Effects of Olefin Substitution on the Ring-Closing Metathesis of Dienes

Article abstract of DOI:10.1021/jo970877p

Ruthenium alkylidene 1 and molybdenum alkylidene 2 have been utilized in the ring-closing metathesis (RCM) of dienes containing gem-disubstituted olefins to yield tri- and tetrasubstituted cyclic olefins. Dienes with sterically demanding and/or electron-withdrawing substituents such as Ph, CO₂Me, and ^tBu were cyclized successfully with 2, but did not cyclize with 1. Tetrasubstituted cyclic olefins could be formed with 2, but not using alkylidene 1. Dienes with allylic functional groups yielded functionalized cyclic olefins when treated with 1.

Full text of DOI:10.1021/jo970877p

7310
J . Org. Chem. 1997, 62, 7310-7318
Effects of Olefin Su bstitu tion on th e Rin g-Closin g Meta th esis of
Dien es
Thomas A. Kirkland 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 May 13, 1997X
Ruthenium alkylidene 1 and molybdenum alkylidene 2 have been utilized in the ring-closing
metathesis (RCM) of dienes containing gem-disubstituted olefins to yield tri- and tetrasubstituted
cyclic olefins. Dienes with sterically demanding and/or electron-withdrawing substituents such as
t
Ph, CO2Me, and Bu were cyclized successfully with 2, but did not cyclize with 1. Tetrasubstituted
cyclic olefins could be formed with 2, but not using alkylidene 1. Dienes with allylic functional
groups yielded functionalized cyclic olefins when treated with 1.
Sch em e 1. Ca ta lytic RCM Yield in g Su bstitu ted
Cyclic Olefin s
In tr od u ction
Ring-closing metathesis (RCM) is a versatile technique
for the formation of five- to seven-membered carbocycles
and heterocycles.1-5 In addition, several examples of
macrocycle formation through RCM have been
reported.5-12 Ruthenium alkylidene 113 and molybdenum
alkylidene 214 are two of the most commonly used
initiators for RCM (Scheme 1), and reports of their use
in organic synthesis have increased steadily.8,15-19 How-
ever, relatively little effort has been directed toward
converting substituted dienes to substituted cyclic olefins
(Scheme 1).1,2,7,8,17,20-24 Since many protocols exist for the
elaboration of functionalized olefins, substituted cyclic
olefins are attractive synthetic intermediates in organic
synthesis.
X Abstract published in Advance ACS Abstracts, October 1, 1997.
(1) Fu, G. C.; Grubbs, R. H. J . Am. Chem. Soc. 1992, 114, 5426-
5427.
(2) Fu, G. C.; Grubbs, R. H. J . Am. Chem. Soc. 1992, 114, 7324-
7325.
(3) Fu, G. C.; Nguyen, S. T.; Grubbs, R. H. J . Am. Chem. Soc. 1993,
115, 9856-9857.
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3801.
(5) Grubbs, R. H.; Miller, S. J .; Fu, G. C. Acc. Chem. Res. 1995, 28,
446-552, and references contained therein.
(6) Xu, Z.; J ohannes, C. W.; Salman, S. S.; Hoyveda, A. H. J . Am.
Chem. Soc. 1996, 118, 10926-10927.
Several examples of the RCM of alkyl-substituted
