Catalytic ring closing metathesis of dienynes: Construction of fused bicyclic [n.m.0] rings

Article abstract of DOI:10.1021/jo951648a

Ruthenium carbene 1 (Cl₂(PCy₃)₂Ru=CHCH=CPh₂) mediates the efficient and selective conversion of acyclic dienynes to fused bicyclic [n.m.0] rings containing five-, six-, and seven-membered rings. Studies with various X-substituted acetylenes (X = H, alkyls, Ph, CO₂Me, SnBu₃, TMS, Cl, Br, I) suggest that the dienyne metathesis is sensitive not only to these substituents but also to the catalysts employed. Among the various metal alkylidenes examined, only the ruthenium catalyst 1 exhibited metathesis activity for a range of substrates. These observations further expand the scope of catalytic RCM for the construction of complex organic compounds.

Full text of DOI:10.1021/jo951648a

J . Org. Chem. 1996, 61, 1073-1081
1073
Ca ta lytic Rin g Closin g Meta th esis of Dien yn es: Con str u ction of
F u sed Bicyclic [n .m .0] Rin gs
Soong-Hoon Kim, William J . Zuercher, Ned B. Bowden, and Robert H. Grubbs*
The Arnold and Mabel Beckman Laboratory of Chemical Synthesis, Division of Chemistry and Chemical
Engineering, California Institute of Technology, Pasadena, California 91125
Received September 8, 1995X
Ruthenium carbene 1 (Cl2(PCy3)2RudCHCHdCPh2) mediates the efficient and selective conversion
of acyclic dienynes to fused bicyclic [n.m.0] rings containing five-, six-, and seven-membered rings.
Studies with various X-substituted acetylenes (X ) H, alkyls, Ph, CO2Me, SnBu3, TMS, Cl, Br, I)
suggest that the dienyne metathesis is sensitive not only to these substituents but also to the
catalysts employed. Among the various metal alkylidenes examined, only the ruthenium catalyst
1 exhibited metathesis activity for a range of substrates. These observations further expand the
scope of catalytic RCM for the construction of complex organic compounds.
Sch em e 1. Ca ta lytic Rin g Closin g Meta th esis
(RCM) of Dien es
In tr od u ction
Fused bicyclic [n.m.0] structural frameworks represent
an important substructure in many natural products, and
the efficient synthesis of functionalized fused bicyclic
rings remains an important goal.1 Strategies and meth-
ods that accomplish the rapid construction of function-
alized fused bicyclic rings from simple precursors are
therefore desired. We recently reported a short and
highly convergent metathesis-based strategy for the
construction of functionalized fused bicyclic rings.2 The
key step of the approach involves the ruthenium carbene
1 catalyzed double ring-closing metathesis (RCM) of
dienynes.3
Sch em e 2. Meta l Ca r ben e Med ia ted En e-Yn e
Meta th esis
Previous reports have established that metal alky-
lidene-mediated catalytic RCM of dienes is a general
approach to the construction of carbocycles and hetero-
cyles (Scheme 1).4 To investigate the scope of this
reaction, a metathesis-based strategy for double ring (or
multiple) cyclization of a single substrate to give a fused
bicyclic [n.m.0] ring was explored.
Several researchers have established that intramo-
lecular ene-yne metathesis can be used to construct ring
structures. Katz and Sivavec first reported that pentac-
arbonyltungsten carbene catalyzes intramolecular ene-
yne metathesis (single ring closure) to generate substi-
tuted 1-vinylcycloolefins (Scheme 2).5 Subsequently,
other researchers have studied the ene-yne-ene trans-
formation (bis-ring annulation) with electrophilic (Fis-
cher) carbenes and rhodium-catalyzed decomposition of
R-diazo ketones to generate compounds containing two
rings linked with a single bond. With the Fischer
carbenes, pre-formed and stoichiometric carbenes were
required, and the second ring closure led to cyclopropanes
through the reductive elimination of the intermediate
metallacyclobutane.6 With the rhodium-catalyzed de-
composition of R-diazo ketones, a complex product dis-
tribution arising from several competing processes was
observed.7
† Contribution No. 9095 from the California Institute of Technology.
X Abstract published in Advance ACS Abstracts, J anuary 15, 1996.
(1) See, for instance: Natural Products Chemistry; Nakanishi, K.,
Ed.; Academic Press: New York, 1974; Vols. 1-3.
(2) Preliminary work was reported in a communication. Kim, S. H.;
Bowden, N.; Grubbs, R. H. J . Am. Chem. Soc. 1994, 116, 10801.
(3) For the preparation and characterization of catalyst 1: (a)
Nguyen, S. T.; J ohnson, L. K.; Grubbs, R. H.; Ziller, J . W. J . Am. Chem.
Soc. 1992, 114, 3974. (b) Nguyen, S. T.; Grubbs, R. H.; Ziller, J . W. J .
Am. Chem. Soc. 1993, 115, 9858.
(4) Previous reports on RCM from this laboratory: (a) Fu, G. C.;
Grubbs, R. H. J . Am. Chem. Soc. 1992, 114, 5426. (b) Fu, G. C.; Grubbs,
R. H. J . Am. Chem. Soc. 1992, 114, 7324. (c) Fu, G. C.; Grubbs, R. H.
J . Am. Chem. Soc. 1993, 115, 3800. (d) Fu, G. C.; Nguyen, S. T.; Grubbs,
R. H. J . Am. Chem. Soc. 1993, 115, 9856. (e) Fujimura, O.; Fu, G. C.;
Grubbs, R. H. J . Org. Chem. 1994, 59, 4029. (f) Miller, S. J .; Kim, S.
H.; Chen, Z.; Grubbs, R. H. J . Am. Chem. Soc. 1995, 117, 2108. (g)
Miller, S. J .; Grubbs, R. H. J . Am. Chem. Soc. 1995, 117, 5855-5856.
(h) Grubbs, R. H.; Miller, S. J .; Fu, G. C. Acc. Chem. Res. 1995, 28,
446-452. For recent applications of RCM to natural product synthe-
sis: (i) Martin, S. F.; Liao, Y.; Rein, T. Tetrahedron Lett. 1994, 35,
691. (j) Borer, B. C.; Deerenberg, S.; Bieraugel, H.; Pandit, U. K.
Tetrahedron Lett. 1994, 35, 3191. (k) Wagman, A. S.; Martin, S. F.
Tetrahedron Lett. 1995, 36, 1169. (l) Houri, A. F.; Xu, Z.; Logan, D. A.;
Hoveyda, A. H. J . Am. Chem. Soc. 1995, 117, 2943. For a review on
applications of olefin metathesis in organic synthesis: Grubbs, R. H.;
Pine, S. H. In Comprehensive Organic Synthesis; Trost, B. M., Ed.;
Pergamon: New York, 1991; Vol. 5, Chapter 9.3.
(5) Katz, T. J .; Sivavec, T. M. J . Am. Chem. Soc. 1985, 107, 737.
(6) (a) Korkowski, P. F.; Hoye, T. R.; Rydberg, D. B. J . Am. Chem.
Soc. 1988, 110, 2676. (b) Harvey, D. F.; Brown, M. F. J . Org. Chem.
1992, 57, 5559. For a review on the chemistry of Fischer carbenes with
ene-yne substrates see: Wulff, W. D. In Comprehensive Organic
Synthesis; Trost, B. M., Ed.; Pergamon: New York, 1991; Vol. 5,
Chapter 9.2.
0022-3263/96/1961-1073$12.00/0 © 1996 American Chemical Society

1074 J . Org. Chem., Vol. 61, No. 3, 1996
Sch em e 3. Ru th en iu m Ca r ben e 1 Ca ta lyzed Dien yn e Meta th esis
Kim et al.
Sch em e 4. Con str u ction of F u sed Bicyclic [n .m .0] Rin gs via Dien yn e Meta th esis
These studies demonstrated that the course of ene-
yne metathesis is dependent on the metal complex
employed. Furthermore, these synthetic methods are
somewhat limited due to the lack of substrate flexibility,8
several unpredictable competing pathways,9 modest yields,
and stoichiometry of reaction.10 Nevertherless, an im-
portant principle was demonstrated: the acetylene acts
as an olefin metathesis relay. Thus, the ene-yne me-
tathesis generates the first ring in addition to the
regenerated carbene which undergoes diene RCM to
generate a second ring. This property of dienyne cycliza-
tion was utilized for a new metathesis-based strategy for
the construction of fused bicyclic [n.m.0] rings (vide infra).
and the regenerated catalyst 7.12 During this process,
two rings are generated, and the resulting rings contain
olefins that may be further functionalized.
