Part 2: Efficient strategies for the construction of variably substituted bicyclo[5.3.1]undecenones (AB-taxane ring systems) and their conversion to tricyclo[9.3.1.03,8]pentadecenones (ABC taxane ring systems) and bicyclo[2.2.2]octanones

Article abstract of DOI:10.1139/v03-201

The extension of our strategies for the construction of cyclic molecules containing variably substituted bicyclo[5.3.1]undecenones (AB taxane ring systems) for the synthesis of the tricyclo[9.3.1.0^3,8]pentadecenone (ABC taxane ring system) and bicyclo[2.2.2]octanones are described. These routes employ a multi-component coupling protocol that employs sequential magnesium-mediated carbometallation of allyl-substituted propargyl alcohols followed by diastereoselective Lewis acid catalyzed intramolecular Diels-Alder reactions (TMDA). Subsequent ring-closing metathesis (RCM) afforded the ABC taxane core structure. Enone accelerated [3,3] sigmatropic rearrangements (Cope rearrangements) generated the bicyclo[2.2.2]octanone nucleus. In the presence of a Lewis acid, the dienophile precursor underwent a tandem reaction via the adduct directly to the bicyclo[2.2.2]octanones. This is the first example of a novel enone accelerated carbocycle Cope rearrangement and provides direct access to bicyclo[2.2.2]octanones by a new route that compliments the traditional cyclohexadiene cycloaddition approach.

Full text of DOI:10.1139/v03-201

2
27
Part 2: Efficient strategies for the construction of
variably substituted bicyclo[5.3.1]undecenones
(
AB-taxane ring systems) and their conversion to
3,8
tricyclo[9.3.1.0 ]pentadecenones (ABC taxane
ring systems) and bicyclo[2.2.2]octanones
1
Nidia P. Villalva-Servín, Alain Laurent, and Alex G. Fallis
Abstract: The extension of our strategies for the construction of cyclic molecules containing variably substituted
3
,8
bicyclo[5.3.1]undecenones (AB taxane ring systems) for the synthesis of the tricyclo[9.3.1.0 ]pentadecenone (ABC
taxane ring system) and bicyclo[2.2.2]octanones are described. These routes employ a multi-component coupling proto-
col that employs sequential magnesium-mediated carbometallation of allyl-substituted propargyl alcohols followed by
diastereoselective Lewis acid catalyzed intramolecular Diels–Alder reactions (IMDA). Subsequent ring-closing metathe-
sis (RCM) afforded the ABC taxane core structure. Enone accelerated [3,3] sigmatropic rearrangements (Cope rear-
rangements) generated the bicyclo[2.2.2]octanone nucleus. In the presence of a Lewis acid, the dienophile precursor
underwent a tandem reaction via the adduct directly to the bicyclo[2.2.2]octanones. This is the first example of a novel
enone accelerated carbocycle Cope rearrangement and provides direct access to bicyclo[2.2.2]octanones by a new route
that compliments the traditional cyclohexadiene cycloaddition approach.
Key words: magnesium chelate, Lewis acid, taxanes, Diels–Alder, sigmatropic rearrangement, oxy-Cope, ring-closing
metathesis, bicyclo[2.2.2]octanone.
Résumé : On décrit une extension de nos stratégies développées pour la construction de molécules cycliques contenant
3,8
des bicyclo[5.3.1]undécénones (noyaux AB du taxane) portant divers substituants à la synthèse d’un tricyclo[9.3.1.0 ]penta-
décénone (noyaux ABC du taxane) et de bicyclo[2.2.2]octanones. Ces voies impliquent un protocole de couplage à plu-
sieurs composants qui fait appel à des réactions séquentielles de carbométallation catalysée par le magnésium d’alcools
propargyliques portant un substituant allyle et de réactions diastéréosélectives de Diels–Alder intramoléculaires cataly-
sées par un acide de Lewis. La réaction subséquente de métathèse de fermeture de cycle conduit au noyau fondamental
ABC du taxane. Des réarrangements sigmatropiques [3,3] accélérés de l’énone (réarrangements de Cope) génèrent le
noyau bicyclo[2.2.2]octanone. En présence d’un acide de Lewis, le précurseur diénophile donne lieu à une réaction en
tandem, par le biais de l’adduit, qui conduit directement à la bicyclo[2.2.2]octanone. Cette réaction correspond au pre-
mier exemple d’un nouveau réarrangement de carbocycle de Cope accéléré par une énone et elle permet d’accéder di-
rectement aux bicyclo[2.2.2]octanones par une nouvelle voie qui est un complément à l’approche traditionnelle des
cycloadditions au cyclohexadiène.
Mots clés : chélate magnésien, acide de Lewis, taxanes, Diels–Alder, réarrangement sigmatropique, oxy-Cope, méta-
thèse avec cyclisation, bicyclo[2.2.2]octanone.
[
Traduit par la Rédaction] Villalva-Servín et al. 239
Introduction
docetaxel). It outlines briefly their utility as cancer chemo-
therapeutic agents and the synthetic challenge they present
to organic chemists. We also described our approach to the
synthesis of key AB taxane building blocks possessing the
The preceding paper provides a brief introduction to the
importance of Taxol (1, paclitaxel) and Taxotere (2,
®
®
Received 25 June 2003. Published on the NRC Research Press Web site at http://canjchem.nrc.ca on 28 January 2004.
This paper is dedicated to Professor Edward Piers on the occasion of his 65th birthday. Presented with respect and gratitude for
his contributions to organic chemistry and to our friendship.
2
3
N.P. Villalva-Servin, A. Laurent, and A.G. Fallis. Centre for Research in Biopharmaceuticals, Department of Chemistry,
University of Ottawa, 10 Marie Curie, Ottawa, ON K1N 6N5, Canada.
1
This article is part of a Special Issue dedicated to Professor Ed Piers.
Present address: Aegera Therapeutics, Inc., 810, chemin du Golf, Nun’s Island, QC H3E 1A8, Canada.
Corresponding author (e-mail: afallis@science.uottawa.ca).
2
3
Can. J. Chem. 82: 227–239 (2004)
doi: 10.1139/V03-201
© 2004 NRC Canada

2
28
Can. J. Chem. Vol. 82, 2004
bicyclo[5.3.1]undecenone skeleton. These investigations have
been expanded to a synthesis of the carbocyclic ABC taxane
core via a carbometallation–cycloaddition-ring-closing me-
tathesis strategy. In addition, the Diels–Alder dienophile
precursors may be converted in a tandem reaction to
bicyclo[2.2.2]octanones (Fig. 1).
Fig. 1. Current taxoid drugs.
Carbometallation – intramolecular
cycloaddition strategy
We have described our magnesium-mediated carbo-
metallation of propargyl alcohols followed by diastereose-
lective Lewis acid catalyzed intramolecular Diels–Alder
reactions for the preparation of bicyclo[5.3.1]undecenones
for the preparation of densely substituted bicyclooctenones
5. The reverse transformation from an oxy-Cope
1
(
AB-taxane ring systems), as illustrated in Scheme 1. Unfor-
tunately, as discussed in the preceding paper, the proposed
4 + 2] combinations with the family represented by 9 or 11
bicyclo[2.2.2]octene precursor was employed in previous
approaches to the taxane AB ring system (5). The ease of
the rearrangement in 9a is a consequence of the excellent
alignment of the reactive diene units in a pre-organized
chair-like conformation that mimics the required transition
state. Our published X-ray analysis of 9a (1) revealed that
the C3—C8 separation is 3.13 Å, a separation less than the
[
failed to give the desired adduct(s) 10.
Cope rearrangements towards ring C
taxanes and bicyclo[2.2.2]octanones
3
.2–3.3 Å c-d separation required for enediynes to undergo
Clearly, a new approach was required to extend and build
on this knowledge and capitalize on our ring assembly pro-
tocol. An efficient method was required to attach the C ring
and assemble the complete ABC taxane nucleus. Two addi-
tional options appeared attractive, but both required repeat-
ing the synthesis from the beginning. Our initial plan was to
prepare 14 from 9d, as illustrated in Scheme 2. Based on
previous studies, we have established that nucleophilic at-
tack at the C2 carbonyl occurred from the underside of 9a.
Thus, it was anticipated that an anion-based [3,3] sigma-
tropic rearrangement would deliver the allyl group from the
concave side of the molecule and thus establish, after
protonation, the correct trans ring stereochemistry of the
taxane natural products. Addition of allyl Grignard to 9d
should generate the bis-allyl secondary alcohol 12. A subse-
quent oxy-Cope rearrangement could then be employed to
install the allyl functionality in 13 for ring-closing metathe-
sis to the tricyclic skeleton 14 (Scheme 2). However, this se-
quence had an inherent risk, owing to the very reactive
nature of the ring A and ring B olefins. This complication
affected our plans but also provided an unexpected, syntheti-
cally useful transformation, discovered earlier (1) and sum-
marized below.
spontaneous cycloaromatization at room temperature (6, 7).
However, an additional, beneficial influence from the car-
bonyl group is also implicated. Reduction of the carbonyl in
9a to provide alcohol 11 (Scheme 1) and subsequent protec-
tion as the p-methoxybenzyl ether produced compound 16,
which was stable to prolonged reflux (20 h) in toluene, and
none of 17 was observed (Scheme 3). Additional evidence
for the importance of the conjugated carbonyl and its elec-
tronic influence was illustrated by the ease with which the
tandem rearrangement 8 to 9 to 15 occurred at 0–22 °C in
the presence of a catalytic amount of Lewis acid (Et AlCl,
2
70%–92%).
For subsequent synthetic applications this tandem conver-
sion provides an attractive entry to highly functionalized
bicyclo[2.2.2]octanones, which will complement the tradi-
tional route from cycloaddition of cyclohexadienes. These
substitution patterns are difficult to achieve by traditional
routes (for example, sorbiquinol, Fig. 2, (8)). This accelerat-
ing influence exerted by a conjugated carbonyl group in a
carbocyclic [3,3] sigmatropic rearrangement does not appear
to have been observed prior to our discovery. We are cur-
rently investigating the potential and generality of this inter-
esting transformation.
The existence of atropisomerism in taxane ring systems is
well established (2, 3). Variable temperature H NMR was
Based on the data above, it seemed reasonable to conclude
that the anionic oxy-Cope rearrangement of a potassium salt
should proceed at approximately 40–50 °C (9), and thus, the
carbocyclic [3,3] rearrangement would not be competitive,
as a consequence of the higher energy required. The adduct
9d was synthesized in a parallel fashion to examine the va-
lidity of this assumption, as outlined in Scheme 4. Allylation
of the ketone 9d provided the allyl alcohol 13. However, at
room temperature the potassium salt derived from treatment
with potassium tert-butoxide did not rearrange to the desired
bis-allyl ketone 18 (Scheme 5) but followed a different path-
way. Instead, the loss of the allyl substituent followed by
double bond migration to 19 was observed. The use of po-
tassium hydride provided no improvement and generated the
isomeric ketone 20. The failure of these mild conditions
prompted a single experiment under more forcing conditions
1
investigated to determine the conformational bias in the
bicyclo[5.3.1]undecene type synthon 9a. It was anticipated
that the details of the carbonyl-exo and carbonyl-endo con-
formers could be examined for their synthetic potential and
stereochemical bias. However, rather than the conformation-
al isomerization expected, the enone 9a underwent a facile
Cope rearrangement (commencing at ~60 °C), to give the
bicyclo[2.2.2]octanone product 15a (Scheme 3). Experi-
mentally, this [3,3]-sigmatropic rearrangement afforded the
same bicyclic ketone 15a directly in 71% yield after 3 h in
refluxing toluene (Scheme 3). The temperature required
(
110 °C) to effect this transformation is significantly lower
than most carbocyclic rearrangements of this type (4). Con-
sequently, this rearrangement provides an attractive method
©
2004 NRC Canada

