Modification of Terpenoid Derivatives with Ruthenium Catalysts Generated in situ

Article abstract of DOI:10.1002/1099-0690(200211)2002:22<3816::AID-EJOC3816>3.0.CO;2-6

Terpenoids derivatives containing geminal ethynyl and allyloxy groups are easily prepared from the corresponding ketones and aldehydes. The catalytic system generated in situ from [RuCl2(p-cymene)]2, 1,3-bis(mesityl)imidazolinium chloride and cesium carbonate is able to transform these substrates into a new class of terpenoids via cycloisomerisation of the enyne structure.

Full text of DOI:10.1002/1099-0690(200211)2002:22<3816::AID-EJOC3816>3.0.CO;2-6

FULL PAPER
Modification of Terpenoid Derivatives with Ruthenium Catalysts
Generated in situ
[a]
[a]
[a]
´ ˆ
ˆ
Jerome Le Notre, Christian Bruneau,* and Pierre H. Dixneuf
Keywords: Homogeneous catalysis / Rearrangement / Ruthenium / Terpenoids
Terpenoids derivatives containing geminal ethynyl and al-
strates into a new class of terpenoids via cycloisomerisation
lyloxy groups are easily prepared from the corresponding ke- of the enyne structure.
tones and aldehydes. The catalytic system generated in situ
from [RuCl2(p-cymene)]2,
1,3-bis(mesityl)imidazolinium
( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
chloride and cesium carbonate is able to transform these sub-
2002)
Introduction
The selective formation of carbonϪcarbon bonds with
concomitant construction of a conjugated diene system by
enyne cycloisomerization represents a powerful tool in syn-
thetic organic chemistry.[1Ϫ3] This catalytic reaction is
mostly performed with alkene metathesis ruthenium cata-
lysts,[4] and constitutes a key step for the synthesis or modi-
fication of natural products such as amino acids,[5a,5b] al-
kaloids,[5c,5d] steroids,[5e,5f] peptides[5g] and carbohyd-
rates.[5h] On the other hand, terpenes and terpenoids repres-
ent a large class of natural compounds with noticeable and
distinctive organoleptic properties.[6] Their simple chemical
modification offers the possibility of producing unpreced-
ented flavours or fragrances. Natural terpenoids have al-
ready been modified through organic transformations to
produce insecticides,[7] and through metal-mediated reac-
tions such as hydrogenation, isomerisation, oxidation, hy-
dride reduction or hydroformylation.[8] The ring closing
metathesis reaction has been used to form modified ter-
penoids from dienes,[9] but to the best of our knowledge no
example of transformation by intramolecular enyne cyclo-
isomerisation has been reported. However, after simple ad-
dition of C5 units to terpenoids, the intramolecular enyne
rearrangement catalysed by metathesis catalysts has the po-
tential to generate a new class of nonnatural terpenoids.
We now wish to report that terpenoids bearing a carbonyl
functionality can easily be transformed with addition of a
C5 fragment into spiro compounds containing both a dihy-
drofuran ring and a diene moiety by enyne rearrangement
in the presence of a simple three component ruthenium
catalytic system generated in situ (Scheme 1).
Scheme 1. Retrosynthetic strategy
Results and Discussion
We have recently shown the efficiency of [RuCl(ϭCϭCϭ
CPh2)(p-cymene)(PCy3)][PF6] to catalyse the skeleton re-
arrangement of allyl propargyl ethers into vinyldihydrofur-
ans.[3] The use of the triflate salt, which was found to be a
[a]
´
Institut de Chimie, UMR 6509, Organometalliques et Catalyse,
´
Universite de Rennes 1
Campus de Beaulieu, 35042 Rennes Cedex, France
Fax: (internat.) ϩ33Ϫ0223236939
E-mail: christian.bruneau@univ-rennes1.fr
Scheme 2. Preparation of allyl propargyl ethers 1bϪ5b
3816
 2002 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/02/1122Ϫ3816 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2002, 3816Ϫ3820

Modification of Terpenoid Derivatives with Ruthenium Catalysts
FULL PAPER
more active catalyst than the hexafluorophosphate salt for (Scheme 3) to give the corresponding spirocycles 1c, 2c, 3c
olefin metathesis,[10] made the metathesis of terpenoid en- or 4c, which were isolated in 66, 66, 54 and 71% yield, re-
yne derivatives, possible. The preparation of the starting en- spectively. Under similar conditions, the conversion of the
ynes derived from terpenoids was carried out in two steps enyne 5b derived from the more bulky (Ϫ)-myrtenal (5) was
from ketones or aldehydes by addition of lithium acetylide very slow, but the use of the catalyst arising from
followed by allylation with allyl bromide (Scheme 2). Most 2.5 mmol % of [RuCl2(p-cymene)]2 allowed a conversion of
of the intermediate propargylic alcohols 1aϪ5a were al- 84% after 21 h at 80 °C and the corresponding cyclic com-
ready known and prepared according to similar proced- pound 5c was isolated with 46% yield.
ures.[11] This two step transformation provided an efficient
method to produce the new enynes 1b, 2b, 3b, 4b and 5b
Conclusion
arising from (Ϫ)-menthone (1), (Ϫ)-carvone (2), (ϩ)-pule-
gone (3), citral (cis ϩ trans) (4) and (Ϫ)-myrtenal (5) isol-
ated in 85, 87, 65, 64, and 65% overall yields, respectively.