Con str u ction of F u sed [n .m .0] Rin gs. The strategy
to generate the fused bicyclic [n.m.0] framework (the
smallest unit of fused polycyclic structure) is shown in
Scheme 4. The key feature is the location of the acetylene
group in a branched position between the two olefins. The
ene-yne metathesis generates the first ring plus the
regenerated carbene, which undergoes a second diene
RCM to produce the fused [n.m.0] bicyclic ring. These
studies indicate that the strategy is general and allows
for the efficient and rapid construction of a variety of
fused bicyclic rings. Futhermore, they suggest that the
rurthenium carbene 1 is the catalyst of choice. Among
the metal alkylidenes examined, only the ruthenium
complex catalyzed dienyne cyclization for a range of
substrates.
A rapid route to a variety of starting dienynes was
established to explore the scope of this reaction. The
synthesis of branched dienynes 9-16 is shown in Scheme
5. The symmetrical dienynes were synthesized by double
Grignard addition to the benzyl ester 8. The unsymetri-
cal dienynes were prepared by the sequential Grignard
addition to the N-methoxy-N-methylamide 11. The
resulting alcohols were protected as their triethylsilyl
ethers.13
Resu lts a n d Discu ssion
In itia l Mod el Stu d ies. Earlier studies from our
group and others have established that the ruthenium
carbene 1 is a efficient catalyst for diene RCM.4d,f Thus,
our first objective was to determine the reactivity of
ruthenium carbene 1 (and other RCM catalysts) toward
the ene-yne metathesis.
From the readily prepared compound 211 under stan-
dard diene RCM conditions (3 mol % 1, C6H6, rt, 4 h),
product 6 was obtained in 90% yield. No other side
products were detected. The steps leading from dienyne
2 to product 6 are shown in Scheme 3. The first step
involves intermolecular acyclic metathesis to generate
intermediate 3, which undergoes intramolecular ene-
yne metathesis to give the first ring plus the regenerated
carbene 5. A second diene RCM produced the second ring
All reactions were initially monitored by 1H NMR
spectroscopy.14 Both the starting vinylcarbene and propa-
gating methylidene R proton resonances are observed
downfield in the range 19-20 ppm. As dienyne metath-
esis proceeds, the vinyl carbene doublet disappears as
(7) Hoye, T. R.; Dinsmore, C. J . J . Am. Chem. Soc. 1991, 113, 4343.
(8) Some substrates possess specific structural requirements such
as pre-formed carbenes and specific R-diazocarbonyl compounds.
(9) For instance, the rhodium-catalyzed reaction showed a complex
product distribution arising from several competing processes (ref 7).
(10) The dienyne cyclization shown in Scheme 2 required a stoichio-
metric amount of pre-formed Fischer carbene (ref 6a).
(12) The possibility that the first step involves an alkyne metathesis
followed by two diene RCM steps cannot be ruled out. However, later
experiments favor the proposed mechanism (see text).
(13) Dienyne RCM proceeds at a somewhat slower rate with the free
alcohols.
(14) NMR reactions were conducted in 0.2-0.3 mmol scale at 0.01-
0.07 M substrate concentration.
(11) Dienyne
2
was synthesized from 2-butyne-1,4-diol: NaH,
CH2dCHCH2Br, DMF.

Construction of Fused Bicyclic [n.m.0] Rings
J . Org. Chem., Vol. 61, No. 3, 1996 1075
Sch em e 5. Syn th esis of Sta r tin g Dien yn esa
a
Key: (a) MgBr(CH2)nCH2CHdCH2, THF; (b) Et3SiOTf, TEA, CH2Cl2; (c) stepwise addition of Grignard reagents, MgBrR3, THF and
MgBrR1R2, THF; (d) MgBr(CH2)2CHdCH2; MgBrMe; NaH, crotyl bromide, DMF.
Sch em e 6. Com p etin g P a th w a ys: Dien e RCM a n d Dien yn e Meta th esis
the methylidene singlet emerges. Each catalytic cycle
produces one molecule of ethylene which appears as a
sharp singlet at 5.35 ppm. Additionally, the character-
istic signal pattern for a terminal olefin disappears as
the reaction progresses.
products.4b These studies have shown that the site of
initial acyclic metathesis (regiochemical control) could be
achieved by different substitution on the olefins. Mono-
substituted olefins undergo intermolecular acyclic me-
tathesis faster than disubstituted olefins. This fact
suggested a simple variable for regiochemical control of
the initial acyclic metathesis, the committed step in the
formation of the bicyclic compound.
The first substrate to be examined was dienyne 9,
which shares a close structural similarity with dienyne
2. The acetylene was disubstituted, and the length of
the diene tether was the same. One important difference
was the possibility of a competing diene RCM to give
cycloheptene (Scheme 6). This possible side reaction was
absent in the linear dienyne 2 since diene RCM would
have involved the unfavorable formation of a 10-
membered ring (Scheme 4). When dienyne 9 was treated
with 3 mol % ruthenium carbene 1 in CH2Cl2, the fused
bicyclo[4.3.0] ring 18 was isolated in 95% yield along with
trace amount (<3%) of cycloheptene 17 arising from
competing RCM of dienes. Thus, the dienyne metathesis
is largely favored over competing diene RCM. The
reaction can be carried out in variety of solvents and
temperatures (Table 1). For instance, the same substrate
cyclized (quantitative yield, 1H NMR scale) in 2 h in
benzene at 65 °C with only 1 mol % catalyst. As shown
in entry 3 (Table 1), increasing each olefinic tether by
one methylene unit yielded the bicyclo[5.4.0] ring 19 in
88% yield. As expected, no product arising from compet-
ing diene RCM was detected.
The sterically-biased dienyne 13 produced bicyclo[4.4.0]
adduct 20 in 83% yield (entry 4, Table 1). Furthermore,
the corresponding bicyclic[5.3.0] ring 21 was isolated as
the sole product when the substitution of the olefin was
reversed (entry 5, Table 1). Not only do these observa-
tions greatly expand the scope of this methodology, they
also provide further evidence for the proposed mecha-
nism. The dienyne 15 with internally substituted olefin
also displayed high regioselectivity, leading to the forma-
tion of tetrasubstituted bicyclo[4.4.0] compound 22 (entry
6, Table 1). It also represented the first example where
a sterically congested tetrasubstituted olefin was con-
structed using the ruthenium catalyst. Finally, the
presence of a heteroatom within the diene tether did not
alter the expected outcome (entry 7, Table 1); a single
bicyclic product 23 was obtained. No complications arose
from possible chelation involving the ether moeity.
Effect of Acetylen e Su bstitu en t. In the proposed
mechanism for dienyne RCM, the acetylenic substituent
is transformed into a vinylic substituent (Scheme 8).
These vinylic substituents of the product might be further
functionalized by any of a number of available tech-
niques. Several different substrates with varying acety-
lenic substituents X were synthesized and subjected to
dienyne metathesis. Concurrently, the comparative re-
activity of 1 with other well-defined metal alkylidenes
was examined.15
When the unsymmetrical dienyne 12 was treated with
the ruthenium catalyst (entry 3, Table 1) two bicyclic
compounds, [4.4.0] and [5.3.0], were isolated in equal
amounts. The steps leading to these products are shown
in Scheme 7. Presumably, the 1:1 product ratio arises
from the unselective (statistical) initial acyclic metathesis
(k1 ≈ k2).
Earlier work from these laboratories on diene RCM
suggested a straightforward solution for control of the

1076 J . Org. Chem., Vol. 61, No. 3, 1996
Ta ble 1. Ca ta lytic RCM of Dien eyn es
Kim et al.
The substituted dienynes 24-33 were readily prepared
from 1,8-nonadien-5-one (Scheme 9). The appropriate
acetylide anions were added to the ketone, and the
resultant alcohols were protected as the triethylsilyl
ethers. For those substrates not accessible by acetylide
addition, the terminal acetylenedienyne 24 was depro-
tonated with n-BuLi and quenched with the appropriate
electrophile. The iodo- and bromoalkyne substrates were
synthesized by the method of Hofmeister.16 Compounds
24-33 were isolated as clear, colorless oils, and all were
stable at ambient temperature.