Villalva-Servín et al.
229
Scheme 1.
Scheme 2.
Scheme 3.
©
2004 NRC Canada

2
30
Can. J. Chem. Vol. 82, 2004
Scheme 4. Reagents and conditions: (a) (i) CH =CHCH MgCl, cyclohexane–THF, room temperature (rt) to 70 °C, 18 h; (ii) 6, –78 °C
2
2
to rt, 3 h, 40%; (b) TBDMSCl, DMAP, CH Cl , rt, 18 h, 81%; (c) NaH, MeI, THF, rt, 18 h, 89%; (d) TBAF, THF, rt, 2 h, 93%;
2
2
(
e) IBX, DMSO–THF, 0 °C to rt, 3 h, 86%; (f) CH =CHMgCl, Et O, –78 to 0 °C, 2 h, 50%; (g) IBX, DMSO–THF, 0 °C to rt, 3 h,
2 2
8
6%; (h) Et AlCl, CH Cl , –78 to 0 °C, 2 h, 70% or BF ·(OEt) , CH Cl , –78 to 10 °C, 2 h, 68%.
2
2
2
3
2
2
2
Fig. 2. Sorbiquinol.
silylation failed and thus eliminated the possibility of direct
palladium coupling from an advanced intermediate.
Consequently the strategy was modified (Scheme 6) to
commence with an allyl-substituted propargyl alcohol 3c fol-
lowed by exposure to an allyl Grignard reagent for conver-
sion to 8f. Cycloaddition would generate the bicyclic ketone
9
f for conversion to the tricyclic compound 24. The prepara-
tion of the desired Diels–Alder adduct 9f and the precursor
compounds is outlined in Scheme 4.
There appear to be two reports in which RCM approaches
have been employed for the assembly of taxane AB (10) and
BC (11) ring systems. However, the route in Scheme 6 for
the construction of taxane ABC ring systems has not been
explored. With the synthesis of the bicyclo[5.3.1]undecene
in which treatment of 13 with 1,8-diazobiocyclo[5.4.0]undec-7-
ene (DBU) under microwave irradiation also failed to pro-
duce the desired ring C precursor but gave instead the mix-
ture of bicyclo[2.2.2]octenes 21 (7%), 22 (16%), and 23
9
f completed it was anticipated that generation of the requi-
site cyclohexadiene 24 could be easily achieved. Indeed,
treatment of 9f with the second generation Grubbs’ catalyst
(
19%).
3
0 ((4,5-dihydroIMES)(PCy )Cl Ru=CHPh) (12) gave rise
3 2
3
,8
Ring-closing metathesis (RCM) for ring C
to the desired tricyclo[9.3.1.0 ]pentadecane nucleus 24 in
high yield (93%) (Scheme 7).
Despite the failure of the previous approach, the idea of
installing the C ring by ring-closing metathesis was attrac-
tive. This variation for ring C is represented by the transfor-
mation 9f to 24 in Scheme 6. One option was the
introduction of a C3 allyl group by modification of the vinyl
silyl group present in 9e (Scheme 4). However, bromode-
Experimental section
See preceding paper for general experimental details (13).
©
2004 NRC Canada

Villalva-Servín et al.
231
Scheme 5. Reagents and conditions: (a) CH =CHCH MgCl, Et O, –78 to 0 °C, 1 h, 59%; (b) . KOtBu, DMF, 40 °C, 3 h, 51%;
2
2
2
(
c) KH, 18-crown-6, THF, rt, 1 h, 69%; (d) DBU, toluene, microwave, 220 °C, 1 h, 21 6%, 22 9%, 23 19%.
Scheme 6.
Scheme 7. Reagents and conditions: (a) 30, CH Cl , 21 °C, 2 h, 93%.
2
2
©
2004 NRC Canada