The propargylic alcohols 1aϪ5a were obtained as a mix-
ture of stereoisomers in the ratios 1:2 (1a and 3a), or 1:1
The catalyst, easily prepared from a ruthenium source
and a bulky heterocarbene ligand makes possible the pre-
paration of modified terpenoids containing additional spiro-
cyclic structure including a conjugated diene arrangement
suitable for further cycloaddition reactions.[12Ϫ14] The facile
introduction of five carbon atoms to terpene ketones and
aldehydes by successive addition of the ethynyl (C2) and
allyl group (C3) leads to new propargylic enynes, and then
after rearrangement by catalytic cycloisomerisation to a
new class of higher terpenoids (from monoterpenoids to
sesquiterpenoids). As the stereoselectivity of the formation
of terpenoid derivatives bearing a propargylic alcohol
functionality can be controlled by the addition of alkynyl-
cerate,[15] the formation of spirocycles in enantiomerically
enriched forms can be envisaged.
1
(2a, 4a, and 5a), as detected from the H NMR signal of
the ethynyl proton. Consequently, the corresponding allyl
ethers and cyclized compounds were obtained as mixtures
of stereoisomers. The citral derivatives 4a, 4b, 4c were ob-
tained as a 1:1 mixture of the cis and trans isomers, identical
to the initial ratio in the starting citral (GC-MS detection).
A complete conversion of the enynes 1b, 2b and 4b into
1c, 2c and 4c was obtained after heating in toluene at 80
°C for 24 h in the presence of 2.5 mol % of [RuCl(ϭCϭCϭ
CPh2)(p-cymene)(PCy3)][OTf], after an initial activation of
the precatalyst by irradiation with a UV lamp (λ ϭ 300 nm)
for 30 min.[3]
Recent studies have shown that new catalytic systems
generated in situ from a source of ruthenium, a precursor
of diaminocarbene and a base, were more efficient for enyne
metathesis than the well-defined allenylidene catalyst pre-
cursors.[12,13] Indeed, a much more active catalytic system
was generated by mixing [RuCl2(p-cymene)]2, 1,3-bis(mesi-
tyl)imidazolinium chloride and cesium carbonate in the
molar ratio 1:2:4.[13] In toluene at 80 °C in the presence of
a catalytic system containing 0.5 mol % of the ruthenium
complex, the complete transformation of 0.5 mmol of the
enynes 1b, 2b, 3b or 4b was achieved within 1, 2, 2 and 1 h
Experimental Section
General Remarks: All experiments were carried out in Schlenk
tubes under an inert atmosphere of nitrogen. The solvents were
dried and distilled prior to use. 1H and 13C NMR were recorded
with a Bruker AC 200 MHz spectrometer and GC-MS were per-
formed with a CE Instrument GC 8000 Top (capillary column
OV1, 25 m ϫ 0.35 mm, 0.1Ϫ0.15 µm) chromatograph linked to a
Automass II Finnigan MAT (70 eV) apparatus.
General Procedure for the Preparation of Allyl Propargyl Ethers
1bϪ5b: Acetylene (3Ϫ5 equiv.) was dissolved in tetrahydrofuran
(2 mL per mmol of ketone) at Ϫ78 °C and n-butyllithium (1.6  in
n-hexane, 1.2 equiv.) was added dropwise. After 30 min at Ϫ78 °C,
the ketone 1؊3 or the aldehyde 4,5 was slowly added to the
acetylide suspension and the reaction was stirred at Ϫ78 °C for 1 h
and then allowed to warm up at room temperature. After quench-
ing with 1  HCl and extraction, the corresponding propargylic
alcohol was isolated in good yield after flash chromatography over
silica gel. Subsequent treatment with NaH (1.2 equiv.) at 0 °C in
dimethylformamide for 30 min and addition of 1.3 equivalent of
allyl bromide afforded the enynes 1bϪ5b after flash column chro-
matography on silica gel.