(15) (WAr)(CHCMe3)(OCMe(CF3)2)2 (Ar ) 2,6-(i-Pr)2C6H3) (34): (a)
Schrock, R. R.; DePue, R. T.; Feldman, J .; Schaverien, C. J .; Dewan,
J . C.; Liu, A. H. J . Am. Chem. Soc. 1988, 110, 1423. (b) Schrock, R. R.;
DePue, R. T.; Feldman, J .; Yap, K. B.; Yang, D. C.; Davis, W. M.; Park,
L.; DiMare, M.; Schofield, M.; Anhaus, J .; Walborsky, E.; Evitt, E.;
Kruger, C.; Betz, P. Organometallics 1990, 9, 2262. (c) Mo(NAr)-
(CHCMe2Ph)(OCMe(CF3)2)2 (Ar ) 2,6-(i-Pr)2C6H3) (35): Schrock, R.
R.; Murdzek, J . S.; Bazan, G. C.; Robbins, J .; DiMare, M.; O’Regan,
M. J . Am. Chem. Soc. 1990, 112, 3875. (d) Bazan, G. C.; Oskam, J . H.;
Cho, H.-N.; Park, L. Y.; Schrock, R. R. J . Am. Chem. Soc. 1991, 113,
6899. Both the tungsten 34 and molybdenum 35 alkylidenes have been
successfully employed for diene RCM (ref 4 and Grubbs, R. H.,
unpublished results).
Results of the RCM reactions of ruthenium alkylidene
1 with compounds 24-33 are summarized in Table 2.17
The ruthenium catalyst 1 showed broad activity with
(16) Hofmeister, H.; Annen, K.; Laurent, H.; Wiechert, R. Angew.
Chem., Int. Ed. Engl. 1984, 23, 727-729.

Construction of Fused Bicyclic [n.m.0] Rings
J . Org. Chem., Vol. 61, No. 3, 1996 1077
Sch em e 7. F or m a tion of Differ en t Bicyclic P r od u cts w ith Un sym m etr ica l Dien yn es
Ta ble 2. Meta th esis of Su bstitu ted Dien yn es Usin g
Ru th en iu m Ca ta lyst 1
Sch em e 8. Meta th esis of Su bstitu ted Dien yn es
entry
acetylene substituent X
24
yield (%), conditions
Sch em e 9. Syn th esis of Su bstitu ted Acetylen esa
1
2
3
4
5
6
7
8
9
H
39, >98, 15 min, rt
18, 95, 8 h, rt
40, 78, 4 h, 60 °C
NR
41, 96, 3 h, 60 °C
42, 82, 4 h, 60 °C
NR
NR
NR
NR
NR
Me
9
25
26
27
28
29
30
31
32
33
iPr
tBu
Ph
CO2Me
TMS
SnBu3
Cl
10
11
Br
I
to the isopropyl-substituted substrate 25 (entry 6, Table
2). Substrates containing heteroatoms directly attached
to the acetylene were not cyclized by 1.
The bromo- and iodoalkyne dienyne substrates did not
cyclize under standard RCM conditions with any of the
catalysts listed.18 However, reaction with a stoichiomet-
ric amount of ruthenium carbene 1 resulted in a halide
exchange reaction. After 2 h at 60 °C, a significant
amount of both 1,1-diphenylbutadiene and a new vinyl
1
carbene species are observed in the H NMR spectrum
of the reaction mixture. The R proton resonance of the
new carbene species is upfield and the â proton is
downfield compared to the starting carbene. These two
signals coincide with the resonances of an intermediate
observed in the reaction of 1 with 20 equiv of LiBr in
benzene to produce the dibromo analogue of 119 and are
consistent with the mixed halide vinyl carbene species
45.
a
Key: (a) XCCH, BuLi, THF; (b) Et3SiOTf, NEt3, CH2Cl2; (c)
BuLi, [ClCO2Me, ClSnBu3, NCS], THF; (d) [NBS, NIS], AgNO3
(cat.), acetone; (e) DBU, BnBr, MeCN; (f) MgBrCH2CH2-
CH2CHdCH2, THF.
various substituents, and without exception, it favored
the dienyne metathesis over the competing diene RCM.
With alkyl substitution, steric effects were important and
reaction rates followed the expected trend (X ) H > Me
> i-Pr ≈ Ph). With the bulky tert-butyl substituent the
dienyne cyclization was not observed. The ester substi-
tuted dienyne 28 cyclized cleanly and with rates similar
(18) Catalyst 1 fails to metathesize vinyl halide species as well. Kim,
S.-H.; Grubbs, R. H. Unpublished results.
(19) Dias, E. L.; Grubbs, R. H. Unpublished results.
(17) Reactions were conducted at 0.05-0.1 M concentration in C6D6
with 3-5 mol % catalyst.

1078 J . Org. Chem., Vol. 61, No. 3, 1996
Kim et al.
Ta ble 3. Meta th esis of Su bstitu ted Dien yn es Usin g Tu n gsten Ca ta lyst 34 a n d Molybd en u m Ca ta lyst 35
acetylene
entry
substituent X
catalyst 34
catalyst 35
1
2
3
4
5
6
7
8
9
H
24
9
39, >98%, 20 min, rt
39, 97%, 20 min, rt
Me
iPr
tBu
Ph
CO2Me
TMS
SnBu3
Cl
cycloheptene and [4.3.0] (1:4)
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
25
26
27
28
29
30
31
32
33
cycloheptene
cycloheptene
NR
44, cycloheptene
cycloheptene
NR
NR
NR
NR
10
11
Br
I
Sch em e 10. Meta th esis of TMS-Su bstitu ted Dien yn e w ith Tu n gsten Ca ta lyst 34
The reactions of tungsten catalyst 34 and molybdenum
catalyst 35 are summarized in Table 3. Some general
trends for all three catalysts were observed.20
product. A homologous methyl-substituted dienyne sub-
strate 10 is cyclized to the bicyclic [5.4.0] ring 19 (Scheme
10), and no cyclononene product is observed. The ho-
mologous TMS substituted dienyne 38 gave no observable
product, and only the unreacted starting dienyne was
recovered. The reactions of 10 and 38, in which diene
RCM was expected to be highly unfavorable since it
would involve the formation of a nine-membered ring,
indicated that the TMS group effectively shuts down
olefin-acetylene metathesis, leaving diene RCM as the
only available pathway. However, the RCM reaction of
substrate 9 reflects competitive rates of the two processes.
In any case, it is evident that the product distribution is
critically dependent on the steric bulk of the acetylenic
substituents when using tungsten catalyst 34.
The substrates with non-carbon substituents (X )
TMS, Cl, Br, I, and SnBu3, compounds 29-33) failed to
produce the bicyclic [4.3.0] compound with all three
catalysts. Another important trend is that the outcome
of a reaction is largely determined by the catalyst
employed. Unlike catalyst 1 (entries 7 and 8, Table 3),
competing diene RCM to cycloheptene was observed with
the tungsten catalyst 34. Among the catalysts, the
molybdenum catalyst 35 is the least productive one; it
produced a bicyclic product only with the unsubstituted
acetylene (X ) H, compound 24, entry 1, Table 2). With
the other substrates (entries 2-11), only the unreacted
starting material was recovered in reaction with the
molybdenum catalyst. Taken together, these results
strongly suggest that the ruthenium alkylidene 1 is the
catalyst of choice for a range of substituted dienynes.
The tungsten catalyst 34 cleanly converted the unsub-
stituted acetylene (X ) H, entry 1, Table 2) to the bicyclic
product. However, with several substrates containing a
variety of acetylenic substitution (iPr, tBu, phenyl, TMS,
SnBu3), diene RCM is favored over ene-yne-ene me-
tathesis, yielding the cycloheptene instead of the bicyclic
compound. The methyl-substituted dienyne 9 yields a
mixture (95:3) of the cycloheptene and the bicyclic
Con clu sion
We have presented metathesis-based methodology for
the construction of fused bicyclic [n.m.0] rings, an im-
portant structural framework in a variety of natural
products. The ruthenium carbene 1 catalyzes the con-
version of acyclic dienynes to fused bicyclic rings contain-
ing five-, six-, and seven-membered rings. The key step
in the strategy involves the metal alkylidene catalyzed
ene-yne-ene metathesis. During this process, two rings
are formed in a single catalytic step. The acetylene plays
a critical strategic role by relaying one RCM to another.