dienes with highly active group VI alkylidenes have been
reported. Molybdenum alkylidene 2 has been used for
the synthesis of a variety of methyl- and ethyl-substituted
cyclic olefins through RCM.1,2,7,8,17,20 Additionally, cyclic
enol ethers have been synthesized from acyclic enol
ethers using alkylidene 2.7,20,23 The high activity dis-
played by alkylidene 2 is accompanied by both a lack of
tolerance for some common functional groups and the
requirement that substrates and solvents be rigorously
purified, dried, and degassed.3 Ruthenium alkylidene 1
will perform RCM in the presence of most of the func-
tional groups commonly used in organic synthesis and
requires far less rigorous conditions than 2.3,5,13
An alternative method for synthesizing functionalized
cyclic olefins via olefin metathesis is through the RCM
of acetylene containing substrates, which has been
explored with several alkylidenes (Scheme 1).21,22,24-26
However, formation of substituted cyclic olefins through
metathesis of substituted dienes has not been reported
for alkylidene 1 and has been confined to the few
examples listed above with alkylidene 2. In this report,
(7) Clark, J . S.; Kettle, J . G. Tetrahedron Lett. 1997, 38, 123-126.
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3943.
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(10) Miller, S. J .; Blackwell, H. E.; Grubbs, R. H. J . Am. Chem. Soc.
1996, 118, 9606-9614.
(11) Meng, D.; Su, D.-S.; Balog, A.; Bertinato, P.; Sorenson, E. J .;
Danishefsky, S. J .; Zheng, Y.-H.; Chou, T.-C.; He, L.; Horwitz, S. J .
Am. Chem. Soc. 1997, 119, 2733-2734.
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Angew. Chem. Int. Eng. Ed. 1996, 35, 2399-2401.
(13) Schwab, P. E.; Grubbs, R. H.; Ziller, J . W. J . Am. Chem. Soc.
1996, 118, 100-110.
(14) Schrock, R. R.; Murdzek, J . S.; Bazan, G. C.; Robbins, J .;
DiMare, M.; O’Regan, M. J . Am. Chem. Soc. 1990, 112, 3875-3886.
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694.
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Tetrahedron Lett. 1994, 35, 3191-3194.
(17) Houri, A. F.; Xu, Z.; Cogan, D.; Hoyveda, A. H. J . Am. Chem.
Soc. 1995, 117, 2943-2944.
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1624.
(19) Overkleeft, H. S.; Pandit, U. K. Tetrahedron Lett. 1996, 37,
547-550.
(20) Clark, J . S.; Kettle, J . G. Tetrahedron Lett. 1997, 38, 127-130.
(21) Kim, S.-H.; Zuercher, W. J .; Grubbs, R. H. J . Org. Chem. 1996,
61, 1073-1081.
(22) Kim, S.-H.; Bowden, N.; Grubbs, R. H. J . Am. Chem. Soc. 1994,
116, 10801-10802.
(23) Fujimura, O.; Fu, G. C.; Grubbs, R. H. J . Org. Chem. 1994, 59,
4029-4031.
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738.
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(24) Kinoshita, A.; Miwako, M. Synlett. 1994, 1020-1022.
S0022-3263(97)00877-3 CCC: $14.00 © 1997 American Chemical Society