2
32
Can. J. Chem. Vol. 82, 2004
1
3
-Trimethylsilanyl-prop-2-yn-1-ol (3b)
1635, 1010, 996, 902. H NMR (C D , 300 MHz) δ: 1.67 (s,
6
6
Butyl lithium (189 mL, 434 mmol, 2.3 mol L–1 in hexane)
3H), 1.74 (s, 3H), 1.75 (s, 3H), 1.77 (s, 3H), 2.25 (dd, J =
13.9, 5.6 Hz, 1H), 2.6 (dd, J = 13.9, 8.1 Hz, 1H), 2.95 (d,
J = 6.2 Hz, 2H), 3.00 (s, br, 2H), 3.93 (d, J = 11.6 Hz, 1H),
4.31 (d, J = 11.6 Hz, 1H), 4.69 (dd, J = 2.6, 0.8 Hz, 1H),
4.83 (dd, J = 8.1, 5.7 Hz, 1H), 4.99 (dd, J = 10.0, 2.0 Hz,
1H), 5.00 (d, 1H), 5.05 (dd, J = 17.1, 2.0 Hz, 1H), 5.78
(dddd, J = 16.9, 10.2, 6.4, 6.4 Hz, 1H). C NMR (C D ,
75 MHz) δ: 13.0, 20.3, 22.1, 22.6, 36.3, 37.2, 60.8, 69.6,
114.3, 115.2, 128.9, 132.5, 133.6, 136.1, 137.3, 146.7. HR-
was added to a solution of propargyl alcohol (11.0 mL,
1
4
89 mmol) in THF (300 mL) cooled to –78 °C. After
5 min, chlorotrimethylsilane (57.6 mL, 453 mmol) was added,
and the solution was warmed to 21 °C for 3 h. After cooling
to 0 °C, 10% aqueous sulfuric acid (250 mL) was added, and
the layers were separated after 15 min, and the aqueous
layer was extracted with ether (2 × 150 mL). The combined
organic extracts were washed with brine (2 × 100 mL), dried
1
3
6
6
+
(
MgSO ), filtered, and concentrated under reduced pressure.
MS (EI) m/z calcd. for C H O ([M – H O]): 232.1827;
4
16 24
2
Purification by flash chromatography (silica gel, ether – pe-
troleum ether) provided the title compound as a colorless oil
found: 232.1829.
–
1
(
15.1 g, 62%). IR (neat) (cm ) ν: 3324, 2961, 2901, 2177.
2-Allyl-6-isopropenyl-7-methyl-3-trimethylsilanyl-octa-
2,6-diene-1,4-diol (7e)
1
H NMR (CDCl , 300 MHz) δ: 0.15 (s, 9H), 1.8 (s, 1H),
3
1
3
–
1
4
1
1
.24 (s, 2H). C NMR (CDCl , 75 MHz) δ: 0.13, 51.9, 91.0,
3
43% from 3b. IR (neat) (cm ) ν: 3386, 3077, 2962–2852,
+
1
04.2. HR-MS (EI) m/z calcd. for C H OSi ([M] ):
6
12
1442, 1250, 1088–996, 838. H NMR (C D , 500 MHz) δ:
6
6
28.0657; found: 128.0686.
0
.31 (s, 9H), 1.66 (s, 3H), 1.69 (s, 3H), 1.73 (s, 3H), 2.10 (d,
J = 14.2 Hz, 1H), 2.31 (s, br, 1H), 2.76 (dd, J = 14.2,
10.4 Hz, 2H), 3.04–3.14 (m, 2H), 4.14 (d, J = 11.8 Hz, 1H),
4.30 (d, J = 11.8 Hz, 1H), 4.65 (dd, J = 1.8, 0.7 Hz, 1H),
4.74 (dd, J = 10.4, 3.1 Hz, 1H), 4.98 (dd, J = 2.4, 1.4 Hz,
1H), 5.03 (ddd, J = 10.1, 3.0, 1.5 Hz, 1H), 5.08 (ddd, J =
17.1, 3.5, 1.7 Hz, 1H), 5.80 (dddd, J = 16.9, 10.4, 6.3,
3
-Allyl-prop-2-yn-1-ol (3c) (14)
Propargyl alcohol (5.8 mL, 0.10 mol) was added to a
stirred solution of acetone (400 mL), followed by allyl bro-
mide (10.4 mL, 0.120 mol), potassium carbonate (27.6 g,
0
.200 mol), sodium iodide (30 g, 0.20 mol), and copper io-
1
3
dide (19.0 g, 0.100 mol). The reaction was stirred under ni-
trogen at 21 °C for 5 h, quenched with 1 N HCl (120 mL),
diluted with water (500 mL), and stirred for 10 min. The re-
action mixture was subsequently filtered and extracted with
diethyl ether (5 × 100 mL). The combined organic extracts
6.3 Hz, 1H). C NMR (C6D6, 125 MHz) δ: 2.2, 20.3, 22.0,
22.6, 39.0, 40.1, 61.7, 72.1, 114.2, 116.6, 129.2, 133.9,
137.1, 142.3, 146.7, 149.0. HR-MS (EI) m/z calcd. for
+
C18H30OSi ([M – H2O]): 290.2066; found: 290.2012.
were dried (MgSO ), filtered, and concentrated under re-
2,3-Diallyl-6-isopropenyl-7-methyl-octa-2,6-diene-1,4-diol
(7f)
4
duced pressure. The title compound was isolated as a colour-
less oil and purified by distillation (80–82 °C at 3 mmHg
–
1
64% from 3c. IR (neat) (cm ) ν: 3303, 2955–2872, 1637,
–
1
1
(
1 mmHg = 133.322 Pa), 92%). IR (neat) (cm ) ν: 3351,
1448, 1060, 993, 890. H NMR (C D , 300 MHz) δ: 1.70 (s,
6
6
1
3
3
2
086–2983, 2918–2872, 1420, 918, 780. H NMR (C D ,
00 MHz) δ: 2.33 (s, 1H), 2.94–2.98 (m, 2H), 4.24 (t, J =
.2 Hz, 2H), 5.07 (ddd, J = 10.0, 3.3, 1.6 Hz, 1H), 5.27
3H), 1.71 (s, 3H), 1.77 (d, 3H), 2.13 (d, br, J = 14.2 Hz,
2H), 2.18 (s, br, 1H), 2.62 (dd, J = 14.1, 10.2 Hz, 1H), 2.81
(dd, J = 15.6, 6.5 Hz, 1H), 2.88–2.96 (m, 3H), 4.03 (d, J =
11.8 Hz, 1H), 4.16 (d, J = 11.8 Hz, 1H), 4.54 (dd, J = 10.1,
3.5 Hz, 1H), 4.61 (t, br, 1H), 4.98–5.02 (m, 4H), 5.06 (dd,
6
6
(
6
8
ddd, J = 17.0, 3.5, 1.7 Hz, 1H), 5.80 (dddd, J = 16.6, 10.6,
1
3
.0, 5.6 Hz, 1H). C NMR (C D , 75 MHz) δ: 23.2, 51.1,
6 6
1
3
1.9, 82.3, 116.1, 132.8. HR-MS (EI) m/z calcd. for C H O
J = 5.1, 1.7 Hz, 1H), 5.70–5.87 (m, 2H). C NMR (C D ,
6
8
6 6
+
(
[M] ): 96.05752; found: 96.05597.
75 MHz) δ: 20.6, 22.4, 22.9, 33.5, 36.4, 37.7, 61.4, 71.1,
14.7, 115.7, 116.1, 130.3, 133.3, 135.4, 136.3, 137.3,
1
+
General procedure for the carbometallation of the
propargylic alcohols
138.2, 146.4. HR-MS (EI) m/z calcd. for C16H26O ([M –
H2O]): 258.1984; found: 258.1978.
Vinyl- or allylmagnesium chloride (2.5 equiv.) was added
to a solution of the propargylic alcohol (1.0 equiv.) in cyclo-
General procedure for silylation of the primary
alcohols
tert-Butyldimethylsilyl chloride (1.1 equiv.) and DMAP
(1.1 equiv.) were sequentially added to a solution of the diol
(1.0 equiv.) in dichloromethane ([diol] = 1.0 mol L ) at
0 °C, and the solution was stirred for 18 h at 21 °C. A satu-
–
1
hexane ([alcohol] = 1.0 mol L ) at 21 °C. The solution was
heated at reflux for 20 h and cooled to –78 °C, and 4-
methyl-3-vinyl-pent-3-enal 6 (0.5 equiv.) in ether ([alde-
–
1
–1
hyde] = 0.3 mol L ) was added. The solution was stirred for
0 min at –78 °C, for 1 h at 0 °C, and for 1 h at 21 °C. The
3
reaction was subsequently cooled to 0 °C, and a saturated
rated aqueous solution of NaHCO was then added; the lay-
3
aqueous solution of NH Cl added. The layers were sepa-
ers were separated, and the aqueous layer was extracted with
ether. The combined organic extracts were washed with
4
rated, and the aqueous layer was extracted with dichloro-
methane. The combined organic extracts were washed with
brine, dried (MgSO ), filtered, and concentrated under re-
4
brine, dried (MgSO ), filtered, and concentrated under re-
duced pressure. The crude material was purified by flash
chromatography (silica gel, ether – petroleum ether).
4
duced pressure. The crude material was purified by flash
chromatography (silica gel, ether – petroleum ether).
7
-(tert-Butyl-dimethyl-silanyloxymethyl)-3-
2
(
-Allyl-6-isopropenyl-3,7-dimethyl-octa-2,6-diene-1,4-diol
7d)
9% from 3a. IR (neat) (cm ) ν: 3361, 3076, 2976, 2915,
isopropylidene-2,6-dimethyl-deca-1,6,9-trien-5-ol (25d)
–
1
94% from 7d. IR (neat) (cm ) ν: 3370, 3076, 2857, 1636,
–
1
1
7
1255, 1070, 837, 776. H NMR (CDCl , 500 MHz) δ: 0.03
3
©
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Villalva-Servín et al.
233
1
(
s, 6H), 0.87 (s, 9H), 1.70 (s, 3H), 1.71 (s, 3H), 1.73 (s, br,
1255, 1100–1051, 837, 775. H NMR (CDCl , 500 MHz) δ:
3
1
1
6
1
4
1
1
1
1
H), 1.73 (s, 3H), 1.78 (s, 3H), 2.04 (dd, J = 14.0, 4.0 Hz,
H), 2.59 (dd, J = 14.0, 9.6 Hz, 1H), 2.87 (dd, J = 14.4,
.4 Hz, 2H), 4.02 (d, J = 11.4 Hz, 1H), 4.17 (d, J = 11.5 Hz,
H), 4.61 (dd, J = 2.0, 0.8 Hz, 1H), 4.70 (dd, J = 9.6,
.1 Hz, 1H), 4.95 (dd, J = 10.2, 1.6 Hz, 1H), 4.97 (dd, J =
7.4, 1.9 Hz, 1H), 4.96–4.99 (m, 1H), 5.73 (dddd, J = 17.2,
0.02 (s, 6H), 0.87 (s, 9H), 1.61 (s, 3H), 1.65 (s, 3H), 1.66 (s,
3H), 1.7 (s, 3H), 2.08 (dd, J = 14.3, 5.6 Hz, 1H), 2.52 (dd,
J = 14.2, 7.8 Hz, 1H), 2.90 (d, br, 2H), 2.97 (s, 3H), 3.91 (d,
J = 11.4 Hz, 1H), 4.17 (dd, J = 7.8, 5.7 Hz, 1H), 4.23 (d, J =
11.4 Hz, 1H), 4.56 (d, J = 2.7 Hz, 1H), 4.94 (dd, J = 16.9,
1.5 Hz, 1H), 4.95–4.96 (m, 1H), 4.97 (dd, J = 10.1, 1.7 Hz,
0.0, 6.5, 6.4 Hz, 1H). 13C NMR (CDCl , 125 MHz) δ: –5.4,
1H), 5.74 (dddd, J = 16.9, 10.4, 6.3, 6.3 Hz, 1H). C NMR
13
3
2.4, 18.4, 20.1, 21.9, 22.6, 26.0, 34.8, 36.8, 60.7, 69.0,
(CDCl , 125 MHz) δ: –5.3, –5.4, 11.9, 20.2, 21.9, 22.7, 25.9,
3
14.0, 114.8, 129.2, 132.0, 133.0, 135.4, 135.8, 146.2. HR-
34.7, 35.7, 56.0, 60.3, 78.2, 113.7, 114.6, 127.3, 133.1,
133.2, 134.1, 135.9, 146.3. Anal calcd. for C H O Si (%):
+
MS (EI) m/z calcd. for C H OSi ([M – H O]): 346.2692;
2
2
38
2
23 42
2
found: 346.2688.
C 72.95, H 11.18; found: C 73.16, H 11.12.
7
2
-(tert-Butyl-dimethyl-silanyloxymethyl)-3-isopropylidene-
4-(tert-Butyl-dimethyl-silanyloxymethyl)-8-isopropenyl-6-
methoxy-9-methyl-5-trimethylsilanyl-deca-1,4,8-triene
(26e)
-methyl-6-trimethylsilanyl-deca-1,6,9-trien-5-ol (25e)
–
1
7
1% from 7e. IR (neat) (cm ) ν: 3371, 3043, 2956, 1433,
1
–1
1
259, 1084–990, 841. H NMR (CDCl , 300 MHz) δ: 0.02
90% from 25e. IR (neat) (cm ) ν: 3077–2814, 1255,
3
1
(
s, 6H), 0.23 (s, 9H), 0.88 (s, 9H), 1.70 (s, 3H), 1.74 (s, 3H),
1102, 839, 775. H NMR (CDCl , 300 MHz) δ: 0.02 (s, 6H),
3
1
1
1
1
1
1
2
1
.78 (s, 4H), 1.97 (d, J = 12.8 Hz, 1H), 2.65 (dd, J = 14.3,
0.7 Hz, 1H), 3.00 (dd, J = 14.1, 6.3 Hz, 1H), 3.12 (dd, J =
4.2, 6.5 Hz, 1H), 4.10 (d, J = 12.2 Hz, 1H), 4.32 (d, J =
2.2 Hz, 1H), 4.63 (dd, J = 2.4, 0.9 Hz, 1H), 4.69 (dd, J =
0.7, 2.9 Hz, 1H), 4.99–5.03 (m, 3H), 5.75 (dddd, J = 17.0,
0.21 (s, 9H), 0.88 (s, 9H), 1.66 (s, 3H), 1.69 (s, 3H), 1.76 (s,
3H), 1.95 (dd, J = 14.4, 3.2 Hz, 1H), 2.65 (dd, J = 14.5,
9.3 Hz, 1H), 3.04 (dd, br, 1H), 3.10 (dd, br, 1H), 3.12 (s,
3H), 3.99 (s, broad, 1H), 4.14 (d, J = 5.3 Hz, 1H), 4.35 (d,
J = 11.8 Hz, 1H), 4.59 (q, 1H), 4.98 (q, 1H), 5.01 (d, J =
9.1 Hz, 1H), 5.02 (d, J = 17.9 Hz, 1H), 5.77 (dddd, J = 16.8,
0.1, 6.6, 6.6 Hz, 1H). 13C NMR (CDCl , 75 MHz) δ: –5.4,
3
1
3
.6, 18.3, 20.3, 21.9, 22.7, 25.9, 37.2, 38.6, 60.8, 71.6,
14.0, 115.8, 129.0, 133.5, 137.1, 140.3, 146.2, 148.1. Anal
10.5, 6.4, 6.4 Hz, 1H). C NMR (CDCl , 75 MHz) δ: –5.5,
3
2.3, 18.2, 20.2, 21.9, 22.7, 25.9, 37.6, 37.7, 56.5, 60.3, 80.7,
113.6, 115.8, 126.8, 133.7, 136.9, 140.9, 146.3, 149.5.
calcd. for C H O Si (%): C 73.78, H 10.84; found: C
2
4
46
2
2
7
3.67, H 10.64.
4
-(tert-Butyl-dimethyl-silanyloxymethyl)-8-isopropenyl-6-
6
-Allyl-7-(tert-butyl-dimethyl-silanyloxymethyl)-3-
methoxy-9-methyl-5-allyl-deca-1,4,8-triene (26f)
–
1
isopropylidene-2-methyl-deca-1,6,9-trien-5-ol (25f)
89% from 25f. IR (neat) (cm ) ν: 3077–2814, 1636,
–
1
1
8
1% from 7f. IR (neat) (cm ) ν: 3298, 1643, 1412, 1095,
1463, 1255, 1102–1069, 837, 775. H NMR (CDCl ,
3
1
9
82, 885. H NMR (CDCl , 300 MHz) δ: 0.02 (s, 6H), 0.86
300 MHz) δ: 0.03 (s, 6H), 0.87 (s, 9H), 1.66 (s, 6H), 1.75 (d,
3H), 1.99 (d, br, 1H), 2.60 (dd, J = 14.5, 9.3 Hz, 1H), 2.82–
2.86 (m, br, 2H), 2.91 (dd, J = 6.2, 4.8 Hz, 2H), 3.09 (s,
3H), 4.02 (d, J = 11.4 Hz, 1H), 4.10 (dd, J = 9.3, 4.1 Hz,
1H), 4.25 (d, J = 11.4 Hz, 1H), 4.59 (d, br, 1H), 4.95–5.07
3
(
s, 9H), 1.70 (s, 3H), 1.71 (s, 3H), 1.78 (d, 3H), 1.81 (s, 1H),
1
4
4
5
.98 (d, 1H), 2.60 (dd, J = 14.1, 10.3 Hz, 1H), 2.81–2.96 (m,
H), 4.06 (d, J = 11.6 Hz, 1H), 4.19 (d, J = 11.6 Hz, 1H),
.62 (d, 1H), 4.68 (dd, J = 10.3, 3.5 Hz, 1H), 4.94–5.09 (m,
H), 5.74 (dddd, J = 16.9, 10.3, 6.4, 6.4 Hz, 1H), 5.86
1
3
(m, 5H), 5.71–5.83 (m, 2H). C NMR (CDCl , 75 MHz) δ:
3
(
dddd, J = 16.9, 10.4, 6.2, 6.2 Hz, 1H). 13C NMR (CDCl3,
–5.0 (2), 18.7, 20.5, 22.3, 23.1, 26.3, 32.5, 34.7, 36.8, 57.0,
60.3, 79.3, 114.1, 115.4, 115.6, 127.5, 133.7, 135.2, 136.2,
136.8, 137.8, 146.6.
7
3
1
5 MHz) δ: –5.0, 18.7, 20.6, 22.3, 23.0, 26.3, 32.2, 34.8,
7.9, 60.7, 69.8, 114.4, 115.2, 115.6, 129.8, 133.3, 134.7,
36.6, 136.8, 138.1, 146.4. Anal calcd. for C H O Si (%):
2
4
42
2
C 73.78, H 10.84; found: C 73.67, H 10.64.
General procedure for deprotection of the primary
alcohols
Tetrabutylammonium fluoride (1.5 equiv., 1.0 mol L–1 in
THF) was added to a solution of silane (1.0 equiv.) in THF
General procedure for methylation of the secondary
alcohols
–
1
Sodium hydride (3.0 equiv., 60% dispersion in mineral
oil) was added to a solution of the alcohol (1.0 equiv.) in
([silane] = 1.0 mol L ) at 0 °C, and the resulting solution
was stirred for 18 h at 21 °C. A saturated aqueous solution
–
1
THF ([alcohol] = 1.0 mol L ) at 0 °C. After 30 min,
iodomethane (20.0 equiv.) was added, and the solution was
stirred for 18 h at 21 °C. A saturated aqueous solution of
of NH Cl was then added; the layers were separated, and the
4
aqueous layer was extracted with ether. The combined or-
ganic extracts were washed with brine, dried (MgSO ), fil-
4
NH Cl was subsequently added; the layers were separated,
and the aqueous layer was extracted with dichloromethane.
The combined organic extracts were washed with brine,
tered, and concentrated under reduced pressure. The crude
material was purified by flash chromatography (silica gel,
ether – petroleum ether).
4
dried (MgSO ), filtered, and concentrated under reduced
4
pressure. The crude material was purified by flash chroma-
tography (silica gel, ether – petroleum ether).
2
-Allyl-6-isopropenyl-4-methoxy-3,7-dimethyl-octa-2,6-
dien-1-ol (27d)
–
1
9
6% from 26d. IR (neat) (cm ) ν: 3442, 3077, 2976,
1
(
2-Allyl-6-isopropenyl-4-methoxy-3,7-dimethyl-octa-2,6-
2919, 2818, 1636, 1445, 1098, 996, 898. H NMR (CDCl ,
3
dienyloxy)-tert-butyl-dimethyl-silane (26d)
300 MHz) δ: 1.39 (s, br, 1H), 1.61 (s, 3H), 1.65 (s, 6H), 1.74
(s, 3H), 2.19 (dd, J = 14.0, 7.3 Hz, 1H), 2.50 (dd, J = 14.0,
–
1
9
2% from 25d. IR (neat) (cm ) ν: 3077, 2956–2820,
©
2004 NRC Canada