Studies with different substituents on the acetylene and
other well-defined alkylidenes have revealed important
reactivity patterns. Product distribution is largely cata-
lyst dependent. Among the well-defined catalysts exam-
ined, only the ruthenuim alkylidene 1 exhibited dienyne
metathesis for a variety of substituents in good yields.
These properties of the catalyst and the dienyne reaction
significantly expand the scope of catalytic RCM for the
construction of complex organic compounds.
(20) The dienyne 9 was treated with other metal alkylidenes. With
Basset’s tungsten catalyst,16a the reaction failed to go to completion
and only 30% of the bicyclo[4.3.0] compound 18 was observed. With
Tebbe reagent,16b only unreacted starting material was recovered. (a)
Couturier, J .-M.; Pailet, C.; Leconte, M.; Basset, J .-M.; Weiss, K.
Angew. Chem., Int. Ed. Engl. 1992, 31, 628. (b) Tebbe, F. N.; Parshall,
G. W.; Overall, D. W. J . Am. Chem. Soc. 1979, 101, 5074.

Construction of Fused Bicyclic [n.m.0] Rings
J . Org. Chem., Vol. 61, No. 3, 1996 1079
A Rep r esen ta tive P r oced u r e for th e Syn th esis of
Un sym m et r ica l Dien yn es: 5-(1-P r op yn yl)-5-[(t r iet h yl-
silyl)oxy]-1,9-d eca d ien e (12). BrCH2CH2CHdCH2 (1.6 mL,
15.7 mmol) in 5 mL of THF was added dropwise over a period
of 30 min to a suspension of Mg (575 mg, 23.6 mmol) in 10
mL of THF at room temperature. The suspension was then
stirred at room temperature for an additional 30 min. The
reaction mixture was then transferred via cannula to MeC-
CCON(OMe)Me (11) (1.0 g, 7.9 mmol) in 10 mL of THF at -78
°C. After 60 min, saturated NH4Cl was added (100 mL), and
the aqueous layer was extracted with Et2O (2 × 50 mL). The
combined organic layers were washed with saturated NaCl (2
× 100 mL), dried over Na2SO4, and concentrated under
reduced pressure. The crude ketone was taken to the next
step without further purification.
BrCH2CH2CH2CHdCH2 (1.9 mL, 15.7 mmol) in 5 mL of
THF was added dropwise over a period of 30 min to a
suspension of Mg (575 mg, 23.6 mmol) in 10 mL of THF at
room temperature. The suspension was then stirred at room
temperature for an additional 30 min. The reaction mixture
was then transferred via cannula to the crude ketone in 10
mL of THF at -78 °C. After 60 min, saturated NH4Cl was
added (100 mL), and the aqueous layer was extracted with
Et2O (2 × 50 mL). The combined organic layers were washed
with saturated NaCl (2 × 100 mL), dried over Na2SO4, and
concentrated under reduced pressure. The crude alcohol was
dried with benzene azeotrope (2 × 5 mL) and taken to the next
step without further purification.
Et3SiOSO2CF3 (1.75 mL, 7.86 mmol) was added to the crude
alcohol and NEt3 (2.2 mL, 15.7 mmol) in 10 mL of CH2Cl2 at
0 °C. After 30 min, the reaction was quenched over saturated
NaHCO3 (50 mL) and extracted with CH2Cl2 (2 × 50 mL), dried
over Na2SO4, concentrated, and purified by flash chromatog-
raphy (petroleum ether) to give 900 mg (38%, three steps) of
12 as colorless oil: 1H NMR (CDCl3, 300 MHz) δ 5.89-5.78
(m, 2H), 5.06-4.91 (m, 4H), 2.23-2.13 (m, 2H), 2.09-2.02 (m,
2H), 1.82 (s, 3H), 1.69-1.47 (m, 6H), 0.97 (t, J ) 7.8 Hz, 9H),
0.66 (q, J ) 7.8 Hz, 6H); 13C NMR (C6D6, 75 MHz) δ 138.89,
138.94, 114.4, 113.5, 82.9, 80.4, 71.8, 42.3, 41.8, 33.9, 28.8, 23.6,
7.1, 6.2, 3.5; IR (neat, cm-1) 3078, 2952, 2918, 2876, 2244, 1416,
1238; HRMS calcd for C19H35OSi (MH+) 307.2458, found
307.2457.
(Z)-5-(1-P r op yn yl)-5-[(t r iet h ylsilyl)oxy]-1,9-u n d eca -
d ien e (13) was isolated in 31% yield (three steps) as a
colorless, clear oil: 1H NMR (C6D6, 300 MHz) δ 5.93-5.80 (m,
1H), 5.50-5.36 (m, 2H), 5.13-4.96 (m, 2H), 2.45-2.35 (m, 2H),
2.06-1.98 (m, 2H), 1.88-1.82 (m, 2H), 1.80-1.62 (m, 4H), 1.58
(d, J ) 4.7 Hz, 3H), 1.44 (s, 3H), 1.11 (q, J ) 7.5 Hz, 6H), 0.82
(t, J ) 7.5 Hz, 9H); 13C NMR (C6D6, 75 MHz) δ 139.0, 131.6,
125.2, 114.4, 83.5, 80.9, 72.4, 42.9, 42.5, 33.2, 29.4, 24.8, 18.1,
7.5, 6.7, 3.1; IR (neat, cm-1) 2951, 2876, 2244, 1415, 1238;
HRMS calcd for C20H37OSi (MH+) 321.2615, found 321.2614.
(E)-6-(1-P r op yn yl)-6-[(t r iet h ylsilyl)oxy]-1,9-d od eca -
d ien e (14) was isolated in 15% yield (three steps) as a
colorless, clear oil: 1H NMR (C6D6, 300 MHz) δ 5.86-5.72 (m,
1H), 5.53-5.40 (m, 2H), 5.07-4.94 (m, 2H), 2.45-2.35 (m, 2H),
2.17-2.06 (m, 2H), 2.04-1.97 (m, 2H), 1.85-1.60 (m, 6H), 1.45
(s, 3H), 1.11 (t, J ) 7.8 Hz, 9H), 0.94 (t, J ) 7.5 Hz, 6H); 13C
NMR (C6D6, 75 MHz) δ 138.9, 131.9, 129.2, 114.8, 83.5, 80.9,
72.5, 43.4, 42.8, 34.3, 24.2, 22.9, 20.9, 14.5, 7.5, 6.7, 3.2; IR
(neat, cm-1) 3006, 2953, 2876, 2243, 1415, 1238; HRMS calcd
for C21H39OSi (MH+) 335.2772, found 335.2770.
Exp er im en ta l Section
Gen er a l Meth od s. High resolution mass spectra were
obtained from the Southern California Mass Spectrometry
Facility (University of California, Riverside). Analytical thin-
layer chromatography (TLC) was performed using silica gel
60 F254 precoated plates (0.25 mm thickness) with a fluores-
cent indicator. Flash column chromatography was performed
using silica gel 60 (230-400 mesh) from EM Science.21
Catalysts 1, 34, and 35 were prepared according to published
procedures.3,15 All reactions were carried out under an argon
atmosphere with dry, degassed solvents under anhydrous
conditions.
2-Bu tyn e-1,4-d iol Dia llyl Eth er (2). NaH (92 mg, 3.9
mmol) was added to a solution of 2-butyne-1,4-diol (200 mg,
1.75 mmol) in 50 mL of DMF at room temperature. ICH2-
CHdCH2 (650 mg, 3.9 mmol) was added, and the resulting
suspension was stirred for 2 h. The reaction was quenched
with H2O (50 mL), extracted with hexanes (3 × 50 mL), dried
over MgSO4, concentrated, and purified by flash chromatog-
raphy to give 250 mg (74%) of 2 as colorless oil: 1H NMR (C6D6,
300 MHz) δ 5.21 (dq, J ) 17.1, 1.8 Hz, 1H), 4.99 (dq, J ) 10.5,
1.5 Hz, 1H), 5.73 (m, 1H), 3.87 (dt, J ) 5.4, 1.5 Hz, 2H), 3.94
(s, 2H); 13C NMR (C6D6, 75 MHz) δ 117.9, 133.9, 82.3, 70.6,
57.4; IR (neat, cm-1) 3081, 2924, 2854, 1250; HRMS calcd for
C10H14O2 (M+) 166.0994, found 166.0989.