The Ring-Closing Metathesis of Dienes
J . Org. Chem., Vol. 62, No. 21, 1997 7311
Sch em e 2. Syn th esis of Alk yl Su bstitu ted Dien es
Der ived fr om Dieth yl Ma lon a tea
Sch em e 3. Syn th esis of F u n ction a lized RCM
Su bstr a tesa
a
(a) CH2dCHR1,2(CH2)m,nBr, NaOEt, DMF, 33-72%; (b) Li-
AlH4, Et2O, 79%; (c) PPh3, CBr4, CH2Cl2, 65-90%; (d) (EtO2C)2-
CHCH2CHdCH2, NaOEt, DMF, 33-75%; (e) TBDPSiCl, NEt3,
CH2Cl2, then PCC, CH2Cl2, 83%; (f) Ph3PCH3Br, BuLi, THF, 93%;
(g) TBAF, THF, 65%; (h) NBS, CCl4, 66%.
the synthesis of a variety of substituted dienes and their
reactivities with these two common metathesis-active
alkylidenes is presented. The substrates were chosen to
test the limits of reactivity of both alkylidenes and to
provide guidelines for their use in constructing complex
synthetic targets.
a
(a) Ac2O (1 equiv), NEt3, CH2Cl2, 48%; (b) PPh3, CBr4, CH2Cl2,
75%; (c) (EtO2C)2CHCH2CHdCH2, NaOEt, DMF, 54-96%; (d) Na,
EtOH, 57%; (e) NBS, CCl4, 27%; (f) CH3I, K2CO3, acetone, 55%;
(g) SO2, benzoquinone, CH3OH, 47%; (h) NBS, CHCl3, then 160
°C, neat, 62%; (i) PhCOCl, NEt3, CH2Cl2, 64%; (j) CH2dC(CH3)-
CH2Cl, NaH, DMF, 38-78%; (k) CH2dCHMgBr, THF, 56%.
Resu lts a n d Discu ssion
Su bstr a te Syn th esis. Standard alkylation of diethyl
malonate with alkyl halides was used to prepare the
alkyl-substituted dienes 3a -10a (Scheme 2).27 Halides
used in the syntheses of these dienes were either com-
mercially available or obtained from the corresponding
alcohol.28 Reduction of ethyl acrolein, subsequent con-
version of the alcohol to the bromide,29,30 and coupling to
diethyl allylmalonate (DAM) provided diene 11a . Syn-
thesis of 2-(bromomethyl)-3-methyl-1-butene31 (Scheme
2) followed by coupling to DAM afforded diene 12a .
Allylic bromination of 2,2,3-trimethylbutene32 followed by
coupling to DAM yielded diene 13a .
Functionalized dienes 14a -21a were prepared in a
similar manner to the alkyl-substituted dienes (Scheme
3). Bromination of 2-(acetoxymethyl)-3-propen-1-ol fol-
lowed by coupling to DAM gave diene 14a , and subse-
quent deprotection afforded diene 15a . Diene 16a was
prepared by allylic bromination of R-methylstyrene33
followed by coupling to DAM. Reaction of 2-(bromo-
methyl)acrylic acid with DAM followed by esterification
afforded diene 17a . The coupling of 2,3-dibromopropene
to DAM yielded diene 18a . Electrocyclic addition of
isoprene to SO2, bromination of the resultant cyclic
sulfone, and thermally induced elimination of SO2 gave
2-(bromomethyl)-1,3-butadiene,34-36 which was reacted
with DAM to yield 19a . Amide 20a and ether 21a were
synthesized through standard alkylation reactions.
RCM of Meth yl-Su bstitu ted Dien es. Initially, it
was necessary to determine if ruthenium alkylidene 1
was active for the RCM of dienes containing a gem-
disubstituted olefin. When diene 3a (0.01 M, CH2Cl2)37,38
was exposed to 5 mol % of 1 for 24 h, cyclopentene 3b
(34) Frank, R. L.; Seven, R. P. Org. Synth. 1955, Collect. Vol. 3, 499-
500.
(35) Thomas, A. F. J . Am. Chem. Soc. 1969, 91, 3281-3289.
(36) Krug, R. C.; Yen, T. F. J . Org. Chem. 1956, 21, 1082-1084.
(37) CH2Cl2 was chosen as the optimal solvent for reactions with 1
based on slightly lower yields obtained in other solvents employed
(C6H6, CHCl3). C6H6 was used as the solvent for reactions with 2 based
on previous work done in this laboratory.1,2
(38) All RCM reactions using alkylidene 1 were performed at room
temperature. Comparison of the conversion obtained at a variety of
temperatures for substrate 3a showed that while RCM was faster at
elevated temperatures, the accelerated decomposition of the ruthenium
methylidene led to a decrease in overall conversion to ring-closed
product under the conditions used. In some other studies with
alkylidene 1 involving different conditions, increased temperature has
resulted in higher overall conversions, notably at higher substrate
concentrations.21,40 With alkylidene 2, elevated temperatures resulted
in the increased conversion of 10a to 10b, and 65 °C was eventually
chosen as the optimal temperature for all RCM reactions with 2.
(27) Doran, W. J .; Shonle, H. A. J . Am. Chem. Soc. 1937, 59, 1625-
1626.
(28) Bhanot, O. S.; Dutta, P. C. J . Chem. Soc. (C) 1968, 2583-2588.
(29) Borg, R. M.; Heuckeroth, R. O.; Lan, A. J . Y.; Quillen, S. L.;
Mariano, P. S. J . Am. Chem. Soc. 1987, 109, 2728-2737.
(30) Takano, S.; Hirama, M.; Araki, T.; Ogasawara, K. J . Am. Chem.
Soc. 1976, 98, 7084-7085.
(31) Barton, D. H. R.; Shioiri, T.; Widdowson, D. A. J . Chem. Soc.
(C) 1971, 1968-1974.
(32) White, W. N.; Norcross, B. E. J . Am. Chem. Soc. 1961, 83,
3265-3269.
(33) Reed, S. F. J . Org. Chem. 1965, 30, 3258.