1-Allyloxy-1-ethynyl-2-isopropyl-5-methylcyclohexane (1b): (Ϫ)-
Menthone (1, 2.6 g, 17.1 mmol) was treated as described in the gen-
eral procedure to give, after column chromatography on silica gel
(eluent: heptane/diethyl ether, 50:1), the enyne 1b in 85% yield
(3.2 g, 14.5 mmol) as a colourless oil. 1H NMR (200 MHz, CDCl3):
3
3
δ ϭ 0.83 (d, J ϭ 6.6 Hz, 3 H, CH3), 0.92 and 0.93 [2 d, J ϭ 7.0
Hz, 6 H, CH(CH3)2], 1.04Ϫ1.18 [m, 1 H, CH2CH(CH3)], 1.25Ϫ1.80
(m, 6 H, 3 ϫ CH2), 2.13Ϫ2.24 [m, 1 H, CHCH(CH3)2], 2.43 (s, 1
H, CϵCH), 2.40 [hept ϫ d, 3J ϭ 6.9, 3JЈ ϭ 1.8 Hz, 1 H,
Scheme 3. Enyne cycloisomerisation
Eur. J. Org. Chem. 2002, 3816Ϫ3820
3817

ˆ
J. Le Notre, C. Bruneau, P. H. Dixneuf
FULL PAPER
CHCH(CH3)2], 3.82Ϫ4.20 (m, 2 H, OCH2CHϭCH2), 5.09 (dm,
CH2], 5.77Ϫ5.99 (m, 1 H, OCH2CHϭCH2) ppm. 13C NMR
3J ϭ 10.4 Hz, cis 1 H, OCH2CHϭCH2), 5.30 (dm, J ϭ 18.3 Hz, (50 MHz, CDCl3): δ ϭ 16.6/17.5 [CHϭC(CH3)CH2], 23.2 (cis
trans 1 H, OCH2CHϭCH2), 5.81Ϫ6.01 (m, 1 H, OCH2CHϭCH2) CH3), 25.5 (trans CH3), 26.0/26.3 (CϭCHCH2), 32.4/39.2 (Cϭ
ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 18.6 (2 ϫ CH3), 20.3 CHCH2CH2), 64.5/64.7 [CH(OR)(CϵCH)], 68.6/68.8 (OCH2CHϭ
[(CH3)2CHCHCH2CH2], 21.9 [CH2CH2CH(CH3)], 23.9 [CH2CH2- CH2), 73.2 (CϵCH), 82.3/82.4 (CϵCH), 117.55 (OCH2CHϭCH2),
CH(CH3)], 28.5 [(CH3)2CHCHCH2CH2], 34.9 [CH2CH2CH- 122.0/122.85 [CH(OR)CHϭC(CH3], 123.4/123.6 [(CH3)2Cϭ
(CH3)], 44.3 [CH2C(OR)], 51.4 [(CH3)2CHCHCH2CH2], 64.1 CHCH2], 131.6/132.0 [CHϭC(CH3)2], 134.1/134.2 (OCH2CHϭ
(OCH2), 73.3 [C(OR)(CϵCH)], 76.8 [C(OR)(CϵCH)], 85.9 CH2), 140.9/141.0 [CHϭC(CH3)CH2] ppm. MS (EI): m/z (%) ϭ
3
[C(OR)(CϵCH)], 114.9 (OCH2CHϭCH2), 135.6 (OCH2CHϭ
218 (Ͻ1) [Mϩ], 144 (66), 116 (19), 90 (36), 68 (45), 53 (14), 41 (100).
CH2) ppm. MS (EI): m/z (%) ϭ 220 (Ͻ1) [Mϩ], 135 (49), 107 (19), C15H22O (218.3): calcd. C 82.52, H 10.16; found C 82.58, H 10.16.
95 (22), 79 (26), 69 (78), 55 (42), 40 (100).
2-(1-Allyloxyprop-2-ynyl)-6,6-dimethylbicyclo[3.1.1]hept-2-ene (5b):
6-Allyloxy-6-ethynyl-4-isopropenyl-1-methylcyclohex-1-ene
(2b):
(Ϫ)-Myrtenal (5, 2.0 g, 13.5 mmol) was treated as described in the
general procedure to give, after column chromatography on silica
gel (eluent: heptane/diethyl ether, 40:1), the enyne 5b in 65% yield
(1.9 g, 8.8 mmol) as a colourless oil. 1H NMR (200 MHz, CDCl3):
δ ϭ 0.80 (s, 3 H, CH3), 1.11Ϫ1.16 [m, 1 H, C(CH3)2CH(CH2)CH2],
1.25 (s, 3 H, CH3), 2.00Ϫ2.17 [m, 1 H, C(CH3)2CH(CH2)CϭCH],
2.21Ϫ2.44 (m, 5 H, CϵCH, CH2, CH2), 3.87Ϫ4.09 (m, 2 H,