1-(4-Oxa -1-cyclop en ten yl)-4-oxa cyclop en ten e (6). Ru-
thenium catalyst 1 (30 mg, 0.032 mmol) was added to a
solution of dienyne 2 (190 mg, 1.14 mmol) in 35 mL of C6H6.
The resulting light brown solution was maintained at room
temperature for 4 h. The solution was quenched by opening
to air, concentrated under reduced pressure, and purified by
flash chromatography to give 6, which was isolated as a
colorless oil (140 mg, 90% yield): 1H NMR (C6D6, 300 MHz) δ
4.92 (br s, 1H), 4.61 (m, 2H), 4.47 (m, 2H); 13C NMR (C6D6, 75
MHz) δ 132.0, 123.2, 76.2, 75.0; IR (neat, cm-1) 2922, 2867,
1743, 1459; HRMS calcd for C8H10O2 (M+) 138.0681, found
138.0680.
A Rep r esen ta tive P r oced u r e for th e Syn th esis of
Sym m etr ica l Dien yn es: 5-(1-P r op yn yl)-5-[(tr ieth ylsilyl)-
oxy]-1,8-n on adien e (9). BrCH2CH2CHdCH2 (5.8 g, 43 mmol)
in 10 mL of THF was added dropwise over a period of 20 min
to a suspension of Mg (1.4 g, 57.4 mmol) in 100 mL of THF at
room temperature. The suspension was then stirred at room
temperature for an additional 40 min. The reaction mixture
was then transferred via cannula to MeCCCO2Bn 8 (2.5 g, 14.3
mmol) in 50 mL of THF at 0 °C. After 15 min, saturated NH4-
Cl was added (200 mL) and the aqueous layer was extracted
with Et2O (2 × 100 mL). The combined organic layers were
washed with saturated NaCl (2 × 100 mL), dried over Na2-
SO4, and concentrated under reduced pressure. The crude
reaction mixture was dried with benzene azeotrope (2 × 5 mL)
and taken to the next step without further purification.
Et3SiOSO2CF3 (3.25 mL, 14.3 mmol) was added to crude
alcohol and NEt3 (4.0 mL, 28.7 mmol) in 50 mL of CH2Cl2 at
0 °C. After 30 min, the reaction was quenched over saturated
NaHCO3 (100 mL), extracted with CH2Cl2 (2 × 50 mL), dried
over Na2SO4, concentrated, and purified by flash chromatog-
raphy (petroleum ether) to give 1.9 g (45%, two steps) of 9 as
a colorless oil: 1H NMR (C6D6, 300 MHz) δ 5.89-5.76 (m, 2H),
5.10-4.94 (m, 4H), 2.35-2.30 (m, 4H), 1.83-1.77 (m, 4H), 1.43
(s, 3H), 1.07 (t, J ) 7.5 Hz, 9H), 0.78 (q, J ) 7.8 Hz, 6H); 13C
NMR (C6D6, 75 MHz) δ 138.9, 114.5, 83.1, 81.1, 72.1, 42.5, 29.4,
7.5, 6.7, 3.1; IR (neat, cm-1) 2952, 2918, 2876, 2247, 1426, 1239;
HRMS calcd for C18H33OSi (MH+) 293.2302, found 293.2301.
6-(1-P r o p y n y l)-6-[(t r ie t h y ls ily l)o x y ]-1,10-u n d e c a -
d ien e (10) was isolated in 62% yield (two steps) as a colorless
oil: 1H NMR (CDCl3, 300 MHz) δ 5.89-5.75 (m, 2H), 4.99-
4.92 (m, 4H), 2.09-2.01 (m, 4H), 1.82 (s, 3H), 1.55 (m, 8H),
0.96 (t, J ) 7.6 Hz, 9H), 0.66 (q, J ) 7.7 Hz, 6H); 13C NMR
(CDCl3, 75 MHz) δ 138.9, 114.3, 83.2, 80.2, 71.9, 42.3, 33.9,
23.6, 7.1, 6.2, 3.5; IR (neat, cm-1) 3077, 2950, 2918, 2876, 2244,
1415, 1238; HRMS calcd for C20H37OSi (MH+) 321.2615, found
321.2614.
2-Me t h yl-5-(1-p r op yn yl)-5-(t r ie t h ylsiloxy)-1,9-d e ca -
d ien e (15) was isolated in 21% yield (three steps) as a
colorless, clear oil: 1H NMR (C6D6, 300 MHz) δ 5.86-5.73 (m,
1H), 5.10-4.95 (m, 2H), 4.88 (m, 1H), 4.81 (m, 1H), 2.42-2.34
(m, 2H), 2.07-1.92 (m, 4H), 1.80-1.62 (m, 7H), 1.44 (s, 3H),
1.12 (t, J ) 7.5 Hz, 9H), 0.83 (q, J ) 7.5 Hz, 6H); 13C NMR
(C6D6, 75 MHz) δ 146.0, 138.9, 114.8, 110.0, 83.5, 80.9, 72.4,
42.8, 41.6, 34.3, 33.1, 24.2, 22.9, 7.5, 6.7, 3.1; IR (neat, cm-1
)
3076, 2952, 2876, 2917, 2242, 1415, 1238; HRMS calcd for
C20H37OSi (MH+) 321.2615, found 321.2614.
6-Met h yl-6-(1-p r op yn yl)-7-oxa -1,9-u n d eca d ien e (16).
Two sequential Grignard reactions (MgBrCH2CH2CH2CHdCH2
and MgBrMe) gave a 60% yield (two steps) of crude alcohol.
Alkylation of crude tertiary alcohol: NaH (95%, 130 mg, 5.3
mmol) was added to the crude tertiary alcohol (540 mg, 3.5
(21) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.

1080 J . Org. Chem., Vol. 61, No. 3, 1996
Kim et al.
mmol) in 5 mL of DMF. After 15 min, excess ClCH2-
CHdCHMe (3.4 mL, 35 mmol) was added and the resulting
mixture was heated to 80 °C for 6 h. The reaction was
quenched with saturated NH4Cl (50 mL), extracted with
hexanes, dried over Na2SO4, concentrated, and purified by
flash chromatography (5% diethyl ether/petroleum ether) to
give 340 mg (47%) of 16 as colorless oil: 1H NMR (C6D6, 300
MHz, ca. 4:1 mixture of Z:E isomers) δ 5.85-5.60 and 5.55-
5.42 (m, 3H), 5.05-4.92 (m, 2H), 4.40-4.08 (m, 2H), 2.05-
1.95 (m, 2H), 1.86-1.60 (m, 4H), 1.55-1.53 (m, 3H), 1.49 (s,
3H), 1.42 (d, J ) 2.4 Hz, 3H); 13C NMR (C6D6, 75 MHz) δ 139.0,
129.5, 129.0, 127.0, 125.9, 114.7, 81.5, 80.9, 80.8, 73.4, 73.3,
64.9, 60.0, 42.1, 42.0, 34.3, 26.9, 24.1, 17.8, 13.3, 3.2; IR (neat,
cm-1) 2978, 2944, 2929, 2858, 2242, 1441, 1248; HRMS calcd
for C11H17O (MH+) 207.1750, found 207.1749.
1.87-1.76 (m, 1H), 1.69 (br s, 3H), 1.58-1.47 (m, 2H), 1.27 (d,
J ) 0.5 Hz, 3H); 13C NMR (C6D6, 75 MHz) δ 138.3, 129.0, 122.4,
120.0, 71.1, 60.8, 36.9, 25.8, 21.9, 20.2, 18.9; IR (neat, cm-1
)
2971, 2938, 2830, 1452, 1391, 1366; HRMS calcd for C11H16
O
(M+) 164.1202, found 164.1201.
5-Eth yn yl-5-[(tr ieth ylsilyl)oxy]-1,8-n on a d ien e (24). To
a stirred solution of the dienyne alcohol (0.95 g, 5.8 mmol) and
anhydrous NEt3 (1.9 mL, 13 mmol) in CH2Cl2 (60 mL) at 0 °C
was added Et3SiOTf (1.1 mL, 5.8 mmol). The addition was
followed by TLC. When finished by TLC, the reaction mixture
was quenched with 60 mL of saturated aqueous NaHCO3 and
extracted with CH2Cl2 (3 × 50 mL). Purification by chroma-
tography (petroleum ether elution) yielded the product as a
1
clear, colorless oil: 1.25 g, 78%; H NMR (C6D6, 300 MHz) δ
5.84-5.74 (m, 2H), 5.09-4.94 (m, 4H), 2.34-2.27 (m, 4H), 1.97
(s, 1H), 1.82-1.76 (m, 4H), 1.05 (t, J ) 7.8 Hz, 9H), 0.78 (q, J
) 7.6 Hz, 6H); 13C NMR (C6D6, 75 MHz) δ 138.5, 114.6, 87.2,
73.7, 71.9, 42.1, 29.1, 7.4, 6.6; IR (neat, cm-1) 3307, 3079, 2953,
2914, 2109; HRMS calcd for C17H31OSi (MH+) 279.2136, found
279.2144.
