Radical Cyclization of Polyenes Initiated by Attack of Trialkyltin or Germanium Radical on an Ynone

Full text of DOI:10.1021/jo9905524

5292
J . Org. Chem. 1999, 64, 5292-5298
Notes
Sch em e 1
Ra d ica l Cycliza tion of P olyen es In itia ted
by Atta ck of Tr ia lk yltin or Ger m a n iu m
Ra d ica l on a n Yn on e
Claude Spino* and Nancy Barriault
De´partement de Chimie, Universite´ de Sherbrooke,
2500 Boul. Universite´, Sherbrooke, PQ, J 1K 2R1, Canada
Received March 29, 1999
Radical multicyclizations on polyunsaturated chains
have been distinctively useful for the construction of
polycyclic molecules.1-3 Several elaborate polycyclizations
to triquinane and triterpene skeletons1 and the attempt
by Curran and co-workers to build the steroid framework
via a formidable tandem radical macrocyclization/cascade
radical cyclizations strategy4 underscore the advances
made in this field in recent years. In most examples of
radical reactions though, a metal hydride is used in a
stoichiometric amount. Radical cyclizations in which the
metal radical source is used in a catalytic amount are
rare despite the few available methods.5 Lee and co-
workers described the cyclization of functionally comple-
mentary alkenes and alkynes into six-membered rings
in modest yields (eq 1) using 0.5 equiv of tin hydride.6
Marco-Contelles reported intramolecular cyclizations of
polyenes in 12-14% yield as byproducts in a strategy for
the formation of polycyclic molecules (eq 2).7 Catalytic
versions of metal hydride mediated radical cyclizations
are desirable in view of the cost and/or toxicity of stannyl,
germyl, or silyl hydrides.
Ta ble 1. Resu lts of th e Ra d ica l P olycycliza tion of 4 w ith
Va r iou s Meta l Hyd r id es
initiation
condition
solvent
(conc, mM) (h)
time
entry
M-H (equiv)
5
6
1
2
3
4
5
6
7
8
9
n-Bu3SnH (0.5) AIBN, ∆
n-Bu3SnH (0.1) AIBN, ∆
n-Bu3GeH (0.3) AIBN, ∆
n-Bu3GeH (1.0) AIBN, ∆
n-Bu3GeH (1.0) AIBN, ∆
n-Bu3GeH (1.0) AIBN, ∆
n-Bu3GeH (1.0) ACCN, ∆
n-Bu3GeH (0.3) ACCN, ∆
PhH (30)
PhH (30)
PhH (30)
PhH (30)
4
22 23
23 15
24 11
0
0
4
29 13
PhH (h.d.)a 16 25 10
PhH (4.5)
9
28
9
PhH (h.d.)a 23 38 10
PhMe
4
40
0
0
0
0
0
(n-Bu3Sn)2 (0.2) AIBN, hν, ∆ PhH (30)
72 12
48 15
96
4
10
11
12
(PhS)2 (0.1)
(PhS)2 (0.2)
AIBN, hν
AIBN, hν
PhH (30)
PhH (4.5)
PhH (30)
5
0
(n-BuS)2 (0.25) hν
a
h.d. ) high dilution from slow addition over 7 h.
We wish to report our initial attempt at developing a
polyenyne cyclization method using a catalytic amount
of metal hydride. In our strategy, an ynone moiety serves
as the pivotal functionality to allow the initial attack by
the metal radical. The requisite precursor 4 was synthe-
sized in a straightforward manner from 5-hexen-1-ol as
described in Scheme 1. Swern oxidation followed by
addition of vinylmagnesium bromide furnished alcohol
2, which underwent a Claisen rearrangement and further
reduction to give aldehyde 3. This aldehyde was reacted
with ethynylmagnesium bromide, and the resulting
alcohol was oxidized to yield 4. The latter suffered a
radical polycyclization to give tricyclic enone 5 in modest
yields under various conditions (Table 1). Proton and
carbon NMR and GCMS analysis confirmed the presence
of four diastereomers of 5 in an approximately 2:2:1:1
ratio. Of course, in such a simple model, we did not expect
* Tel: (819) 821-7087. Fax: (819) 821-8017. E-mail: cspino@
courrier.usherb.ca.
(1) For a review see: Malacria, M. Chem. Rev. 1996, 96, 289.
(2) Curran, D. P. Synthesis 1988, 417 and 489.
(3) Giese, B. Radicals in Organic Synthesis: Formation of C-C
bonds; Pergamon Press: New York, 1986.
(4) J ahn, U.; Curran, D. P. Tetrahedron Lett. 1995, 36, 8921.
(5) For versions of classical radical reactions using catalytic tin
hydride see: Terstiege, I.; Maleczka, R. E., J r. J . Org. Chem. 1999,
64, 342 and references therein.
(6) Lee, E.; Hur, C. U.; Rhee, Y. H.; Park, Y. C.; Kim, S. Y. J . Chem.
Soc., Chem. Commun. 1993, 1466.
(7) Marco-Contelles, J . J . Chem. Soc., Chem. Commun. 1996, 2629.
10.1021/jo9905524 CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/24/1999

Notes
J . Org. Chem., Vol. 64, No. 14, 1999 5293
Sch em e 2
Sch em e 3
addition product 6. Germanium is a poorer hydride donor
than tin, and that may be responsible for a cleaner
reaction. Decreasing the hydride concentration, though,
changed little of the outcome (entries 5 and 6). Silanes
were not used in the polycyclization. They are known to
efficiently add to many alkenes under radical reaction
conditions, and it is unlikely that the silyl radical would
be ejected in the last step (E f D in Scheme 2).9
Surprisingly, little or no monocyclization or bicycliza-
tion product 7 or 8 was detected in any of the experiments
tried. The strong signals for both remaining double bonds
in the proton NMR spectra of the byproducts were
evidence of this. The absence of mono- and bicyclization
products seemed to indicate that the first cyclization was
slower than intermolecular attack or hydride abstraction
by the vinyl radical. This problem should have been
solved by using hydride-free conditions (entries 9-12).
Unfortunately, the starting ynone and/or the product
enone were decomposed by light sources necessary in
some of these hydride-free conditions. Others gave no
product or only byproducts. The ynone functionality is
not only necessary to accelerate the initial addition of
metal radical but also to ensure formation of the six-
membered final ring. The competing final 5-exo-trig
cyclization would give a metal-containing tricyclic adduct
(cf. G Scheme 2). Triethyl borane as an initiator (not
listed) led to no reaction at all.
any control over the stereochemistry.8 This model was
chosen because the first two cyclizations are 5-exo-trig
cyclizations and thought to be favorable ones.2 However,
the all-syn isomer of 5 seems fairly strained, and its
formation is surprising. We could not assign the stereo-
chemistry of the major isomers or any particular isomer
mostly because of signal overlap in the NMR spectra.
Scheme 2 depicts the steps necessary for the formation
of 5 and possible byproducts (X ) H2). Table 1 lists the
various conditions that were tried on this system. Un-
fortunately, in all entries that produced 5, the desired
product was accompanied by many byproducts (possibly
oligomers or polymers), which made purification difficult.
We believe the actual yields of 5 were higher (ca. 50%
range). Although modest, these yields are promising
considering a conversion in which three new bonds and
three rings were formed. We often had to add more metal
hydride to consume more of the starting material (entries
4-7). The process to form 5 was nevertheless catalytic
in metal radical, but the latter was consumed in the
process of oligomerization which does not regenerate it.
This caused the metal radical source to slowly vanish
during the reaction and accounts for the incomplete
conversions. Indeed, the desired tricyclic compound 5
started to appear at the beginning of each reaction at
the same time as byproducts. After a while, the reaction
stopped, and more hydride and initiator had to be added.
Germanium seems to be more efficient than tin and
gave better conversions with smaller amounts of mono-
We reasoned that conjugating an electron-withdrawing
group to the internal alkene could enhance the rate of
the first cyclization and probably the yield of the final
product (cf. Scheme 2, X ) O). Although R to a carbonyl,
(8) For a review of stereochemical control in radical reactions see:
Curran, D. P.; Porter, N. A.; Giese, B. Stereochemistry of radical
reactions; VCH: Weinheim, 1996.