2
34
Can. J. Chem. Vol. 82, 2004
6
1
4
1
6
2
1
7
.4 Hz, 1H), 2.90 (t, 2H), 3.03 (s, 3H), 4.00 (d, J = 11.9 Hz,
H), 4.09 (d, J = 11.9 Hz, 1H), 4.17 (d, J = 6.8 Hz, 1H),
.56 (d, J = 2.0 Hz, 1H), 4.94–4.98 (m, 2H), 5.00 (ddd, J =
1.8, 3.3, 1.6 Hz, 1H), 5.77 (dddd, J = 16.7, 10.0, 6.6,
dried (MgSO ), filtered, and concentrated. The crude mate-
rial was purified by flash chromatography (silica gel, ether –
petroleum ether).
4
1
3
.4 Hz, 1H). C NMR (CDCl , 75 MHz) δ: 12.4, 20.5, 22.2,
3
2
-Allyl-6-isopropenyl-4-methoxy-3,7-dimethyl-octa-2,6-
dienal (28d)
0% from 27d. IR (neat) (cm ) ν: 2924, 1671, 1443,
3.0, 35.6, 36.3, 56.2, 61.2, 78.7, 114.2, 115.6, 128.6, 133.7,
34.9, 135.3, 135.9, 146.5. Anal calcd. for C H O (%): C
1
7
28
2
–1
9
7.22, H 10.67; found: C 77.36, H 10.51.
1
1
100, 906. H NMR (CDCl , 300 MHz) δ: 1.62 (s, 6H), 1.73
3
(
(
s, 3H), 1.88 (s, 3H), 2.27 (dd, J = 14.2, 6.8 Hz, 1H), 2.60
dd, J = 14.1, 7.8 Hz, 1H), 2.95 (dd, J = 15.1, 5.8 Hz, 1H),
2
-Allyl-6-isopropenyl-4-methoxy-7-methyl-3-
trimethylsilanyl-octa-2,6-dien-1-ol (27e)
3
6
.08 (dd, J = 15.1, 5.8 Hz, 1H), 3.16 (s, 3H), 4.78 (t, J =
.8 Hz, 1H), 4.89 (d, J = 17.8 Hz, 1H), 4.92 (d, J = 10.6 Hz,
–
1
9
0% from 26e. IR (neat) (cm ) ν: 3433, 3076, 2963–
1
2
3
3
814, 1636, 1443, 1250, 1100, 996, 838. H NMR (CDCl ,
3
1H), 4.97 (s, 1H), 5.67 (ddd, J = 16.6, 11.0, 6.0 Hz, 1H),
00 MHz) δ: 0.19 (s, 9H), 1.65 (s, 3H), 1.68 (s, 3H), 1.75 (s,
H), 2.04 (dd, J = 14.5, 3.8 Hz, 1H), 2.18 (s, br, 1H), 2.71
13
1
2
1
0.07 (s, 1H). C NMR (CDCl , 75 MHz) δ: 14.7, 20.4,
3
2.3, 22.8, 30.4, 35.8, 56.9, 76.8, 115.3 (2), 129.5, 132.0,
34.8, 138.3, 145.7, 158.9, 189.4. HR-MS (EI) m/z calcd.
for C H O ([M – CH ]): 247.1698; found: 247.1721 or
(
dd, J = 14.5, 8.9 Hz, 1H), 3.04 (dd, J = 6.1, 1.1 Hz, 2H),
3
4
1
.16 (s, 3H), 4.08 (d, J = 12.7 Hz, 1H), 4.11 (dd, J = 8.7,
.4 Hz, 1H), 4.18 (d, J = 12.7 Hz, 1H), 4.60 (d, J = 1.9 Hz,
H), 5.02 (d, br, J = 18.0 Hz, 1H), 5.05 (s, br, 1H), 5.08
+
1
6
23
2
3
+
calcd. for C H O ([M – CH OH]): 230.1671; found:
1
6
22
3
2
30.1643.
-Allyl-6-isopropenyl-4-methoxy-7-methyl-3-
(
ddd, J = 11.0, 3.6, 1.6 Hz, 1H), 5.78 (dddd, J = 17.6, 9.6,
1
3
6
2
1
.1, 6.1 Hz, 1H). C NMR (CDCl , 75 MHz) δ: 2.2, 20.6,
3
2
2.3, 23.1, 37.9, 40.2, 57.2, 62.2, 81.6, 114.3, 117.1, 127.9,
34.0, 137.0, 141.2, 146.6, 149.7. Anal calcd. for
trimethylsilanyl-octa-2,6-dienal (28e)
–
1
7
3% from 27e. IR (neat) (cm ) ν: 3077–2817, 1673,
C H O Si (%): C 73.78, H 10.84; found: C 73.67, H 10.64.
1
9
34
2
1
1
9
1
3
252, 1100, 905. H NMR (CDCl , 300 MHz) δ: 0.24 (s,
3
H), 1.65 (s, 3H), 1.66 (s, 3H), 1.74 (s, 3H), 2.14 (dd, J =
4.7, 3.2 Hz, 1H), 2.71 (dd, J = 14.7, 9.2 Hz, 1H), 3.15 (s,
H), 3.11–3.17 (m, 2H), 4.48 (dd, J = 8.8, 3.2 Hz, 1H), 4.58
2
,3-Diallyl-6-isopropenyl-4-methoxy-7-methyl-octa-2,6-
dien-1-ol (27f)
–
1
9
3% from 26f. IR (neat) (cm ) ν: 3423, 3077, 2977–
(
d, J = 2.0 Hz, 1H), 4.92 (dd, J = 17.8, 1.6 Hz, 1H), 4.96 (s,
1
2
3
814, 1635, 1446, 1100, 992, 909. H NMR (CDCl ,
3
1
1
7
1
H), 4.97 (dd, J = 10.8, 1.3 Hz, 1H), 5.77 (dddd, J = 16.9,
0.9, 5.6, 5.6 Hz, 1H), 10.19 (s, 1H). C NMR (CDCl3,
5 MHz) δ: 1.5, 20.6, 22.3, 23.0, 34.4, 38.7, 57.3, 80.4,
14.8, 116.2, 128.7, 132.9, 136.3, 146.1, 147.8, 193.5.
00 MHz) δ: 1.63 (s, 6H), 1.79 (s, 3H), 1.88 (s, 1H), 2.12
13
(
dd, J = 14.4, 4.6 Hz, 1H), 2.62 (dd, J = 14.3, 8.3 Hz, 1H),
2
2
3
1
5
2
1
1
.74 (dd, J = 15.2, 7.1 Hz, 1H), 2.85 (d, J = 5.9 Hz, 1H),
.90 (d, J = 6.0 Hz, 1H), 2.94 (d, J = 6.1 Hz, 1H), 3.17 (s,
H), 4.03 (dd, J = 8.2, 5.0 Hz, 1H), 4.07 (d, J = 12.2 Hz,
H), 4.16 (d, J = 12.2 Hz, 1H), 4.58 (s, 1H), 4.96–5.07 (m,
2
,3-Diallyl-6-isopropenyl-4-methoxy-7-methyl-octa-2,6-
H), 5.68–5.85 (m, 2H). 13C NMR (CDCl , 75 MHz) δ:
dienal (28f)
3% from 27f. .IR (neat) (cm ) ν: 3079–2821, 1671,
1
1
2
1
3
–
1
9
0.5, 22.3, 23.0, 33.5, 36.1, 36.6, 57.2, 61.4, 80.2, 114.3,
15.8, 116.2, 128.2, 133.7, 136.1, 136.4, 136.9, 137.1,
46.6. Anal calcd. for C H O (%): C 78.57, H 10.41;
1
446, 1101, 911. H NMR (C D , 300 MHz) δ: 1.59 (s, 3H),
6 6
.66 (s, 3H), 1.68 (s, 3H), 2.16 (dd, J = 14.4, 4.5 Hz, 1H),
.73 (dd, J = 14.4, 8.6 Hz, 1H), 2.84 (dd, J = 14.3, 7.3 Hz,
H), 2.91 (s, 3H), 2.99 (dd, J = 13.7, 5.1 Hz, 1H), 3.06 (dd,
1
9
30
2
found: C 77.09, H 9.97.
J = 14.3, 5.3 Hz, 1H), 3.24 (dd, J = 15.0, 6.2 Hz, 1H), 4.51
dd, J = 8.5, 4.6 Hz, 1H), 4.66 (d, 1H), 4.95 (dd, br, 3H),
General procedures for oxidation of the primary
alcohols
(
5
6
.01 (dd, J = 16.7, 1.6 Hz, 2H), 5.66 (dddd, J = 16.8, 10.2,
.5, 6.5 Hz, 1H), 5.82 (dddd, J = 16.9, 10.4, 6.3, 6.3 Hz,
Oxalyl chloride (1.5 equiv.) was added to a solution of
DMSO (3.0 equiv.) in dichloromethane ([oxalyl chloride] =
1
3
–
1
1H), 10.49 (s, 1H). C NMR (C D , 75 MHz) δ: 20.4, 22.2,
6
6
1
.0 mol L ) at –78 °C. After 5 min, the alcohol (1.0 equiv.)
2
1
2.6, 30.6, 34.8, 37.5, 57.0, 79.0, 114.9, 115.4, 117.2, 128.8,
was added, and the solution was stirred for 1 h at –78 °C.
Triethylamine (7.0 equiv.) was added, and the solution was
warmed to 0 °C for 1 h. A saturated aqueous solution of
32.9, 134.9, 135.9, 138.3, 146.1, 157.1, 189.9. HR-MS (EI)
+
m/z calcd. for C H O ([M – CH OH]): 256.1827; found:
1
8
24
3
2
56.1808.
NH Cl was added; the layers were separated, and the aque-
4
ous layer was extracted with ether. The combined organic
extracts were washed with brine, dried (MgSO ), filtered,
General procedure for vinyl Grignard addition to the
aldehydes
4
and concentrated under reduced pressure. The crude material
was purified by flash chromatography (silica gel, ether –
petroleum ether).
Vinylmagnesium chloride (2.0 equiv., 1.60 mol L–1 in
THF) was added to a solution of the aldehyde (1.0 equiv.) in
–
1
The alcohol (1.0 equiv.) in THF was added to a solution
of o-iodoxybenzoic acid (IBX) (1.5 equiv.) in DMSO (such
ether ([aldehyde] = 1.0 mol L ) at –78 °C. The solution was
stirred for 1 h at –78 °C and for 30 min at 0 °C. A saturated
–
1
that [alcohol] = 1.0 mol L ) at 0 °C. The resulting solution
was stirred for 3 h at 21 °C prior to the addition of water.
Following filtration, the solution was extracted with ether.
The combined organic extracts were washed with brine,
aqueous solution of NH Cl was then added; the layers were
4
separated, and the aqueous layer was extracted with ether.
The combined organic extracts were washed with brine,
dried (MgSO ), filtered, and concentrated under reduced
4
©
2004 NRC Canada

