Diastereoselective double ring closing metathesis reactions as an approach to symmetrical bicyclodienes

Article abstract of DOI:10.1139/v00-075

A new class of bicyclic dienes which contain a σ plane of symmetry are efficiently prepared in a diastereoselective fashion using ring closing metathesis reactions. These molecules have potential as starting materials for a wide range of organic targets.

Full text of DOI:10.1139/v00-075

868
Diastereoselective double ring closing metathesis
reactions as an approach to symmetrical
bicyclodienes
Mark Lautens, Gregory Hughes, and Valentin Zunic
Abstract: A new class of bicyclic dienes which contain a σ plane of symmetry are efficiently prepared in a
diastereoselective fashion using ring closing metathesis reactions. These molecules have potential as starting materials
for a wide range of organic targets.
Key words: metathesis, catalysis, stereoselective, decalin, desymmetrization.
Résumé : Faisant appel à des réactions de métathèse de fermeture de cycle, on a développé une méthode efficace de
préparer de façon diastéréosélective une nouvelle classe de diènes bicycliques qui contiennent un plan de symétrie σ.
Ces molécules pourraient éventuellement servir de produit de départ pour une grande variété de cibles organiques.
Mots clés : métathèse, catalyse, stéréosélective, décaline, désymétrisation.
Lautens et al. 883
Introduction
We opted to use unsubstituted tetraenes C for our initial
studies. This simplified system is particularly attractive since
the product of double ring closing metathesis, D, is a useful
starting material for subsequent investigations in the area of
enantioselective alkene differentiation reactions.
In recent years there has been tremendous interest in ring
closing olefin metathesis (RCM) chemistry due largely
to the development of well defined transition metal alkyl-
idenes such as [Cl2(Cy3P)2Ru=CHPh] (1) and [PhMe2-
CCH=Mo=N{2,6-(iPr)2C6H3}{OCMe(CF3)2}2] (2) which
display tolerance to a significant range of functional groups
(for recent reviews of olefin metathesis see ref. (1)). We be-
came interested in using RCM methodology as a key step in
the projected total synthesis of the HMG CoA reductase in-
hibitor (+)-mevinolin (Scheme 1). We reasoned that a dia-
stereoselective double ring closing metathesis strategy
involving A, followed by an alkene selective sigmatropic
rearrangement of a substrate such as B, would provide con-
venient access to the carbon skeleton of the hexahydronapht-
halene portion of the target (for other examples of
diastereoselective RCM reactions see ref. (2)); (for other ex-
amples of double RCM reactions see ref. (3)). A preliminary
report on these investigations has appeared (4).
Results
We envisioned a general approach to a variety of tertiary
diallylic alcohols involving dialkylation of malonate,
Krapcho decarboxylation and addition of two equivalents of
a vinyl organometallic reagent (Scheme 2).
For our first investigations we wanted to prepare a tetraene
derived from double alkylation of malonate with a butenyl
electrophile. The most obvious butenyl source would be
commercially available 4-bromo-1-butene, or a derivative of
3-buten-1-ol (e.g., CH2=CH(CH2)2OTs, CH2=CH(CH2)2OTf,
CH2=CH(CH2)2I). However, the expense of both 4-bromo-1-
butene and 3-buten-1-ol,2 as well as the need to use these
electrophiles in moderate excess due to their tendency to un-
dergo elimination under basic conditions made this approach
less attractive for the large scale preparation of materials
needed for our investigations. We examined an alternative
approach involving sequential additions of malonate to
acrolein, followed by Wittig olefination. While the route fur-
nished the desired dibutenylated malonate, the procedure was
laborious, and the yields were low to moderate. In addition,
the large quantities of triphenyl phosphine oxide produced
on scaling up the reaction made this approach unattractive.
Inspired by the work of Tsuji and co-workers (5) and
Shimizu and co-workers (5), we developed an alternative
strategy for the butenylation of malonates, as well as a vari-
ety of other nucleophiles (6). In this approach, the appropri-
ate nucleophile is alkylated with 1,4-dichlorobutene, which
is a fraction of the cost of either 4-bromo-1-butene or
3-buten-1-ol,2 to afford an allyl chloride. Formate reduction
Received March 7, 2000. Published on the NRC Research
Press website on June 15, 2000.
Dedicated to Professor Stephen Hanessian on the occasion of
his 65th birthday.
M. Lautens,1 G. Hughes, and V. Zunic. University of
Toronto, Department of Chemistry, 80 St. George St.,
Toronto, ON M5S 3H6, Canada.
1Author to whom correspondence may be addressed.
Telephone: (416) 978-6083. Fax: (416) 978-6083.
e-mail: mlautens@alchemy.chem.utoronto.ca
24-Bromo-1-butene: $1088.91/mol; 3-buten-1-ol: $432.44/mol;
1,4-dichlorobut-2-ene (mixture of cis and trans): $20.70/mol.
Prices in Canadian dollars listed in Aldrich’s 1999 catalogue
for the largest available denomination.
Can. J. Chem. 78: 868–883 (2000)
© 2000 NRC Canada

Lautens et al.
869
Scheme 1. Potential retrosynthetic approach to (+)-Mevinolin.
Scheme 2. Synthetic approach to model systems.
verted to ethers 11 and 12 under standard conditions
(Scheme 4).
Scheme 3. Preparation of a dibutenylated malonate: (a) MeO–
Na+ (1.5 equiv.), ClCH2CH=CHCH2Cl (4.0 equiv., mixture of cis
and trans), MeOH, 23°C→reflux, 57%; (b) HCO2NH4 (2.2
equiv.), Pd2dba3 (0.25 mol%), nBu3P (2 mol%), toluene, 100°C,
16 h, 90%.
With the desired tetraenes in hand we initiated the
diastereoselective RCM (DSRCM) studies. Treating 11 with
3 mol% of 1 for 3 h gave the cycloheptene 13 in 70% yield.
Ring closing metathesis via sequential reaction of the two
less hindered alkenes occurs, in spite of the fact that this
leads to seven-membered ring formation rather than the
cyclohexene. However, by increasing the catalyst loading to
10–12mol%, increasing the reaction time to 22 h, and con-
ducting the reaction in the presence of ethylene, it was pos-
sible to isolate cis- and trans-14 in 80% as an 8:1 mixture of
diastereomers with the syn product predominating
(Scheme 5). Similar results were realized using 2 as a cata-
lyst. The successful conversion of 13 to 14 suggested a more
efficient route to 14 using 16. Fortunately, this methyl ester
can be prepared on large scale in good yield from inexpen-
sive materials as outlined in Scheme 6 (9).
In contrast to the reactions of ethers 10 or 12 which give
cis-fused bicyclic compounds, treating free alcohol 9 with 1
for 30 min gave a 2.7:1 mixture of diastereomers where the
trans-fused isomer of 15 is favored (Scheme 5).
We could also form cis-fused diquinane 19 from tetraene
12 by treating it with 4 mol% of 1 for 18 h (Scheme 7). A
6.5:1 ratio was observed between 19 and cyclopentene 20
which fails to undergo further RCM reactions as this would
under Pd catalysis affords the desired butenylated compound
as a single regioisomer within the detection limits of
1H NMR. Dimethyl monobutenylated malonate 3 was
prepared from dimethyl malonate and trans-1,4-dichloro-2-
butene according to a two step procedure described by
Shimizu and Aida (6a). This product was then converted to
allyl chloride 4 using standard alkylation chemistry and fi-
nally to 5 by a Pd catalyzed formate reduction (Scheme 3).
In this manner, 5 could be easily prepared in good overall
yield in batches of 50 g.
Decarboxylation of 5 and its diallyl analogue 6 proceeded
in good yield to give the desired methyl esters 7 and 8. The
addition of 2 equiv. of vinyl lithium or magnesium reagents
to 7 and 8 proved troublesome as the second equivalent
strongly preferred to undergo conjugate addition, to afford
less than 10% of the desired tertiary alcohols 9 and 10 (7). It
had been reported that the addition of two equivalents of a
vinyl cerium reagent to an ester could generate a tertiary al-
cohol in 35% yield (8). The literature conditions called for
the use of 3 equiv. each of vinylmagnesium bromide and
predried CeCl3 at 0°C. We found that more extensive drying
of the CeCl3·7H2O (6–12 h at 140°C, <0.1 mmHg), lower
reaction temperatures (–78°C), and the use of 3.5 equiv. of
vinylmagnesium bromide and 4.0 equiv. of CeCl3 gave 9 and
10 in 86 and 90% respectively. The alcohols were then con-
result in the formation of
a highly strained trans
bicyclo[3.3.0]octadiene system. Again, cyclization with the
less hindered olefin appears to occur initially to give sym-
metrical cyclopentene 18, but upon prolonged reaction times
this intermediate then ring opens and recyclizes to give the
desired bicyclic product.
To examine the diastereoselectivity in the first step of the
cyclization and its reversibility, trienes 22, 23, 26, and 27
were prepared as outlined in Scheme 8. Six-membered ring
precursors were prepared by alkylation of
3
with
TBDPSO(CH2)3Br, followed by Krapcho decarboxylation
and vinylcerium addition to give 22. Protection of the free
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Can. J. Chem. Vol. 78, 2000
Scheme 4. Synthesis of tetraene 3° diallylic alcohols and ethers: (a) NaCl (2.4 equiv.), H2O, DMSO, 180°C, 4 h; (b) CH2=CHMgBr
(3.5 equiv.), CeCl3 (4.0 equiv., anhydrous), THF, –78°C; (c) 9→11: NaH (2.0 equiv.), PMBBr (2.0 equiv.), DMF, 23°C; 10→12: THF,
60°C, KH (2.0 equiv.), BnBr (1.5 equiv.); PMB = p-methoxybenzyl.
Scheme 6. Alternative approach to cycloheptenoates: (a) THF,
0°C; (b) (i) MeI, THF; (ii) NaOH; (iii) H2SO4 (cat.), MeOH.
Scheme 5. DSRCM as an approach to cis- and trans-fused
decalin systems: (a) (PCy)2Cl2Ru=CHPh (3 mol%), CH2Cl2, 3 h;
(b) (PCy3)2Cl2Ru=CHPh (12 mol%), CH2Cl2, ethylene atm, 18 h;
(c) ((CF3)2CH3CO)2Mo(=NAr)(=CHC(CH3)2Ph) (Ar = 2,6-
diisopropylphenyl) (12 mol%), C6H6, 30 min;
(d) (PCy3)2Cl2Ru=CHPh (10 mol%), CH2Cl2, ethylene atm, 18 h;
(e) (PCy3)2Cl2Ru=CHPh (10 mol%), CH2Cl2, closed system,
30 min; (f) CH2=CHMgBr (3.5 equiv.), CeCl3 (4.0 equiv., anhy-
drous), THF, –78°C; (g) NaH (2.0 equiv.), PMBBr (2.0 equiv.),
DMF, 23°C.
Scheme 7. DSRCM as an approach to diquinane systems: 1 (4
mol%), CH2Cl2, 18 h.
alcohol gave 23. Five-membered ring precursors were pre-
pared by alkylation of dimethylmalonate with TBSO(CH2)3Br,
followed by allylation. Krapcho decarboxylation and vinyl
cerium addition then gave 26 and protection of the free alco-
hol gave 27.
Results from treating these trienes with 1 and 2 are sum-
marized in Table 1. Treating 22 with 1 gave a 1:2.8 mixture
of diastereomers favoring trans-28 (CH2=CH : (CH2)3OSiR3)
(entry 1),3 whereas treating 23 with 1 gave a 6.1:1 mixture
of diastereomers favoring the cis (CH2=CH:(CH2)3OSiR3)
isomer (entry 2), and switching to 2 gave slightly higher lev-
els of stereoselectivity (7.8:1, entry 3). Cyclopentenol 30
was formed as a 1:1 mixture of diastereomers upon treat-
ment with 1 (entry 4), whereas the benzyl ether gave rise to
cyclopentene 31 in an 8.0:1 mixture of diastereomers, favor-
ing cis-31 (entry 5). The use of 2 gave the same sense of se-
lectivity in forming 31, but with significantly lower levels of
stereoselectivity (1.7:1, entry 6).
These results parallel the observations made in bicycle
formation suggesting that although RCM transformations are
potentially reversible we did not observe that process in this
series. In fact submitting the minor isomers isolated from the
reaction mixtures to the original reaction conditions failed to
show any equilibration.
3 While somewhat unorthodox, the nomenclature used here to designate relative stereochemistry was chosen for the sake of clarity. In using
(R*,S*) vs. (R*,R*) nomenclature, the designation reverses when ring size is changed from five to six without changing the relative orienta-
tions of the vinyl and alkyl substiuents. The cis and trans designations were chosen on the basis of whether a cis- or trans-fused bicyclic
system would be formed were a second RCM reaction possible. For proof of stereochemistry, see supporting information of ref. (2).
© 2000 NRC Canada