(Ϫ)-Carvone (2, 2.7 g, 18.1 mmol) was treated as described in the
general procedure to give, after column chromatography on silica
gel (eluent: heptane/diethyl ether, 40:1), the enyne 2b in 87% yield
(3.4 g, 15.7 mmol) as a colourless oil. 1H NMR (200 MHz, CDCl3):
δ ϭ 1.69Ϫ1.74 [m, 3 H, CHϭC(CH3)], 1.77Ϫ1.84 [m, 3 H, H2Cϭ
C(CH3)], 1.86Ϫ2.35 [m, 4 H, CH2CH(C(CH3)ϭCH2)CH2C(O-al-
lyl)], 2.50 (s, 1 H, CϵCH), 2.35Ϫ2.62 [m, 1 H, CHC(CH3)ϭCH2],
OCH2CHϭCH2), 4.42Ϫ4.47 [m,
1 H, CH(O-allyl)(CϵCH)],
3.92Ϫ4.25 (m,
2 H, OCH2CHϭCH2), 4.68Ϫ4.80 [m, 2 H,
5.07Ϫ5.29 (m, 2 H, OCH2CHϭCH2), 5.57Ϫ5.71 (m, 1 H, Cϭ
CHCH2), 5.75Ϫ5.95 (m, 1 H, OCH2CHϭCH2) ppm. 13C NMR
(50 MHz, CDCl3): δ ϭ 20.8/21.0 (CH3), 25.9 (CH3), 31.2/31.4
(CH2), 37.7/37.9 [C(CH3)2], 40.6/41.2 [HCϭCCH[C(CH3)2](CH2)],
42.0/42.2 [CH2CH[C(CH3)2](CH2)], 42.6/42.7 (CH2), 68.4/68.5
(CϵCH), 70.7/71.1 (OCH2), 74.0/74.3 [CH(OR)(CϵCH)], 80.6/
80.8 (CϵCH), 117.0/117.2 (OCH2CHϭCH2), 121.3/121.8 (Cϭ
CHCH2), 134.2 (OCH2CHϭCH2), 144.2/144.4 (CϭCH) ppm. MS
(EI): m/z (%) ϭ 216 (Ͻ1) [Mϩ], 143 (12), 128 (29), 115 (100), 105
(20), 91 (35), 77 (27), 67 (22), 53 (19), 40 (34). C15H20O (216.3):
calcd. C 83.28, H 9.32; found C 82.93, H 9.24.
3
C(CH3)ϭCH2], 5.10 (dm, J ϭ 10.3 Hz, cis 1 H, OCH2CHϭCH2),
5.27 (dm, 3J ϭ 17.2 Hz, trans 1 H, OCH2CHϭCH2), 5.50Ϫ5.65
[m, 1 H, CH2CHϭC(CH3)], 5.82Ϫ6.03 (m, 1 H, OCH2CHϭCH2)
ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 17.5 [CHϭC(CH3)], 20.6
[H2CϭC(CH3)], 30.7 (CϭCHCH2CH), 39.2 [CHC(CH3)ϭCH2],
39.6 [CHCH2C(OH)], 64.5 (OCH2), 73.7 [C(OH)(CϵCH)], 74.9
(CϵCH), 84.4 (CϵCH), 109.2 [H2CϭC(CH3)], 115.82
(OCH2CHϭCH2), 125.5 [CH2CHϭC(CH3)], 135.11 (OCH2CHϭ
CH2), 135.2 [CHϭC(CH3)], 148.3 [H2CϭC(CH3)] ppm. MS (EI):
m/z (%) ϭ 216 (Ͻ1) [Mϩ], 158 (36); 143 (34), 129 (33), 117 (81),
105 (46), 91 (67), 77 (89), 65 (29), 53 (47), 41 (100). C15H20O
(216.3): calcd. C 83.28, H 9.32; found C 83.08, H 9.52.
General Procedure for the Preparation of Cyclic Compounds 1cϪ5c:
[RuCl2(p-cymene)]2 (0.5 to 1.25 mmol %), 1,3-bis(mesityl)imidazol-
inium chloride and cesium carbonate (molar ratio: 1/2/4) were dis-
solved in toluene (5 mL per mmol of enyne) and the mixture was
stirred for 5 min at room temperature. The enyne (1bϪ5b) was ad-
ded to the orange-red solution and the mixture was stirred at 80
°C until GC-MS analysis indicated the complete conversion to the
cyclic product. The solvent was then removed and the residue was
dissolved in heptane, filtered and evaporated to dryness. For reac-
tion times and purification, see below.