A R ep r esen t a t ive P r oced u r e for Ca t a lyt ic Dien yn e
Meta th esis: 2-Meth yl-6-[(tr ieth ylsilyl)oxy]bicyclo[4.4.0]-
d eca -2,10-d ien e (20). Ruthenium catalyst 1 (FW 925.1, 0.03
equiv, 5.6 mg) in C6H6 (1.0 mL) was added through a cannula
to a solution of dienyne 13 (FW 334.6, 1.0 equiv, 0.2 mmol, 67
mg, entry 4) in C6H6 (5.7 mL, 0.03 M). The resulting light
brown solution was placed in a 65 °C oil bath. After 6.5 h,
the starting material was completely converted to a compound
with a Rf ) 0.4 (petroleum ether) on TLC. The solution was
concentrated under reduced pressure and purified by flash
chromatography. The fused bicyclo[4.4.0] ring 20 was isolated
as a colorless, volatile oil (46 mg, 83% yield): 1H NMR (C6D6,
300 MHz) δ 5.54-5.47 (br m, 2H), 2.55-2.40 (br m, 1H), 2.12-
2.02 (br m, 1H), 1.97-1.77 (m, 4H), 1.76-1.72 (br m, 3H),
1.75-1.3 (m, 4H), 1.03 (t, J ) 7.8 Hz, 9H), 0.65 (q, J ) 7.8 Hz,
6H); 13C NMR (C6D6, 75 MHz) δ 138.7, 131.0, 125.5, 123.1,
6-[(Tr ieth ylsilyl)oxy]bicyclo[4.3.0]n on a -2,9-d ien e (39):
1H NMR (C6D6, 300 MHz) δ 6.20 (dd, J ) 9.9, 2.4 Hz, 1 H),
5.73-5.68 (m, 1H), 5.35 (d, J ) 0.9 Hz, 1H), 2.59-2.47 (m,
2H), 2.12-1.86 (m, 4H), 1.70-1.35 (m, 2H), 1.02 (t, J ) 7.9
Hz, 9H), 0.62 (q, J ) 7.8 Hz, 6H); 13C NMR (C6D6, 75 MHz) δ
143.2, 129.8, 125.6, 122.7, 82.5, 38.9, 36.9, 29.9, 23.7, 7.2, 6.2;
IR (neat, cm-1) 3030, 2953, 2875; HRMS calcd for C15H26OSi
(M+) 250.1746, found 250.1743.
1,8-Non a d ien -5-on e. In a dry 500 mL round-bottom flask
were placed Mg (40-80 mesh powder, 3.6 g, 147 mmol), I2 (10
mg), and THF (200 mL). To this mixture was added 4-bromo-
1-butene (15 mL, 147 mmol) in anhydrous THF (50 mL)
dropwise over 15 min and stirred for an additional 30 min.
The Grignard reagent was transferred to an addition funnel
connected to a 1000 mL round-bottom flask containing N-meth-
oxy-N-methyl-4-pentenamide22 in THF (500 mL) at -10 °C.
The Grignard reagent was added dropwise to a solution of the
Weinreb amide in THF over 20 min. After addition was
complete, the reaction was stirred until complete by TLC (ca.
45 min). The reaction was quenched with NH4Cl (saturated
aqueous, 200 mL) and extracted with Et2O (3 × 200 mL). The
organics were combined, dried over Na2SO4, and concentrated
under vacuum to yield a yellow oil. This oil was purified by
flash chromatography (10% EtOAc in petroleum ether elution)
70.0, 38.9, 38.2, 26.5, 22.8, 20.2, 18.2, 7.7, 7.0; IR (neat, cm-1
)
2937, 2875, 1440, 1237; HRMS calcd for C17H30OSi (M+)
278.2067, found 278.2066.
2-Met h yl-6-[(t r iet h ylsilyl)oxy]b icyclo[4.3.0]n on a -2,9-
1
d ien e (18): H NMR (C6D6, 300 MHz) δ 5.47 (d, J ) 3.9 Hz,
1H), 5.42 (br s, 1H), 2.65-2.47 (br m, 2H), 2.18-1.87 (m, 4H),
1.78 (q, J ) 1.1 Hz), 1.71 (ddt, J ) 8.6, 8.6, 13.6 Hz, 1H), 1.47-
1.35 (m, 1H), 1.01 (t, J ) 8.1 Hz, 9H), 0.59 (q, J ) 8.1 Hz,
6H); 13C NMR (C6D6, 75 MHz) δ 145.6, 128.7, 126.7, 124.3,
83.3, 39.6, 37.5, 30.1, 24.2, 19.3, 7.5, 6.5; IR (neat, cm-1) 2935,
2876, 1455, 1237; HRMS calcd for C16H28OSi (M+) 264.1910,
found 264.1909.
2-Meth yl-7-[(tr ieth ylsilyl)oxy]bicyclo[5.4.0]u n d eca -2,-
11-d ien e (19): 1H NMR (C6D6, 300 MHz) δ 5.59 (dt, J ) 5.4,
1.3 Hz, 1H), 5.48 (t, J ) 3.8 Hz, 1H), 2.3-2.17 (br m, 1H),
2.13-1.96 (br m, 1H), 1.94 (q, J ) 1.5 Hz, 3H), 1.92-1.68 (m,
6H), 1.65-1.45 (m, 4H), 1.06 (t, J ) 7.8 Hz, 9H), 0.64 (q, J )
7.8 Hz); 13C NMR (C6D6, 75 MHz) δ 145.1, 135.1, 125.9, 124.3,
76.3, 43.7, 40.4, 29.2, 26.3, 25.7, 23.6, 20.7, 7.6, 7.4; IR (neat,
cm-1) 2937, 2834, 1456, 1238; HRMS calcd for C18H32OSi (M+)
292.2224, found 292.2222.
2-Meth yl-7-[(tr ieth ylsilyl)oxy]bicyclo[5.3.0]d eca -2,11-
d ien e (21): 1H NMR (C6D6, 300 MHz) δ 5.58 (t, J ) 5 Hz,
1H), 5.5 (t, J ) 2.5 Hz, 1H), 2.47-2.26 (m, 2H), 2.17-1.92 (m,
4H), 1.9 (d, J ) 1.2 Hz, 3H), 1.87-1.8 (m, 2H), 1.66-1.45 (m,
4H), 1.04 (t, J ) 8 Hz, 9H), 0.64 (q, J ) 8 Hz, 6H); 13C NMR
(CDCl3, 75 MHz) δ 150.0, 130.3, 128.2, 127.9, 87.2, 42.4, 41.9,
29.3, 29.2, 24.8, 22.5, 7.2, 6.3; IR (neat, cm-1) 2951, 2875, 1455,
1237; HRMS calcd for C17H31OSi (MH+) 279.2145, found
279.2144. 21 is a somewhat unstable compound when con-
centrated; the sample contains a small amount (<3%) of
unidentified decomposition substance.
2,3-Dim eth yl-6-[(tr ieth ylsilyl)oxy]bicyclo[4.4.0]d eca -2,-
10-d ien e (22): 1H NMR (C6D6, 300 MHz, sample contains a
small amount (<3%) of unknown decomposition product) δ
5.54-5.51 (br m, 1H), 2.56-2.4 (br m, 1H), 2.2-1.95 (br m,
1H), 1.94-1.76 (m, 4H), 1.68 (br s, 3H), 1.72 (br s, 3H), 1.55-
1.32 (m, 4H), 1.03 (t, J ) 7.9 Hz, 9H), 0.63 (q, J ) 7.7 Hz,
6H); 13C NMR (C6D6, 75 MHz) δ 139.4, 130.2, 124.6, 121.3,
69.9, 39.4, 38.2, 29.5, 26.7, 20.5, 18.1, 14.6, 7.7, 6.9; IR (neat,
cm-1) 2936, 2829, 1455, 1237; HRMS calcd for C18H33OSi
(MH+) 293.2302, found 293.2301.