Lautens et al.
871
Table 1. DSRCM from monocycloalkene formation.
Entry
Starting material
Product
Catalyst
Mol%/Time (h)
Yield (%)
cis:trans CH2=CH:(CH2)3OP
1
2
3
4
5
6
22
23
23
26
27
27
28
29
29
30
31
29
1
1
2
1
1
2
12/5
3/3
6/1.5
6/1.5
3/1
80
96
86
65
99
94
1:2.8
6.1:1
7.8:1
1:1
8.0:1
1.7:1
6/0.5
Scheme 8. Synthesis of triene tertiary diallylic alcohols and
ethers: (a) NaH (5.0 equiv.), Br(CH2)3OTBDPS (1.5 equiv.),
THF, 60°C, 48%; (b) NaCl (2.4 equiv.), H2O, DMSO, 180°C,
4 h, 58%; (c) CH2=CHMgBr (3.5 equiv.), CeCl3 (4.0 equiv., an-
hydrous), THF, –78°C, 57% (22), 32% (26); (d) NaH (2.0
equiv.), PMBBr (2.0 equiv.), DMF, 23°C, 67%; (e) (i) NaH (1.0
equiv.), Br(CH2)3OTBS (0.3 equiv.), THF, 60°C, 31%; (ii) NaH
(2.0 equiv.), allyl bromide (1.5 equiv.) THF, 60°C, 83%; (f) KH
(1.5 equiv.), BnBr (1.5 equiv.), THF, 60°C, 89%.
Scheme 10. Preparation of 3° alcohols from α,α-disubstituted
lactones: (a) n = 0: LDA, allyl bromide, THF, –78°C, 80%; n =
1: (i) LDA, 1,4-dichlorobut-2-ene, THF– HMPA (7:1), –78°C;
(ii) HCO2NH4, Pd2dba3, nBu3P, toluene, 100°C, 3 h, 45% (2
steps); (b) LDA, BnBr, THF, 77% (36), 74% (38);
(c) (i) CH2=CHMgBr (3.5 equiv.), CeCl3 (4.0 equiv., anhydrous),
THF, –78°C; (ii) TBSCl (1.05 equiv.), imidazole (1.5 equiv.),
DMF, 23°C, 57% (39), 48% (41); (d) KH (3.0 equiv.), BnBr (1.5
equiv.), THF, 23°C, 12 h, 85% (40), 90% (42).
by reaction with vinylcerium gave tertiary alcohols 39 and
41 in good overall yields as outlined in Scheme 10. Selec-
tive protection of the primary alcohols followed by benzyl-
ation of the tertiary alcohols furnished ethers 40 and 42.
The butenylation of butyrolactone with conventional
methodologies gave only low yields of 37 (<10%), but the
two step approach mentioned above for the butenylation of a
variety of nucleophiles proved to be more successful (6).
Thus, alkylation with 1,4-dichlorobut-2-ene, followed by Pd
catalyzed formate reduction furnished 37 in 45% yield over
two steps.
The results from treating these trienes with Grubbs’ catalyst
are summarized in Table 2. Reaction of 39 with 1 (24-hour
portion-wise addition) gave cyclopentene 43 as essentially a
single diastereomer in 60% isolated yield. This diastereomer
was shown to be trans-43 (CH2=CH:(CH2)2OSiR3) by
ROSEY experiments (10). Treatment of 40 with the same
catalyst gave a 2:1 mixture with cis-44 (CH2=CH:(CH2)3OSiR3)
now being favored.
Scheme 9. Failure of esters having an α tertiary center to un-
dergo reaction with vinyl cerium.
To probe the effect of bridgehead substituents on the effi-
ciency and diastereoselectivity of the DRCM, substrates 32
and 33 were treated with the vinylcerium reagent but both
failed to give the desired products. Steric effects at the α po-
sition may be responsible. (Scheme 9).
This problem was overcome by the use of lactones, where
the third substituent is incorporated into the ring. For exam-
ple, double alkylation to give lactones 36 and 38 followed
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Can. J. Chem. Vol. 78, 2000
Table 2. DSRCM for 3° diallylic systems having an α tertiary center.
Entry
Starting Material
Product
Mol%/ Time (h)
Yield (%)
cis:trans CH2=CH:(CH2)3OP
1
2
3
4
39
40
41
42
43
44
45
46
15/24
15/24
8/12
60a
100b
100b
100b
<1:>20
2:1
1:1
8/12
4.5:1
aIsolated yield.
1
bBased on 100% conversion by H NMR (400 MHz) analysis.
free alcohol cis-15 was converted to propargyl ether 53 in
two steps. Treatment with t-BuLi at –78οC gave the [2,3]-
Wittig rearrangement product in 63% yield as a 2:1 mixture
of diastereomeric alcohols.
Scheme 11. [2,3] Wittig rearrangements as an approach to the
hexahydronaphthalene portion (+)–melvinolin: (a) KH (3.0
equiv.), 18-crown-6 (cat.), ICH2SnBu3 (1.5 equiv.), THF, reflux,
93%; (b) 1 (12 mol%), CH2=CH2, CH2Cl2, reflux, 86%;
(c) MeLi (1.05 equiv.), HMPA (4.0 equiv.), THF, –78°C, 67%;
(d) KH (2.0 equiv.), TMSCl (1.05 equiv.), THF, 90%; (e) 2 (10
mol%), C6H6, 99%, dr = 5:1; (f) TBAF (3.0 equiv.), THF, 23°C,
86%; (g) NaH (5.0 equiv.), BrCH2CϵCH (5.0 equiv.), THF, 46%;
(h) n-BuLi (1.1 equiv.), MeI (1.5 equiv.), THF, –78°C, 90%;
(i) t-BuLi (4.0 equiv.), THF,–78°C, 63%
Discussion
Based on our studies and previous work outlining the re-
activity patterns of various olefins (13), we propose the fol-
lowing reaction pathway for decalin formation from 11 and
12.
(dr = 2:1).
Transalkylidenation in 11 or 12 occurs at one of the two
olefins lacking an α substituent to give 55/56 (Scheme 12).
These intermediates then cyclizes initially to give cyclo-
alkenes 13 or 18. The formation of both 13 and 18 is revers-
ible, as demonstrated by the observation that 13 and 18 are
alternative entries into the catalytic cycle. A second less fa-
vorable but irreversible pathway involves cyclization onto
one of the two more sterically hindered diastereotopic olefins
to give either cis-57/20 or trans-57/20. The formation of
these cycloalkenes has been proven to be irreversible under
all conditions examined to date. RCM between the two re-
maining acyclic olefins then affords bicyclic products, a pro-
cess which should also be initiated by reaction at the less
hindered alkene. While both cis- and trans-57 will go on to give
the corresponding cis- and trans-fused hexahydronaphtha-
lenes, only cis-20 goes onto to cis-fused diquinane as further
cyclization of trans-20 would give rise to a highly unstable
trans-fused bicyclo[3.3.0] compound.
Double cyclization of free alcohols display interesting dif-
ferences in diastereoselectivity compared to their protected
analogues. As others have previously noted (14), free alco-
hols appear to cyclize at accelerated rates relative to the
analogous ethers. For example whereas the p-methoxybenzyl
ether 11 reacts to give the cycloheptene 13 faster than to
form a cyclohexene 57, we have been unable to observe the
formation of cycloheptene 17 when free alcohol 9 is used as
starting material. In fact, when 17 is used as starting mate-
rial, no conversion to decalin is observed, suggesting that
alkylidene formation may be taking place at the more
hindered olefin (Scheme 13). The implications of these
observations with regard to stereoselectivity issues are in-
triguing and are currently under investigation.
Cyclohexenes having a bridgehead substituent were also
formed in good yields. Treatment of the free alcohol 41 with
1 provided 45 as a 1:1 mixture of diastereomers. The analo-
gous benzyl protected ethers were formed in a 4.5:1 mixture
of diastereomers, favoring cis-46.
We have investigated potentially useful derivatizations of
the bicyclic compounds. Deprotonation of 8 with KH, fol-
lowed by alkylation with an iodomethyl stannane proceeds
in good yield. DSRCM occurred in high yield to give the de-
sired bicycle 48. Treating this stannyl methyl ether with
MeLi at –78οC afforded a 67% yield of the [2,3]-Wittig rear-
rangement product 49 (Scheme 11) (11).
A variation of the Wittig rearrangement was also investi-
gated involving methyl propargyl ether 53, prepared as out-
lined in Scheme 11 (12). DSRCM of 50 with 2 (12 mol%,
0.5 h) gave a 5:1 mixture of diastereomers. Desilylation af-
forded a separable mixture of free alcohols. The cis-fused
© 2000 NRC Canada