(9) See, for example: Kopping, B.; Chatgilialoglu, C.; Zehnder, M.;
Giese, B. J . Org. Chem. 1992, 57, 3994.

5294 J . Org. Chem., Vol. 64, No. 14, 1999
Notes
Sch em e 4
or polymerization problem on terminal ynones, it could
allow substituted ones to cyclize cleanly without inter-
ruption. We are presently developing and optimizing the
method further.
Exp er im en ta l Section
All reactions were performed under nitrogen, otherwise noted.
Solvents such as diethyl ether, THF, benzene, toluene, and tert-
butylbenzene were distilled over sodium-benzophenone. Dichlo-
romethane, triethylamine, diisopropylamine, and acetonitrile
were distilled over calcium hydride, and methanol was distilled
over magnesium and iodine. Flash column chromatography was
performed on silica gel, 230-400 mesh.
1,7-Oct a d ien -3-ol (2). Molecular sieves (4 Å) (2.5 g) were
added to a 0 °C solution of 5-hexen-1-ol (1.2 mL, 1.0 g, 10.0
mmol) in dichloromethane (100 mL). The reaction mixture was
stirred for 5 min. Pyridinium chlorochromate (3.23 g, 15.0 mmol)
was added by portions over a 5 min period, and the mixture was
stirred at room temperature for 4 h. The reaction was diluted
with diethyl ether (100 mL) and filtered on a fritted glass funnel
containing silica gel, activated charcoal, and Celite. The residue
was washed with diethyl ether (200 mL). The greenish solution
was concentrated by distillation under normal pressure. The
greenish oil was used without further purification. 1H NMR (300
MHz, CDCl3) δ (ppm): 9.77 (t, 1H, J ) 1.5 Hz), 5.39 (ddt, 1H,
J ) 17.0, 10.5 and 6.5 Hz), 5.06-4.98 (m, 2H), 2.45 (td, 2H, J )
7.3, 1.5 Hz), 2.10 (m, 2H), 1.74 (quintet, 2H, J ) 7.3 Hz).
Vinylmagnesium bromide (1.0 M) (12 mL, 12.0 mmol) was
added dropwise to a -78 °C solution of 5-hexenal (979 mg, 10.0
mmol) in THF (100 mL), and the solution was stirred for 45 min.
The reaction was quenched with 50 mL of a saturated solution
of NH4Cl and allowed to warm to room temperature. The layers
were separated, and the aqueous phase was extracted with
diethyl ether (3 × 30 mL). The organic portions were combined,
washed with brine (30 mL), dried over magnesium sulfate,
filtered, and concentrated by rotary evaporation to give 1.07 g
of 1,7-octadien-3-ol (2), which was used without further purifica-
tion. 1H NMR (300 MHz, CDCl3) δ (ppm): 5.92-5.73 (m, 2H),
5.25-4.94 (m, 4H), 4.14-4.08 (m, 1H), 2.11-2.04 (m, 2H), 1.59-
1.41 (m, 4H). GCMS (m/z, relative intensity): 125 (M+ - 1, 0.2).
(E)-4,9-Deca d ien a l (3). Propionic acid (164 µL, 163 mg, 2.2
mmol), triethyl orthoacetate (14 mL, 12.5 g, 77 mmol), and 1,7-
octadien-3-ol (2) (1.4 g, 11.1 mmol) were heated to reflux in
toluene (20 mL) for 15 h. Then, the toluene was removed by
rotary evaporation, leaving an oil that was vacuum distilled to
yield ethyl (E)-4,9-decadienoate (1.91 g, 88%) as a clear oil. Bp:
78-82 °C (0.1-0.5 mmHg). 1H NMR (300 MHz, CDCl3) δ
(ppm): 5.79 (ddt, 1H, J ) 17.0, 10.5, and 6.5 Hz), 5.51-5.37 (m,
2H), 5.02-4.92 (m, 2H), 4.14 (q, 2H, J ) 7.0 Hz), 2.39-2.26 (m,
4H), 2.07-1.96 (m, 4H), 1.43 (quintet, 2H, J ) 7.5 Hz), 1.25
(t, 3H, J ) 7 Hz). IR (CHCl3, cm-1): 1727. LRMS (m/z, relative
intensity): 196 (M+, 0.8). HRMS calculated for C12H20O2:
196.1463, observed 196.1469. Anal. Calcd for C12H20O2: H 10.28,
C 73.41, O 16.31. Found: H 10.12 C 73.44.
Diisobutylaluminum hydride (1.0 M) (19.6 mL, 19.6 mmol)
was added dropwise to a -78 °C solution of ethyl (E)-4,9-
decadienoate (3.5 g, 17.8 mmol) in diethyl ether (220 mL), and
the solution was stirred for 15 min. The reaction mixture was
quenched with a 1 N HCl solution (30 mL). The separated
aqueous layer was extracted with diethyl ether (3 × 50 mL).
The organic phases were combined, washed with brine (50 mL),
dried over magnesium sulfate, filtered, and concentrated by
rotary evaporation. The crude oil was purified by flash chroma-
tography on silica gel using a 1:9 solution of ethyl acetate and
hexanes to yield (E)-4,9-decadienal (3) (2.56 g, 94%) as an oil.
1H NMR (300 MHz, CDCl3) δ (ppm): 9.76 (t, 1H, J ) 1.5 Hz),
5.79 (ddt, 1H, J ) 17.0, 10.2, and 6.8 Hz), 5.51-5.35 (m, 2H),
5.03-4.92 (m, 2H), 2.49 (td, 2H, J ) 7.0, 1.5 Hz), 2.36-2.30 (m,
2H), 2.07-1.96 (m, 4H), 1.43 (quintet, 2H, J ) 7.0 Hz). IR
(CHCl3, cm-1): 1723. LRMS (m/z, relative intensity): 151 (M+
- 1, 1.0), 134 (M+ - H2O, 3). HRMS calculated for C10H15O (M+
- 1): 151.1123, observed 151.1131.
radical B (Scheme 2) is moderately nucleophilic because
it is not conjugated to the carbonyl and the polarity of
the C-M bond imparts a higher electron density.6 Lee
pointed out that such radicals only add to electron-
deficient alkenes when the reaction is intermolecular.6
Moreover, the resulting radical C (X ) O) would become
electrophilic and should react well with an electron-rich
double bond. To that effect, we built compound 13a as
shown in Scheme 3 and submitted it to the usual
conditions. Disappointingly, the yield of tricycle 14a was
no higher, and side products still formed. Installing a
methyl group on the alkyne led to a very clean reaction
but gave monocyclization product 15b only. A trace of
tricyclic product 14b was detected, but none of the mono-
addition or biscyclization products were found. This
result indicates that the unsubstituted ynones in 4 and
13a are probably responsible for the high amount of
byproducts that was found. A substituted ynone, how-
ever, is slower to react intermolecularly because of the
added bulk, but it may understandably slow the second
and perhaps third cyclizations as well.
Restricting the freedom of rotation of the chain to
increase the rate of the first cyclization proved futile as
20, prepared as per Scheme 4, gave no discernible
tricyclic product and only a collection of byproducts.
Although these initial results are modest, they do supply
important clues to making the method successful. It
seems terminal ynones will lead to unclean reactions,
whereas internal ones should provide clean adducts.