Villalva-Servín et al.
235
pressure. The crude material was purified by flash chroma-
tography (silica gel, ether – petroleum ether).
72.0, 80.3, 114.2, 114.4, 115.2, 115.8, 128.0, 134.0, 136.6,
136.8, 137.1, 137.9, 139.9, 146.9.
4
-Allyl-8-isopropenyl-6-methoxy-5,9-dimethyl-deca-1,4,8-
trien-3-ol (29d)
5% from 28d. IR (neat) (cm ) ν: 3456, 3076, 2976,
910, 2815, 1634, 1445, 1100, 992, 919.
1
6
6
–
1
7
2
Isomer A
1
6
5%. H NMR (C D , 300 MHz) δ: 1.61 (s, br, 1H), 1.67
6
6
C
(
s, 6H), 1.70 (s, 3H), 1.76 (s, 3H), 2.28 (dd, J = 14.1,
5
1
3
1
5
7
7
1
.9 Hz, 1H), 2.71 (dd, J = 14.1, 7.4 Hz, 1H), 2.81 (dd, J =
5.7, 5.8 Hz, 1H), 2.92 (dd, J = 15.7, 6.0 Hz, 1H), 3.01 (s,
H), 4.35 (t, J = 6.7 Hz, 1H), 4.78 (s, 1H), 4.97 (d, J =
0.2 Hz, 2H), 5.04 (d, J = 17.3 Hz, 2H), 5.26 (s, broad, 1H),
.35 (d, J = 17.1 Hz, 1H), 5.82 (m, 2H). 13C NMR (C D ,
6
6
6
5 MHz) δ: 12.8, 20.4, 22.2, 22.8, 32.8, 36.2, 56.1, 71.1,
8.6, 114.2, 114.3, 114.9, 127.6, 133.9, 135.3, 135.4, 137.3,
39.5, 146.8.
–
1
was added, and the solution was stirred for 1 h at –78 °C.
Triethylamine (7.0 equiv.) was added, and the solution was
warmed to 0 °C for 1 h. A saturated aqueous solution of
1
6
6
4
6
4
5
.4 Hz, 1H), 2.76 (dd, J = 14.2, 8.6 Hz, 1H), 2.86 (d, J =
.0 Hz, 2H), 3.06 (s, 3H), 4.38 (dd, J = 8.6, 4.6 Hz, 1H),
.76 (d, J = 2.1 Hz, 1H), 4.96–5.03 (m, 3H), 5.07 (d, 1H),
.29 (s, br, 1H), 5.36 (ddd, J = 17.1, 1.7, 1.7 Hz, 1H), 5.77
NH Cl was added; the layers were separated, and the aque-
ous layer was extracted with ether. The combined organic
4
extracts were washed with brine, dried (MgSO ), filtered,
4
and concentrated under reduced pressure. The crude material
was purified by flash chromatography (silica gel, ether – pe-
troleum ether).
(
ddd, J = 17.1, 10.5, 4.5 Hz, 1H), 5.84 (dddd, J = 16.9, 10.4,
1
3
6
2
1
.3, 6.2 Hz, 1H). C NMR (C D , 75 MHz) δ: 12.8, 20.3,
6 6
2.2, 22.9, 32.6, 36.0, 56.0, 70.8, 78.0, 114.0, 114.1, 114.9,
The alcohol (1.0 equiv.) in THF was added to a solution
–
1
27.8, 133.6, 135.0, 135.5, 137.7, 139.8, 147.0. HR-MS (EI)
of IBX (1.5 equiv.) in DMSO ([alcohol] = 1.0 mol L ) at
0 °C. The resulting solution was stirred for 3 h at 21 °C
prior to the addition of water. Following filtration, the solu-
tion was extracted with ether. The combined organic extracts
+
m/z calcd. for C H O ([M – H O]): 272.2140; found:
1
9
28
2
2
72.2112.
were washed with brine, dried (MgSO ), filtered, and con-
centrated. The crude material was purified by flash chroma-
tography (silica gel, ether – petroleum ether).
4
-Allyl-6-methoxy-9-methyl-5-trimethylsilanyl-8-vinyl-
4
deca-1,4,8-trien-3-ol (29e)
–
1
5
7% from 28e. IR (neat) (cm ) ν: 3445, 3076–2814,
1
1
0
1
443, 1250, 1100, 851–839. H NMR (C D , 300 MHz) δ:
.31 (s, 9H), 1.73 (s, 3H), 1.80 (s, 6H), 2.17 (d, J = 14.0 Hz,
6 6
4-Allyl-8-isopropenyl-6-methoxy-5,9-dimethyl-deca-1,4,8-
trien-3-one (8d)
H), 3.07 (s, 3H), 2.96–3.11 (m, 3H), 4.36 (s, br, 1H), 4.81
–
1
(
d, J = 2.0 Hz, 1H), 4.98 (ddd, J = 10.2, 1.7 Hz, 1H), 5.04–
97% from 29d. IR (neat) (cm ) ν: 2978, 2923, 1660,
1
5
1
5
2
1
.12 (m, 3H), 5.37 (d, J = 17.1 Hz, 2H), 5.88 (dddd, J =
7.0, 10.5, 6.1, 6.1 Hz, 1H), 5.98 (ddd, J = 17.2, 10.4,
1638, 1443, 1399, 1099, 992. H NMR (C D , 300 MHz) δ:
6
6
1.63 (s, 3H), 1.72 (s, 3H), 1.73 (s, 3H), 1.83 (s, 3H), 2.18
(dd, J = 14.1, 2.6 Hz, 1H), 2.72 (dd, J = 14.1, 9.3 Hz, 1H),
2.82 (d, J = 6.5 Hz, 2H), 3.05 (s, 3H), 4.10 (ddd, J = 9.2,
4.0, 1.6 Hz, 1H), 4.76 (d, 1H), 4.94 (dd, J = 10.1, 1.5 Hz,
1
3
.4 Hz, 1H). C NMR (C D , 75 MHz) δ: 2.6, 20.5, 22.2,
6
6
3.0, 37.2, 38.3, 57.3, 73.6, 81.2, 114.3, 114.7, 116.2, 127.8,
28.1, 128.4, 134.2, 139.2, 140.1, 146.9.
1
H), 5.01 (t, 1H), 5.03 (dd, J = 16.5, 1.0 Hz, 1H), 5.33 (dd,
J = 10.4, 1.5 Hz, 1H), 5.66 (dddd, J = 16.8, 10.3, 6.4,
4
,5-Diallyl-8-isopropenyl-6-methoxy-9-methyl-deca-1,4,8-
6
1
2
1
.4 Hz, 1H), 5.95 (dd, J = 17.5, 1.5 Hz, 1H), 6.30 (dd, J =
trien-3-ol (29f)
0% from 28f. IR (neat) (cm ) ν: 3421, 3077–2819,
636, 1444, 1100, 992, 909.
1
3
–
1
7.5, 10.4 Hz, 1H). C NMR (C D , 75 MHz) δ: 11.9, 20.3,
6
6
6
2.2, 22.8, 34.9, 35.8, 56.4, 80.3, 114.2, 116.2, 127.7, 129.0,
1
33.6, 134.5, 136.1, 137.3, 139.9, 146.7, 197.6. HR-MS (EI)
+
m/z calcd. for C H O ([M] ): 288.2089; found: 288.2056
or calcd. for C H O ([M – CH OH]): 256.1827; found:
2
Isomer A
19 28
2
+
1
4
2%. H NMR (C D , 300 MHz) δ: 1.73 (s, 3H), 1.74 (s,
18 24 3
6
6
56.1837.
H), 1.79 (s, 3H), 1.93 (d, br, 1H), 2.22 (dd, J = 14.3,
.1 Hz, 1H), 2.85 (s, 1H), 2.78–2.90 (m, 1H), 2.93–3.01 (m,
H), 3.06 (s, 3H), 4.18 (dd, J = 9.3, 3.8 Hz, 1H), 4.78 (d, br,
H), 4.99 (dd, J = 9.2, 1.8 Hz, 2H), 5.02–5.08 (m, 3H), 5.11
4-Allyl-8-isopropenyl-6-methoxy-9-methyl-5-
trimethysilanyl-deca-1,4,8-trien-3-one (8e)
–
1
83% from 29e. IR (neat) (cm ) ν: 3075–2821, 1664,
1
3
1
2
H), 5.90 (ddd, J = 17.2, 10.3, 4.7 Hz, 1H). C NMR
1251, 1102, 852–840. H NMR (C D , 300 MHz) δ: 0.31 (s,
9H), 1.74 (s, 3H), 1.78 (s, 3H), 1.82 (s, 3H), 2.13 (d, J =
6
6
(
C D , 75 MHz) δ: 20.4, 22.2, 22.9, 33.0, 34.1, 37.3, 57.1,
6
6
©
2004 NRC Canada