Lautens et al.
873
Scheme 12. Reaction pathway of decalin and diquinane formation.
Scheme 13. DSRCM reactions involving free alcohols.
sieves. HMPA was distilled under reduced pressure from
CaH2. CH2Cl2 was distilled from CaH2. Grubbs’ catalyst
was prepared according to a literature procedure (16) and
triturated for 12–18 h in a 1:1 mixture of acetone and metha-
nol. The absence of free tricyclohexyl phosphine and
tricyclohexyl phosphine oxide was confirmed by 31P NMR,
and was crucial in order for the double metathesis reactions
to proceed. Schrock’s catalyst was used as received from
Strem. Computational work was done using MacSpartan Plus©,
version 1.1.7 (Wavefunction Int. Irvine, Calif. 1996–1997).
The effect of added ethylene depends on the structure of
the tetraene (for examples of other systems where added eth-
ylene was found to enhance RCM see ref. (15)), enhancing
the conversion with some substrates and hindering the cycli-
zation of others. For example, when cyclizing free alcohol 9,
the use of an ethylene atmosphere resulted in incomplete
conversion (~50%) before the catalyst decomposed. If the
reaction was repeated but using a stream of Ar, the reaction
also failed to go to completion. However when the reaction
was conducted in a sealed system so that the ethylene pro-
duced upon cyclization was retained, complete consumption
of starting material was observed. The cause of these effects
are somewhat puzzling and warrant further study.
General procedure for the decarboxylation of dimethyl
malonates
To a 23°C solution of malonate in DMSO (1.0 M) was
added NaCl (1.5 equiv.) and water (1 drop/1 mL DMSO).
The resulting mixture was heated to 180°C for 5–10 h. The
mixture was cooled to 23°C, diluted with ether and washed
with water. The aqueous layer was extracted three times with
ether. The organic layers were combined, washed with brine,
dried over magnesium sulfate, and filtered. The filtrate was
concentrated in vacuo and purified by flash chromatography
on silica gel.
The relative sensitivities of the cis- and trans-fused
decalins also warrants further mention. As one might expect,
the tertiary diallylic alcohols and ethers are susceptible to
solvolysis under acidic conditions. While most of the RCM
precursors and the monocyclic intermediates could be iso-
lated without difficulty, bicyclic materials were found to de-
compose upon chromatography unless the silica gel was
neutralized with triethyl amine. The trans-fused decalins
were found to be particularly acid sensitive, decomposing
during TLC development, while the cis-fused analogues did
not. Geometry optimization calculations (3–21G*) of cis-15
and trans-15 revealed that the dihedral angles between the
olefin planes and the allylic C—O bond are 130° and 97° for
cis-15, whereas both dihedral angles in trans-15 are 90°,
leaving the C—O bond in an antiperiplanar orientation with
both double bonds, which would be expected to lower the
energy barrier to carbenium ion formation.
General procedure for the conversion of methyl esters
to diallylic tertiary alcohols
CeCl3·7H20 (4.0 equiv.) was ground with a mortar and
pestle, placed under vacuum (<0.1 mmHg) and warmed to
140°C for 2 h. A stir bar was added and heating under vac-
uum continued for a further 4–10 h. The resulting powder
was cooled to 0°C and THF (3 mL/mmol of CeCl3) was
added via cannula under vacuum. The remaining vacuum
was displaced with N2 and the resulting suspension stirred
for 24 h, then cooled to –78°C. Vinylmagnesium bromide
(~1 M in THF, 3.5 equiv.) was added via syringe at a rate
such that the internal temperature was kept below –65°C.
Experimental
Toluene and THF were distilled from sodium–benzophe-
none. DMF was dried by prolonged standing over molecular
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Can. J. Chem. Vol. 78, 2000
After 1 h a solution of ester (1.0 equiv.) in THF (~1 M) was
added via cannula at a rate such that the internal tempera-
ture did not exceed –65°C. After 30 min, the mixture was di-
luted with ethyl acetate and water was added. The organic
layer was decanted off and the aqueous slurry extracted
three times with ethyl acetate. The organic layers were com-
bined, washed with brine, dried over sodium sulfate, and fil-
tered. The filtrate was concentrated in vacuo and purified by
flash chromatography on triethyl amine washed silica gel.
orless oil (606 mg, 53%). IR (neat): 3478, 3078, 2934, 2978,
1640, 1456, 1414, 1300, 996, 912, 735. 1H NMR (400 MHz,
CDCl3) δ : 1.18–1.28 (m, 2H), 1.41–1.49 (m, 2H), 1.59–1.69
(m 2H), 1.97–2.08 (m, 2H), 2.09–2.20 (m, 2H), 4.92
(dm, J = 10 Hz, 2H), 4.98 (dq, J = 17, 2 Hz, 2H), 5.14(dd,
J = 11, 1 Hz, 2H), 5.25 (dd, J = 17, 1 Hz, 2H), 5.71–5.82
(m, 2H), 5.94 (dd, J = 17, 11 Hz, 2H). 13C NMR (100 MHz,
CDCl3) δ : 29.39, 32.99, 45.78, 79.05, 113.42, 114.41,
138.97, 142.07.
General procedure for the p-methoxy benzylation of
tertiary diallylic alcohols
4-Allyl-3-vinyl-hepta-1,5-dien-3-ol (10)
Methyl 2-propenylpent-4-enoate 8 (600 mg, 3.89 mmol)
was reacted according to the general procedure for the for-
mation of a tertiary diallylic alcohol. Purification by flash
chromatography (5% ether–hexanes) on triethyl amine
washed silica gel yielded the title compound as a colorless
oil (460 mg, 66%). Rf = 0.19 (5% ether). IR (neat): 3072,
2933, 2859, 1738, 1642, 1473, 1428, 1390, 1195, 1164,
1112, 998, 917, 824, 741, 703, 614. 1NMR (400 MHz,
CDCl3) δ : 1.70 (sept., J = 4 Hz, 1H), 1.87 (s, 1H), 2.07
(quint, J = 8 Hz, 2H), 2.28–2.36 (m, 2H), 5.00 (d, J = 9 Hz,
2H), 5.03 (d, J = 17 Hz, 2H), 5.79–5.91 (m, 2H), 5.95 (dd,
J = 17 Hz, 11 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ :
19.20, 23.65, 26.85, 31.60, 32.38, 36.42, 45.32, 51.33, 63.60,
116.62, 127.57, 129.49, 134.05, 135.50, 135.54, 176.04.
HRMS calcd. for (M-H)+: 177.1279; found: 177.1287.
NaH (60% suspension in oil, 5.0 equiv.) was washed three
times with pentane, dried under a stream of N2 and sus-
pended in DMF (0.3 M). A solution of alcohol in DMF (1.0
M) was added via cannula at a rate such the H2 evolution is
controlled. After 5 min, PMBBr was added via syringe and
the resulting mixture was stirred at 23°C for 16 h. The mix-
ture was diluted with ether and the reaction carefully
quenched by drop-wise addition of saturated ammonium
chloride. The aqueous layer was extracted three times with
ether; the organic layers were combined, washed with brine,
dried over sodium sulfate, and filtered. The filtrate was con-
centrated in vacuo and purified by flash chromatography on
triethyl amine washed silica gel.
General procedure for the benzylation of tertiary
diallylic alcohols
[2-But-3-enyl-1,1-divinyl-hex-5-enyloxymethyl]-4-methoxy-
Potassium hydride (35% suspension in oil, 1.5 equiv.) was
washed three times with pentane, dried under a stream of ar-
gon, and suspended in THF (half of total reaction volume).
A solution of alcohol in THF (half of reaction volume, reac-
tion concentration of 0.2 M) was added via cannula. The re-
sulting suspension was warmed to 60°C and after 10 min
benzyl bromide (1.5 equiv.) was added via syringe and the
resulting mixture was stirred for an hour, cooled to 23°C, di-
luted with ether, and quenched carefully by drop-wise addi-
tion of water. The aqueous layer was extracted two times
with ether, the organic layers were combined, washed with
brine, dried over sodium sulfate, filtered and concentrated in
vacuo. The residue was purified by flash chromatography on
triethyl amine washed silica gel.
benzene (11)
Alcohol 9 (200 mg, 0.969 mmol), was reacted according
to the general procedure for the p-methoxy benzylation of
tertiary diallylic alcohols. The crude mixture was purified by
flash chromatography (5% ether–hexanes) on triethyl amine
washed silica gel to yield the title compound as a pale green
oil (240 mg, 76%). IR (neat): 3478, 3078, 2934, 2978, 1640,
1456, 1414, 1300, 996, 912, 735. 1H NMR (400 MHz,
CDCl3) δ : 1.11–1.22 (m, 2H), 1.60 (hept, J = 4 Hz, 1H),
1.67–1.77 (m, 2H), 2.02–2.21 (m, 4H), 3.81 (s, 3H), 4.31 (s,
2H), 4.94 (dm, J = 10 Hz, 2H), 5.01 (dq, J = 17, 2 Hz, 2H),
5.31 (dd, J = 18, 1.5 Hz, 2H), 5.37 (dd, J = 11, 2 Hz, 2H),
5.76–5.86 (m, 2H), 5.88 (dd, J = 18, 11 Hz, 2H), 6.88 (AB,
J = 9 Hz, 2H), 7.26 (AB, J = 9 Hz, 2H). 13C NMR
(100 MHz, CDCl3) δ : 30.05, 33.37, 47.30, 55.24, 64.82,
83.96, 113.57, 114.18, 117.39.
Methyl 2-(but-3-enyl) hex-5-enoate (7)
2,2 Di-(2-but-3-enyl) malonic acid dimethyl ester 5
(6.70 g, 27.9 mmol) was reacted according to the general
procedure for decarboxylation. The crude product was puri-
fied by flash chromatography (3% ether–hexanes) to yield
the title compound as a colorless oil (3.62 g, 71%). 1H NMR
(400 MHz, CDCl3) δ : 1.48–1.57 (m, 2H), 1.64–1.76 (m,
2H), 1.94–2.08 (m, 4H), 2.35–2.43 (m, 1H), 4.94 (dq, J = 9,
1 Hz, 2H), 4.98 (dm, J = 17, 2 Hz, 2H), 5.69–5.79 (m, 2H).
13C NMR (100 MHz, CDCl3) δ : 31.52, 44.35, 51.36, 114.89,
137.70, 176.00.
[2-Allyl-1,1-divinyl-pent-4-enyloxymethyl] benzene (12)
Tertiary alcohol 10 (500 mg, 2.80 mmol) was reacted ac-
cording to the general procedure for the benzylation of ter-
tiary diallylic alcohols. The crude product was purified by
flash chromatography (100% hexanes –> 2% ether–hexanes)
on triethyl amine washed silica gel to yield the title com-
pound as a colorless oil (590 mg, 78%). Rf = 0.29 (2%
ether–hexanes). IR (neat): 3074, 2920, 1639, 1497, 1453,
1414, 1377, 1096, 1064, 1000, 910, 729. 1H NMR
(400 MHz, CDCl3) δ : 1.84 (sept., J = 4 Hz, 1H), 1.96 (dt,
J = 14, 8 Hz, 2H), 2.44 (dm, J = 14.5 Hz, 2H), 4.38 (s, 2H),
4.94 (d, J = 11 Hz, 2H), 4.98 (d, J = 18 Hz, 2H), 5.79–5.90
(m, 2H), 5.90 (dd, J = 18, 11 Hz, 2H), 7.21–7.26 (m, 1H),
7.29–7.36 (m, 4H). 13C NMR (100 MHz, CDCl3) δ : 34.41,
48.07, 65.15, 83.53, 115.12, 117.63, 126.79, 126.85, 128.15,
2-But-3-enyl-1-vinyl-octa-1,7-dien-3-ol (9)
Methyl ester 7 (1.00 g, 5.49 mmol) was reacted according
to the general procedure for the conversion of methyl esters
to tertiary diallylic alcohols. The crude mixture was purified
by flash chromatography (3% ether–hexanes) on triethyl
amine washed silica gel to yield the title compound as a col-
© 2000 NRC Canada

Lautens et al.
875
137.87, 138.73, 139.88. HRMS calcd. for (M-H)+: 267.1749;
found: 267.1734.
2H). 13C NMR δ: 23.11, 24.27, 39.70, 38.34, 128.19,
131.34. HRMS calcd. for C10H14O+ (M+): 150.1045; found:
150.1044.
4a-(4-Methoxy-benzyloxy)-1,2,4a,7,8,8a-hexahydronaph-
thalene (14) (Ru Cat.)
cis-3a-Benzyloxy-1,3a,6,6a-tetrahydro-pentalene (19) (Ru Cat.)
To a solution of benzyl ether 12 (100 mg, 0.372 mmol) in
dichloromethane (4 mL) at 23°C was added 1 (12 mg, 0.04
equiv.). The resulting solution was stirred under an ethylene
atmosphere for 20 h before PPh3 (14 mg, 0.053 mmol) was
added and the mixture concentrated in vacuo. The residue
was purified by flash chromatography (2% ether–hexanes)
on triethyl amine washed silica gel to yield the title com-
pound as a colorless oil along with cyclopentene 20 (63 mg,
80%) and (12 mg, 13%), respectively. Rf = 0.11 and 0.34
(2% ether–hexanes) respectively. IR (neat) 3053, 2919,
2848, 1497, 1448, 1378, 1349, 1216, 1139, 1099, 1028, 991,
To a solution of 11 (200 mg, 0.613 mmol) in dichloro-
methane (12 mL) at 23°C was added 1 (61 mg, 0.073 mmol)
and the mixture was placed under an atmosphere of ethyl-
ene. After 18 h, the mixture was concentrated in vacuo. The
residue was purified by flash chromatography (3% ether–
hexanes) on triethyl amine washed silica gel to yield the title
compound as a colorless oil (115 mg, 70%). Rf = 0.15 (4%
ether–hexanes). IR (neat): 3019, 2826, 1653, 1613, 1586,
1559, 1513, 1456, 1374, 1301, 1248, 1172, 1034, 947, 821.
1H NMR (400 MHz, CDCl3) δ : 1.50–1.61 (m, 2H), 1.85
(quintd, J = 6.5, 3.5 Hz, 2H), 1.98–2.14 (m, 4H), 2.19 (hept,
J = 4 Hz, 1H), 3.79 (s, 3H), 4.38 (s, 2H), 5.61 (dt, J = 10,
2 Hz, 2H), 5.87 (dt, J = 10, 4 Hz, 2H), 6.85 (AB, J = 9 Hz,
2H), 7.25 (AB, J = 9 Hz, 2H). 13C NMR (100 MHz, CDCl3)
δ : 23.32, 24.29, 34.43, 55.25, 64.10, 74.14, 113.70, 129.05,
129.64, 130.27, 132.18, 158.87. HRMS calcd. form M+:
270.1620; found: 270.1611.
1
733, 697. H NMR (400 MHz, CDCl3) δ: 2.06–2.15 (m,
2H), 2.81–2.91 (m, 3H), 4.42 (s, 2H), 5.83 (dt, J = 6, 2 Hz,
2H), 5.92 (dt, J = 6, 2 Hz, 2H), 7.21–7.26 (m, 1H), 7.28–
7.35 (m, 4H). 13C NMR δ: 40.72, 43.03, 65.58, 105.70,
127.16, 127.55, 128.25, 132.54, 134.27, 139.56. HRMS
calcd. for C15H16O (M+): 212.1201; found: 212.1196.
1
Cyclopentene intermediate 11: H NMR (400 MHz, CDCl3)
Cycloheptene intermediate: 5-(penta-1,4-dien-3-ol, p-methoxy
benzyl ether)-cyclohept-1-ene (13): Rf = 0.37 (4% ether–
hexanes). IR (neat): 2919, 1612, 1585, 1512, 1450, 1300,
δ: 2.38 (d, J = 6 Hz, 4H), 2.74 (quint, J = 8Hz, 1H), 4.43 (s,
2H), 5.32 (AB, J = 1.5 Hz, 2H), 5.35 (q, J = 1.5 Hz, 2H),
5.62 (s, 2H), 5.90 (dd, J = 18, 10.5 Hz, 2H), 7.22–7.26 (m,
1H), 7.30–7.37 (m, 4H). 13C NMR δ: 34.27, 45.33, 65.089,
82.77, 117.11, 126.82, 126.87, 128.15, 129.74, 138.04.
1
1247, 1108, 1037, 927, 820, 737, 697. H NMR (400 MHz,
CDCl3) δ: 1.05 (q, J = 11 Hz, 2H)1.77 (tt, J = 11, 3 Hz, 1H),
1.92–2.06 (m, 4H), 2.21–2.33 (m, 2H), 3.79 (s, 3H), 4.29 (s,
2H), 5.28 (dd, J = 18, 6 Hz, 2H), 5.35 (dd, J = 11, 2 Hz,
2H), 5.72–5.80 (m, 2H), 5.86 (dd, J = 18, 11 Hz, 2H), 6.87
(AB, J = 9 Hz, 2H), 7.26 (AB, J = 9 Hz, 2H). 13C NMR
(100 MHz, CDCl3) δ: 27.98, 28.02, 52.62, 55.24, 64.72,
83.36, 117.25, 128.21, 131.87, 132.06, 138.16, 158.65.
2-But-3-enyl-2-(3-tert-butyldiphenylsiloxy-propyl) malonic
acid dimethyl ester (20)
Sodium hydride (1.10 g, 32.2 mmol) was washed three
times with pentane, dried under a stream of nitrogen, and
suspended in DMF (40 mL). A solution of dimethyl but-3-
enyl malonate 3 (4.00 g, 21.5 mmol) in DMF (10 mL) was
added via cannula at a rate such that hydrogen evolution was
controlled. After 30 min, a solution TBDPSO(CH2)3Br in
DMF (10 mL) was added via cannula. After 20 h, the mix-
ture diluted with ether and quenched by careful addition of
water. The aqueous layer was extracted with ether, the
organic layers were combined, washed with brine, dried over
magnesium sulfate, filtered and concentrated in vacuo. The
residue was purified by flash chromatography (5% ether–
hexanes) to yield the title compound as a colorless oil
(5.00 g, 48%). IR (neat): 2954, 2858, 1732, 1434, 1257,
1104, 837, 776. 1H NMR (400 MHz, CDCl3) δ: 1.05 (s, 9H),
1.36–1.46 (m, 3H), 1.89–2.05 (m, 7H) 3.65 (t, J = 6 Hz,
2H), 3.70 (s, 6H), 4.97 (dd, J = 10, 1.5 Hz, 1H), 5.03 (dd, J
= 17, 1.5 Hz, 1H), 5.72–5.83 (m, 1H), 7.36–7.45 (m, 6H),
7.64–7.67 (m, 4H). 13C NMR (100 MHz, CDCl3) δ: 19.17,
26.81, 27.28, 28.30, 28.91, 31.60, 52.29, 57.04, 63.57,
115.00, 127.60, 129.56, 133.79, 135.52, 137.46, 172.02.
HRMS calcd. for C24H29O5Si (M-C4H9): 425.1784; found:
425.1793.
4a-(4-Methoxy-benzyloxy)-1,2,4a,7,8,8a-hexahydronaphthalene
(14) (Mo Cat.)
To a solution of 11 (47 mg, 0.142 mmol) in C6H6 (0.5 mL)
at 23°C was added a solution of 2 (12 mg, 0.016 mmol) in
C6H6 (1.5 mL). After 20 h the mixture was concentrated in
vacuo and the residue purified by flash chromatography (3%
ether–hexanes) on triethyl amine washed silica gel to yield
the title compound as a colorless oil (28 mg, 73%).
cis- and trans-2,7,8,8a-Tetrahydro-1H-naphthalen-4-ol (15)
To a solution of 9 (100 mg, 0.242 mmol) in dichloro-
methane (4.5 mL) at 23°C was added
1 (40 mg,
0.049 mmol). After 1 hour PPh3 (17 mg, 0.065 mmol) was
added and the mixture was concentrated in vacuo and the
residue was purified by flash chromatography (30% ether–
hexanes) on triethyl amine washed silica gel to yield the title
compounds as a white solid and a colorless oil (45 mg, 62%
(trans)), (16 mg, 22% (cis)). Due to the sensitivity of the
trans compound, it was immediately hydrogenated and char-
acterized. The structure of the resulting decahydrona-
phthalenol was confirmed by comparison to spectral data
reported in the literature (17).
2-(3-tert-Butyldiphenylsiloxy-propyl)-hex-5-enoic acid
methyl ester (21)
cis-: IR (neat): 3351, 3023, 2908, 1429, 1383, 1326, 1204,
1021, 960. H NMR (400 Mhz, CDCl3) δ: 1.49–1.60 (m,
2H), 1.76–1.84 (m, 2H), 1.87–1.94 (m, 1H), 2.01–2.07 (m,
4H), 5.58 (dt, J = 10, 2 Hz, 2H), 5.77 (dt, J = 10, 3.7 Hz,
Malonate 20 (5.00 g, 10.4 mmol) was reacted according
to the general procedure for decarboxylation. The crude
mixture was purified by flash chromatography (5% ether–
hexanes) to yield title compound as a colorless oil (2.58 g,
1
© 2000 NRC Canada