However, presumably because of steric congestion around
the olefin, so far only monocyclization adducts have been
obtained. Other R groups on model 13, including ones
that could be removed after the cyclization, should be
screened so as to maximize the cyclization rate while
minimizing byproduct formation. Other sources of metal
radical or reaction conditions for hydride-free metal
radicals should also be designed and prepared. Although
hydride-free conditions will not solve the oligomerization
(E)-6,11-Dod eca d ien -1-yn -3-on e (4). Ethynylmagnesium
bromide (0.5 M) (90 mL, 45.0 mmol) was added over a 10 min
period to a -78 °C solution of (E)-4,9-decadienal (3) (2.27 g, 14.9

Notes
J . Org. Chem., Vol. 64, No. 14, 1999 5295
mmol) in THF (150 mL), and the solution was stirred for 5 h,
allowing the temperature to reach 0 °C slowly. The reaction was
quenched with a saturated ammonium chloride solution (80 mL)
and warmed to room temperature. The separated aqueous layer
was extracted with diethyl ether (3 × 50 mL), and the organic
portions were combined, washed with brine (80 mL), dried over
magnesium sulfate, filtered, and concentrated by rotary evapo-
ration. The crude oil was purified by flash chromatography on
silica gel using a 1:9 solution of ethyl acetate and hexanes to
yield (E)-6,11-dodecadien-1-yn-3-ol (1.93 g, 73%) as a colorless
oil. 1H NMR (300 MHz, CDCl3) δ (ppm): 5.80 (ddt, 1H, J ) 17.0,
10.0, and 7.0 Hz), 5.53-5.36 (m, 2H), 5.03-4.93 (m, 2H), 4.38
(td, 1H, J ) 7.0, 2.0 Hz), 2.47 (d, 1H, J ) 2.0 Hz), 2.18 (q, 2H,
J ) 7.0 Hz), 2.08-1.97 (m, 4H), 1.82-1.74 (m, 2H), 1.44 (quintet,
2H, J ) 7.0 Hz). IR (neat, cm-1): 3550-3200 (br). LRMS (m/z,
relative intensity): 196 (MNH4+, 0.8), 177 (M+ - 1, 6), 160 (M+
- H2O, 8). HRMS calculated for C12H22NO (MNH4+): 196.1701,
observed 196.1704. Anal. Calcd for C12H18O: H 10.18, C 80.84,
O 8.98. Found: H 10.09, C 80.81.
A solution of (E)-6,11-dodecadien-1-yn-3-ol (180 mg, 1.01
mmol) in dichloromethane (5 mL) was added to a solution of
Dess-Martin’s periodinane (471 mg, 1.11 mmol) in dichloro-
methane (10 mL). The resulting mixture was stirred at room
temperature for 15 min. Then, the mixture was diluted with
diethyl ether (15 mL) and a saturated aqueous bicarbonate
solution (15 mL) containing sodium thiosulfate (3 g), which had
been previously stirred for 5 min. A second portion of diethyl
ether was added (15 mL), and the layers were separated. The
organic layer was washed with a saturated aqueous bicarbonate
solution (30 mL), water (30 mL) and brine (30 mL), dried over
magnesium sulfate, filtered, and concentrated by rotary evapo-
ration. The crude oil was purified by flash chromatography on
silica gel using a 4:96 solution of ethyl acetate and hexanes to
yield (E)-6,11-dodecadien-1-yn-3-one (4) (176 mg, 99%) as a
colorless oil. 1H NMR (300 MHz, CDCl3) δ (ppm): 5.79 (ddt, 1H,
J ) 17.0, 10.2, and 6.8 Hz), 5.50-5.35 (m, 2H), 5.03-4.93 (m,
2H), 3.21 (s, 1H), 2.65 (t, 2H, J ) 7.0 Hz), 2.37 (q, 2H, J ) 7.0
Hz), 2.07-1.95 (m, 4H), 1.43 (quintet, 2H, J ) 7.5 Hz).13C NMR
(75.5 MHz, CDCl3) δ (ppm): 186.8 (s), 138.7 (d), 131.8 (d), 127.6
(d), 114.5 (t), 81.4 (d), 78.6 (s), 45.2 (t), 33.1 (t), 31.8 (t), 28.5 (t),
26.7 (t). IR (neat, cm-1): 2093, 1683. LRMS (m/z, relative
intensity): 194 (MNH4+, 2), 161 (M+ - CH3, 3). HRMS calculated
for C12H20NO (MNH4+): 194.1545, observed 194.1550. Anal.
Calcd for C12H16O: H 9.16, C 81.76, O 9.08. Found: H 9.18, C
81.69.
(m/z, relative intensity): 411 (M+ - Bu, 70). Isomer B: 1H NMR
(300 MHz, CDCl3) δ (ppm): 7.57 (d, 1H, J ) 19.7 Hz), 6.54 (d,
1H, J ) 19.7 Hz), 5.79 (ddt, 1H, J ) 17.0, 10.4, and 6.6 Hz),
5.45-5.42 (m, 2H), 5.02-4.92 (m, 2H), 2.66 (t, 2H, J ) 7.4 Hz),
2.38-2.29 (m, 2H), 2.07-1.95 (m, 4H), 1.56-1.41 (m, 8H), 1.31
(sextet, 6H, J ) 7.3 Hz), 1.00-0.87 (m, 15H). GCMS (m/z,
relative intensity): 411 (M+ - Bu, 41).
(E)-10-ter t-Bu tyldiph en ylsilyloxy)deca-1,6-dien -5-on e (11).
At -78 °C, n-butyllithium (2.00 M) (2.5 mL, 5.05 mmol) was
added dropwise to a solution of diisopropylamine (710 µL, 510
mg, 5.05 mmol) in THF (40 mL), and the solution was stirred at
0 °C during 10 min. At -78 °C, 5-hexen-2-one (590 µL, 496 mg,
5.05 mmol) was added slowly, and the solution was stirred for
1 h. Then, 10 (1.5 g, 4.59 mmol) in THF (10 mL) was added
slowly to the reaction mixture, which was stirred at -78 °C for
2 h. Acetic anhydride (around 5 mL) was added, and the reaction
was allowed to warm to room temperature and stirred for 20
min. Water (10 mL) and a 1 N HCl solution (5 mL) were poured
over the mixture, and the layers were separated. The aqueous
phase was extracted with diethyl ether (3 × 50 mL), and the
combined organic portions were stirred with a saturated aqueous
sodium bicarbonate solution (50 mL) for 1 h. The layers were
separated, and the organic phase was dried over magnesium
sulfate, filtered, and concentrated by rotary evaporation to yield
(E)-10-(tert-butyldiphenylsilyloxy)-5-acetoxy-1,6-decadiene as a
colorless oil, which was used without further purification. 1H
NMR (300 MHz, CDCl3) δ (ppm): 7.65 (dd, 4H, J ) 7.6, 1.7 Hz),
7.45-7.35 (m, 6H), 5.79 (ddt, 1H, J ) 17.0, 10.5, and 6.5 Hz),
5.29-5.20 (m, 1H), 5.06-4.96 (m, 2H), 3.65 (t, 2H, J ) 6.0 Hz),
2.72 (dd, 1H, J ) 16.1, 7.4 Hz), 2.58-2.48 (m, 3H), 2.31 (q, 2H,
J ) 6.9 Hz), 1.99 (s, 3H), 1.69-1.52 (m, 4H), 1.04 (s, 9H). IR
(neat, cm-1): 1739, 1717. LRMS (m/z, relative intensity): 467
(MH+, 0.6). HRMS calculated for C28H39O4Si (MH+): 467.2617,
observed 467.2610.
1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) (690 µL, 699 mg,
4.59 mmol) was added dropwise to a 0 °C solution of (E)-10-
(tert-butyldiphenylsilyloxy)-5-acetoxy-1,6-decadiene (2.14 g, 4.59
mmol) in THF (50 mL), and the solution was stirred at room
temperature for 2.5 h. The reaction mixture was diluted with
water (20 mL) and a 1 N HCl solution (1.0 M) (10 mL). The
layers were separated, and the aqueous phase was extracted
with ethyl acetate (3 × 50 mL). The combined organic portions
were washed with a saturated aqueous sodium bicarbonate
solution (50 mL), water (50 mL), and brine (50 mL), dried over
magnesium sulfate, filtered, and concentrated by rotary evapo-
ration. The crude oil was purified by flash chromatography on
silica gel using a 3:97 solution of ethyl acetate and hexanes to
yield 11 (1.32 g, 70%, 2 steps) as a colorless oil. 1H NMR (300
MHz, CDCl3) δ (ppm): 7.65 (dd, 4H, J ) 7.6, 1.7 Hz), 7.46-7.35
(m, 6H), 6.82 (dt, 1H, J ) 15.9, 6.9 Hz), 6.09 (d, 1H, J ) 15.9
Hz), 5.83 (ddt, 1H, J ) 17.0, 10.5 and 6.5 Hz), 5.08-4.96 (m,
2H), 3.68 (t, 2H, J ) 6.1 Hz), 2.61 (t, 2H, J ) 7.1 Hz), 2.39-2.27
(m, 4H), 1.71 (quintuplet, 2H, J ) 6.1 Hz), 1.05 (s, 9H). IR (neat,
cm-1): 1697. LRMS (m/z, relative intensity): 349 (M+ - t-Bu,
92). HRMS calculated for C22H25O2Si (M+ - t-Bu): 349.1624,
observed 349.1618.