1-Allyloxy-1-ethynyl-2-isopropylidene-5-methylcyclohexane
(3b):
(ϩ)-Pulegone (3, 1.4 g, 9.2 mmol) was treated as described in the
general procedure to give, after column chromatography on silica
gel (eluent: heptane/diethyl ether, 40:1), the enyne 3b in 65% yield
1
(1.3 g, 6 mmol) as a colourless oil. H NMR (200 MHz, CDCl3):
δ ϭ 1.54 (s, 3 H, CH3), 1.62Ϫ1.65 [m, 6 H, CϭC(CH3)2], 1.71Ϫ1.73
[m,
1 H, CH2CH(CH3)], 1.96Ϫ2.11 [m, 4 H, CH2CH2Cϭ
C(CH3)2, C(OH)CH2CH(CH3)], 2.38Ϫ2.40 (m, 1 H, CϵCH),
3.90Ϫ4.12 (m, 2 H, OCH2CHϭCH2), 4.73 (dd, 3J ϭ 8.5, 2J ϭ
2.1 Hz, cis 1 H, OCH2CHϭCH2), 4.99Ϫ5.10 [m, 1 H, CH2CH2Cϭ
C(CH3)2], 5.16 (dm, 3J ϭ 16.9 Hz, trans 1 H, OCH2CHϭCH2),
5.24Ϫ5.30 [m, 1 H, CH2CH2CϭC(CH3)2], 5.75Ϫ5.96 (m, 1 H,
OCH2CHϭCH2) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 16.5/17.5
6-Isopropyl-9-methyl-4-vinyl-1-oxaspiro[4.5]dec-3-ene (1c): Starting
from the enyne 1b (150 mg, 0.7 mmol) and by using 0.5 mol % of
the ruthenium dimer, the total conversion was observed after 1 h
and after a bulb-to-bulb distillation, 1c (100 mg, 0.5 mmol, 66%)
was obtained as a colourless oil. 1H NMR (200 MHz, CDCl3): δ ϭ
0.70Ϫ0.90 (m, 9 H, 3 ϫ CH3), 1.01Ϫ1.09 [m, 1 H, CH2CH(CH3)],
1.16Ϫ1.89 [m, 8 H, 3 ϫ CH2, CHCH(CH3)2, CHCH(CH3)2],
(2
C(CH3)2],
[CH2CH2CH(CH3)CH2],
ϫ CH3), 23.1 (CH3), 25.5 (CHCH3), 26.0/26.2 [CH2Cϭ
32.3
[CH2CH2CH(CH3)CH2],
64.5/64.7 (CϵCH),
39.1
68.5/68.6
3
4.48Ϫ4.56 (m, 2 H, OCH2CHϭC), 5.08 (d, J ϭ 11.2 Hz, cis 1 H,
(OCH2CHϭCH2), 73.1 (C quat.), 82.2/82.3 (CϵCH), 117.4
(OCH2CHϭCH2), 131.5/131.8 [CϭC(CH3)2], 134.1/134.2
(OCH2CHϭCH2), 140.7/140.8 [CϭC(CH3)2] ppm. MS (EI): m/z
(%) ϭ 218 (Ͻ1) [Mϩ], 145 (34), 91 (59), 77 (29), 69 (100), 55 (27),
39 (29).
CHϭCH2), 5.40 (d, 3J ϭ 17.0 Hz, trans 1 H, CHϭCH2), 5.82 (m, 1
H, CHϭCH2), 6.04Ϫ6.20 (m, 1 H, OCH2CHϭC) ppm. 13C NMR
(50 MHz, CDCl3):
δ ϭ 18.1 (2 ϫ CH3), 21.4 [(CH3)2-
CHCHCH2CH2], 22.4 [CH2CH2CH(CH3)], 23.5 [CH2CH2CH-
(CH3)], 27.0 [(CH3)2CHCHCH2CH2], 35.2 [CH2CH2CH(CH3)],
45.6 [CH2C(OR)], 47.3 [(CH3)2CHCHCH2CH2], 72.1 (OCH2), 93.0
(C spiro), 115.6 (CHϭCH2), 123.51 (OCH2CHϭC), 129.3 (CHϭ
CH2), 143.7 [CHϭC(CHϭCH2)] ppm. MS (EI): m/z (%) ϭ 220
(33) [Mϩ], 135 (100), 91 (15), 79 (28), 69 (18), 55 (29), 41 (35).
3-Allyloxy-5,9-dimethyldeca-4,8-dien-1-yne (4b): Citral (4, 2.6 g,
17.2 mmol) was treated as described in the general procedure to
give, after column chromatography on silica gel (eluent: heptane/
diethyl ether, 50:1), the enyne 4b in 64% yield (2.4 g, 11 mmol) as
1
a colourless oil. H NMR (200 MHz, CDCl3): δ ϭ 1.52Ϫ1.75 (m,
9 H, 3 ϫ CH3), 1.93Ϫ2.17 (m, 4 H, 2 ϫ CH2), 2.41/2.42 (2 ϫ d,
9-Isopropenyl-6-methyl-4-vinyl-1-oxaspiro[4.5]deca-3,6-diene (2c):
4J ϭ 2.1 Hz, 1 H, CϵCH), 3.89Ϫ4.18 (m, 2 H, OCH2CHϭCH2), Starting from the enyne 2b (100 mg, 0.46 mmol) and by using 0.5
4.75 [dd, 3J ϭ 8.5, 4J ϭ 2.1 Hz, 1 H, CH(OR)(CϵCH)], 4.96Ϫ5.34
[m, 4 H, CHϭC(CH3)2, CH(OH)CHϭC(CH3)CH2, OCH2CHϭ
mol % of the ruthenium dimer, the total conversion was observed