876
Can. J. Chem. Vol. 78, 2000
1
58%). IR (neat): 2930, 1734, 1428, 1111. H NMR (CDCl3)
δ: 1.05 (s, 9H), 1.49–1.79 (m, 6H), 2.00–2.08 (m, 2H), 2.35–
2.44 (m, 1H), 3.63–3.68 (m, 5H), 4.97 (dm, J = 10 Hz, 1H),
5.02 (dq, J = 17, 2 Hz, 1H), 5.72–5.83 (m, 1H), 7.36–7.46
(m, 6H), 7.65–7.69 (m, 4H). 13C NMR (100 MHz, CDCl3) δ:
19.20, 26.84, 28.59, 30.22, 31.47, 31.54, 44.62, 51.33,
63.51, 115.02, 127.59, 129.53, 133.94, 135.54, 137.85,
temperature. After 30 min, a solution of TBDPSO(CH2)3Br
(8.80 g, 34.7 mmol) in DMF (10 mL) was added via can-
nula. After 14 h, the mixture was diluted with ether and
quenched carefully with water. The aqueous layer was
washed three times with ether; the organic layers were com-
bined, washed with brine, dried over magnesium sulfate, and
filtered. The filtrate was concentrated in vacuo and the resi-
due purified by fractional distillation. Collection of the frac-
tion boiling between 100–110°C (0.1 mmHg) yielded the
monoalkylated malonate as a colorless liquid (3.26 g, 31%).
Rf = 0.23 (15% ether–hexanes). IR (neat): 2955, 2858, 1768,
+
176.51. HRMS calcd. for C22H25O3Si (M-C4H9 ): 367.1729;
found: 367.1725.
4-(3-tert-Butyldiphenylsiloxy-propyl)-3-vinyl-hepta-1,6-dien-
3-ol (22)
1
1436, 1389, 1255, 1155, 1099, 1009, 837, 777. H NMR
(400 MHz, CDCl3) δ: 0.03 (s, 6H), 0.88 (s, 9H), 1.49–1.57
(m, 2H), 1.91–2.00 (m, 2H), 3.41 (t, J = 8 Hz, 1H), 3.62 (t,
J = 6 Hz, 2H), 3.73 (s, 6H). 13C NMR (100 MHz, CDCl3) δ:
–5.41, 18.26, 25.47, 25.87, 30.27, 51.35, 52.39, 62.40,
169.86. HRMS calcd. for (M-CH3)+: 289.1471; found:
289.1474.
Methyl ester 26 (1.25 g, 2.94 mmol) was reacted accord-
ing to the general procedure for the conversion of a methyl
ester to a tertiary diallylic alcohol. The crude product was
purified by flash chromatography (8% ether–hexanes) on
triethyl amine washed silica gel to yield the title compound
as a pale green oil (754 mg, 57%). Rf = 0.25 (10% ether–
1
Sodium hydride (0.509 g, 21.2 mmol) was washed three
times with pentane and suspended in THF (20 mL). A solu-
tion of the monoalkylated malonate prepared as described
above (3.00 g, 9.85 mmol) in THF (20 mL) was added via
cannula at a rate such that H2 evolution is controlled. After
15 min, allyl bromide (1.86 mL, 21.2 mmol) was added via
syringe. After 1 h the mixture was diluted with ether,
quenched carefully with water, and the aqueous layer was
extracted two times with ether. The organic layers were
combined, washed with brine, dried over magnesium sulfate
and filtered. The filtrate was concentrated in vacuo and puri-
fied by flash chromatography (10% ether–hexanes) on silica
gel to yield the title compound as a colorless oil (2.80 g,
83%). Rf = 0.32 (15% ether–hexanes). IR (neat): 2954, 2858,
1737, 1435, 1388, 1361, 1256, 1210, 1099, 1034, 921, 837,
hexanes). IR (neat): 3475, 2930, 1636, 1472, 1427, 1111. H
NMR (400 MHz, CDCl3) δ: 1.05 (s, 9H), 1.14–1.26 (m, 2H),
1.38–1.44 (m, 1H), 1.46–1.69 (m, 5H), 1.94–2.06 (m, 1H),
2.09–2.20 (m, 1H), 3.63 (t, J = 6 Hz, 2H), 4.93 (dm, J =
10 Hz, 1H), 4.98 (dq, J = 17, 2 Hz, 1H), 5.14 (ddd, J = 11,
3.5, 1 Hz, 2H), 5.25 (ddd, J = 17, 4, 1 Hz, 2H), 5.71–5.82
(m, 1H), 5.94 (ddd, J = 17, 11, 2 Hz, 2H), 7.35–7.45 (m,
6H), 7.65–7.69 (m, 4H). 13C NMR (100 MHz, CDCl3) δ:
19.19, 26.09, 26.87, 29.38, 31.86, 32.86, 46.18, 64.14,
79.10, 113.37, 114.39, 127.56, 129.50, 134.05, 135.57,
139.02, 142.06, 142.15. HRMS calcd. for C25H31O2Si (M-
+
C4H9 ): 391.2093; found: 391.2098.
[2-(3-tert-Butyldiphenylsiloxy-propyl)-1,1-divinyl-hex-5-
enyloxymethyl]-4-methoxy-benzene (23)
1
776. H NMR (400 MHz, CDCl3) δ: 0.03 (s, 6H), 0.87 (s,
Alcohol 22 (400 mg, 0.891 mmol) was reacted according
to the general procedure for the p-methoxy benzylation of
tertiary diallylic alcohols. The crude material was purified
by flash chromatography (2% ether–hexanes) on triethyl
amine washed silica gel to yield the title compound as a col-
orless oil (325 mg, 65%). Rf = 0.22 (5% ether–hexanes). IR
(neat): 2930, 1615, 1513, 1428, 1247, 1111. 1H NMR
(400 MHz, CDCl3) δ: 1.08 (s, 9H), 1.12–1.24 (m, 2H), 1.55–
1.80 (m, 5H), 2.02–2.23 (m, 2H), 3.66 (t, J = 6 Hz, 2H),
3.81 (s, 3H), 4.32 (s, 2H), 4.95 (dm, J = 10 Hz, 1H), 5.01
(dq, J = 17, 2 Hz, 1H), 5.31 (dt, J = 18, 1.5 Hz, 2H), 5.37
(ddd, J = 11, 4, 1.5 Hz, 2H), 5.78–5.87 (m 1H), 5.88 (ddd,
J = 18, 11, 1 Hz, 2H), 6.87 (AB, J = 9 Hz, 2H), 7.27 (AB,
J = 9 Hz, 2H), 7.37–7.47 (m, 6H), 7.68–7.72 (m, 4H). 13C
NMR (100 MHz, CDCl3) δ: 19.20, 26.81, 26.88, 30.01,
32.29, 33.28, 47.70, 55.22, 64.37, 64.82, 84.01, 113.58,
114.13, 117.28, 127.54, 128.13, 129.45, 132.14, 134.16,
135.57, 138.15, 138.23, 139.35, 158.54. HRMS calcd. for
9H), 1.35–1.44 (m, 2H), 1.87–1.95 (m, 2H), 2.64 (d, J =
7 Hz, 2H), 3.58 (t, J = 6 Hz, 2H), 3.70 (s, 6H), 5.05–5.13
(m, 2H), 5.57–5.69 (m, 1H). 13C NMR (100 MHz, CDCl3) δ:
–5.36, 18.26, 25.89, 27.45, 28.84, 37.09, 52.29, 57.38,
62.86, 118.91, 132.38, 171.68. HRMS calcd. for (M-CH3)+:
329.1784; found: 329.1801.
2-(3-tert-Butyldimethylsiloxy-propyl)-pentenoic acid methyl
ester (25)
Malonate 24 (2.61 g, 7.58 mmol) was reacted according
to the general decarboxylation procedure. The crude mixture
was purified by flash chromatography (7% ether–hexanes) to
yield the title compound as a colorless oil (960 mg, 44%).
Rf = 0.20 (5% ether–hexanes). IR (neat): 2952, 2858, 1740,
1361, 1256, 1167, 1102, 1006, 915, 837, 776. 1H NMR
(400 MHz, CDCl3) δ: 0.02 (s, 6H), 0.87 (s, 9H), 1.44–1.66
(m, 4H), 2.18–2.26 (m, 1H), 2.30–2.40 (m, 1H), 2.41–2.49
(m, 1H), 3.58 (td, J = 6, J = 2 Hz, 2H), 3.65 (s, 3H), 4.97–
5.08 (m, 2H), 5.66–5.78 (m, 1H). 13C NMR (100 MHz,
CDCl3) δ: –5.36, 18.27, 25.89, 28.07, 30.40, 36.45, 44.97,
51.34, 62.72, 116.68, 135.41, 175.97. HRMS calcd. for (M-
CH3)+: 271.1729; found: 271.1742.
+
C33H39O3Si (M-C4H9 ): 511.2668; found: 511.2689.
2-Allyl-(3-tert-Butyldimethylsiloxy-propyl)-malonic acid
dimethyl ester (24)
Sodium hydride (4.16 g, 104.1 mmol) and potassium hy-
dride (cat.) were washed three times with pentane, sus-
pended in DMF (75 mL) and cooled to 0°C. A solution of
dimethyl malonate (11.9 mL, 104.1 mmol) in DMF (50 mL)
was added via addition funnel at a rate such that the evolu-
tion of H2 was controlled. The mixture was warmed to room
4-(3-tert-Butyldimethylsiloxy-propyl)-3-vinyl-hepta-1,6-dien-
3-ol (26)
Methyl ester 25 (0.900 g, 3.13 mmol) was reacted under
standard condition for the conversion of methyl esters to
© 2000 NRC Canada