Tr icyclo[7.3.0.02,6]d od ec-8-en -10-on e (5). See Table 1 for
the different conditions. A typical procedure (entry 8) is as
follows: AIBN (28 mg, 0.17 mmol) and tributylgermanium
hydride (193 mg, 146 µL, 0.57 mmol) were added to a solution
of 4 (100 mg, 0.57 mmol) in benzene (20 mL), and the solution
was stirred under reflux for 4 h. The solution was concentrated
under reduced pressure without complete drying. The crude
product was purified by flash chromatography on silica gel using
a (0:100 to 20:80) solution of ethyl acetate and hexanes to yield
two mixtures of two products. The two compounds in the first
mixture could not be separated, but the other two were isolated
by preparative chromatography on a plate of silica gel, eluting
with a solution of ethyl acetate and hexanes to yield 5 as four
isomers (A + B, 11.3 mg, 11%), (C, 7.6 mg, 8%), and (D, 9.5 mg,
10%). Isomers A + B: 1H NMR (300 MHz, CDCl3) δ (ppm):
(E)-1-(ter t-Bu tyld ip h en ylsilyloxy)-6-(tetr a h yd r op yr a n -
2-yloxy)d eca -4,9-d ien e (12). Sodium borohydride (54 mg, 1.43
mmol) was added to a solution of 11 (580 mg, 1.43 mmol) and
cerium(III) chloride heptahydrate (531 mg, 1.43 mmol) in a
mixture of methanol/dichloromethane (10 mL/10 mL). The
resulting suspension was stirred for 15 min. The reaction was
concentrated by rotary evaporation and diluted with water (20
mL) and a 1 N HCl solution (10 mL). The layers were separated,
and the aqueous phase was extracted with diethyl ether (3 ×
20 mL). The combined organic portions were washed with brine
(20 mL), dried over magnesium sulfate, filtered, and concen-
trated by rotary evaporation to yield (E)-10-(tert-butyldiphenyl-
silyloxy)deca-1,6-dien-5-ol (583 mg, 100%) as a clear oil, which
was used without further purification. 1H NMR (300 MHz,
CDCl3) δ (ppm): 7.66 (dd, 4H, J ) 7.5, 1.6 Hz), 7.43-7.35 (m,
6H), 5.82 (ddt, 1H, J ) 17.0, 10.5, and 6.5 Hz), 5.60 (dt, 1H,
J ) 15.4, 6.6 Hz), 5.44 (dd, 1H, J ) 15.4, 7.0 Hz), 5.06-4.95
(m, 2H), 4.04 (q, 1H, J ) 7.0 Hz), 3.66 (t, 2H, J ) 6.3 Hz), 2.17-
2.06 (m, 4H), 1.69-1.58 (m, 4H), 1.05 (s, 9H). IR (neat, cm-1):
3500-3200 (br). LRMS (m/z, relative intensity): 351 (M+ - t-Bu,
1
6.77-6.65 (m, 1HA + 1HB), 2.58-1.04 (m, 15H). Isomer C: H
NMR (300 MHz, CDCl3) δ (ppm): 5.81 (s, 1H), 2.89-1.14 (m,
15H). Isomer D: 1H NMR (300 MHz, CDCl3) δ (ppm): 5.89 (s,
1H), 2.89-2.80 (m, 2H), 2.67-2.60 (m, 1H), 2.57 (dd, 1H, J )
16.2, 8.1 Hz), 2.46 (ddd, 1H, J ) 16.5, 4.3, and 2.6 Hz), 2.30
(ddd, 1H, J ) 16.5, 14.4 and 4.9 Hz), 2.18-1.92 (m, 3H), 1.81-
1.12 (m, 6H). 13C NMR (75.5 MHz, CDCl3) δ (ppm): 200.1 (s),
175.3 (s), 122.9 (d), 47.8 (d0, 44.7 (d), 41.2 (d), 39.8 (t), 37.4 (t),
33.5 (t), 27.5 (t), 26.0 (t), 25.7 (t). IR (neat, cm-1): 1670. LRMS
(m/z, relative intensity): 176 (M+, 42). HRMS calculated for
C
12H16O: 176.1201, observed 176.1198.
(6E)-1-Tr ibu tylsta n n yl-1,6,11-d od eca tr ien -3-on e (6). Iso-
mer A: 1H NMR (300 MHz, CDCl3) δ (ppm): 7.17 (d, 1H, J )
12.4 Hz), 7.10 (d, 1H, J ) 12.4 Hz), 5.80 (ddt, 1H, J ) 17.0,
10.0, and 7.0 Hz), 5.44-5.40 (m, 2H), 5.03-4.91 (m, 2H), 2.58
(t, 2H, J ) 7.2 Hz), 2.33-2.28 (m, 2H), 2.04-1.96 (m, 4H), 1.52-
1.40 (m, 6H), 1.36-1.22 (m, 8H), 0.98-0.83 (m, 15H). GCMS

5296 J . Org. Chem., Vol. 64, No. 14, 1999
Notes
3). HRMS calculated for C22H25O2Si (M+ - t-Bu): 351.1780,
observed 351.1775.
3.19 mmol) in THF (30 mL), and the solution was stirred for 3
h, allowing the temperature to reach 0 °C. The reaction mixture
was quenched at -60 °C with a saturated aqueous ammonium
chloride solution (20 mL) and warmed to room temperature. The
layers were separated, and the aqueous phase was extracted
with ethyl acetate (3 × 20 mL). The combined organic portions
were washed with brine (20 mL), dried over magnesium sulfate,
filtered, and concentrated by rotary evaporation to yield a 1:1
mixture of two diastereomers of (E)-8-(tetrahydropyran-2-yloxy)-
dodeca-6,11-dien-1-yn-3-ol, which was used without further
purification. 1H NMR (300 MHz, CDCl3) δ (ppm): 5.88-5.76 (m,
1H), 5.68-5.50 (m, 1H + 1HA), 5.30 (dd, 1HB, J ) 15.4, 8.3
Hz), 5.04-4.93 (m, 2H), 4.66 (t, 1H, J ) 3.3 Hz), 4.42-4.35 (m,
1H), 4.09-3.82 (m, 2H), 3.52-3.43 (m, 1H), 2.48 (d, 1HB, J )
2.1 Hz), 2.46 (d, 1HA, J ) 2.1 Hz), 2.31-2.03 (m, 4H), 1.89-
1.49 (m, 10H). IR (neat, cm-1): 3550-3100 (br). LRMS (m/z,
relative intensity): 223 (M+ - C4H7, 6). HRMS calculated for
C13H19O3 (M+ - C4H7): 223.1334, observed 223.1332.
J ones reagent (5 mL) was added to a 0 °C solution of the
previous alcohol (880 mg, 3.16 mmol) in acetone (20 mL). An
excess of J ones reagent (10 mL) was added by portions over a
period of 5 h. The reaction was followed by TLC. Chromium
excesses were reduced with propan-2-ol (10 mL) until a green
color persisted. Water (15 mL) was added, and the acetone was
removed by rotary evaporation. The aqueous mixture was
extracted with diethyl ether (3 × 30 mL). The combined organic
portions were washed with brine (40 mL), dried over magnesium
sulfate, filtered, and concentrated by rotary evaporation. The
crude product was purified by flash chromatography on silica
gel using a (5:95 to 10:90) solution of ethyl acetate and hexanes
to yield 13 (311 mg, 52%, 2 steps) as a colorless oil. 1H NMR
(300 MHz, CDCl3) δ (ppm): 6.79 (dt, 1H, J ) 15.9, 6.6 Hz), 6.13
(dt, 1H, J ) 15.9, 1.5 Hz), 5.82 (ddt, 1H, J ) 17.0, 10.5, and 6.5
Hz), 5.07-4.96 (m, 2H), 3.27 (s, 1H), 2.79 (t, 2H, J ) 7.2 Hz),
2.65-2.54 (m, 4H), 2.35 (q, 2H, J ) 7.0 Hz). 13C NMR (75.5 MHz,
CDCl3) δ (ppm): 199.2 (s), 185.2 (s), 143.8 (d), 137.0 (d), 130.9
(d), 115.1 (t), 80.9 (d), 79.3 (s), 43.3 (t), 39.2 (t), 27.8 (t), 25.8 (t).