after 2 h and after a bulb-to-bulb distillation, 2c (66 mg, 0.3 mmol,
3818
Eur. J. Org. Chem. 2002, 3816Ϫ3820

Modification of Terpenoid Derivatives with Ruthenium Catalysts
66%) was obtained as a colourless oil. 1H NMR (200 MHz,
FULL PAPER
2.23Ϫ2.50 (m, 4 H, 2 ϫ CH2), 4.56Ϫ4.62 (m, 2 H, OCH2CHϭ
CDCl3): δ ϭ 1.56 [s, 3 H, CHϭC(CH3)], 1.67 [s, 3 H, H2Cϭ CCHϭCH2), 4.76Ϫ4.97 (m, 1 H, CHOCH2), 5.01Ϫ5.36 (m, 2 H,
C(CH3)], 1.75Ϫ2.12 [m, 4 H, CH2CH[C(CH3)ϭCH2)CH2C(O- OCH2CHϭCCHϭCH2), 5.50Ϫ5.66 (m, 1 H, CHCϭCHCH2),
ring)], 2.39Ϫ2.57 [m, 1 H, CHC(CH3)ϭCH2], 4.59Ϫ4.72 [m, 4 H, 5.85Ϫ5.98 (m, 1 H, OCH2CHϭCCHϭCH2), 6.21Ϫ6.42 [m, 1 H,
3
OCH2, C(CH3)ϭCH2], 5.06 (d, J ϭ 11.0 Hz, cis 1 H, OCH2CHϭ
CH2CHϭC(vinyl)] ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 20.9/
21.2 (CH3), 25.8/26.0 (CH3), 31.3/31.5 (CH2), 37.5 [C(CH3)2], 40.3/
3
CCHϭCH2), 5.44 (d, J ϭ 17.6 Hz, trans 1 H, OCH2CHϭCCHϭ
CH2), 5.57Ϫ5.68 [m, 1 H, CH2CHϭC(CH3)], 5.87 (m, 1 H, 40.6 [HCϭCCH[C(CH3)2](CH2)], 42.2 [CH2CH[C(CH3)2](CH2)],
OCH2CHϭCCHϭCH2), 6.06Ϫ6.25 [m, 1 H, CH2CHϭC(vinyl)] 42.8/43.0 (CH2), 71.4 (OCH2), 85.5 [CH(OR)], 114.5 (CHϭCH2),
ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 17.2 [CHϭC(CH3)], 20.6 117.7 (CϭCHCH2), 122.1 (OCH2CHϭC), 132.5 (CHϭCH2), 136.8
[H2CϭC(CH3)], 30.1 (CϭCHCH2CH), 39.1 [CHC(CH3)ϭCH2], [CHϭC(vinyl)], 145.7 (CϭCHCH2CH) ppm. MS (EI): m/z (%) ϭ
40.7 (CHCH2Cspira), 73.2 (OCH2), 90.1 (C spira), 109.0 [H2Cϭ
C(CH3)], 116.1 (CHϭCH2), 123.1 [OCH2CHϭC(vinyl)], 125.6 (100). C15H20O (216.3): calcd. C 83.28, H 9.32; found C 82.99,
215 (3) [Mϩ Ϫ H], 172 (20), 154 (14), 128 (11), 67 (42), 53 (22), 41
[CH2CHϭC(CH3)], 129.4 (CHϭCH2), 135.4 [CHϭC(CH3)], 143.6
[C(vinyl)], 148.5 [H2CϭC(CH3)] ppm. MS (EI): m/z (%) ϭ 216 (9)
[Mϩ], 201 (15), 198 (14), 148 (30), 133 (100), 119 (29), 105 (58), 91
(75), 81 (16), 77 (68), 65 (49), 53 (45), 39 (72). C15H20O (216.3):
calcd. C 83.28, H 9.32; found C 83.39, H 9.35.
H 9.41.
Acknowledgments
The authors are grateful to the Region Bretagne for a grant to JLN
´
6-Isopropylidene-9-methyl-4-vinyl-1-oxaspiro[4.5]dec-3-ene
(3c):
and to the European COST Programme (D12/0025/99).
Starting from the enyne 3b (250 mg, 1.1 mmol) and by using 0.5
mol % of ruthenium dimer, the total conversion was observed after
2 h and after a bulb-to-bulb distillation, 3c (135 mg, 0.6 mmol,
54%) was obtained as a colourless oil. 1H NMR (200 MHz,
CDCl3): δ ϭ 1.47Ϫ1.52 (m, 3 H, CH3), 1.59Ϫ1.67 [m, 6 H, Cϭ
C(CH3)2], 1.75Ϫ1.79 [m, 1 H, CH2CH(CH3)], 1.99Ϫ2.20 [m, 4 H,
CH2CH2CϭC(CH3)2, C(O-ring)CH2CH(CH3)], 4.34Ϫ4.49 (m, 2
[1]
M. Mori, Top. Organomet. Chem. 1998, 1, 133Ϫ154.
[2] [2a]
A. Fürstner, F. Stelzer, H. Szillat, J. Am. Chem. Soc. 2001,
123, 11863Ϫ11869. [2b] A. Fürstner, H. Szillat, F. Stelzer, J. Am.
[2c]
Chem. Soc. 2000, 122, 6785Ϫ6786.
N. Chatani, N. Furu-
kawa, H. Sakurai, S. Murai, Organometallics 1996, 15,
3
H, OCH2CHϭC), 5.00 (d, J ϭ 10.9 Hz, cis 1 H, CHϭCH2), 5.35
[2d]
901Ϫ903.