Lautens et al.
877
trans-: IR (neat): 3471, 3071, 3020, 2931, 1649, 1589,
1472, 1428, 1390, 1361, 1304, 1111, 997, 954, 921, 823,
937, 701, 614. H NMR (400 MHz, CDCl3) δ: 1.07 (s, 9H),
diallylic tertiary alcohols. The crude product was purified by
flash chromatography (7% ether–hexanes) on triethyl amine
washed silica gel to yield the title compound as a pale green
oil (314 mg, 32%). Rf = 0.25 (10% ether–hexanes). IR
(neat): 3475, 3079, 2929, 2858, 1639, 1472, 4109, 1361,
1
1.10–1.21 (m, 1H), 1.34–1.54 (m, 4H), 1.60–1.78 (m, 3H),
1.92–2.04 (m, 1H), 2.07–2.16 (m, 1H), 3.68 (t, J = 6 Hz,
2H), 5.14 (dd, J = 11, 1.5 Hz, 1H), 5.32 (dd, J = 17, 1.5 Hz,
1H), 5.52 (dt, J = 10, 2 Hz, 1H), 5.83 (dd, J = 17, 11 Hz,
1H), 5.87 (dq, J = 10, 2.5 Hz, 1H), 7.36–7.46 (m, 6H), 7.66–
7.71 (m, 4H). 13C NMR (100 MHz, CDCl3) δ: 19.19, 22.85,
24.67, 25.43, 26.89, 30.75, 42.84, 64.18, 72.71, 113.14,
127.54, 129.47, 130.35, 131.78, 134.15, 135.58, 144.45.
HRMS calcd. for (M-C4H9)+: 363.1780; found: 363.1887.
1
1256, 1100, 999, 921, 836, 775, 735. H NMR (400 MHz,
CDCl3) δ: 0.04 (s, 6H), 0.88 (s, 9H), 1.16–1.26 (m, 1H),
1.42–1.52 (m, 1H), 1.53–1.70 (m, 3H), 1.83 (s, 1H), 2.02
(quint, J = 7 Hz, 1H), 2.30–2.38 (m, 1H), 3.56 (t, J = 6 Hz,
2H), 4.98 (dquint, J = 10, 0.5 Hz, 1H), 5.02 (dq, J = 17,
0.5 Hz, 1H), 5.16 (dd, J = 11, 1 Hz, 2H), 5.28 (dt, J = 17,
1 Hz, 2H), 5.81–6.00 (m, 3H). 13C NMR (100 MHz, CDCl3)
δ: –5.29, 18.31, 25.32, 25.94, 31.75, 34.34, 46.51, 63.31,
79.23, 113.48, 115.80, 138.37, 141.79, 142.20. HRMS calcd.
for C17H31O2Si (M-CH3)+: 295.2091; found: 295.2091.
cis- and trans-[6-(3-tert-Butyldiphenylsiloxy-propyl)-1-vinyl-
cyclohex-2-enyloxymethyl]-4-methoxy-benzene (29) (Mo Cat.)
To a solution of triene 23 (51 mg, 0.089 mmol) in C6H6
(0.5 mL) at 23°C was added a solution of 2 (4 mg,
0.006 mmol) in C6H6 (0.5 mL). The resulting solution was
stirred for 90 min before the mixture was concentrated in
2-(3-tert-Butyldimethylsiloxy-propyl)-1,1-divinyl-pent-4-
enyloxymethyl)-benzene (27)
Alcohol 26 (288 mg, 0.927 mmol) was reacted according
to the general benzylation procedure to yield the title com-
pound as a colorless oil (329 mg, 89%). Rf = 0.21 (2%
ether–hexanes). IR (neat): 3086, 2929, 2858, 1639, 1497,
1472, 1408, 1380, 1255, 1099, 1027, 1004, 929, 836, 775,
1
vacuo. A crude H NMR showed a 7.8:1 mixture favoring
the cis-diastereomer. The ratio was determined by compar-
ing the integration of the doublets of triplets appearing at δ
5.61 (cis-) and δ 5.75 (trans-) in the crude 1H NMR. The res-
idue was purified by flash chromatography (2% ether–hex-
anes) on triethyl amine washed silica gel to yield the title
compounds as colorless oils (42 mg, 86%).
1
728, 695, 661. H NMR (400 MHz, CDCl3) δ: 0.03 (s, 6H),
0.88 (s, 9H), 1.10–1.20 (m, 1H), 1.46–1.57 (m, 1H), 1.58–
1.74 (m, 3H), 1.82–1.94 (m, 1H), 2.46–2.54 (m, 1H), 3.55 (t,
J = 6 Hz, 2H), 4.37 (s, 2H), 4.93 (d, J = 10 Hz, 1H), 4.99
(dq J = 17, 1 Hz, 1H), 5.30 (dd, J = 17, 1.5 Hz, 2H), 5.36
(dd, J = 11, 1.5 Hz, 2H), 5.80–5.90 (m, 1H), 5.89 (dd, J =
18, 11 Hz, 2H), 7.21–7.26 (m, 1H), 7.29–7.36 (m, 4H). 13C
NMR (100 MHz, CDCl3) δ: –5.26, 18.33, 25.97, 26.36,
32.30, 35.13, 48.00, 63.56, 65.12, 83.79, 114.92, 117.48,
117.55, 126.75, 126.81, 128.14, 137.81, 138.16, 139.06,
139.98. HRMS calcd. for (M-CH3)+: 385.2563; found:
385.2581.
cis-: Rf = 0.20, (5% ether–hexanes). IR (neat) 2931, 1613,
1513, 1472, 1428, 1301, 1247, 1171, 1111, 998, 822, 702.
1H NMR (400 MHz, CDCl3) δ: 0.92–1.10 (m, 1H), 1.05 (s,
9H), 1.26–1.38 (m, 1H), 1.44–1.55 (m, 1H), 1.63–1.89 (m,
4H), 2.03–2.09 (m, 2H), 3.66 (td, J = 6, 1.5 Hz, 2H), 3.79 (s,
3H), 4.38 (s, 2H), 5.18 (dd, J = 17, 2 Hz, 1H), 5.22 (dd, J =
11, 2 Hz, 1H), 5.61 (dt, J = 10, 2 Hz, 1H), 5.88 (dd, J = 17,
11 Hz, 1H), 5.99 (dt, J = 10, 3.5 Hz, 1H) 6.84 (AB, J =
9 Hz, 2H), 7.24 (AB, J = 9 Hz, 2H), 7.35–7.45 (m, 6H),
7.66–7.70 (m, 4H). 13C NMR (100 MHz, CDCl3) δ: 19.00,
23.86, 25.03, 25.19, 26.68, 30.58, 40.43, 55.06, 65.93, 64.27,
76.48, 30.58, 40.43, 55.06, 65.93, 64.27, 76.48, 80.56,
113.44, 116.25, 127.35, 128.469, 129.22, 129.26, 131.08,
132.87, 134.96, 135.37, 140.89, 158.53. HRMS calcd. for
C31H35O3Si (M-C4H9)+: 483.2355; found: 483.2363.
cis- and trans-6-(3-tert-Butyldiphenylsiloxy-propyl)-1-vinyl-
cyclohex-2-enol (28)
To a 23°C solution of triene 22 (200 mg, 0.446 mmol) in
dichloromethane (4.5 mL) was added
1
(44 mg,
0.053 mmol). After 5 h PPh3 (28 mg, 0.107 mmol) was
1
added and the mixture concentrated in vacuo. A crude H
1
trans-: Rf = 0.29, (5% ether–hexanes). H NMR (400 MHz,
NMR showed a 2.8:1 mixture of diastereomers in favor of
the product having the methine proton and OH substituent
trans to one another. The residue was purified by flash chro-
matography (15% ether–hexanes) on triethyl amine washed
silica gel to yield the title product as a colorless oil (151 mg,
80%).
CDCl3) δ: 1.04 (s, 9H), 1.26–1.50 (m, 3H), 1.56–1.76 (m,
3H), 1.76–1.86 (m, 1H), 1.92–2.04 (m, 1H), 2.07–2.17 (m,
1H), 3.64 (t, J = 6.5 Hz, 2H), 3.78 (s, 3H), 4.39 (AB, J =
11 Hz, 1H), 4.42 (AB, J = 11 Hz, 1H), 5.18 (dd, J = 6,
1.5 Hz, 1H), 5.22 (s, 1H), 5.75 (dt, J = 10, 2 Hz, 1H), 5.88–
5.96 (m, 1H), 6.01 (dq, J = 10, 2 Hz, 1H), 6.84 (AB, J =
9 Hz, 2H), 7.24 (AB, J = 9 Hz, 2H), 7.34–7.44 (m, 6H),
7.65–7.70 (m, 4H). 13C NMR (100 MHz, CDCl3) δ: 19.21,
22.73, 24.08, 25.30, 26.88, 31.03, 43.83, 55.26, 64.36,
64.58, 110.39, 113.56, 115.25, 127.53, 128.16, 128.49,
129.42, 132.05, 132.49, 134.21, 135.58, 143.14, 158.50.
cis-: IR (neat): 3441, 3071, 2931, 1651, 1590, 1472, 1428,
1390, 1361, 1175, 1111, 998, 822. 1H NMR (400 MHz,
CDCl3) δ: 0.94–1.08 (m, 1H), 1.05 (s, 9H), 1.20–1.33 (m,
1H), 1.47–1.59 (m, 2H), 1.62–1.78 (m, 3H), 2.01–2.07 (m,
2H), 3.62–3.71 (m, 2H), 5.14 (dd, J = 11, 2 Hz, 1H), 5.18
(dd, J = 17, 2 Hz, 1H), 5.41 (dt, J = 10, 2 Hz, 1H), 5.87 (dt,
J = 10, 4 Hz, 1H), 5.87 (dd, J = 17, 11 Hz, 1H), 7.35–7.45
(m, 6H), 7.65–7.69 (m, 4H). 13C NMR (100 MHz, CDCl3) δ:
19.22, 24.78, 25.21, 25.92, 26.91, 30.79, 45.21, 64.30,
75.31, 114.38, 127.58, 128.44, 129.50, 132.63, 134.15,
135.60, 140.37.
cis- and trans-[6-(3-tert-Butyldiphenylsiloxy-propyl)-1-vinyl-
cyclohex-2-enyloxymethyl]-4-methoxy-benzene (29) (Ru
Cat.)
To a solution of triene 23 (200 mg, 0.351 mmol) in di-
chloromethane (3.5 mL) at 23°C was added 1 (12 mg,
0.014 mmol). After 3 h, PPh3 (7 mg, 0.029 mmol) was
© 2000 NRC Canada