IR (neat, cm-1): 3242, 1679. GCMS (m/z, relative intensity): 190
(M+, 2). HRMS calculated for C12H14O2: 190.0994, observed
190.0987. Anal. Calcd for C12H14O2: H 7.42, C 75.75, O 16.83.
Found: H 7.47, C 75.77.
3,4-Dihydro-2H-pyran (400 µL, 371 mg, 4.40 mmol) was added
to a solution of (E)-10-(tert-butyldiphenylsilyloxy)deca-1,6-dien-
5-ol (900 mg, 2.20 mmol) and pyridinium p-toluenesulfonate (221
mg, 0.88 mmol) in dichloromethane (30 mL), and the solution
was stirred overnight. The reaction mixture was concentrated
under rotary evaporation and diluted with diethyl ether (20 mL)
and a saturated aqueous sodium bicarbonate solution (20 mL).
The layers were separated, and the aqueous phase was extracted
with diethyl ether (2 × 20 mL). The combined organic portions
were washed with brine (20 mL), dried over magnesium sulfate,
filtered, and concentrated by rotary evaporation. The crude
product was purified by flash chromatography on silica gel using
a 3:97 solution of ethyl acetate and hexanes to yield a mixture
of inseparable diastereomers of 12 (1.06 g, 98%) as a colorless
1
oil. H NMR (300 MHz, CDCl3) δ (ppm): 7.66 (dd, 4H, J ) 7.5,
1.4 Hz), 7.42-7.34 (m, 6H), 5.85-5.79 (m, 1H), 5.64-5.54 (m,
1H), 5.47 (dd, 1HA, J ) 15.5, 7.1 Hz), 5.21 (dd, 1HB, J ) 15.4,
8.4 Hz), 5.04-4.93 (m, 2H), 4.67-4.63 (m, 1H), 4.04-3.97 (m,
1H), 3.89-3.82 (m, 1H), 3.66 (t, 2H, J ) 6.3 Hz), 3.49-3.42 (m,
1H), 2.17-2.01 (m, 4H), 1.84-1.48 (m, 10H), 1.05 (s, 9H). IR
(neat, cm-1): 1471. LRMS (m/z, relative intensity): 435 (M+
-
t-Bu, 3). HRMS calculated for C27H35O3Si (M+ - t-Bu): 435.2355,
observed 435.2361. Anal. Calcd for C31H44O3Si: H 9.00, C 75.56,
O 9.74, Si 5.70. Found: H 8.87, C 75.62.
(E)-Dod eca -6,11-d ien -1-yn -3,8-d ion e (13a ). Tetrabutyl-
ammonium fluoride (1.0 M) (11 mL, 11 mmol) was added
dropwise to a 0 °C solution of 12 (4.81 g, 9.77 mmol) in THF
(100 mL), and the solution was stirred at room temperature for
1.5 h. The reaction mixture was diluted with water (60 mL).
The layers were separated, and the aqueous phase was extracted
with diethyl ether (2 × 60 mL). The combined organic portions
were washed with brine (100 mL), dried over magnesium sulfate,
filtered, and concentrated by rotary evaporation. The crude oil
was purified by flash chromatography on silica gel using a (2:
98 to 30:70) solution of ethyl acetate and hexanes to yield a 1:1
mixture of inseparable diastereomers A and B of (E)-6-(tetra-
hydropyran-2-yloxy)deca-4,9-dien-1-ol (2.40 g, 97%) as a colorless
oil. 1H NMR (300 MHz, CDCl3) δ (ppm): 5.91-5.74 (m, 1H),
5.69-5.58 (m, 1H), 5.52 (dd, 1HA, J ) 15.5, 7.1 Hz), 5.26 (dd,
1HB, J ) 15.3, 8.3 Hz), 5.05-4.94 (m, 2H), 4.66 (t, 1H, J ) 3.3
Hz), 4.05 (q, 1HB, J ) 7.0 Hz), 3.98 (q, 1HA, J ) 6.6 Hz), 3.93-
3.83 (m, 1H), 3.69-3.63 (m, 2H), 3.52-3.41 (m, 1H), 2.18-2.04
(m, 4H), 1.86-1.50 (m, 10H). IR (neat, cm-1): 3550-3150 (br).
LRMS (m/z, relative intensity): 254 (M+, 0.01), 237 (M+ - OH,
Tr icyclo[7.3.0.02,6]d od eca -6-en -5,12-d ion e (14a ). Typ ica l
P r oced u r e. 1,1′-Azobis(cyclohexanecarbonitrile) (ACCN, 11 mg,
0.04 mmol) and tributylgermanium hydride (22 µL, 21 mg, 0.09
mmol) were added to a solution of (E)-dodeca-6,11-dien-1-yn-
3,8-dione (13) (54.9 mg, 0.29 mmol) in toluene (25 mL), and the
solution was stirred at reflux temperature for 3 h. Three portions
of tributylgermanium hydride (10 µL, 9 mg, 0.04 mmol) and
ACCN (5 mg, 0.02 mmol) were added every 2 h for a total of 7
h. The reaction mixture was stirred for another 30 min and then
cooled to room temperature. The solution was concentrated by
rotary evaporation until 5 mL of toluene remained. The crude
product was purified by flash chromatography on silica gel using
a (0:100 to 20:80) solution of ethyl acetate and hexanes to yield
a mixture of four inseparable compounds, which was further
purified by preparative plate of silica gel with a solution of 20:
80 ethyl acetate and hexanes as eluent to yield tricyclo[7.3.0.02,6]-
dodeca-6-en-5,12-dione 14 as four isomers A, B, C, and D (11
1). HRMS calculated for
observed 237.1857. Anal. Calcd for C15H26O3: H 10.31, C 70.81,
O 18.88. Found: H 10.37, C 70.73.
C
15H25O2 (M+ - OH): 237.1854,
Oxalyl chloride (420 µL, 614 mg, 4.84 mmol) was dissolved in
dichloromethane (20 mL) and cooled to -78 °C. Dimethyl
sulfoxide (660 µL, 727 mg, 9.30 mmol) was added, and the
solution was stirred at -78 °C for 15 min. The alcohol from 12
(947 mg, 3.72 mmol) in dichloromethane (20 mL) was added via
cannula, and the solution was stirred at -78 °C during 45 min.
At -78 °C, triethylamine (2.9 mL, 2.1 g, 20.8 mmol) was added
in one portion to the reaction, which was stirred for another 45
min, diluted with water (20 mL), and allowed to warm to room
temperature. The layers were separated, and the aqueous phase
was extracted with dichloromethane (2 × 30 mL). The combined
organic portions were washed with water (2 × 20 mL) and brine
(30 mL), dried over magnesium sulfate, filtered, and concen-
trated by rotary evaporation. The crude product was purified
by flash chromatography on silica gel using a (5:95 to 15:85)
solution of ethyl acetate and hexanes to yield a 1:1 mixture of
inseparable diastereomers A and B of (E)-6-(tetrahydropyran-
2-yloxy)deca-4,9-dienal (811 mg, 86%) as a colorless oil. 1H NMR
(300 MHz, CDCl3) δ (ppm): 9.77 (t, 1H, J ) 1.4 Hz), 5.90-5.73
(m, 1H), 5.69-5.49 (m, 1H + 1HA), 5.28 (dd, 1HB, J ) 15.5, 8.2
Hz), 5.04-4.93 (m, 2H), 4.65-4.60 (m, 1H), 4.13-3.97 (m, 1H),
3.89-3.82 (m, 1H), 3.51-3.40 (m, 1H), 2.53 (td, 2H, J ) 7.3, 1.4
Hz), 2.38 (q, 2H, J ) 6.8 Hz), 2.20-2.02 (m, 2H), 1.88-1.49 (m,
8H). IR (neat, cm-1): 1726. LRMS (m/z, relative intensity): 252
(M+, 0.01), 197 (M+ - C4H7, 56). HRMS calculated for C11H17O3
(M+ - C4H7): 197.1178, observed 197.1174.