N. Chatani, T. Morimoto, T. Muto, S. Murai, J.
3
(d, J ϭ 16.8 Hz, trans 1 H, CHϭCH2), 5.79Ϫ5.88 (m, 1 H, CHϭ
Am. Chem. Soc. 1994, 116, 6049Ϫ6050.
M. Picquet, C. Bruneau, P. H. Dixneuf, Chem. Commun.
1998, 2249Ϫ2250.
CH2), 5.99Ϫ6.15 (m, 1 H, OCH2CHϭC) ppm. 13C NMR (50 MHz,
CDCl3): δ ϭ 16.0/16.2 (2 ϫ CH3), 20.7 (CH3), 25.4 (CHCH3), 25.9/
26.0 [CH2CϭC(CH3)2], 34.1 [CH2CH2CH(CH3)CH2], 38.8
[CH2CH2CH(CH3)CH2], 69.8 (OCH2), 92.0 (C spira), 114.7 (CHϭ
CH2), 121.9 (OCH2CHϭC), 130.1 (CHϭCH2), 132.5 [Cϭ
C(CH3)2], 140.2 [CϭC(CH3)2], 143.7 [CHϭC(CHϭCH2)] ppm.
MS (EI): m/z (%) ϭ 218 (41) [Mϩ], 203 (100), 175 (16), 147 (21),
133 (23), 119 (31), 105 (51), 91 (71), 79 (50), 67 (36), 55 (42), 41
(72).
[3]
[4] [4a]
S.-H. Kim, N. Bowden, R. H. Grubbs, J. Am. Chem. Soc.
1994, 116, 10801Ϫ10802. [4b] A. G. M. Barrett, S. P. D. Baugh,
D. C. Braddock, K. Flack, V. C. Gibson, P. A. Procopiou,
[4c]
Chem. Commun. 1997, 1375Ϫ1376.
R. Stragies, M. Schus-
ter, S. Blechert, Angew. Chem. Int. Ed. Engl. 1997, 36,
[4d]
2518Ϫ2520.
M. Mori, T. Kitamura, Y. Sato, Synthesis
2001, 654Ϫ664.
[5] [5a]
´
ˆ
D. Semeril, J. Le Notre, C. Bruneau, P. H. Dixneuf, A. F.
Kolomiets, S. N. Osipov, New J. Chem. 2001, 25, 16Ϫ18. [5b] S.
Kotha, N. Sreenivasachary, E. Brachmachary, Tetrahedron
2-(2,6-Dimethylhepta-1,5-dienyl)-3-vinyl-2,5-dihydrofuran
(4c):
Starting from the enyne 4b (100 mg, 0.46 mmol) and by using 0.5
mol % of ruthenium dimer, the total conversion was observed after
1 h and after a bulb-to-bulb distillation, 4c (71 mg, 0.3 mmol, 71%)
was obtained as a colourless oil. 1H NMR (200 MHz, CDCl3): δ ϭ
1.61Ϫ1.80 (m, 9 H, 3 ϫ CH3), 1.99Ϫ2.18 (m, 4 H, CH2CH2),
2.80Ϫ3.04 (m, 2 H, OCH2CHϭC), 4.79Ϫ4.91 (m, 1 H, cis CHϭ
CH2), 5.05Ϫ5.21 [m, 3 H, trans CHϭCH2, (CH3)CϭCHCH(O-
ring)], 5.22Ϫ5.66 [m, 2 H, (CH3)2CϭCH, CHϭCH2], 6.63Ϫ6.75
(m, 1 H, OCH2CHϭC) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ
17.7 [CHϭC(CH3)CH2], 19.3 (cis CH3), 22.2 (trans CH3), 25.7 (Cϭ
CHCH2), 39.7 (CϭCHCH2CH2), 63.6 (OCH2), 77.9 [CH(O-ring)],
115.7 (CHϭCH2), 117.9 [(CH3)CϭCHCH(O-cycle)], 121.4 (CHϭ
CH2), 122.3 [(CH3)2CϭCHCH2], 124.0 (OCH2CHϭC), 135.1
[CHϭC(CH3)2], 135.9 [CHϭC(CH3)CH2], 148.2 [CHϭC(CHϭ
CH2)] ppm. MS (EI): m/z (%) ϭ 218 (21) [Mϩ], 205 (14), 137 (17),
95 (21), 81 (32), 69 (100), 55 (35), 41 (93). C15H22O (218.3): calcd.
C 82.52, H 10.16; found C 82.17, H 10.24.
[5c]
Lett. 1998, 39, 2805Ϫ2808.
J. S. Clark, R. J. Townsend,
A. J. Blake, S. J. Teat, A. Johns, Tetrahedron Lett. 2001, 42,
[5d]
3235Ϫ3238.
A. Kinoshita, M. Mori, J. Org. Chem. 1996,
61, 8356Ϫ8357. [5e] M. Rosillo, L. Casarrubios, G. Dominguez,
[5f]
J. Perez-Castells, Tetrahedron Lett. 2001, 42, 7029Ϫ7031.
B.