2,6-Dim et h yl-5-oxa b icyclo[4.4.0]d eca -2,10-d ien e (23):
1H NMR (C6D6, 300 MHz, somewhat unstable compound when
concentrated) δ 5.39 (m, 1H), 5.21 (br s, 1H), 5.37 (br d, J )
17 Hz, 1H), 4.04 (br d, J ) 17 Hz, 1H), 1.97-1.89 (m, 2H),
1
to yield the desired product: 9.4 g, 76%; H NMR (C6D6, 300
MHz) δ 5.74-5.61 (m, 2H), 4.97-4.88 (m, 4H), 2.22-2.15 (m,
4H), 1.98-1.94 (m, 4H); 13C NMR (C6D6, 75 MHz) δ 206.8,
137.7, 115.0, 41.7, 28.0; IR (neat, cm-1) 3080, 2979, 1715.
A Rep r esen ta tive P r oced u r e for th e Syn th esis of
Dien yn es via Acet ylid e Ad d it ion t o Ket on e: 5-[(Tr i-
m e t h ylsilyl)e t h yn yl]-5-[(t r ie t h ylsilyl)oxy]-1,8-n on a -
d ien e (29). To a solution of (trimethylsilyl)acetylene (0.25 mL,
1.8 mmol) in THF (10 mL) at -78 °C was added BuLi (1.1
mL, 1.6 M in hexanes, 1.8 mmol) and the resulting mixture
stirred for 10 min. The deprotonated acetylene was then
added via cannula to a stirring solution of 1,8-nonadien-5-one
(202 mg, 1.46 mmol) in THF (10 mL) over 3 min. The reaction
was stirred at -78 °C until complete by TLC (about 30 min).
The reaction was quenched with NH4Cl (saturated aqueous,
20 mL) and extracted with EtOAc (3 × 10 mL). The organic
fractions were combined, dried over Na2SO4, and concentrated
under vacuum to yield a brown oil. The oil was dissolved in
10 mL of CH2Cl2, and NEt3 (1.0 mL, 3.0 mmol) was added to
the solution. The solution was cooled to 0 °C, and Et3SiOTf
(0.55 mL) was added until the reaction was complete by TLC
(petroleum ether elution). The reaction mixture was quenched
with NaHCO3 (aqueous, 20 mL) and extracted with Et2O (3 ×
10 mL). The organics were combined, dried over Na2SO4, and
concentrated under vacuum to yield a yellow oil. This oil was
purified by silica gel chromatography (10% EtOAc in petroleum
ether elution) to yield the product as a clear, colorless oil: 330
mg, 96%; 1H NMR (C6D6, 300 MHz) δ 5.87-5.78 (m, 2H), 5.10-
4.94 (m, 4H), 2.39-2.33 (m, 4H), 1.87-1.81 (m, 4H), 1.09 (t, J
) 7.8 Hz, 9H), 0.84 (q, J ) 7.8 Hz, 6H), 0.15 (s, 9H); 13C NMR
(22) Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815-
3818.

Construction of Fused Bicyclic [n.m.0] Rings
J . Org. Chem., Vol. 61, No. 3, 1996 1081
(C6D6, 75 MHz) δ 138.7, 114.6, 110.0, 89.7, 72.4, 42.2, 29.3,
7.4, 6.7, -0.2; IR (neat, cm-1) 3079, 2954, 2914, 2164; HRMS
calcd for C20H39OSi2 (MH+) 351.2529, found 351.2539.
5-[(Tr ieth ylsilyl)oxy]-5-[(tr im eth ylsilyl)eth yn yl]cyclo-
h ep ten e (44): 1H NMR (C6D6, 300 MHz) δ 5.76-5.73 (m, 2H),
2.22-1.84 (m, 8H), 1.12 (t, J ) 7.8 Hz, 9H), 0.84 (q, J ) 7.8
Hz, 6H), 0.16 (s, 9H); 13C NMR (C6D6, 75 MHz) δ 132.2, 111.0,
89.5, 73.8, 42.3, 23.3, 7.5, 7.4, -0.2; IR (neat, cm-1) 3022, 2954,
2162; HRMS calcd for C18H34OSi2 (M+) 322.2139, found
322.2148.
yield the product as a clear, colorless oil: 351 mg, 92%; 1H
NMR (C6D6, 300 MHz) δ 5.72-5.67 (m, 2H), 5.03-4.92 (m, 4H),
3.21 (s, 3H), 2.26-2.20 (m, 4H), 1.03 (t, J ) 7.8 Hz, 9H), 0.77
(q, J ) 7.8 Hz, 6H); 13C NMR (C6D6, 75 MHz) δ 153.6, 138.0,
115.0, 90.3, 77.8, 72.0, 52.1, 41.5, 28.8, 7.3, 6.5; IR (neat, cm-1
)
3079, 2954, 2914, 2232, 1827, 1721; HRMS calcd for C19H33O3-
Si (MH+) 337.2190, found 337.2199.
2-(Ca r bom eth oxy)-6-[(tr ieth ylsilyl)oxy]bicyclo[4.3.0]-
n on a -1,9-d ien e (42) was isolated as an orange oil that was
somewhat unstable at ambient temperature: 1H NMR (C6D6,
300 MHz) δ 6.96 (m, 1H), 6.66 (m, 1H), 3.41 (s, 3H), 2.61-
2.46 (m, 2H), 2.19-2.10 (m, 1H), 2.02-1.87 (m, 3H), 1.80-
1.58 (m, 1H), 1.39-1.09 (m, 1H), 0.97 (t, J ) 7.9 Hz, 9H), 0.58
(q, J ) 7.8 Hz, 6H); 13C NMR (C6D6) δ 166.3, 140.6, 138.7,
131.8, 130.1, 83.9, 51.0, 38.4, 36.6, 30.7, 24.8, 7.4, 6.5; IR (neat,
cm-1) 3044, 2951, 2934, 1721, 1255; HRMS calcd for C17H29O3-
Si (MH+) 309.1886, found 309.1895.
5-(P h e n y le t h y n y l)-5-[(t r ie t h y ls ily l)o x y ]-1,8-n o n a -
1
d ien e (27): H NMR (C6D6, 300 MHz) δ 7.41-7.38 (m, 2H),
6.97-6.95 (m, 3H), 5.88-5.82 (m, 2H), 5.13-4.98 (m, 4H),
2.45-2.41 (m, 4H0, 1.97-1.91 (m, 4H), 1.08 (t, J ) 7.8 Hz,
9H), 0.85 (q, J ) 7.8 Hz, 6H); 13C NMR (C6D6, 75 MHz) δ 138.7,
131.7, 128.6, 128.4, 123.4, 114.7, 93.2, 85.8, 72.5, 42.2, 29.4,
7.4, 6.7; IR (neat, cm-1) 3079, 3034, 2952, 2913, 2226; HRMS
calcd for C23H34OSi (M+) 354.2370, found 354.2359.
5-(C h lo r o e t h y n y l)-5-[(t r ie t h y ls ily l)o x y ]n o n a -1,8-
1
2-P h en yl-6-[(t r iet h ylsilyl)oxy]b icyclo[4.3.0]n on a -1,9-
d ien e (31): H NMR (C6D6, 300 MHz) δ 5.82-5.70 (m, 2H),
1
d ien e (41): H NMR (C6D6, 300 MHz) δ 7.47-7.12 (m, 5H),
5.05-4.93 (m, 4H), 2.27-2.18 (m, 4H), 1.76-1.70 (m, 4H), 1.03
(t, J ) 8.0 Hz, 9H), 0.73 (q, J ) 7.8 Hz, 6H); 13C NMR (C6D6,
75 MHz) δ 138.3, 114.7, 73.2, 72.5, 63.8, 42.0, 29.0, 7.3, 6.5;
5.81-5.79 (m, 1H), 5.63 (s, 1H), 2.16-2.00(m, 4H), 1.80-1.69
(m, 2H), 1.52-1.44 (m, 2H), 1.04 (t, J ) 7.9 Hz, 9H), 0.66 (q,
J ) 7.7 Hz, 6H); 13C NMR (C6D6, 75 MHz) δ 143.6, 141.7, 135.7,
128.8, 128.5, 128.4, 127.3, 127.2, 85.6, 39.3, 37.4, 30.1, 24.7,
7.6, 6.6; IR (neat, cm-1) 3078, 3055, 3022, 2952; HRMS calcd
for C21H31OSi (MH+) 327.2137, found 327.2153.