2
36
Can. J. Chem. Vol. 82, 2004
1
3
2
4.0 Hz, 1H), 2.88 (dd, J = 14.3, 10.5 Hz, 1H), 3.04 (s, 3H),
.11 (d, br, 2H), 4.01 (dd, J = 10.4, 2.9 Hz, 1H), 4.75 (d, J =
.3 Hz, 1H), 4.94–5.05 (m, 3H), 5.34 (dd, J = 10.4, 1.1 Hz,
H), 5.69 (dddd, J = 16.9, 10.2, 6.7, 6.7 Hz, 1H), 5.91 (dd,
37.9, 57.6, 63.0, 82.3, 115.8, 131.5, 132.2, 134.0, 135.2,
+
138.8, 213.4. HR-MS (EI) m/z calcd. for C H O ([M] ):
1
9
28
2
288.2089; found: 288.2078.
1
1
3
J = 17.0, 1.1 Hz, 1H), 6.23 (dd, J = 17.6, 10.4 Hz, 1H).
C
3
-Allyl-5-methoxy-4,8,11,11-trimethyl-4-trimethylsilanyl-
NMR (C D , 75 MHz) δ: 2.0, 20.5, 22.2, 22.9, 37.6, 38.7,
5
1
6
6
bicyclo[5.3.1]undeca-3,7-dien-2-one (9e)
7.0, 83.0, 114.2, 117.5, 127.4, 128.9, 134.0, 134.7, 137.5,
42.5, 146.7, 150.3, 199.5.
–1
6
5% from 8e. IR (neat) (cm ) ν: 3074–2819, 1667, 1464,
1
1
245, 1128–1095, 841. H NMR (C D , 300 MHz) δ: 0.36
6
6
(
s, 9H), 0.92 (s, 3H), 1.22 (s, 3H), 1.34 (s, br, 1H), 1.47 (s,
4
,5-Diallyl-8-isopropenyl-6-methoxy-9-methyl-deca-1,4,8-
3H), 1.63–1.76 (m, 2H), 2.16–2.22 (m, 1H), 2.32 (t, J =
11.8 Hz, 1H), 2.43 (d, J = 5.9 Hz, 1H), 2.56–2.65 (m, 2H),
3.06 (s, 3H), 3.25 (dd, J = 16.1, 6.0 Hz, 1H), 4.15 (dd, J =
11.4, 5.7 Hz, 1H), 5.00 (ddd, J = 10.1, 3.2, 1.6 Hz, 1H), 5.09
(ddd, J = 17.1, 3.4, 1.7 Hz, 1H), 5.89 (dddd, J = 17.0, 10.1,
trien-3-one (8f)
2% from 29f. IR (neat) (cm ) ν: 3077–2823, 1662,
1
6
1
2
–
1
7
1
637, 1102, 991, 897. H NMR (C D , 300 MHz) δ: 1.62 (s,
6
6
H), 1.69 (s, 3H), 1.98 (d, J = 14.5 Hz, 1H), 2.59 (dd, J =
4.5, 10.0 Hz, 1H), 2.89 (d, J = 6.6 Hz, 2H), 3.03 (s, 3H),
.90–3.10 (m, 2H), 3.73 (dd, J = 10.0, 3.1 Hz, 1H), 4.51 (d,
1
3
6.9, 6.9 Hz, 1H). C NMR (C D , 75 MHz) δ: 3.4, 19.1,
6
6
22.4, 24.9, 28.7, 28.9, 35.8, 37.6, 38.4, 57.5, 63.0, 86.1,
116.4, 133.2, 133.4, 135.5, 136.2, 152.7, 213.8. HR-MS (EI)
J = 2.4 Hz, 1H), 4.91 (s, 1H), 4.99 (d, J = 9.6 Hz, 1H), 5.04
d, J = 16.9 Hz, 1H), 5.05 (d, J = 9.8 Hz, 1H), 5.11 (d, J =
+
(
m/z calcd. for C H O Si ([M] ): 346.2328; found: 346.2339.
21
34
2
1
5
1
1
3
1
7.2 Hz, 1H), 5.69 (dddd, J = 17.1, 10.5, 6.9, 6.9 Hz, 1H),
.93 (dddd, J = 17.1, 10.5, 6.7, 6.7 Hz, 1H), 5.89 (d, J =
0.4 Hz, 1H), 6.10 (d, J = 17.5 Hz, 1H), 6.38 (dd, J = 17.6,
3
,4-Diallyl-5-methoxy-8,11,11-trimethyl-bicyclo[5.3.1]-
undeca-3,7-dien-2-one (9f)
1
3
–
1
0.4 Hz, 1H). C NMR (C D , 75 MHz) δ: 20.4, 22.3, 22.9,
6
6
68% from 8f. IR (neat) (cm ) ν: 3076, 2934–2827, 1672,
1
1.9, 35.3, 36.1, 57.3, 81.0, 114.2, 116.4, 117.2, 127.8, 130.2,
1
637, 1448, 1098, 911. H NMR (C D , 300 MHz) δ: 0.89
6
6
33.4, 134.5, 136.3, 137.3, 138.0, 139.5, 146.3, 199.9. HR-
(
s, 3H), 1.21 (s, 3H), 1.34 (s, 3H), 1.67–1.75 (m, 2H), 1.80
+
MS (EI) m/z calcd. for C H O ([M] ): 314.2246; found:
3
2
1
30
2
(s, br, 1H), 2.13–2.20 (m, 1H), 2.35 (t, J = 11.8 Hz, 1H),
.44 (d, J = 6.4 Hz, 1H), 2.59 (d, J = 6.8 Hz, 1H), 2.63 (d,
14.2261.
2
J = 6.7 Hz, 1H), 2.70 (d, J = 6.0 Hz, 1H), 3.05–3.07 (m,
2H), 3.11 (s, 3H), 4.08 (dd, J = 11.0, 6.1 Hz, 1H), 4.97 (d,
J = 10.5 Hz, 1H), 4.99–5.03 (d, br, 2H), 5.14 (d, J =
General procedures for Diels–Alder cyclizations
–
1
Diethylaluminum chloride (1.1 equiv., 1.0 mol L in hex-
ane) was added to a solution of ketone (1.0 equiv.) in di-
1
3
17.3 Hz, 1H), 5.81–5.98 (m, 2H). C NMR (C6D6, 75 MHz)
δ: 18.8, 21.6, 25.0, 28.6, 28.6, 31.7, 35.9, 36.3, 37.9, 58.6,
63.0, 82.2, 115.1, 116.4, 131.8, 132.4, 134.0, 135.7, 137.1,
–
1
chloromethane ([ketone] = 1.0 mol L ) at –78 °C. The
solution was slowly warmed to 0 °C and, after 5 min, cooled
+
to –78 °C. A saturated aqueous solution of NaHCO was
added; the layers were separated, and the aqueous layer was
extracted with ether. The combined organic extracts were
141.0, 214.5. HR-MS (EI) m/z calcd. for C21H30O2 ([M] ):
3
314.2246; found: 314.2255.
washed with brine, dried (MgSO ), filtered, and concen-
5-Methoxy-4,8,11,11-tetramethyl-3-propenyl-
4
trated under reduced pressure. The crude material was puri-
fied by flash chromatography (silica gel, ether – petroleum
ether).
bicyclo[5.3.1]undeca-3,7-dien-2-one (19)
Potassium tert-butoxide (0.042 g, 0.37 mmol) was added
to a solution of 13 (0.081 g, 0.24 mmol) in DMF (10 mL) at
21 °C, and the solution was subsequently warmed to 40 °C.
After stirring for 3 h, the suspension was filtered, neutral-
ized, and extracted with ether (2 × 30 mL). The combined
organic extracts were washed with brine (2 × 30 mL), dried
Borontrifluoride etherate (1.0 equiv.) was added to a solu-
tion of ketone (1.0 equiv.) in dichloromethane (such that
–
1
[
ketone] = 1.0 mol L ) at –78 °C, and the solution was
stirred for 2 h. A saturated aqueous solution of NaHCO was
3
then added; the layers were separated, and the aqueous layer
was extracted with ether. The combined organic extracts
(MgSO ), filtered, and concentrated under reduced pressure.
4
Purification by flash chromatography (silica gel, ether –
petroleum) provided the title compound as a white solid
were washed with brine, dried (MgSO ), filtered, and con-
4
–
1
centrated under reduced pressure. The crude material was
purified by flash chromatography (silica gel, ether – petro-
leum ether).
(0.041 g, 51%). IR (neat) (cm ) ν: 3025–2819, 1663, 1456–
1
1438, 1101, 961. H NMR (C D , 300 MHz) δ: 0.94 (s, 3H),
6
6
1.29 (s, 3H), 1.40 (s, 3H), 1.51 (d, J = 6.5 Hz, 3H), 1.52 (s,
3
2
H), 1.70 (s, 3H), 1.66–1.80 (m, 1H), 1.81–1.97 (m, 2H),
.17 (t, br, 1H), 2.53–2.57 (m, 2H), 2.62 (dd, br, 1H), 3.04
3
-Allyl-5-methoxy-4,8,11,11-tetramethyl-bicyclo[5.3.1]-
undeca-3,7-dien-2-one (9d)
2% from 8d. IR (neat) (cm ) ν: 3077–2824, 1669, 1464,
(
s, 3H), 4.15 (dd, J = 10.9, 6.6 Hz, 1H), 5.51 (dd, J = 15.8,
1
3
–
1
6.7 Hz, 1H), 6.24 (dd, J = 15.8, 1.7 Hz, 1H). C NMR
(C D , 75 MHz) : 12.2, 18.7, 19.9, 21.7, 25.2, 28.2, 29.2,
7
1
δ
1
3
1
2
4
1
103. H NMR (C D , 300 MHz) δ: 0.89 (s, 3H), 1.22 (s,
6
6
6
6
3
1
5.6, 38.0, 57.7, 63.3, 82.4, 126.7, 128.4, 131.8, 132.0,
34.5, 141.2, 212.8. HR-MS (EI) m/z calcd. for C H O
H), 1.35 (s, 3H), 1.58 (s, 3H), 1.61–1.69 (m, 2H), 1.74–
.82 (m, 1H), 2.12–2.23 (m, 1H), 2.43–2.51 (m, 2H), 2.52–
.64 (m, 2H), 2.87 (dd, J = 15.8, 6.6 Hz, 1H), 3.06 (s, 3H),
.05 (dd, J = 11.1, 6.3 Hz, 1H), 4.98 (ddd, J = 10.0, 3.3,
.6 Hz, 1H), 5.06 (ddd, J = 17.0, 3.5, 1.7 Hz, 1H), 5.83
19 28
2
+
(
[M] ): 288.2089; found: 288.2076.
5-Methoxy-8,11,11-trimethyl-4-methylene-3-propenyl-
bicyclo[5.3.1]undec-7-en-2-one (20)
(
dddd, J = 16.8, 10.2, 6.5, 6.5 Hz, 1H). 13C NMR (C D ,
6 6
7
5 MHz) δ: 12.1, 19.2, 21.6, 25.1, 28.5, 28.8, 35.6, 36.4,
Potassium hydride (0.240 g, 2.10 mmol, 35% in mineral
©
2004 NRC Canada