1
mg, 20%). H NMR (300 MHz, CDCl3) δ (ppm): 6.91 (dd, 1HA,
J ) 7.7 et 3.0 Hz), 6.75-6.71 (m, 1HB), 6.65-6.62 (m, 1HC +
1HD), 2.98-1.07 (m, 13H). 13C NMR (75.5 MHz, CDCl3) δ
(ppm): 218.6 (s), 216.9 (s), 212.1 (s), 211.3 (s), 205.4 (s), 204.8
(s), 204.7 (s), 204.3 (s), 142.8 (s), 141.0 (s), 140.3 (s), 138.5 (s),
134.2 (d), 132.6 (d), 131.7 (d), 131.0 (d), 56.7 (d), 52.4 (d), 48.2
(d), 47.4 (d), 41.5 (d), 41.1 (d), 39.3 (d), 38.5 (d), 37.9 (t), 37.6 (t),
37.0 (t), 36.6 (t), 36.0 (t), 35.7 (t), 35.0 (t), 34.4 (d), 34.1 (t), 33.8
(d), 32.2 (t), 31.3 (t), 31.0 (t), 29.0 (d), 28.8 (d), 28.0 (t), 27.6 (t),
27.3 (t), 27.0 (t), 26.9 (t), 26.6 (t), 25.5 (t), 25.0 (t), 24.1 (t). IR
(neat, cm-1): 1737, 1718. GCMS (m/z, relative intensity): 190
(M+, 100). HRMS calculated for C12H14O2: 190.0994, observed
190.0991.
(E)-Tr id eca -7,12-d ien -2-yn -4,9-d ion e (13b). Propyne (1 mL,
706 mg, 17.6 mmol) was condensed in THF (30 mL) at -78 °C.
n-Butyllithium (1.21 M) (7.8 mL, 9.3 mmol) was added dropwise,
and the solution was stirred for 15 min. A solution of (E)-6-
(tetrahydropyran-2-yloxy)deca-4,9-dienal (940 mg, 3.72 mmol)
in THF (10 mL) was added via cannula, and the solution was
Ethynylmagnesium bromide (0.5 M) (19.0 mL, 9.57 mmol) was
added to a -60 °C solution of the previous aldehyde (804 mg,

Notes
J . Org. Chem., Vol. 64, No. 14, 1999 5297
stirred for 1.5 h at -78 °C. The reaction mixture was quenched
with a saturated solution of NH4Cl (20 mL) and warmed to room
temperature. The layers were separated, and the aqueous phase
was extracted with ethyl acetate (3 × 20 mL). The combined
organic portions were washed with brine (20 mL), dried over
magnesium sulfate, filtered, and concentrated by rotary evapo-
ration. The crude product was purified by flash chromatography
on silica gel using a (5:95 to 20:80) solution of ethyl acetate and
hexanes to yield a 1:1 mixture of inseparable diastereomers A
and B of (E)-9-(tetrahydropyran-2-yloxy)trideca-7,12-dien-2-yn-
4-ol (821 mg, 75%) as a colorless oil. 1H NMR (300 MHz, CDCl3)
δ (ppm): 5.91-5.74 (m, 1H), 5.68-5.49 (m, 1H+1HA), 5.28 (dd,
1HB, J ) 15.4, 8.3 Hz), 5.05-4.93 (m, 2H), 4.66-4.64 (m, 1H),
4.38-4.30 (m, 1H), 4.08-3.96 (m, 1H), 3.93-3.82 (m, 1H), 3.52-
3.41 (m, 1H), 2.30-2.03 (m, 4H), 1.85 (d, 3H, J ) 1.8 Hz), 1.83-
1.49 (m, 10H). IR (neat, cm-1): 3700-3150 (br). LRMS (m/z,
relative intensity): 310 (MNH4+, 7), 292 (M+, 1). HRMS calcu-
lated for C18H32NO3 (MNH4+): 310.2382, observed 310.2388.
J ones reagent (5 mL) was added to a 0 °C solution of (E)-9-
(tetrahydropyran-2-yloxy)trideca-7,12-dien-2-yn-4-ol (807 mg,
2.76 mmol) in acetone (30 mL). An excess of J ones reagent (10
mL) was added by portions over a period of 5 h. The reaction
mixture was monitored by thin-layer chromatography. The
excess chromium was reduced with propan-2-ol (10 mL) until a
green color persisted. Water (20 mL) was then added, and the
acetone was removed by rotary evaporation. The aqueous
mixture was extracted with diethyl ether (3 × 30 mL). The
combined organic portions were washed with brine (40 mL),
dried over magnesium sulfate, filtered, and concentrated by
rotary evaporation. The crude product was purified by flash
chromatography on silica gel using a (5:95 to 12:88) solution of
diene (50 mL) was added dropwise to the hot oil while the rate
of addition was regulated so that the temperature stayed over
210 °C and the top of the column was below 42 °C. Cyclo-
pentadiene was recovered in an ice-cold flask and added (40 mL,
26.4 g, 400 mmol) to a solution of 5-hydroxy-2(5H)-furanone (2.0
g, 20.0 mmol) in diethyl ether (10 mL). The reaction mixture
was stirred for 5.5 h at room temperature. The solvent was
removed by rotary evaporation to give a white solid. The crude
product was purified by flash chromatography on silica gel using
a (30:70 to 80:20) solution of ethyl acetate and hexanes to yield
1
17 (3.14 g, 95%) as a white solid. Mp: 101-4 °C. H NMR (300
MHz, CDCl3) δ (ppm): 6.25-6.18 (m, 2H), 5.23 (s, 1H), 4.3-3.7
(bs, 1H), 3.39 (dd, 1H, J ) 8.7, 4.7 Hz), 3.32 (m, 1H), 3.21 (bs,
1H), 2.95 (ddd, 1H, J ) 8.7, 4.3 and 1.3 Hz), 1.63 (dt, 1H, J )
8.6, 1.5 Hz), 1.45 (d, 1H, 8.7 Hz). IR (neat, cm-1): 3700-3200
(br), 1766, 1738. LRMS (m/z, relative intensity): 166 (M+, 1.5).
HRMS calculated for C9H10O3: 166.0630, observed 166.0633.
Anal. Calcd for C9H10O3: H 6.07, C 65.04, O 28.9. Found: H
6.02, C 64.96.
1-Iod oh ex-5-en e. Triphenylphosphine (8.7 g, 33.2 mmol),
imidazole (2.26 g, 33.2 mmol), and iodine (8.4 g, 33.2 mmol) were
successively added to 5-hexen-1-ol (2.0 mL, 1.67 g, 16.6 mmol)
in a mixture of diethyl ether/acetonitrile (80 mL/20 mL). The
reaction mixture was stirred for 20 min. Diethyl ether (50 mL)
was added, and the mixture was filtered on Celite and washed
with diethyl ether (20 mL). The yellow solution recovered was
washed with a saturated sodium bicarbonate solution (2 × 50
mL) and brine (50 mL), dried over magnesium sulfate, filtered,
and concentrated by rotary evaporation. The crude oil was
purified by flash chromatography on silica gel using hexanes to
yield 1-iodohex-5-ene (3.40 g, 98%) as an oil. 1H NMR (300 MHz,
CDCl3) δ (ppm): 5.79 (ddt, 1H, J ) 17.0, 10.3, and 6.6 Hz), 5.06-
4.96 (m, 2H), 3.19 (t, 2H, J ) 7.0 Hz), 2.07 (q, 2H, J ) 7.1 Hz),
1.84 (quintet, 2H, J ) 7.1 Hz), 1.50 (quintet, 2H, J ) 7.2 Hz).