878
Can. J. Chem. Vol. 78, 2000
added and the mixture was concentrated in vacuo. A crude
1H NMR showed a 6.1:1 mixture favoring the cis-diastereomer.
The ratio was determined by comparing the integration of
the doublets of triplets appearing at δ 5.61 (cis-) and δ 5.75
63.44, 65.64, 93.08, 115.19, 127.01, 127.11, 128.19, 132.74,
134.44, 138.85, 139.90. HRMS calcd. for C23H36O2Si (M+):
372.2453; found: 372.2469.
1
(trans-) in the crude H NMR. The residue was purified by
trans-: Rf = 0.10, (2% ether–hexanes). IR (neat): 3056, 2929,
flash chromatography (5% ether–hexanes) on triethyl amine
washed silica gel to yield the title compounds as colorless
oils (181 mg, 96%).
2857, 1741, 1608, 1472, 1434, 1380, 1255, 1094, 996, 924,
835, 775, 742, 695. H NMR (400 MHz, CDCl3) δ: 0.05 (s,
1
6H), 0.90 (s, 9H), 1.51–1.68 (m, 3H), 1.68–1.80 (m, 1H),
2.22 (ddt, J = 16.5, 8, 2 Hz, 1H), 2.52 (dddd, J = 16.5, 9, 3,
1.5 Hz, 1H), 3.59–3.68 (m, 2H), 4.36, 4.48 (AB, 12 Hz, 2H),
5.14 (dd, J = 11, 2 Hz, 1H), 5.24 (dd, J = 18, 2 Hz, 1H),
5.81 (dq, J = 6, 1.5 Hz, 1H), 6.04 (dd, J = 18, 11 Hz, 1H),
6.17 (dt, J = 6 Hz, 2 Hz, 1H), 7.20–7.26 (m, 1H), 7.28–7.36
(m, 4H). 13C NMR (100 MHz, CDCl3) δ: –5.25, 18.37,
24.36, 25.99, 31.96, 38.32, 50.08, 63.59, 65.26, 77.31,
89.21, 113.84, 126.65, 126.76, 128.06, 132.63, 137.06,
140.30, 142.13. HRMS calcd. for C19H27O2Si (M-C4H9):
315.1780; found: 315.1781.
cis- and trans-5-(3-tert-Butyldimethylsiloxy-propyl)-1-vinyl-
cyclopent-2-enol (30)
To a solution of triene 26 (29 mg, 0.093 mmol) in C6H6
(1.0 mL) at 23°C was added 1 (4.6 mg, 0.0056 mmol). The
resulting solution was stirred for 90 min before PPh3 (6 mg,
0.0075 mmol) was added and the mixture concentrated in
vacuo. A crude 1H NMR showed a 1:1 mixture of
diastereomers. The ratio was determined by comparing the
integration of the doublets of quartets appearing at δ 5.59
1
and δ 5.69 in the crude H NMR. The mixture was purified
by flash chromatography (10% ether–hexanes) on triethyl
amine washed silica gel to yield the title compounds as a
colorless oil (17 mg, 65%).
cis- and trans-5-(3-tert-Butyldimethylsiloxy-propyl)-1-vinyl-
cyclopent-2-enyloxy benzyl ether (31) (Ru Cat.)
To a solution of triene 27 (39 mg, 0.097 mmol) in di-
chloromethane (1.0 mL) at 23°C was added 1 (2.4 mg,
0.003 mmol). The resulting solution was stirred for 1 h be-
fore PPh3 (3 mg, 0.014 mmol) was added and the mixture
concentrated in vacuo. A crude 1H NMR showed an 8:1
mixture favoring the (cis-). The ratio was determined by
comparing the integration of the doublets of triplets appear-
cis- and trans-mixture: IR (neat): 3418, 2929, 1472, 1255,
1
1097, 995, 922, 836, 775, 663. H NMR (400 MHz, CDCl3)
δ: 0.04 (s, 6H), 0.88 (s, 9H), 1.20–1.32 (m, 1H), 1.34–1.44
(m, 1H), 1.50–1.64 (m, 2H), 1.87 (s, 1H), 1.86–2.18 (m, 2
H), 2.54 (tdq, J = 16.5, 7.5, 1.5 Hz, 1H), 3.62 (m, 2H),
5.06–5.31 (series of doublets, 2H), 5.59, (dq, J = 6, 1 Hz,
0.5 H), 5.69 (dq, J = 6, 1 Hz, 0.5H), 5.82 (dd, J = 17, 11 Hz,
0.5 H), 5.98 (dd, J = 17, 11 Hz, 0.5 H), 5.91 (quint., J =
2 Hz, 0.5H), 5.99–6.03 (m, 0.5H). 13NMR (100 MHz,
CDCl3) δ: –5.26, 18.37, 25.99, 26.70, 31.65, 37.59, 37.64,
47.66, 51.96, 63.39, 63.48, 84.77, 87.21, 112.31, 113.05,
132.32, 134.19, 136.12, 136.79, 143.43.
1
ing at δ 5.81 (cis-) and δ 6.17 (trans-) in the crude H NMR.
The mixture was purified by flash chromatography (1%
ether–hexanes) on triethyl amine washed silica gel to yield
the title compounds as colorless oils (36 mg, 99%).
3-Allyl-3-benzyl-dihydro-furan-2-one (36)
Diisopropylamine (10.98 mmol, 1.32 mL) is added to
THF (13 mL) and the resulting solution is cooled to –78°C.
n-BuLi (10.98 mmol, 2.5 M in hexanes, 4.39 mL) is then
added dropwise. The solution is stirred for an additional
30 min at –78°C at which time 3-allyl-dihydro-furan-2-one
(18) in THF (13mL) is added dropwise by cannula addi-
tion. The solution is stirred for an additional 30 min at
–78°C followed by dropwise addition of benzyl bromide
(11.98 mmol, 1.42 mL) in HMPA(2.2 mL). The solution is
stirred for an additional 3 h at –78°C. The reaction is
quenched with aq. sat’d. ammonium chloride solution and
the mixture is diluted with ether. The layers are separated
and the aqueous layer is extracted with ether (three times).
The combined organic layers are dried over MgSO4, fil-
tered, and concentrated. The crude product is purified by
flash chromatography (20% Et2O–hexanes) to yield the ti-
tle compound as a colorless oil (1.39 g, 77%). IR (neat):
2915 (m), 1757 (s), 1212 (w), 1166 (s), 1029 (s), 920 (m),
cis- and trans-5-(3-tert-Butyldimethylsiloxy-propyl)-1-vinyl-
cyclopent-2-enyloxy benzyl ether (31) (Mo Cat.)
To a solution of triene 27 (20 mg, 0.050 mmol) in C6H6
(0.5 mL) at 23°C was added a solution of 2 (2.5 mg,
0.003 mmol) in C6H6 (0.5 mL). The resulting solution was
stirred for 30 min before PPh3 (10 mg, 0.038 mmol) was
1
added and the mixture concentrated in vacuo. A crude H
NMR showed a 1.7:1 mixture favoring the (R*,S*) diastereo-
mer. The ratio was determined by comparing the integration
of the doublets of triplets appearing at δ 5.81 (cis-) and δ
1
6.17 (trans-) in the crude H NMR. The mixture was puri-
fied by flash chromatography (1% ether–hexanes) on triethyl
amine washed silica gel to yield the title compounds as col-
orless oils (35 mg, 94%).
cis-: Rf = 0.15, (2% ether–hexanes). IR (neat): 3062, 2929,
2856, 1497, 1472, 1406, 1381, 1360, 1255, 1096, 1064,
1028, 1005, 924, 836, 775, 733, 696, 667. 1H NMR
(400 MHz, CDCl3) δ: 0.04 (s, 6H), 0.89 (s, 9H), 1.17–1.28
(m, 1H), 1.50–1.66 (m, 3H), 1.87 (qt, J = 8, 2 Hz, 1H),
2.31–2.41 (m, 1H), 2.56 (qq, J = 8, 1.5, 1H), 3.55–3.64 (m,
2H), 4.49, 4.53 (AB, 12 Hz, 2H), 5.12 (dd, J = 18, 2 Hz,
1H), 5.19 (dd J = 11, 2 Hz, 1H), 5.81 (dt, J = 6, 2 Hz, 1H),
5.89 (dd, J = 18, 11 Hz, 1H), 6.05 (dt, J = 6, 1.5 Hz, 1H),
7.21–7.26 (m, 1H), 7.28–7.36 (m, 4H). 13C NMR (100 MHz,
CDCl3) δ : –5.27, 18.33, 25.97, 26.81, 31.78, 37.06, 47.79,
1
702 (m). H NMR (400 MHz, CDCl3) δ: 2.15 (t, J = 8 Hz,
2H), 2.33 (dd, J = 13.8 Hz, 8 Hz, 1H), 2.51 (dd, J = 14 Hz,
6.4 Hz, 1H), 2.74 (d, J = 13.2 Hz, 1H), 3.07 (d, J =
13.2 Hz, 1H), 3.46 (q, J = 8.8 Hz, 1H), 4.02 (q, J = 6.4 Hz,
1H), 5.17 (dd, J = 9.2 Hz, 1.2 Hz, 1H), 5.21 (s, 1H), 5.79
(qt, J = 8.4 Hz, 2 Hz, 1H), 7.19–7.32 (m, 5H). 13C NMR
(100MHz, CDCl3) δ : 29.87, 42.15, 42.88, 48.07, 65.43,
119.98, 127.23, 128.68, 130.08, 132.80, 136.63, 180.96.
HRMS calcd. (M+): 216.1150; found: 216.1152.
© 2000 NRC Canada

Lautens et al.
879
4-Benzyl-4-(2-tert-butyldimethylsiloxy-ethyl)-3-vinyl-hepta-
1,6-diene-3-ol (39)
acccording to the general benzylation procedure to yield the
title compound as a colorless oil (314 mg, 85%) after flash
chromatography(100% hexanes). Rf = 0.6 (5% Et2O–hex-
anes). IR (neat): 2950 (s), 2852 (m), 1634 (w), 1461 (w),
3-Allyl-3-benzyl-dihydro-furan-2-one (1.0 g, 4.6 mmol)
was reacted under standard conditions for the conversion of
methyl esters to diallylic tertiary alcohols. The crude product
was dissolved in DMF (40 mL) and imidazole (0.469 g,
6.9 mmol) and tert-butyldimethylsilyl chloride (0.69 g,
4.6 mmol) were added. The solution is stirred at room tem-
perature for 12 h. The reaction volume is doubled with water
and extract with ether (three times). Wash the organic layers
with water, dry over Na2SO4, filter, and concentrate. Flash
chromatography (5% Et2O–hexanes) provided the title com-
pound as a colourless oil (1.0 g, 57% over two steps). IR
(neat): 3359 (s), 2936 (s), 2838 (w), 2309 (w), 1254 (m),
1
1254 (m), 1085 (s), 1064 (s), 930 (m), 835 (m), 772 (w). H
NMR (400 MHz, CDCl3) δ: 0.01 (s, 6H), 0.87 (s, 9H), 1.745
(m, 2H), 2.21 (dd, J = 14.8 Hz, 6.8 Hz, 1H), 2.37 (dd, J =
14.8 Hz, 7.6 Hz, 1H), 2.87 (d, J = 13.6 Hz, 1H), 2.97 (d, J =
13.6 Hz, 1H), 3.68 (m, 1H), 3.87 (m, 1H), 4.32 (s, 2H), 4.92
(dd, J = 10 Hz, 2 Hz, 1H), 4.95 (dd, J = 17.2 Hz, 2 Hz, 1H),
5.30 (dd, J = 4 Hz, 1.6 Hz, 1H), 5.35 (dd, J = 4 Hz, 1.6 Hz,
1H), 5.44 (dd, J = 8 Hz, 1.6 Hz, 1H), 5.47 (dd, J = 6.8 Hz,
1.6 Hz, 1H), 5.794 (m, 1H), 6.04 (dd, J = 16 Hz, 11.2 Hz,
1H), 6.09 (dd, J = 16 Hz, 11.2 Hz, 1H), 7.21–7.37 (m, 10H).
13C NMR (100 MHz, CDCl3) δ: –5.01, 18.50, 26.18, 27.06,
37.81, 39.39, 47.79, 60.71, 65.67, 86.48, 116.00, 118.42,
118.60, 126.06, 127.05, 127.12, 127.94, 128.35, 131.36,
136.26, 136.52, 136.89, 139.56, 139.66. HRMS calcd. (M-
C4H9): 419.2406; found: 419.2392.
1
1081 (s), 997 (m), 916 (m), 839 (m), 772 (w). H NMR
(400 MHz, CDCl3) δ: 0.08 (s, 6H), 0.91 (s, 9H), 1.72 (t, J =
6 Hz, 2H), 2.20 (dd, J = 15 Hz, 6.4 Hz, 1H), 2.41 (dd, J =
15 Hz, 6.4 Hz, 1H), 2.80 (d, J = 14 Hz, 1H), 2.88 (d, J =
14 Hz, 1H), 3.77 (t, J = 6 Hz, 2H), 4.10 (brs, 1H), 4.93–5.01
(m, 2H), 5.19 (ddd, J = 10.8 Hz, 4.8 Hz, 1.6 Hz, 2H), 5.35
(ddd, J = 18.5 Hz, 3 Hz, 1.6 Hz, 2H), 5.59–5.70 (m, 1H),
6.15 (dd, J = 14.8 Hz, 10.8 Hz, 1H), 6.20 (dd, 14.8 Hz,
10.8 Hz, 1H), 7.16–2.27 (m, 5H). 13C NMR (100 MHz,
CDCl3) δ: –5.23, –5.18, 18.57, 26.17, 36.33, 38.99, 40.49,
47.62, 60.35, 80.24, 114.73, 114.76, 116.98, 126.23, 128.11,
131.21, 1136.70, 139.36, 140.55, 140.58. HRMS calcd.
(M-CH3)+: 371.2406; found: 371.2414.
[2-Benzyloxy-1-(2-tert-butyldimethylsiloxy-ethyl)-2-vinyl-
cyclopent-3-enylmethyl]-benzene (44)
To a solution of triene 40 (30 mg, 0.063 mmol) in di-
chloromethane(1 mL) at 23°C was added 1 (5.168 mg,
0.0063 mmol). After 12 h at room temperature, the reaction
is opened to air and the solvent is removed in vacuo. A
1
crude H NMR showed a 2:1 mixture of diastereomers, fa-
vouring the cis-diastereomer. The two diastereomers were
inseparable by flash chromatography. To confirm the stereo-
chemistry of the diastereomers, alcohol trans-43 (30 mg,
0.083 mmol) was reacted under the general benzylation pro-
cedure to yield trans-44 (35 mg, 95%) as a colourless oil af-
ter flash chromatography (100% hexanes).
trans-5-Benzyl-5-(2-tert-butyldimethylsiloxy-ethyl)-1-vinyl-
cyclopent-2-enol (43)
To a solution of triene (240 mg, 0.6217 mmol) in di-
chloromethane (25 mL) at 23°C was added 1 (25.5 mg,
0.03 mmol). The solution is stirred for 6 h at room tempera-
ture at which time 1 (25.5 mg, 0.03 mmol) is again added.
The solution is stirred for an additional 12 h at room temper-
ature, when 1 (25.5 mg, 0.03 mmol) is added for the final
time. After stirring at room temperature for an additional
6 h, the reaction is opened to air and the solvent is removed
in vacuo. Flash chromatography(5% Et2O– hexanes) pro-
vides the title compound (134 mg, 60%) as a single
diastereomer, as a colourless oil. The stereochemistry was
determined by ROESY experiment. Rf = 0.10 (5% Et2O–
hexanes). IR (neat): 3397 (s), 2928 (s), 1495 (m), 1257(s),
trans-: IR (neat): 2950 (m), 2852 (m), 1602 (w), 1451 (m),
1
1254 (m), 1081 (s), 906 (m), 737 (s), 691 (s). H NMR
(400 MHz, CDCl3) δ: –0.04 (s, 3H), –0.03 (s, 3H), 0.84 (s,
9H), 1.86 (t, 7.6 Hz, 2H), 2.10 (dt, J = 16.8 Hz, 2 Hz, 1H),
2.33 (ddd, J = 16.6 Hz, 2.8 Hz, 1.6 Hz, 1H), 2.45 (d, J =
13.6 Hz, 1H), 2.69 (d, J = 13.6 Hz, 1H), 3.69–3.76 (m, 1H),
3.84–3.91 (m, 1H), 4.39 (d, J = 11.6 Hz, 1H), 4.50 (d, J =
11.6 Hz, 1H), 5.26 (dd, J = 17.6 Hz, 1.6 Hz, 1H), 5.34 (dd,
J = 10.8 Hz, 1.6 Hz, 1H), 5.94 (dd, J = 17.6 Hz, 10.8 Hz,
1H), 5.99 (dt, J = 6 Hz, 1.6 Hz, 1H), 6.08 (dt, J = 6 Hz,
2.4 Hz, 1H), 7.15–7.39 (m, 10H). HRMS calcd. (M+):
448.2797; found: 448.2802.
1
1079 (s), 1023 (m), 836 (m), 720 (m). H NMR (400 MHz,
CDCl3) δ: 0.55 (s, 6H), 0.90 (s, 9H), 1.26 (m, 2H), 1.86
(ddd, J = 15.2 Hz, 10.4 Hz, 2.4 Hz, 1H), 1.20 (dd, J =
16.2 Hz, 1.6 Hz, 1H), 2.55 (d, J = 16.4 Hz, 1H), 2.64 (d, J =
13.6 Hz, 1H), 2.80 (d, J = 13.6 Hz, 1H), 3.54 (td, J =
10.4 Hz, 1.2 Hz, 1H), 3.65 (ddd, J = 10.5 Hz, 5.8 Hz,
2.8 Hz, 1H), 5.16 (dd, J = 10.6 Hz, 2 Hz, 1H), 5.21 (s, 1H),
5.25 (dd, J = 17.4 Hz, 2 Hz, 1H), 5.64–5.66 (m, 1H), 5.84–
5.87 (m, 1H), 5.97 (dd, J = 17.4 Hz, 10.8 Hz, 1H), 7.11–
7.26 (m, 5H). 13C NMR (100 MHz, CDCl3) δ: –5.57, –5.38,
18.38, 26.05, 37.81, 41.81, 43.20, 52.59, 59.92, 87.75, 112.91,
126.03, 128.06, 129.32, 130.46, 138.24, 140.22, 140.72.
HRMS calcd. (M-C4H9)+: 301.1623; found: 301.1618.
cis-: IR (neat): 2950 (m), 2852 (m), 1602 (w), 1451 (m),
1
1254 (m), 1081 (s), 906 (m), 737 (s), 691 (s). H NMR
(400 MHz, CDCl3) δ: –0.02 (s, 3H), –0.01 (s, 3H), 0.84 (s,
9H), 1.53 (t, J = 7.6 Hz, 2H), 2.08 (d, J = 16.4 Hz, 1H), 2.58
(d, J = 16.4 Hz, 1H), 2.97 (d, J = 13.6 Hz, 1H), 3.06 (d, J =
13.6 Hz, 1H), 3.38–3.45 (m, 1H), 3.55–3.61 (m, 1H), 4.37
(d, J = 11.6 Hz, 1H), 4.47 (d, J = 11.6 Hz, 1H), 5.25 (s, 1H),
5.28 (dd, J = 5.2 Hz, 1.6 Hz, 1H), 5.79 (dd, J = 18 Hz,
10.4 Hz, 1H), 6.04 (s, 2H), 7.15–7.34 (m, 10H). HRMS
calcd. (M+): 448.2797; found: 448.2802.
[2-Allyl-3-benzyloxy-2-(2-tert-butyldimethylsiloxy-ethyl)-3-
vinyl-pent-4-enyl]-benzene (40)
4-Benzyl-4-(2-tert-butyldimethylsiloxy-ethyl)-3-vinyl-
hepta-1,6-diene-3-ol (300 mg, 0.77 mmol) was reacted
13C NMR (100 MHz, CDCl3) mixture of diastereomers δ:
–5.10, –5.06, 18.41, 26.12, 33.68, 36.57, 41.00, 41.72,
52.65, 61.41, 65.84, 93.07, 117.10, 125.99, 127.04, 127.10,
© 2000 NRC Canada