IR (neat, cm-1) 3080, 2954, 2914, 2223; HRMS calcd for C17H30
ClOSi (MH+) 313.1754, found 313.1762.
-
A Rep r esen ta tive P r oced u r e for th e Syn th esis of
Br om o- or Iod oa cetylen ic Dien yn es: 5-(Br om oeth yn yl)-
5-[(tr ieth ylsilyl)oxy]n on a -1,8-d ien e (32). The terminal
acetylene substrate 24 (306 mg, 1.10 mmol) was dissolved in
acetone (8 mL). To this solution was added NBS (231 mg, 1.30
mmol) followed by AgNO3 (42 mg, 0.25 mmol). After being
stirred for 25 min, the reaction was complete as judged by TLC
and was quenched by pouring it into 10 mL of ice-water. The
aqueous solution was extracted with EtOAc (5 × 15 mL) and
purified by silica gel chromatography to yield the product as
5-(3-Met h yl-1-b u t yn yl)-5-[(t r iet h ylsilyl)oxy]n on a -1,8-
1
d ien e (25): H NMR (C6D6, 300 MHz) δ 5.92-5.78 (m, 2H),
5.12-4.95 (m, 4H), 2.39-2.32 (m, 5H), 1.86-1.80 (m, 4H), 1.09
(t, J ) 7.9 Hz, 9H), 1.01 (d, J ) 6.8 Hz, 6H), 0.82 (q, J ) 7.7
Hz, 6H); 13C NMR (C6D6, 75 MHz) δ 138.8, 114.5, 90.9, 83.3,
72.1, 42.6, 29.4, 23.0, 20.7, 7.6, 6.6; IR (neat, cm-1) 3078, 2952,
2235: HRMS calcd for C20H37OSi (MH+) 321.2605, found
321.2622.
1
2-(2-P r op yl)-6-[(t r iet h ylsilyl)oxy]b icyclo[4.3.0]n on a --
a clear oil: 383 mg, 97%; H NMR (C6D6, 300 MHz) δ 5.79-
1
1,9-d ien e (40): H NMR (C6D6, 300 MHz) δ 5.56 (d, J ) 5.1
5.70 (m, 2H), 5.04-4.92 (m, 4H), 2.27-2.21 (m, 4H), 1.77-
1.71 (m, 4H), 1.03 (t, J ) 7.8 Hz, 9H), 0.74 (q, J ) 7.8 Hz,
6H); 13C NMR (C6D6, 75 MHz) δ 138.4, 114.7, 83.9, 73.1, 45.7,
42.0, 29.0, 7.4, 6.5; IR (neat, cm-1) 3078, 2955, 2931, 2140;
HRMS calcd for C17H30BrOSi (MH+) 357.1235, found 357.1249.
5-(Iodoeth yn yl)-5-[(tr ieth ylsilyl)oxy]n on a-1,8-dien e (33):
1H NMR (C6D6, 300 MHz) δ 5.81-5.68 (m, 2H), 5.05-4.92 (m,
4H), 2.30-2.21 (m, 4H), 1.78-1.72 (m, 4H), 1.04 (t, J ) 8.0
Hz, 9H), 0.75 (t, J ) 7.6 Hz, 6H); 13C NMR (C6D6, 75 MHz) δ
138.4, 114.7, 102.9, 98.2, 73.7, 42.2, 29.1, 7.4, 6.5; IR (neat,
cm-1) 3078, 2952, 2913, 2176; HRMS calcd for C17H30IOSi
(MH+) 405.1111, found 405.1127.
Hz, 1H), 5.49 (s, 1H), 2.60-2.49 (m, 2H), 2.18-1.96 (m, 3H),
1.75-1.65 (m, 2H), 1.46-1.36 (m, 2H), 1.13 (d, J ) 3.0 Hz,
3H), 1.11 (d, J ) 2.7 Hz, 3H), 1.02 (t, J ) 8.0 Hz, 9H), 0.61 (q,
J ) 8.0 Hz, 6H); 13C NMR (C6D6) δ 144.5, 139.3, 123.4, 122.5,
83.9, 39.4, 37.4, 30.4, 30.2, 24.2, 23.0, 22.1, 7.4, 6.7; IR (neat,
cm-1) 3044, 2957, 2929; HRMS calcd for C18H34OSi (MH+)
293.2293, found 293.2300.
5-(ter t-Bu t ylet h yn yl)-5-[(t r iet h ylysilyl)oxy]n on a -1,8-
1
d ien e (26): H NMR (C6D6, 300 MHz) δ 5.91-5.82 (m, 2H),
5.14-4.96 (m, 4H), 2.41-2.33 (m, 4H), 1.87-1.81 (m, 4H), 1.13
(s, 9H), 1.10 (t, J ) 7.8 Hz, 9H), 0.83 (q, J ) 7.8 Hz, 6H); 13C
NMR (C6D6, 75 MHz) δ 139.0, 114.5, 93.6, 82.6, 72.0, 42.7, 30.9,
29.5, 27.5, 7.5, 6.7; IR (neat, cm-1) 3078, 2951, 2239; HRMS
calcd for C21H39OSi (MH+) 335.2760, found 335.2770.
6-[(Tr ieth ylsilyl)oxy]-6-[(tr im eth ylsilyl)eth yn yl]-1,10-
u n d eca d ien e (38): 1H NMR (C6D6, 300 MHz) δ 5.86-5.72 (m,
2H), 5.08-4.95 (m, 4H), 2.04-1.98 (m, 4H), 1.80-1.68 (m, 8H),
1.13 (t, J ) 7.8 Hz, 9H), 0.87 (q, J ) 7.9 Hz, 6H), 0.16 (s, 9H);
13C NMR (C6D6, 75 MHz) δ 138.8, 114.8, 110.7, 89.2, 72.7, 42.1,
34.1, 23.8, 7.4, 6.6, -0.5; IR (neat, cm-1) 3075, 2953, 2924,
2280, 2163; HRMS calcd for C22H43OSi (MH+) 379.2852, found
379.2830.
5-(t er t -B u t y le t h y n y l)-5-[(t r ie t h y ls ily l)o x y ]c y c lo -
h ep ten e (43): 1H NMR (C6D6, 300 MHz) δ 5.81-5.78 (m, 2H),
2.22-2.00 (m, 4H), 1.90-1.82 (m, 4H), 1.13 (t, J ) 7.8 Hz, 9H),
1.15 (s, 9H), 0.84 (q, J ) 7.8 Hz, 6H); 13C NMR (C6D6, 75 MHz)
δ 132.3, 94.2, 83.4, 73.7, 42.8, 31.0, 27.5, 23.5, 7.5, 6.8; IR (neat,
cm-1) 3021, 2951, 2237; HRMS calcd for C19H34OSi (M+)
306.2370, found 306.2379.
A Rep r esen ta tive P r oced u r e for Syn th esis of Su bsti-
tu ted Acetylen es via Dep r oton a tion of Su bstr a te 24:
5-(Ca r b om et h oxyet h yn yl)-5-[(t r iet h ylysilyl)oxy]n on a -
1,8-d ien e (28). To a stirring solution of 24 (316 mg, 1.13
mmol) in 8 mL of THF at -78 °C was added BuLi (2.5 M in
hexanes, 0.50 mL, 1.2 mmol, 1.1 equiv) and the resulting
mixture allowed to stir for 3 min. The acetylide was trans-
ferred via cannula to a stirring solution of ClCO2Me (119 mg,
1.26 mmol, 1.1 equiv) in 12 mL of THF. The reaction was
slowly warmed to ambient temperature. When TLC showed
complete conversion, the reaction was quenched by addition
of 25 mL of saturated aqueous NH4Cl. The aqueous solution
was extracted with EtOAc (3 × 25 mL) and purified by silica
gel chromatography (10% Et2O in petroleum ether elution) to
Ack n ow led gm en t. We want to thank Professor
Gregory C. Fu (MIT) and Professor Andrew G. Myers
(Caltech) for helpful discussions and suggestions. W.J.Z.
thanks the NSF for a Predoctoral Fellowship. Support
for this research was provided by the National Institutes
of Health.
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
spectra (33 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
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J O951648A