IR (neat, cm-1): 1640. GCMS (m/z, relative intensity): 210 (M+,
3). HRMS calculated for C6H11I: 209.9905, observed 209.9911.
r a c-(Z)-(1R,2S,3R,4S)-2-Ca r b oxy-3-(1,6-h ep t a d ien yl)b i-
cyclo[2.2.1]h ep ta n e (18). Palladium on charcoal (10%) (1.5 g)
was mixed with ethyl acetate (80 mL), and the solution was
stirred under hydrogen (1 atm) during 20 min. A solution of 17
(3.14 g, 18.9 mmol) in ethyl acetate (20 mL) was added, and the
mixture was stirred for 3 h under a hydrogen atmosphere. The
mixture was filtered on Celite and washed with ethyl acetate
(50 mL). The solution was concentrated by rotary evaporation
to give a white solid, which was recrystallized with hot ethyl
acetate and pentane to yield rac-(1R,2S,6R,7S)-4-oxa-3-oxotricyclo-
[5.2.1.02,6]decan-5-ol (3.15 g, 99%) as colorless crystals. Mp:
1
ethyl acetate and hexanes to yield 13b (318 mg, 56%). H NMR
(300 MHz, CDCl3) δ (ppm): 6.80 (dt, 1H, J ) 15.9, 6.6 Hz), 6.11
(dt, 1H, J ) 15.9, 1.3 Hz), 5.82 (ddt, 1H, J ) 17.0, 10.4, and 6.5
Hz), 5.05-4.96 (m, 2H), 2.72 (t, 2H, J ) 7.2 Hz), 2.63 (t, 2H, J
) 7.2 Hz), 2.59-2.52 (m, 2H), 2.38-2.29 (m, 2H), 2.03 (s, 3H).
13C NMR (75.5 MHz, CDCl3) δ (ppm): 199.0 (s), 185.6 (s), 144.2
(d), 136.9 (d), 130.6 (d), 114.8 (t), 90.7 (s), 79.6 (s), 43.0 (t), 38.9
(t), 27.6 (t), 26.1 (t), 3.8 (q). IR (neat, cm-1): 3325. GCMS (m/z,
relative intensity): 204 (M+, 6). HRMS calculated for C13H16O2:
204.1150, observed 204.1146. Anal. Calcd for C13H16O2: H 7.90,
C 76.43, O 15.67. Found: H 7.92, C 76.49.
2-(1-Tr ibu tylsta n n yl-1-eth ylid en e)-3-(2-oxoh ex-5-en yl)-
cyclop en t a n on e (15b ). Typ ica l P r oced u r e. R,R′-Azobis-
(isobutyronitrile) (AIBN, 2 mg, 0.01 mmol) and tributyltin
hydride (20 µL, 21 mg, 0.07 mmol) were added to a solution of
13b (50 mg, 0.24 mmol) in benzene (8 mL), and the solution was
stirred at reflux temperature during a total of 10 h. Two other
portions of tributyltin hydride and AIBN were added after 2 and
6 h (20 µL and 34 µL, respectively, for Bu3SnH and 5 mg each
time for AIBN). The reaction was cooled to room temperature.
The solution was concentrated by rotary evaporation until 2 mL
of benzene remained. The crude product was purified by flash
chromatography on silica gel using a (0:100 to 20:80) solution
of ethyl acetate and hexanes to yield two separable isomers
of 2-(1-tributylstannyl-1-ethylidene)-3-(2-oxohex-5-enyl)cyclo-
pentanone (15b) (A: 19 mg, 15% and B: 25 mg, 21%). Isomer
A: 1H NMR (300 MHz, CDCl3) δ (ppm): 5.80 (ddt, 1H, J ) 17.0,
10.5, and 6.5 Hz), 5.07-4.96 (m, 2H), 3.62 (q, 1H, J ) 7.1 Hz),
2.55-2.48 (m, 4H), 2.41-2.31 (m, 4H), 2.09 (s, 3H), 1.99-1.92
(m, 1H), 1.79-1.71 (m, 1H), 1.49-1.39 (m, 6H), 1.27 (sextet, 6H,
J ) 7.1 Hz), 1.00-0.80 (m, 15H). Isomer B: 1H NMR (300 MHz,
CDCl3) δ (ppm): 5.81 (ddt, 1H, J ) 17.0, 10.6 and 6.4 Hz), 5.08-
4.98 (m, 2H), 2.89 (sextet, 1H, J ) 4.3 Hz), 2.68-2.52 (m, 4H),
2.39-2.32 (m, 4H), 2.09-2.00 (m, 1H), 1.96 (s, 3H), 1.76 (dq,
1H, J ) 13.5, 4.5 Hz), 1.51-1.40 (m, 6H), 1.30 (sextet, 6H, J )
7.2 Hz), 1.07-0.86 (m, 6H), 0.87 (t, 9H, J ) 7.2 Hz). 13C NMR
(75.5 MHz, CDCl3) δ (ppm): 208.3 (s), 202.3 (s), 171.6 (s), 142.2
(s), 136.7 (d), 115.6 (t), 43.9 (t), 42.4 (t), 37.0 (t), 33.0 (t), 29.2
(t), 29.1 (t), 27.3 (t), 26.7 (t), 24.9 (q), 13.7 (q), 11.8 (t). IR (neat,
cm-1): 1718. GCMS (m/z, relative intensity): 439 (M+ - Bu,
100). HRMS calculated for C21H35O2Sn (M+ - Bu): 439.1659,
observed 439.1665.
1
115-116 °C. H NMR (300 MHz, CDCl3) δ (ppm): 5.69 (s, 1H),
3.75-3.60 (bs, 1H), 3.11 (dd, 1H, J ) 10.6, 5.6 Hz), 2.68-2.61
(m, 1H), 2.54 (m, 1H), 1.75-1.40 (m, 5H), 1.42 (dd, 1H, J ) 9.6,
4.7 Hz). IR (neat, cm-1): 3600-3100 (br), 1770, 1746. LRMS
(m/z, relative intensity): 168 (M+, 0.4). HRMS calculated
for C9H12O3: 168.0786, observed 168.0782. Anal. Calcd for
C9H12O3: H 7.2, C 64.26, O 28.55. Found: H 7.23, C 64.28.
Triphenylphosphine (7.5 g, 28.6 mmol) was added to 1-iodo-
hex-5-ene (3.0 g, 14.3 mmol) in a mixture of toluene/acetonitrile
(60 mL/60 mL). The reaction mixture was heated at 75 °C for
72 h, after which time it was cooled to 0 °C and solvent was
removed under vacuum to give a white solid (the flask was
flushed with dry nitrogen after solvent removal). A suspension
of the phosphonium salt (6.7 g, 14.3 mmol) in THF (70 mL)
was cooled to -78 °C. n-Butyllithium (1.87 M) (7.7 mL, 14.3
mmol) was added dropwise, and the solution was stirred for 1 h
at -78 °C. Then
a solution of rac-(1R,2S,6R,7S)-4-oxa-3-
oxotricyclo[5.2.1.02,6]decan-5-ol (1.2 g, 7.15 mmol) in THF (10
mL) was added to the reaction mixture, and the resulting
solution was stirred during 16 h at room temperature. Distilled
water (20 mL) and a 1 N HCl solution (10 mL) were added, and
the layers were separated. The aqueous layer was extracted with
ethyl acetate (3 × 50 mL). The organic phases were combined,
washed with brine (50 mL), dried over magnesium sulfate,
filtered and concentrated by rotary evaporation. The crude
product was purified by flash chromatography on silica gel using
a (10:90 to 80:20) solution of ethyl acetate and hexanes to
yield 18 (1.57 g, 94%). 1H NMR (300 MHz, CDCl3) δ (ppm): 5.81
(ddt, 1H, J ) 17.0, 10.3, and 6.6 Hz), 5.60 (dd, 1H, J ) 10.9, 9.7
Hz), 5.45 (dt, 1H, J ) 10.9, 7.2 Hz), 5.04-4.93 (m, 2H), 3.06 (td,
r a c-(1R,2S,6R,7S)-4-Oxa -3-oxotr icyclo[5.2.1.02,6]d ec-8-en -
5-ol (17). A 50 mL three-neck round-bottom flask, equipped with
a 20 cm Vigreux column and a distillation system, was charged
with paraffin oil (20 mL) and heated to 240 °C. Dicyclopenta-

5298 J . Org. Chem., Vol. 64, No. 14, 1999
Notes
1H, J ) 10.7, 4.2 Hz), 2.90 (ddd, 1H, J ) 11.8, 3.9 and 1.7 Hz),
2.52 (s, 1H), 2.20 (s, 1H), 2.09-1.94 (m, 5H), 1.73-1.65 (m, 1H),
1.51-1.32 (m, 6H). IR (neat, cm-1): 3450-2450 (br), 1770, 1704.