M. Trost, G. A. Doherty, J. Am. Chem. Soc. 2000, 122,
3801Ϫ3810. [5g] K. Undheim, J. Efskind, Tetrahedron 2000, 56,
[5h]
4847Ϫ4857.
M. A. Leeuwenburgh, C. Kulker, H. I.
Duynstee, H. S. Overkleeft, G. van der Marel, J. H. van Boom,
Tetrahedron 1999, 55, 8253Ϫ8262.
S. Dev, A. P. S. Narula, J. S. Yadav, in CRC Handbook of Ter-
penoids; (Ed.: S. Dev); CRC: Boca Raton, 1982, vol. 1, pp.
7Ϫ27.
[6]
[7]
[8]
R. Tsao, J. R. Coats, Chemtech 1995, 7, 23Ϫ28.
[8a] A. V. Malkov, P. Kocovsky, Collect. Czech, Chem. Commun.
[8b]
2001, 66, 1257Ϫ1267.
C. Chapuis, D. Jacoby, Appl. Catal.
[8c]
A: General 2001, 221, 93Ϫ117.
M. Ihara, Tetrahedron Lett. 2000, 41, 8929Ϫ8932.
erno, M. P. Gamasa, J. Gimeno, J. Organomet. Chem. 2001,
M. Toyota, M. Rudyanto,
[8d]
V. Cadi-
[8e]
621, 39Ϫ46.
G. Lenoble, M. Urrutigo¨ıty, P. Kalck, J. Or-
2-(6,6-Dimethylbicyclo[3.1.1]hept-2-en-2-yl)-3-vinyl-2,5-dihydro-
furan (5c): Starting from the enyne 5b (300 mg, 1.4 mmol) and by
using 1.25 mol % of the ruthenium dimer, 84% of conversion was
observed after 21 h and after flash column chromatography (eluent:
heptane/diethyl ether, 40:1), 5c (138 mg, 0.6 mmol, 46%) was ob-
ganomet. Chem. 2002, 643Ϫ644, 12Ϫ18.
[9]
[9a] V. P. Kamat, H. Hagiwara, T. Katsumi, T. Hoshi, T. Suzuki,
[9b]
M. Ando, Tetrahedron 2000, 56, 4397Ϫ4403.
Y. Du, D. F.
Wiemer, Tetrahedron Lett. 2001, 42, 6069Ϫ6072. [9c] D. C. Har-
rowven, M. C. Lucas, P. D. Howes, Tetrahedron 2001, 57,
1
[9d]
tained as a colourless oil. H NMR (200 MHz, CDCl3): δ ϭ 0.84
9157Ϫ9162.
G. Mehta, J. Nandakumar, Tetrahedron Lett.
2002, 43, 699Ϫ702. [9e] A. Srikrishna, M. Srinivasa Rao, Synlett
2002, 340Ϫ342.
(s, 3 H, CH3), 1.02Ϫ1.12 [m, 1 H, C(CH3)2CH(CH2)CH2], 1.27 (s,
3
H, CH3), 1.97Ϫ2.19 [m,
1 H, C(CH3)2CH(CH2)CϭCH],
Eur. J. Org. Chem. 2002, 3816Ϫ3820
3819

ˆ
J. Le Notre, C. Bruneau, P. H. Dixneuf
FULL PAPER
[10]
[14] [14a]
M. Picquet, D. Touchard, C. Bruneau, P. H. Dixneuf, New J.
S. Blechert, Pure Appl. Chem. 1999, 71, 1393Ϫ1399. [14b]
Chem. 1999, 141Ϫ143.
M. Mori, N. Sakakibara, A. Kinoshita, J. Org. Chem. 1998,
[11] [11a]
M. Perry, Y. Maroni-Barnaud, Bull. Soc. Chim. Fr. 1969,
63, 6082Ϫ6083. [14c] S. Kotha, N. Sreenivasachary, Chem. Com-
[11b]
[14d]
´
R. Duboc, C. Henaut, M. Savignac,
J. P. Genet, N. Bhatnagar, Tetrahedron Lett. 2001, 42,
3574Ϫ3580.
J. Philippe, M.-L. Capmau, W. Chodkiewicz,
mun. 2000, 503Ϫ504.
[11c]
Bull. Soc. Chim. Fr. 1971, 2248Ϫ2255.
K. Suga, S. Watan-
abe, T. Suzuki, Can. J. Chem. 1968, 3041Ϫ3045.
L. Ackermann, C. Bruneau, P. H. Dixneuf, Synlett 2001,
397Ϫ399.
D. Semeril, M. Cleran, C. Bruneau, P. H. Dixneuf, Adv. Synth.
Catal. 2001, 343, 184Ϫ187.
2461Ϫ2464.
[12]
[13]
[15]
`
C. Spins, C. Beaulieu, J. Lafreniere, J. Org. Chem. 2000, 65,
7091Ϫ7097.
´
´
Received May 16, 2002
[O02258]
3820
Eur. J. Org. Chem. 2002, 3816Ϫ3820