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Can. J. Chem. Vol. 78, 2000
127.88, 128.25, 128.54, 128.92, 129.15, 130.98, 131.44,
135.52, 137.92, 139.09, 139.81, 140.07.
(dd, J = 11.2 Hz, 1.2 Hz, 1H), 5.65–5.75 (m, 1H), 6.02 (dd,
J = 17.8 Hz, 11 Hz, 1H), 6.07 (dd, J = 17.8 Hz, 11 Hz, 1H),
7.19–7.36 (m, 10H). 13C NMR (100 MHz, CDCl3) δ: –5.00,
18.49, 26.19, 29.45, 33.58, 37.54, 40.03, 47.45, 60.83,
65.77, 86.63, 113.85, 118.47, 118.70, 126.06, 127.07,
127.10, 128.00, 128.37, 131.11, 136.16, 136.52, 139.65,
139.76, 139.81. HRMS calcd. (M-C4H9)+: 433.2562; found:
433.2576.
3-Benzyl-3-but-3-enyl-dihydro-furan-2-one (38)
3-But-3-enyl-hihydrofuran-2-one (37) (1.1 g, 7.857 mmol)
was reacted according to the same procedure for the synthe-
sis of 3-allyl-3-benzyl-dihydro-furan-2-one (36). Flash chro-
matography (20% Et2O–hexanes) provides 1.32 g (74%) of
the title compound as a colourless oil. Rf = 0.5 (50% Et2O–
hexanes). IR (neat): 2910 (m), 1760 (s), 1634 (w), 1447 (m),
6-Benzyl-6-(2-tert-butyldimethylsiloxy-ethyl)-1-vinyl-
cyclohex-2-en-1-ol (45)
1
1173 (s), 1029 (s), 913 (m). H NMR (400 MHz, CDCl3) δ:
1.68–1.81 (m, 2H), 2.06–2.25 (m, 4H), 2.75 (d, J = 13.6 Hz,
1H), 3.05 (d, J = 13.6 Hz), 3.45–3.51 (m, 1H), 4.00–4.06
(m, 1H), 4.98 (d, J = 10.4 Hz, 1H), 5.05 (dt, J = 17.2 Hz,
1.6 Hz, 1H), 5.75–5.85 (m, 1H), 7.18–7.30 (m, 5H). 13C
NMR (100 MHz, CDCl3) δ: 28.82, 30.60, 36.74, 42.76,
47.91, 65.26, 115.41, 127.22, 128.67, 130.06, 136.65,
137.52, 181.07. HRMS calcd. (M+): 230.1306; found:
230.1259.
To a solution of triene 41 (100 mg, 0.25 mmol) id di-
chloromethane(20 mL) is added 1 (24 mg, 0.03 mmol). The
solution is stirred for 12 h at room temperature at which
time the reaction is opened to air and the solvent is removed
in vacuo. A crude 1H NMR showed a 1:1 mixture of
diastereomers at 100% conversion. The residue is purified by
flash chromatography (5% Et2O–hexanes) to provide the R*,S*
diastereomer (37.6 mg, 40%) and the R*,R* diastereomer
(30 mg, 32%) as colourless oils. The stereochemistry of the
R*,S* diastereomer was proven by ROESY experiment.
4-Benzyloxy-4-(2-tert-butyldimethylsiloxy-ethyl)-3-vinyl-
octa-1,7-dien-3-ol (41)
3-Benzyl-3-but-3-enyl-dihydro-furan-2-one 38 (1.0 g,
4.37 mmol) was reacted under standard conditions for the
conversion of methyl esters to tertiary diallylic alcohols. The
crude product was dissolved in DMF (50 mL) and imidazole
(0.469 g, 6.9 mmol) and tert-butyldimethylsilyl chloride
(0.69 g, 4.6 mmol) were added. After stirring at room tem-
perature for 12 h, water (50 mL) is added. Extract with ether
(three times) and wash with water. Dry over Na2SO4, filter,
and concentrate. Flash chromatography (5% Et2O–hexanes)
provides 0.825 g (48% over two steps) of the title compound
as a colourless oil. Rf = 0.3 (5% Et O–hexanes). IR (neat):
3371 (s), 2929 (s), 1639 (w), 1471 (2m), 1255 (m), 1079 (s),
trans-: IR (neat): 3388 (s), 2929 (m), 1471 (w), 1255 (m),
1078 (s), 1003 (m), 836 (s), 777 (m), 702 (w). H NMR
1
(400 MHz, CDCl3)) δ: 0.08 (s, 6H), 0.91 (s, 9H), 1.43–1.53
(m, 2H), 1.58–1.66 (m, 1H), 1.73 (ddd, J = 17.6 Hz, 8.4 Hz,
2.4 Hz, 1H), 1.93–2.13 (m, 2H), 2.59 (d, J = 13.6 Hz, 1H),
3.04 (d, J = 13.6 Hz, 1H), 3.68–3.73 (m, 1H), 4.01 (ddd, J =
11 Hz, 8.8 Hz, 2.4 Hz, 1H), 4.89 (s, 1H), 5.22 (dd, J =
10.8 Hz, 2 Hz, 1H), 5.29 (dd, J = 17.4 Hz, 2 Hz, 1H), 5.48
(dt, J = 10 Hz, 2.4 Hz, 1H), 5.69 (dt, J = 10 Hz, 2.4 Hz,
1H), 6.10 (ddd, J = 17.2 Hz, 10.8 Hz, 0.8 Hz, 1H), 7.07–
7.27 (m, 5H). 13C NMR (100 MHz, CDCl3) δ: –5.29, –5.18,
18.33, 22.69, 26.00, 26.21, 29.10, 35.18, 39.38, 43.31,
60.20, 76.49, 114.46, 125.98, 126.13, 127.98, 131.23,
134.02, 139.08, 142.19. HRMS calcd. (M+): 372.2482;
found: 372.2483.
1
910 (s), 836 (m), 733 (m). H NMR (400 MHz, CDCl3) δ:
0.12 (s, 6H), 0.94 (s, 9H), 1.50–1.96 (m, 6H), 2.81 (d, J =
14 Hz, 1H), 2.86 (d, J = 14 Hz, 1H), 3.76–3.84 (m, 2H),
3.98 (br s, 1H), 4.88 (s, 1H), 4.91 (d, J = 6.8 Hz, 1H), 5.20
(dd, J = 12 Hz, 1.6 Hz, 1H), 5.23 (dd, J = 12 Hz, 1.6 Hz,
1H), 5.38 (dd, J = 17.2 Hz, 2 Hz, 1H), 5.39 (dd, J =
17.2 Hz, 2 Hz, 1H), 5.66–5.76 (m, 1H), 6.20 (dd, J =
17.2 Hz, 10.8 Hz, 1H), 6.20 (dd, J = 17.2 Hz, 10.8 Hz, 1H),
7.17–7.29 (m, 5H). 13C NMR (100 MHz, CDCl3) δ: –5.21,
–5.17, 18.55, 26.16, 29.30, 33.00, 36.30, 40.78, 47.17,
60.39, 80.19, 114.02, 114.02, 114.73, 114.84, 126.20,
128.11, 130.97, 139.40, 139.54, 140.59, 140.76. HRMS
calcd. (M-C4H9)+: 343.0183; found: 343.0187.
cis-: IR (neat): 3388 (s), 2929 (m), 1471 (w), 1255 (m),
1
1078 (s), 1003 (m), 836 (s), 777 (m), 702 (w). H NMR
(CDCl3) δ: 0.13 (d, J = 0.8 Hz, 6H), 0.94 (s, 9H), 1.23–1.49
(m, 3H), 1.62–1.69 (m, 1H), 2.20–2.30 (m, 1H), 2.79 (d, J =
14.8 Hz, 1H), 3.19 (d, J = 14.8 Hz, 1H), 3.48 (dt, J =
11.2 Hz, 4.4 Hz, 1H), 4.11 (td, J = 10.88 Hz, 3.2 Hz, 1H),
4.31 (br s, 1H), 5.12 (dd, J = 10.6 Hz, 1.6 Hz, 1H), 5.19 (J =
16 Hz, 2 Hz, 1H), 5.43 (dt, J = 9.6 Hz, 2.4 Hz, 1H), 5.81 (dt,
J = 10 Hz, 3.6 Hz, 1H), 6.14 (dd, J = 17.2 Hz, 10.4 Hz, 1H),
7.16–7.28 (m, 5H). 13C NMR δ: –0.53, –5.15, 0.14, 22.92,
26.22, 28.90, 37.39, 43.38, 60.60, 95.61, 114.31, 125.96,
128.12, 130.77, 131.99, 142.65. HRMS calcd. (M+):
372.2482; found: 372.2483.
[2-(1-Benzyloxy-1-vinyl-allyl)-2-(2-tert-butyldimethylsiloxy-
ethyl)-hex-5-enyl]-benzene (42)
Alcohol 41 (150 mg, 0.375 mmol) was reacted according
to the general benzylation procedure to yield the title com-
pound as a colourless oil (165 mg, 90%) after flash chroma-
tography (100% hexanes). Rf = 0.7 (5% Et2O–hexanes). IR
(neat): 2950 (m), 2859 (m), 1641 (m), 1451 (m), 1254 (m),
[2-Benzyloxy-1-(2-tert-butyldimethylsiloxy-ethyl)-2-vinyl-
cyclohex-3-enylmethyl]-benzene (46)
A solution of triene 42 (100 mg, 0.204 mmol) in dichloro-
methane (10 mL) is added 1 (16 mg, 0.02 mmol). The solu-
tion is stirred for 12 h at room temperature at which time the
reaction is opened to air and the solvent removed in vacuo.
1
1081 (s), 930 (m), 835 (s). H NMR (400 MHz, CDCl3) δ:
0.01 (s, 6H), 0.87 (s, 9H), 1.42–2.11 (m, 6H), 2.86 (d, J =
14 Hz, 1H), 2.92 (d, J = 13.6 Hz, 1H), 3.60–3.67 (m, 1H),
3.82–3.88 (m, 1H), 4.33 (s, 2H), 4.87 (s, 1H), 4.90 (d, J =
7.8 Hz, 1H), 5.34 (dd, J = 19.4 Hz, 2 Hz, 1H), 5.34 (dd, J =
17.6 Hz, 1.6 Hz, 1H), 5.46 (dd, J = 11 Hz, 2 Hz, 1H), 5.46
1
A crude H NMR showed a 4.5:1 mixture of diastereomers,
favouring the R*,R* cis-diastereomer. Unable to separate the
diastereomers by flash chromatography, the diastereomeric
© 2000 NRC Canada