LRMS (m/z, relative intensity): 234 (M+, 2). HRMS calculated
for C15H22O2: 234.1620, observed 234.1624. Anal. Calcd for
was extracted with ethyl acetate (3 × 20 mL). The combine
organic portions were washed with brine (20 mL), dried over
magnesium sulfate, filtered, and concentrated by rotary evapo-
ration. The crude product was purified by flash chromatography
on silica gel using a (5:95 to 10:90) solution of ethyl acetate and
hexanes to yield two separable diastereomers A and B of rac-
(Z)-(1R,2S,3R,4S)-2-(1-hydroxy-2-propynyl)-3-(1,6-heptadienyl)-
bicyclo[2.2.1]-heptane (A: 112.5 mg, 50% and B: 83.5 mg, 37%)
as colorless oils. Isomer A: 1H NMR (300 MHz, CDCl3) δ (ppm):
5.86-5.60 (m, 3H), 5.04-4.94 (m, 2H), 4.46 (dd, 1H, J ) 10.8,
2.1 Hz), 2.91 (td, 1H, J ) 10.9, 4.1 Hz), 2.46-2.44 (m, 1H), 2.45
(d, 1H, J ) 2.1 Hz), 2.22-2.02 (m, 6H), 1.72-1.41 (m, 8H). IR
(neat, cm-1): 3550-3150 (br). LRMS (m/z, relative intensity):
243 (M+ - 1, 2). HRMS calculated for C17H23O: 243.1749,
observed 243.1754. Anal. Calcd for C17H23O: H 9.53, C 83.89, O
6.58. Found: H 9.53, C 83.89. Isomer B: 1H NMR (300 MHz,
CDCl3) δ (ppm): 5.81 (ddt, 1H, J ) 17.0, 10.3, and 6.7 Hz), 5.47-
5.44 (m, 2H), 5.03-4.93 (m, 2H), 4.29 (dd, 1H, J ) 11.3, 2.0 Hz),
2.97-2.91 (m, 1H), 2.43 (s, 1H), 2.38 (d, 1H, J ) 2.0 Hz), 2.23
(dd, 1H, J ) 11.4, 3.4 Hz), 2.19-2.00 (m, 5H), 1.67-1.32 (m,
8H).
Molecular sieves (4 Å) (400 mg) were added to a 0 °C solution
of a mixture of the isomers of the previous alcohols (167 mg,
0.68 mmol) in dichloromethane (10 mL), and the solution was
stirred for 5 min. Pyridinium chlorochromate (220 mg, 1.02
mmol) was added to the reaction, and the solution was stirred
at room temperature during 1 h. Diethyl ether (10 mL) was
added, and the mixture was filtered on a fritted glass containing
silica gel, activated charcoal, and Celite. The residue was washed
with diethyl ether (20 mL). The solution was concentrated by
rotary evaporation. The crude product was purified by flash
chromatography on silica gel using a (0:100 to 2:98) solution of
ethyl acetate and hexanes to yield a mixture of inseparable
isomers of 20 (132.1 mg, 80%) as an oil (unstable). 1H NMR (300
MHz, CDCl3) δ (ppm): 5.85-5.74 (m, 1H), 5.55-5.32 (m, 2H),
5.04-4.93 (m, 2H), 3.19 (s, 1HB), 3.17-3.12 (m, 1H), 3.08 (s,
1HA), 2.64 (s, 1H), 2.22 (s, 1H), 2.19-2.01 (m, 4H), 1.77-1.23
(m, 9H). GCMS (m/z, relative intensity): 241 (M+ - 1, 0.5).
C
15H22O2: H 9.47, C 76.87, O 13.66. Found: H 9.41, C 76.79.
r a c-(Z)-(1R ,2S ,3R ,4S )-2-H yd r oxym e t h yl-3-(1,6-h e p t a -
d ien yl)bicyclo[2.2.1]h ep ta n e (19). Lithium aluminum hydride
(1.0 M) (1.7 mL, 1.66 mmol) was added dropwise to a 0 °C
solution of 18 (379 mg, 1.62 mmol) in THF (15 mL). When the
bubbling stopped, the mixture was allowed to warm to room
temperature and stirred for 24 h. Water (10 mL) was slowly
added, then a 1 N HCl solution (5 mL) was added, and the layers
were separated. The aqueous layer was extracted with ethyl
acetate (3 × 20 mL). The combined organic portions were washed
with brine (20 mL), dried over magnesium sulfate, filtered, and
concentrated by rotary evaporation to yield rac-(Z)-(1R,2S,3R,4S)-
2-hydroxymethyl-3-(1,6-heptadienyl)bicyclo[2.2.1]heptane (349.4
mg, 95%) as a colorless oil, which was used without further
purification. 1H NMR (300 MHz, CDCl3) δ (ppm): 5.80 (ddt, 1H,
J ) 17.0, 10.3, and 6.7 Hz), 5.60-5.47 (m, 2H), 5.04-4.94 (m,
2H), 3.66 (dd, 1H, J ) 11.1, 8.1 Hz), 3.52 (dd, 1H, J ) 11.2, 7.9
Hz), 2.87 (ddd, 1H, J ) 12.3, 8.1 and 3.3 Hz), 2.29 (s, 1H), 2.19-
2.02 (m, 5H), 1.60 (td, 1H, J ) 7.3, 2.3 Hz), 1.52-1.32 (m, 8H).
IR (neat, cm-1): 3600-3050 (br), 1707. LRMS (m/z, relative
intensity): 220 (M+, 0.01), 202 (M+ - H2O, 1). HRMS calculated
for C15H22 (M+ - H2O): 202.1721, observed 202.1720.
Molecular sieves (4 Å) (125 mg) were added to a 0 °C solution
of rac-(Z)-(1R,2S,3R,4S)-2-hydroxymethyl-3-(1,6-heptadienyl)-
bicyclo[2.2.1]heptane (50 mg, 0.23 mmol) in dichloromethane (3
mL), and the solution was stirred for 5 min. Pyridinium
chlorochromate (54 mg, 0.25 mmol) was added to the reaction
mixture, and the solution was stirred at room temperature
during 1 h. Diethyl ether (5 mL) was added, and the solution
was filtered on a fritted glass containing silica gel, activated
charcoal, and Celite and washed with diethyl ether (15 mL). The
solution was concentrated by rotary evaporation, and the crude
product was purified by flash chromatography on silica gel using
a (0:100 to 10:90) solution of ethyl acetate and hexanes to yield
1
Ack n ow led gm en t. We acknowledge the financial
support of the Natural Sciences and Engineering Re-
search Council of Canada, the Fond pour la Formation
de Chercheur et l′Aide a` la Recherche, and the Univer-
site´ de Sherbrooke.
19 (38.3 mg, 77%) as a colorless oil. H NMR (300 MHz, CDCl3)
δ (ppm): 9.73 (t, 1H, J ) 2.2 Hz), 5.80 (ddt, 1H, J ) 17.0, 10.3,
and 6.7 Hz), 5.55-5.52 (m, 2H), 5.03-4.94 (m, 2H), 3.22-3.13
(m, 1H), 2.63-2.58 (m, 2H), 2.26-2.25 (m, 1H), 2.09-2.01 (m,
4H), 1.74-1.64 (m, 2H), 1.51-1.40 (m, 6H). IR (neat, cm-1):
1716. LRMS (m/z, relative intensity): 218 (M+, 2). HRMS
calculated for C15H22O: 218.1671, observed 218.1667.
r a c-(Z)-(1R,2S,3R,4S)-2-(1-Oxop r op yn yl)-3-(1,6-h ep t a -
d ien yl)bicyclo[2.2.1]h ep ta n e (20). Ethynylmagnesium bro-
mide (0.5 M) (4.6 mL, 2.29 mmol) was added to a -78 °C solution
of 19 (200 mg, 0.92 mmol) in THF (10 mL), and the solution
was stirred for 4 h, during which time the temperature was
allowed to reach 0 °C. The reaction mixture was quenched with
a 1 N HCl solution (10 mL) and allowed to warm to room
temperature. The layers were separated, and the aqueous phase
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
compounds 14a (mixture of all isomers), 15 (mixture of two
isomers A and B), 15 (mixture of two isomers C and D), 15
(one isomer C). 13C NMR spectra as well as the DEPT 90 and
DEPT 135 of compounds 14a (mixture of all isomers), 15 (one
isomer C). This material is available free of charge via the
Internet at http://pubs.acs.org.
J O9905524