
Helvetica Chimica Acta – Vol. 88 (2005)
[64] O. Miersch, G. Sembdner, K. Schreiber, Phytochemistry 1989, 28, 339.
[65] H. Matsuura, F. Ohmori, M. Kobayashi, A. Sakurai, T. Yoshihara, Biosci. Biotechnol. Biochem. 2000, 64,
2380; O. Miersch, Z. Naturforsch. B 1991, 46, 1727.
[66] B. Schaub, Ph. D. Thesis, University of Basel, 5 March 1985, p. 115.
[67] H. Kiyota, S.-Y. Takigawa, S. Kuwahara, Helv. Chim. Acta 2004, 87, 1854.
[68] Q. Wang, M. El Khoury, M. Schlosser, Chem.–Eur. J. 2000, 6, 420.
[69] H. Schulz, H. Wagner, Angew. Chem. 1950, 62, 105; S. J. Kim, T. Takizawa, J. Chem. Soc., Chem. Commun.
1974, 356; S. Juric, O. Kronja, J. Phys. Org. Chem. 2002, 15, 556.
[70] E. Bosone, P. Farina, G. Guazzi, S. Innocenti, V. Marotta, Synthesis 1983, 11, 942; M. Kolb, L. van Hijfte, R.
E. Ireland, Tetrahedron Lett. 1988, 29, 6769.
[71] K. Yamada, T. Arai, H. Sasai, M. Shibasaki, J. Org. Chem. 1998, 63, 3666.
[72] a) F. Roth, P. Gygax, G. Fràter, Tetrahedron Lett. 1992, 33, 1045; b) G. H. P. Roos, R. J. Haines, C. E. Raab,
Synth. Commun. 1993, 23, 1251; c) T. Oishi, H. Oguri, M. Hirama, Tetrahedron: Asymmetry 1995, 6, 1241;
d) I. E. Markò, P. R. Giles, N. J. Hindley, Tetrahedron 1997, 53, 1015; e) A. G. M. Barrett, A. S. Cook, A.
Kamimura, Chem. Commun. 1998, 2533; f) T. Hayase, T. Shibata, K. Soai, Y. Wakatsuki, Chem. Commun.
1998, 1271; g) V. K. Aggarwal, A. Mereu, G. J. Tarver, R. J. Mc Cague, J. Org. Chem. 1998, 63, 7183; h) Y.
Iwabuchi, M. Nakatani, N. Yokoyama, S. Hatakeyama, J. Am. Chem. Soc. 1999, 121, 10219; i) Y. Iwabuchi,
M. Furukawa, T. Esumi, S. Hatakeyama, Chem. Commun. 2001, 2030; j) Y. Iwabuchi, M. Furukawa, T.
Esumi, S. Hatakeyama, Tetrahedron Lett. 2001, 42, 7867; k) L. M. Walsh, C. L. Winn, J. M. Goodman, Tet-
rahedron Lett. 2002, 43, 8219; l) M. Shi, J.-K. Jiang, Tetrahedron: Asymmetry 2002, 13, 1941; m) M. Shi, J.-
K. Jiang, C.-Q. Li, Tetrahedron Lett. 2002, 43, 127; n) M. Shi, Y.-M. Xu, Angew. Chem. 2002, 114, 4689;
Angew. Chem., Int. Ed. 2002, 41, 4507; o) S. Kawahara, A. Nakano, T. Esumi, Y. Iwabuchi, S. Hatakeyama,
Org. Lett. 2003, 5, 3103; p) D. Balan, H. Adolfsson, Tetrahedron Lett. 2003, 44, 2521; q) J. E. Imbriglio, M.
M. Vasbinder, S. J. Miller, Org. Lett. 2003, 5, 3741; r) K.-S. Yang, W.-D. Lee, J.-F. Pan, K. Chen, J. Org.
Chem. 2003, 68, 915; s) C. M. Mocquet, S. L. Warriner, Synlett 2004, 356; t) P. Radha Krishna, V. Kannan,
P. V. Narasimha Reddy, Adv. Synth. Catal. 2004, 346, 603; u) H. Yujiro, T. Tomohiro, S. Mitsuru, Adv. Synth.
Catal. 2004, 346, 1106; v) Y. Sohtome, A. Tanatani, Y. Hashimoto, K. Nagasawa, Tetrahedron Lett. 2004, 45,
5589; w) B. Pegot, G. Vo-Thanh, D. Gori, A. Loupy, Tetrahedron Lett. 2004, 45, 6425; x) K. Matsui, S. Taki-
zawa, H. Sasai, Tetrahedron Lett. 2005, 46, 1943; y) M. Shi, Y.-M. Xu, Y.-L. Shi, Chem.–Eur. J. 2005, 11,
1794; z) M. Shi, C.-Q. Li, Tetrahedron: Asymmetry 2005, 16, 1385; aa) K. Matsui, S. Takizawa, H. Sasai,
J. Am. Chem. Soc. 2005, 127, 3680; bb) M. Shi, L.-H. Chen, C.-Q. Li, J. Am. Chem. Soc. 2005, 127, 3790.
[73] D. S. Lingenfelter, R. C. Helgeson, D. J. Cram, J. Org. Chem. 1981, 46, 393.
[74] C. Chapuis, D. Jacoby, Appl. Catal. 2001, 221, 93.
[75] C.-C. Pai, Y.-M. Li, Z.-Y. Zhou, A. S. Chan, Tetrahedron Lett. 2002, 43, 2789; S. Duprat de Paule, S. Jeulin,
V. Ratovelomanana-Vidal, J.-P. Genêt, N. Champion, P. Dellis, Eur. J. Org. Chem. 2003, 10, 1991.
[76] S. Duprat de Paule, S. Jeulin, V. Ratovelomanana-Vidal, J.-P. Genêt, N. Champion, P. Dellis, Tetrahedron
Lett. 2003, 44, 823.
[77] a) Y. Chen, S. Yekta, A. K. Yudin, Chem. Rev. 2003, 103, 3155; b) J.-M. Brunel, Chem. Rev. 2005, 105, 857;
c) T. Takada, M. Arisawa, M. Gyoten, R. Hamada, H. Tohma, Y. Kita, J. Org. Chem. 1998, 63, 7698.
[78] N. T. Mc Dougal, S. E. Schaus, J. Am. Chem. Soc. 2003, 125, 12094.
[79] C. Fehr, J. Galindo, O. Etter, Eur. J. Org. Chem. 2004, 1953; C. Fehr, J. Galindo, I. Farris, A. Cuenca, Helv.
Chim. Acta 2004, 87, 1737.
[80] R. E. Ireland, R. H. Mueller, A. K. Willard, J. Am. Chem. Soc. 1976, 98, 2868; R. E. Ireland, P. Wipf, J. D.
Armstrong, J. Org. Chem. 1991, 56, 650; S. Pereira, M. Srebnik, Aldrichim. Acta 1993, 26, 17.
[81] C. Chapuis, M. Barthe, J.-Y de Saint Laumer, Helv. Chim. Acta 2001, 84, 230.
Received August 18, 2005