Lautens et al.
881
alcohols 45 reacted under the general benzylation procedure
to yield the title compounds as colourless oils.
3.53 (t, J(H-Sn) = 10 Hz, 2H), 5.51 (dt, J = 10, 2 Hz, 2H),
5.80 (dt, J = 10, 4 Hz, 2H). 13C NMR (100 MHz, CDCl3)
δ: 8.93 (t, J(C-Sn) = 61 Hz), 13.74, 23.41, 24.30, 27.31
(t, J(C-Sn) = 26 Hz), 29.17 (t, J(C-Sn) = 10 Hz), 32.99, 50.86,
74.69, 129.02, 130.49.
cis- and trans-mixture: IR (neat): 2927 (m), 1495 (w), 1254
1
(m), 1067 (s), 929 (w), 835 (m), 774 (w), 731 (w), 701 (m). H
NMR (400 MHz, CDCl3) δ: –0.11 (s, 6H), 0.77 (s, 9H), 1.32–
1.45 (m, 2H), 1.75–1.85 (m, 3H), 2.08–2.23 (m, 2H), 2.54
(d, J = 13.6 Hz, 1H), 2.71 (d, J = 13.6 Hz, 1H), 3.35–3.46
(m, 1H), 3.62–3.69 (m, 1H), 4.38 (d, J = 11.6 Hz, 1H), 4.46
(d, J = 11.6 Hz, 1H), 5.23 (dd, J = 17.6 Hz, l.6 Hz, 1H),
5.41 (dd, J = 10.8 Hz, 1.6 Hz, 1H), 5.79 (dt, J = 10.4 Hz, 2
Hz, 1H), 6.00 (dt, J = 10.4 Hz, 3.6 Hz, 1H), 6.05 (dd, J =
17.8 Hz, 11.2 Hz, 1H), 7.14–7.28 (m, 10H). 13C NMR (100
MHz, CDCl3) δ: –5.08, 18.43, 23.47, 25.47, 26.15, 36.98,
40.12, 43.53, 61.19, 64.88, 118.69, 125.99, 126.95, 126.99,
127.18, 127.98, 128.24, 131.09, 131.18, 139.41, 140.21,
140.79.
cis-(2,3,4,4a,5,6-Hexahydronaphthalen-2-yl)-methanol (49)
MeLi (1.08 M, 214 µL): To a solution of stannyl methyl
ether 48 (100 mg, 0.221 mmol) and HMPA (154 µL,
0.882 mmol) was added MeLi (1.08 M, 214 µL). After
15 min the reaction was quenched by adding MeOH (2
drops). The mixture was purified by adding the crude reac-
tion directly to column of triethyl amine washed silica gel
and eluting with 30% ether–hexanes to yield the title com-
pound as a colorless oil (25 mg, 67%). Rf = 0.17 (30%
1
ether–hexanes). H NMR (400 MHz, CDCl3) δ: 1.21–1.36
(m, 3H), 1.36–1.47 (m, 1H), 1.77–1.94 (m, 3H), 2.08–2.26
(m, 3H), 2.39–2.49 (bs, 1H), 3.50–3.61 (m, 2H), 5.37 (s,
1H), 5.72–5.78 (m, 1H), 6.02 (dm, J = 10 Hz, 1H). 13C
NMR (100 MHz, CDCl3) δ: 25.97, 26.07, 30.10, 30.21,
35.76, 39.71, 67.50, 123.77, 128.62, 129.12, 139.59.
5-(1-Tributylstannylmethoxy-1-vinyl-allyl)-nona-1,8-diene (47)
Potassium hydride (729 mg, 7.27 mmol) was washed
three times with pentane, dried under a stream of argon and
suspended in THF (5 mL). A solution of alcohol 8 (500 mg,
2.42 mmol) in THF (3 mL) was added via cannula. After
5 min, a solution of ICH2SnBu3 in THF (2 mL) was added
via cannula followed by a small crystal of dry 18-crown-6.
The resulting mixture was heated to reflux for 1 h, cooled to
23°C, diluted with ether, and quenched carefully by drop-
wise addition of water. The aqueous layer was extracted two
times with ether, the organic layers were combined, washed
with brine, dried over sodium sulfate, filtered and concen-
trated in vacuo. The residue was purified by flash chroma-
tography (100% hexanes) on triethyl amine washed silica gel
to yield the title compound as a colorless oil (1.15 g, 93%).
Rf = 0.55 (100% hexanes). IR (neat): 3079, 2926, 1640,
5-(1-Trimethylsiloxy-1-vinyl-allyl)-nona-1,8-diene (50)
A 23°C suspension of KH (161 mg, 1.27 mmol, 35% sus-
pension in oil, washed three times with pentane) in THF
(5 mL) was added to 9 (250.09, 1.21 mmol). After 15 min,
TMSCl (161 µL, 1.27 mmol) was added via syringe. After
30 min, water was added, and the mixture extracted three
times with Et2O. The organic layers were washed with brine,
dried over Na2SO4, filtered and concentrated to dryness. The
residue was purified by flash chromatography (100% hex-
anes) on triethyl amine washed silica gel to yield the title
compound as a colorless oil (310 mg, 92%). 1H NMR
(400 MHz, CDCl3) δ: 0.88 (s, 9H), 1.05 (m, 2H), 1.39 (sep-
tet, J = 3.5, 1H), 1.58–1.65 (m, 2H), 1.99–2.19 (m, 4H),
4.92 (dm, J = 10 Hz, 2H), 4.99 (dq, J = 17, 1.7 Hz, 2H),
5.21 (dd, J = 10.5, 2 Hz, 2H), 5.25 (dd, J = 17.5, 2 Hz, 2H),
5.73–5.84 (m, 2H), 5.92 (dd, J = 17.5, 10.5 Hz, 2H). 13C
NMR (100 MHz, CDCl3) δ: 2.59, 30.09, 33.50, 48.05,
81.60, 114.14, 115.81, 139.38, 141.03. HRMS calcd. for
C15H27OSi (M-C2H3)+: 251.1831; found: 251.1824.
1
1456, 1416, 1017, 909. H NMR (400 MHz, CDCl3) δ: 0.89
(t, J = 7 Hz, 9H), 0.89 (tt, J(H-Sn) = 25 Hz, J(H-H) = 8 Hz,
6H), 1.04–1.14 (m, 2H), 1.30 (hex., J = 7 Hz, 6H), 1.40–
1.82 (m, 11H), 1.86–2.18 (m, 5H), 3.40 (t, J(H-Sn) = 10 Hz,
2H), 4.92 (dm, J = 10 Hz, 2H), 4.97 (dq, J = 17, 2 Hz, 2H),
5.17 (dd, J = 18, 2 Hz, 2H), 5.34 (dd, 11, 2 Hz, 2H), 5.74
(dd, J = 18, 11 Hz, 2H), 5.72–5.86 (m, 2H). 13C NMR
(100 MHz, CDCl3) δ: 8.84 (t, J(C-Sn) = 61 Hz), 13.73, 27.36
(t, J(C-Sn) = 26 Hz), 29.21 (t, J(C-Sn) = 10 Hz), 30.12, 33.46,
47.02, 52.46, 85.45, 114.03, 117.42, 137.92, 139.40. HRMS
cis-4a-Trimethylsiloxy-1, 2, 4a, 7, 8, 8a-hexahydro-
naphthalene (51)
+
calcd. for C23H41OSn (M-C4H9 ): 453.2179; found:
A solution of 2 (174 mg, 0.23 mmol) in C6H6 (5 mL) was
added to a flask containing 50 (603 mg, 2.30 mmol). After
30 min, 600 mg of PPh3 was added and the mixture concen-
trated to dryness. The residue was purified by flash chroma-
tography (2% Et2O on triethylamine washed silica gel) to
yield to title compound as a colorless oil consisting of a 5:1
mixture of diastereomers favoring the cis-isomer (64 mg,
453.2181.
cis-4a-Tributylstannylmethoxy-1,2,4a,7,8,8a-hexahydro-
haphthalene (48)
To a solution of 47 (1.00 g, 1.96 mmol) in dichloro-
methane (20 mL) at 23°C was added 1 (194 mg,
0.240 mmol). The reaction mixture was placed under an at-
mosphere of ethylene and heated to reflux. After 7 h the re-
action was concentrated in vacuo and the residue purified by
flash chromatography (100% hexanes → 0.5% → 1% → 2%
ether–hexanes) on triethyl amine washed silica gel to yield
the title compound as a colorless oil (760 mg, 86%). Rf =
0.19 (1% ether–hexanes). IR (neat) 3051, 2924, 1464, 1348,
1
99%). H NMR (400 MHz, CDCl3) δ: 0.12 (s, 9H), 1.44–
1.53 (m, 2H), 1.76–1.84 (m, 2H), 1.91–1.98 (m, 1H), 1.99–
2.12 (m, 4H), 5.57 (dt, J = 10, 2Hz, 2H), 5.71 (dt, J = 10,
3.7 Hz, 2H). 13C NMR δ : 2.66, 23.23, 24.24, 39.85, 71.25,
127.38, 132.35.
1
cis-4a-(Prop-2-enyloxy)-1, 2, 4a, 7, 8, 8a-hexahydro-
naphthalene (52)
A THF (1 mL) solution of 15 (100 mg, 0.67 mmol) was
added to a 23°C suspension of sodium hydride (133 mg,
1040, 758. H NMR (400 MHz, CDCl3) δ: 0.88 (t, J = 7 Hz,
9H), 0.88 (tt, J(H-Sn) = 25 Hz, J(H-H) = 8 Hz, 6H), 1.25–1.34
(m, 6H), 1.43–1.54 (m, 6H), 1.70–1.79 (m, 2H), 1.98–2.05
(m, 4H), 2.13 (hept., J = 3.5 Hz, 1H), 2.71–2.84 (m, 3H),
© 2000 NRC Canada

882
Can. J. Chem. Vol. 78, 2000
3.33 mmol, 60% suspension in oil) which had been washed
three times with pentane. After five minutes, propargyl bro-
mide (375 µL, 3.33 mmol, 70% solution in toluene) was
added via syringe. After 16 h, the reaction was quenched by
the careful addition of water. The mixture was extracted
three times with Et2O, the organic layers were combined,
washed with brine, dried over Na2SO4, filtered and concen-
trated to dryness. The residue was purified by flash chroma-
tography (5% Et2O– hexanes) on triethylamine washed silica
gel to yield the title compound as a colorless liquid (58 mg,
proach to the synthesis of bicyclo[4.4.0]decadienes and
bicyclo[3.3.0]octadienes. The new bicyclic compounds al-
low for further synthetic transformations enabling the con-
struction of valuable intermediates such as that found in the
HMG CoA Reductase inhibitor (+)-Mevinolin. Present ef-
forts are directed towards enantioselective alkene differenti-
ation reactions that would allow the synthesis of
enantioenriched bicyclic compounds. The methodology and
concepts outlined in this paper should prove useful in the
synthesis of complex natural products.
1
46%). IR (neat, cm–1): 3298, 3025, 2919, 1436, 1052. H
NMR (400 MHz, CDCl3) δ: 1.46–1.56 (m, 2H), 1.78–1.87
(m, 2H), 1.96–2.15 (m, 5H), 2.36 (t, J = 2.5 Hz, 1H), 4.07
(d, J = 2.5 Hz, 2H), 5.54 (dt, J = 10, 2Hz, 2H), 5.88 (dt, J =
10, 3.7 Hz, 2H). 13C NMR δ: 23.26, 24.17, 34.25, 50.53,
72.90, 75.24, 81.89, 129.35, 130.53. HRMS calcd. for M+:
187.1123; found: 187.1126.
Acknowledgements
M.L. thanks the Merck Frosst Center for Therapeutic Re-
search and Natural Sciences and Engineering Research
Council of Canada (NSERC) for support of this work. G.H.
and V.Z. both thank NSERC for predoctoral fellowships.
G.H. thanks the Walter C. Sumner Foundation for a
predoctoral fellowship. We thank Professor Ian Flemming,
Cambridge, for bringing the synthesis outlined in Scheme 6
to our attention.
cis-4a-(But-2-yloxy), 1, 2, 4a, 7, 8, 8a, hexahydro-
naphthalene (53)
A solution of n-BuLi (90 µL, 0.233 mmol, 2.5 M solution
in hexanes) was added via syringe to a –78°C solution of 52
(40 mg, 0.212 mmol) in THF (2 mL). After 15 min, methyl
iodide (20 µL, 0.318 mmol) was added via syringe and the
mixture was allowed to warm to 23°C. After 2 h, water was
added and the mixture was extracted three times with Et2O,
the organic layers were combined, washed with brine, dried
over Na2SO4, filtered and concentrated to dryness. The resi-
due was purified by flash chromatography (5% Et2O–hex-
anes) on triethyl amine washed silica gel to yield the title
compound as a colorless liquid (39 mg, 65%). 1H NMR
(400 MHz, CDCl3) δ: 1.49 (sextet, J = 7 Hz, 2H), 1.75–1.88
(m, 4H), 1.94–2.12 (m, 5H), 3.98–4.05 (m 2H), 5.56 (d, J =
10 Hz, 2H), 5.87 (dt, J = 10, 3.7 Hz, 2H). 13C NMR δ: 3.70,
23.23, 24.18, 34.07, 50.89, 74.67, 76.86, 80.97, 129.54,
130.13.
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1
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Conclusions
In conclusion, we have demonstrated a novel diastereo-
selective double ring closing metathesis reaction as an ap-
© 2000 NRC Canada

Lautens et al.
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© 2000 NRC Canada

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