Villalva-Servín et al.
237
+
oil) was washed with pentane (3 × 1 mL) and suspended in
THF (2 mL). The resultant mixture was treated with iodine
213.8. HR-MS (EI) m/z calcd. for C H O Si ([M] ):
332.2172; found: 332.2179.
2
0
32
2
(
0.053 g, 0.21 mmol) in THF (0.5 mL). After 15 min, 18-
crown-6 (0.554 g, 2.10 mmol) and alcohol 13 (0.120 g,
.420 mmol) in THF (1 mL) were sequentially added, and
3
-(2-Methoxy-vinyl)-4,6,6-trimethyl-5-methylene-3-vinyl-
0
bicyclo[2.2.2]octan-2-one (15c)
the resultant mixture was stirred for 1 h at 21 °C. The reac-
tion was then cooled to –78 °C and quenched with ethanol
–1
9
2% from 9c. IR (neat) (cm ) ν: 2966, 2830, 1722, 1642.
1
H NMR (C D , 500 MHz) δ: 0.89 (s, 3H), 0.96 (s, 3H),
6
6
(
2 mL). A saturated aqueous solution of NH Cl (10 mL) and
4
1.03 (s, 3H), 1.17–1.22 (m, 1H), 1.51–1.70 (m, 3H), 2.00
m, 1H), 3.11 (s, 3H), 4.68 (d, J = 12.7 Hz, 1H), 4.85 (s,
H), 4.87 (s, 1H), 5.09 (dd, J = 10.7, 1.3 Hz, 1H), 5.32 (dd,
ether (10 mL) were added; the layers were separated, and
the aqueous layer was extracted with ether (2 × 30 mL). The
combined organic extracts were washed with brine (2 ×
(
1
J = 17.3, 1.3 Hz, 1H), 5.64 (dd, J = 17.5, 10.7 Hz, 1H), 6.62
3
0 mL), dried (MgSO ), filtered, and concentrated under re-
13
4
(d, J = 12.7 Hz, 1H). C NMR (C D , 125 MHz) δ: 17.7,
6
6
duced pressure. Purification by flash chromatography (silica
gel, petroleum ether – ether) provided the title compound as
1
1
8.5, 28.3, 29.4, 30.6, 37.3, 45.2, 55.8, 55.9, 58.2, 102.5,
07.3, 117.1, 136.8, 153.1, 160.4, 212.3. HR-MS (EI) m/z
–
1
a colorless oil (0.083 g, 69%). IR (neat) (cm ) ν: 2950,
+
calcd. for C H O ([M] ): 260.1776; found: 260.1771.
1
7
24
2
1
1
705, 1640. H NMR (C D , 300 MHz) δ: 0.95 (s, 3H), 1.11
6
6
(
s, 3H), 1.52 (dd, J = 6.5, 1.6 Hz, 3H), 1.54–1.68 (m, 1H),
3
-Allyl-3-(2-methoxy-1-methyl-vinyl)-4,6,6-trimethyl-5-
1
3
1
1
.70–1.82 (m, 1H), 1.91 (dd, J = 9.3, 1.6 Hz, 1H), 1.97 (s,
H), 2.35 (dd, J = 14.5, 5.2 Hz, 2H), 2.66 (dd, J = 9.8,
.7 Hz, 1H), 2.91 (s, br, 1H), 2.95 (s, 3H), 3.50 (dd, J = 4.9,
.6 Hz, 1H), 4.37 (d, J = 9.8 Hz, 1H), 4.88 (s, 1H), 5.27
methylene-bicyclo[2.2.2]octan-2one (15d)
–1
1
7
9% from 9d. IR (neat) (cm ) ν: 2923, 1718, 1637. H
NMR (CDCl , 500 MHz) δ: 0.93 (s, 3H), 0.96 (s, 3H), 1.12
3
(
(
(
s, 3H), 1.17–1.23 (m, 1H), 1.48 (d, J = 9.3 Hz, 2H), 1.64
dd, J = 12.2, 3.3 Hz, 1H), 1.78 (s, 3H), 1.99 (s, 1H), 2.35
dd, J = 15.5, 5.4 Hz, 1H), 2.51 (dd, J = 15.6, 7.3 Hz, 1H),
(
(
dddd, J = 14.5, 7.0, 7.0, 7.0 Hz, 1H), 5.47 (s 1H), 6.17
ddd, J = 15.1, 9.9, 1.7 Hz, 1H). 13C NMR (C D , 75 MHz)
6
6
δ: 17.7, 19.2, 23.4, 28.9, 29.1, 29.3, 33.9, 37.2, 50.5, 56.0,
3
1
1
2
1
.16 (s, 3H), 4.79 (d, J = 6.5 Hz, 2H), 4.97 (d, J = 17.3 Hz,
6
3.1, 87.3, 118.6, 124.2, 131.7, 133.6, 134.3, 148.9, 210.4.
H), 5.04 (d, J = 10.1 Hz, 1H), 5.79 (s, 1H), 6.25–6.38 (m,
+
HR-MS (EI) m/z calcd. for C H O ([M] ): 288.2089;
13
1
9
28
2
H). C NMR (CDCl , 125 MHz) δ: 13.7, 19.8, 20.3, 29.5,
3
found: 288.2090.
9.7, 30.9, 36.6, 37.3, 46.6, 56.6, 58.7, 59.0, 106.8, 110.7,
15.8, 136.7, 149.9, 160.3, 214.5. HR-MS (EI) m/z calcd.
+
Carbocyclic Cope rearrangements
A solution of trienone 9 in toluene ([trieneone] = 0.05 mol
L ) was heated in a sealed tube at an external temperature
of 110 °C for 3 h. Following removal of the solvent under
reduced pressure, the residue was purified by flash chroma-
tography (silica gel, ether – petroleum ether).
for C19H28O2 ([M] ): 288.2089; found: 288.2089.
–
1
2,3-Diallyl-5-methoxy-4,8,11,11-tetramethyl-
bicyclo[5.3.1]undeca-3,7-dien-2-ol (13)
Allylmagnesium chloride (1.3 mL, 2.6 mmol, 1.6 mol L–1
in THF) was added to a solution of ketone 9d (0.376 g,
1
.3 mmol) in ether (20 mL) at –78 °C. The solution was
stirred for 1 h at –78 °C and for 30 min at 0 °C. A saturated
3
-(2-Methoxy-1-methyl-vinyl)-4,6,6-trimethyl-5-
aqueous solution of NH Cl (30 mL) was then added; the lay-
ers were separated, and the aqueous layer was extracted with
ether (2 × 30 mL). The combined organic extracts were
4
methylene-3-vinyl-bicyclo[2.2.2]octan-2-one (15a)
–
1
7
1% from 9a. IR (neat) (cm ) ν: 2959, 2930, 17016,
1
660, 1461, 1382, 1229, 1131, 764, 750, 621. H NMR
washed with brine (2 × 30 mL), dried (MgSO ), filtered, and
4
6 6
concentrated under reduced pressure. Purification by flash
chromatography (silica gel, ether – petroleum ether) pro-
.55–1.71 (m, 4H), 1.84 (d, J = 1.3 Hz, 3H), 2.03 (d, J =
.2 Hz, 1H), 3.17 (s, 3H), 4.80 (s, 1H), 4.85 (s, 1H), 5.05
vided the title compound as a viscous oil (0.253 g, 59%). IR
(
dd, J = 10.8, 1.3 Hz, 1H), 5.35 (dd, J = 17.5, 1.3 Hz, 1H),
–1
(
neat) (cm ) ν: 3458, 3052–2814, 1640, 1463, 1093, 911.
1
3
5
.87 (dd, J = 17.5, 10.8 Hz, 1H), 5.94 (m, 1H). C NMR
6 6
5.4, 56.3, 58.9, 62.4, 106.9, 114.2, 116.7, 137.0, 148.9,
1
H NMR (C D , 300 MHz) δ: 0.99 (s, 1H), 1.04 (s, 3H),
.27–1.35 (m, 1H), 1.43 (s, 3H), 1.64 (s, 3H), 1.67–1.69 (m,
H), 1.76 (s, 3H), 1.79–1.84 (m, 1H), 2.18 (dd, br, 1H), 2.33
6
6
(
C D , 125 MHz) δ: 13.9, 18.2, 19.1, 29.8, 30.6, 31.0, 38.3,
1
2
4
1
2
7
+
61.6, 212.1. HR-MS (EI) m/z calcd. for C H O ([M] ):
1
8
26
2
(
2
(
dd, J = 14.0, 6.2 Hz, 1H), 2.51 (dd, J = 17.3, 5.7 Hz, 1H),
.58–2.70 (m, 2H), 2.74–2.90 (m, 2H), 3.30 (s, 3H), 4.99
dd, J = 17.3 Hz, 2H), 5.05 (dd, J = 9.6 Hz, 2H), 5.73 (dddd,
74.1934; found: 274.1945. Anal calcd. for C H O (%): C
1
8
26
2
8.79, H 9.55; found: C 78.75, H 9.47.
J = 16.7, 10.4, 6.1, 4.8 Hz, 1H), 5.87 (dddd, J = 17.2, 10.2,
7.6, 5.8 Hz, 1H), 5.93 (dd, J = 11.0, 6.3 Hz, 1H). 13C NMR
(C6D6, 75 MHz) δ: 15.0, 20.8, 21.3, 28.3, 29.3, 32.8, 36.5,
38.0, 39.9, 45.8, 52.3, 57.3, 81.1, 82.4, 115.1, 119.1, 131.2,
3
-(2-Methoxy-1-trimethylsilanyl-vinyl)-4,6,6-trimethyl-5-
methylene-3-vinyl-bicyclo[2.2.2]octan-2-one (15b)
–
1
1
7
8% from 9b. IR (neat) (cm ) ν: 2955, 2891, 1725. H
1
33.2, 135.6, 135.8, 137.7, 138.5. HR-MS (EI) m/z calcd.
NMR (C D , 500 MHz) δ: 0.43 (s, 9H), 0.99 (s, 3H), 1.03 (s,
3
1
6
6
+
for C H O ([M] ): 330.2559; found: 330.2559.
H), 1.10 (s, 3H), 1.16–1.22 (m, 1H), 1.53–1.60 (m, 3H),
.98 (s, 1H), 3.07 (s, 3H), 4.79 (s, 1H), 4.83 (s, 1H), 5.09 (d,
22 34
2
J = 10.7 Hz, 1H), 5.39 (d, J = 17.3 Hz, 1H), 5.95 (dd, J =
Attempted oxy-Cope rearrangement
1
3
1
1
5
7.3, 10.7 Hz, 1H), 6.45 (s, 1H). C NMR (C D ,
25 MHz) δ: 2.9, 18.2, 19.6, 29.8, 30.3, 30.4, 37.8, 46.5,
6.4, 58.8, 61.8, 106.6, 115.8, 118.2, 139.2, 159.4, 161.0,
A solution of alcohol 13 (0.119 g, 0.360 mmol) and DBU
(0.110 g, 0.720 mmol) in dry, deoxygenated toluene (10 mL)
was heated in a quartz tube for 1 h at 220 °C. The solution
6
6
©
2004 NRC Canada

2
38
Can. J. Chem. Vol. 82, 2004
was then cooled to 21 °C, transferred to a round-bottom
flask, and concentrated under reduced pressure. The residue
was purified by flash chromatography (silica gel, ether – pe-
troleum ether) to afford the compounds 21 (7%), 22 (16%),
and 23 (19%) as a mixture of white solids.
9-Methoxy-12,15,15-trimethyl-
3
,8
tricyclo[9.3.1.0 ]pentadeca-3(8),5,11-trien-2-one (24)
Grubbs’ catalyst 30 ((4,5-dihydroIMES)(PCy )Cl Ru=CHPh,
3
2
5 mol%) dissolved in dichloromethane (3 mL) was added to
–
1
a solution of 9f in dichloromethane ([30] = 0.02 mol L ).
The solution was subsequently stirred at 21 °C for 2 h, at
which point the solvent was removed under reduced pres-
sure. The residue was purified by flash chromatography to
afford the title compound as a white solid (93%), mp 90 to
2
5
,3-Diallyl-3-(2-methoxy-1-methyl-vinyl)-4,6,6-trimethyl-
-methylene-bicyclo[2.2.2]octan-2-ol (21)
–
1
–
1
7
% from 13. IR (neat) (cm ) ν: 3559, 3076–2827, 1637,
1
9
1 °C. IR (neat) (cm ) ν: 3031–2822, 1665, 1465, 1103,
1
1
467, 1098, 998, 883. H NMR (CDCl , 500 MHz) δ: 1.18
3
1072, 949. H NMR (C D , 300 MHz) δ: 0.89 (s, 3H),
.21(s, 3H), 1.42 (s, 3H), 1.54 (dd, J = 10.4, 3.2 Hz, 1H),
.63–1.78 (m, 1H), 1.82 (dd, J = 10.3, 3.8 Hz, 1H), 2.14 (t,
6
6
(
s, 3H), 1.26 (s, br, 2H), 1.27 (s, 3H), 1.37 (s, 3H), 1.68 (s,
1
1
3
2
2
1
1
H), 1.69–1.72 (m, 2H), 1.78–1.83 (m, 1H), 2.02 (s, 1H),
.06–2.12 (m, 1H), 2.38 (ddd, J = 14.5, 7.4, 7.4 Hz, 1H),
.41 (dd, J = 14.5, 8.1 Hz, 1H), 2.66 (dd, J = 14.6, 6.5 Hz,
H), 3.19 (s, 3H), 4.70 (s, 1H), 4.80 (s, 1H), 5.01 (dd, J =
0.2, 1.1 Hz, 1H), 5.08 (dd, J = 17.1, 1.5 Hz, 1H), 5.17 (dd,
br, 1H), 2.42–2.50 (m, 3H), 2.63 (ddd, J = 12.4, 6.3, 2.1 Hz,
H), 2.71–2.85 (m, 2H), 2.90 (dd, br, 1H), 3.03 (s, 3H), 4.07
dd, J = 10.9, 6.4 Hz, 1H), 5.47 (dd, J = 9.8, 2.2 Hz, 1H),
1
(
1
3
5.58 (dd, J = 10.1, 2.9 Hz, 1H). C NMR (C D , 75 MHz)
δ: 20.3, 21.3, 24.9, 25.3, 28.1, 28.8, 30.6, 35.5, 37.6, 57.9,
63.3, 82.4, 123.4, 124.4, 127.5, 131.9, 134.6, 136.5, 214.5.
HR-MS (EI) m/z calcd. for C H O ([M] ): 286.1933;
found: 286.1906.
6
6
J = 15.7, 5.6 Hz, 1H), 5.20 (d, J = 9.6 Hz, 1H), 5.22 (dd, J =
8
1
.4, 5.5 Hz, 1H), 5.81 (dddd, J = 18.0, 10.3, 7.0, 7.0 Hz,
H), 5.96 (dddd, J = 18.4, 8.8, 8.8, 6.5 Hz, 1H). C NMR
1
3
+
1
9
26
2
(
CDCl , 125 MHz) δ: 13.7, 19.5, 25.6, 30.4, 33.6, 36.6, 38.6,
3
3
1
8.6, 44.1, 47.7, 49.5, 55.7, 78.1, 78.8, 101.5, 116.0, 119.4,
33.6, 134.5, 136.0, 144.6, 163.3. Anal calcd. for C H O
2
2
2
34
Conclusion
(
%): C 79.95, H 10.37; found: C 76.62, H 9.57.
We have demonstrated the utility of bis-allylpropargyl al-
cohol in our magnesium-mediated carbometallation protocol
for the synthesis of the AB taxane ring by a cis-alkene tether
controlled intramolecular Diels–Alder reaction, followed by
closing metathesis (RCM), to generate a substituted
1
-(2-Allyl-3-methoxymethyl-3,4,6,6-tetramethyl-5-
methylene-bicyclo[2.2.2]oct-2-yl)-but-2-en-1-one (22)
–
1
1
6% from 13. IR (neat) (cm ) ν: 3072–2813, 1690,
1
1
660.7, 1625, 1442, 1095, 906. H NMR (CDCl , 500 MHz)
3,8
3
tricyclo[9.3.1.0 ]pentadecenone (ABC taxane) ring system.
δ: 0.93 (s, 3H), 1.04 (dd, J = 13.9, 4.2 Hz, 1H), 1.14 (s, 3H),
We have discovered the first example of an enone acceler-
ated Cope rearrangement. This isomerization of conjugated
bicyclo[5.3.1]undecadienes provides a rapid entry into
bicyclo[2.2.2]octanone skeletons that complements the more
traditional [4 + 2] cyclizations from cyclohexadienes. We are
examining the generality of this conjugative effect. In total,
the procedures described above provide direct access to a
number of useful unsaturated compounds and bicyclic ring
systems, which may be employed for a variety of synthetic
objectives.
1
1
1
3
1
1
1
1
1
.29 (s, 3H), 1.48 (dd, J = 13.9, 3.6 Hz, 1H), 1.69 (s, 3H),
.86 (dd, J = 6.9, 1.6 Hz, 3H), 2.07 (dd, J = 12.4, 3.4 Hz,
H), 2.27 (dd, J = 14.5, 3.4 Hz, 1H), 2.57 (dd, J = 12.3,
.7 Hz, 1H), 3.03 (dd, J = 15.9, 7.2 Hz, 1H), 3.12–3.16 (m,
H), 3.24 (s, 3H), 3.90 (d, J = 10.7 Hz, 1H), 4.16 (d, J =
0.7 Hz, 1H), 4.99 (dd, J = 10.1, 1.3 Hz, 1H), 5.03 (dd, J =
7.2, 1.6 Hz, 1H), 5.09 (d, J = 6.5 Hz, 2H), 5.76 (dddd, J =
7.2, 10.1, 7.1, 5.4 Hz, 1H), 6.14 (dd, J = 15.6, 3.4, 1.6 Hz,
1
3
H), 6.80 (ddd, J = 15.5, 13.8, 6.8 Hz, 1H). C NMR
(
CDCl , 125 MHz) δ: 18.2, 18.8, 23.1, 23.9, 30.1, 32.0, 35.1,
3
4
1
0.3, 41.1, 46.2, 58.1, 58.9, 72.7, 108.4, 115.1, 130.9, 133.3,
Acknowledgements
37.9, 139.1, 141.9, 162.7, 202.3. HR-MS (EI) m/z calcd.
+
for C H O ([M] ): 330.2559; found: 330.2555.
2
2
34
2
We are grateful to the Natural Sciences and Engineering
Research Council of Canada (NSERC) and the Canadian
Breast Cancer Research Initiative (NCI, Canada) for finan-
cial support of this research. N. P. Villalva-Servín thanks
Consejo Nacional de Ciencia y Tecnología (CONACYT)
Government of Mexico for a Graduate Scholarship.
2
,6-Diallyl-5,7,9,9-tetramethyl-8-methylene-3-oxa-
2
,6
tricyclo[5.2.2.0 ]undec-4-ene (23)
–
1
1
9% from 13. IR (neat) (cm ) ν: 3068, 3032–2867, 1671,
1
1
5
1
1
8
631, 1154, 1120, 1002, 921, 888, 859. H NMR (CDCl ,
3
00 MHz) δ: 1.07 (s, 3H), 1.10 (s, 3H), 1.28 (s, 3H), 1.21–
.32 (m, 1H), 1.42–1.47 (m, 1H), 1.50 (d, J = 1.5 Hz, 3H),
.56–1.65 (m, 2H), 1.70–1.81 (m, 1H), 2.44 (dd, J = 16.3,
.1 Hz, 2H), 2.55–2.60 (m, 1H), 2.62–2.64 (m, 1H), 4.78 (d,
References
1
. P. Forgione, P.D. Wilson, G.P.A. Yap, and A.G. Fallis. Synthe-
sis, 921 (2000).
J = 8.3 Hz, 2H), 4.98 (d, J = 9.8 Hz, 1H), 5.00 (d, J =
2
. (a) K.J. Shea and J.W. Gilman. Tetrahedron Lett. 25, 2451
1
1
5.9 Hz, 1H), 5.02 (d, J = 17.9 Hz, 1H), 5.08 (d, J = 8.8 Hz,
(
1984); (b) K.J. Shea, J.W. Gilman, C.D. Haffner, and T.K.
1
3
H), 5.90 (d, J = 1.3 Hz, 1H), 5.80–5.94 (m, 2H). C NMR
Dougherty. J. Am. Chem. Soc. 108, 4953 (1986); (c) R.W.
Jackson and K.J. Shea. Tetrahedron Lett. 35, 1317 (1994).
(
CDCl , 125 MHz) δ: 11.2, 19.1, 21.6, 28.8, 31.7, 32.7, 35.2,
3
3
1
7.4, 42.5, 43.7, 44.3, 57.6, 94.2, 103.8, 114.1, 115.3, 117.1,
3. (a) Y.-F. Lu and A.G. Fallis. Tetrahedron Lett. 34, 3367
(1993); (b) Y.-F. Lu and A.G. Fallis. Can. J. Chem. 73, 2239
(1995).
35.9, 138.6, 140.3, 163.6. HR-MS (EI) m/z calcd. for
+
C H O ([M] ): 298.2297; found: 298.2305.
2
1
30
©
2004 NRC Canada

Villalva-Servín et al.
239
4
. (a) R.K. Hill. In Comprehensive organic synthesis. Vol 5.
Edited by B.M. Trost and I. Flemming. Pergamon Press, Ox-
ford, 1991. Chap 7.1; (b) For oxy-Cope examples see L.A.
Paquette. Tetrahedron, 53, 13 971 (1997).
8. R. Andrade, W.A. Ayer, and L.S. Tifonov. Can. J. Chem. 74,
371 (1996).
9. (a) G. Bérubé and A.G. Fallis. Tetrahedron Lett. 30, 4045
(1989); (b) G. Bérubé and A.G. Fallis. Can. J. Chem. 69, 77
(1991).
5
. For oxy-Cope AB ring syntheses, see (a) F.S. Martin, J.B.
White, and R. Wagner. J. Org. Chem. 47, 3190 (1982);
10. M. Wenz, D. Groβbach, M. Beitzel, and S. Blechert. Synthesis,
(
b) M.G. Banwell, V.S. Bridges, J.R. Dupuche, S. Richards,
607 (1999)
and J.M. Walter. J. Org. Chem. 59, 6338 (1994). For a related
unsuccessful AB ring synthesis approach, see (c) P.A. Zucker
and J.A. Lupia. Synlett, 729 (1990). For a different oxy-Cope
route to Taxusin, see (d) L.A. Paquette and M. Zhao. J. Am.
Chem. Soc. 120, 5203 (1998).
11. D. Bourgeois, A. Pancrazi, S. Nolan, and J. Prunet. Synthesis,
869 (2000).
12. M. Scholl, Ch.S. Ding, W. Lee, and R.H. Grubbs. Org. Lett. 6,
953 (1999).
13. A. Laurent, N.P. Villalva-Servín, P. Forgione, P.D. Wilson,
D.V. Smil, and A.G. Fallis. Can. J. Chem. 82, 215 (2004).
14. N. Bumagin, B. Ponomarev, and P. Beletskaya. Izv. Akad.
Nauk SSSR Ser. Khim. 7, 1565 (1987).
6
7
. (a) Y.-F. Lu, C.W. Harwig, and A.G. Fallis. J. Org. Chem. 58,
4
202 (1993); (b) Y.-F. Lu, C.W. Harwig, and A.G. Fallis. Can.
J. Chem. 73, 2253 (1995).
. K.C. Nicolaou, C.F. Claiborne, P.G. Nantermet, E.A.
Couladouros, and E.J. Sorensen. J. Am. Chem. Soc. 116, 1591
(
1994).
©
2004 NRC Canada