7312 J . Org. Chem., Vol. 62, No. 21, 1997
Kirkland and Grubbs
Ta ble 1. Resu lts of th e RCM of Meth yl Su bstitu ted
Dien es
concentration, no dimer formation was detected. In
addition, RCM of some substituted dienes which are
unreactive with 1 can be carried out in good synthetic
yield with alkylidene 2.
The difference in reactivity between 1 and 2 can be
understood through an examination of the kinetics of
formation of trisubstituted cyclic olefins through RCM
(Figure 1). From this analysis, it can be seen that the
catalyst dependent term for productive RCM vs dimer
formation is kmore/kless. Because this ratio is much smaller
for the more selective ruthenium alkylidene (kless >> kmore
for 1), dimer formation is frequently competitive with
RCM. Since the rate of dimer formation is dependent
upon the concentration of substrate but the rate of RCM
is independent of substrate concentration, performing
RCM reactions under dilute conditions can reduce the
rate of dimerization to the point where it is not observed.
Because the molybdenum alkylidene 2 is much less
selective than 1, the intramolecular reaction occurs much
faster than any intermolecular reaction under the range
of concentrations examined in this study.
In order to explain the increased conversion observed
when the concentration of substrate is increased in
molybdenum-mediated cyclizations, another kinetic term
involving the methylidene41 must be considered. Due to
the limited stability of the molybdenum methylidene,14
the decomposition of the catalytic species is competitive
with the rate of RCM. Because the rate of RCM increases
with the concentration of substrate, the increased yield
results from higher turnover of substrate before catalyst
decomposition. This problem is significantly reduced in
the case of the ruthenium methylidene, which is much
more stable in solution and can even be isolated as a solid
which is stable indefinitely at room temperature.13
However, in cases where reaction with the more substi-
tuted olefin is extremely slow for the ruthenium alkyli-
dene, the rate of catalyst decomposition exceeds the rate
of RCM and little or no conversion to product is observed.
In these cases decreasing the substrate concentration and
increasing catalyst loading can significantly increase the
conversion of substrate to product for the reasons out-
lined above.
Under the standard conditions discussed previously,
alkylidenes 1 and 2 converted diene 4a to the substituted
cyclohexene 4b in good yield (Table 1, entries 2-4).
Formation of the seven-membered cyclic 5b with alkyli-
dene 1 required extended reaction times (4 days) to
achieve a 96% yield. However, formation of the struc-
tural isomer 6b was less favorable, with only 25%
conversion to 6b observed after 5 days. Quantitative
conversion of both 5a and 6a to the respective cyclohep-
tenes is seen with alkylidene 2.
1
Numbers in parentheses represent the conversion to product
as measured by 1H NMR. In these cases, only starting material
2
and a product which was assigned as an acyclic dimer based on
1H NMR and TLC were observed.
was obtained in 93% isolated yield with no side products
detected (Table 1, entry 1). A relatively low concentration
of substituted diene is required for optimized yields when
RCM is performed with alkylidene 1. Upon addition of
1 to a 0.1 M solution of 3a , significant formation of
another species is observed. This species is postulated
to be the dimer formed through acyclic diene metathesis
of the monosubstituted olefins of two molecules of 3a .39
Several examples of dimerization have been seen in other
RCM applications of 1.10,40 However, no dimerization
could be detected upon analysis of all of the reactions
using 1 at a substrate concentration of 0.01 M. There-
fore, the conditions reported above were used as the
standard conditions for RCM with 1 for all of the
reactions reported.
Differences in the rates of formation of isomeric cyclo-
heptenes have been reported elsewhere,42,43 although the
reason for this drop in reactivity is unclear. In the case
of substrates derived from malonic acid, the gem-diesters
on the backbone of the substrate favor cyclization due to
a Thorpe-Ingold effect.44,45 Thus, the higher reactivity
of 5a may be due to the gem-diesters biasing the
substrate to adopt a conformation which is favorable for
cyclization. This bias may be less in the asymmetrical
substrate 6a . Another possible explanation is that the
esters in 6a , being closer to the disubstituted olefin,
Exposure of 3a (0.1 M, C6D6)37,38 to the molybdenum
alkylidene 2 (5 mol %) also showed high reactivity in
converting this substrate to 3b. Upon examining the
reactions of trisubstituted dienes with alkylidene 2 at this
(39) Tentative assignment of the species which did not correspond
to the desired product in the reaction mixture as dimeric was done
through 1H NMR.
(40) Zuercher, W. J .; Hashimoto, M.; Grubbs, R. H. J . Am. Chem.
Soc. 1996, 118, 6634-6640.
(41) The methylidene (LnMdCH2) is the active catalytic species in
RCM of dienes which contain only mono- and gem-disubstituted olefins.
It is formed through reaction of the starting alkylidene with one
molecule of substrate. After this, the methylidene is the propagating
species for the remainder of the catalytic cycles.
(42) Hammer, K.; Undheim, K. Tetrahedron 1997, 53, 2309-2322.
(43) Rutjes, F. P. J . T.; Shoemaker, H. E. Tetrahedron Lett. 1997,
38, 677-680.

The Ring-Closing Metathesis of Dienes
J . Org. Chem., Vol. 62, No. 21, 1997 7313
F igu r e 1. The kinetics of ring-closing versus dimerization for monosubstituted dienes.
Ta ble 2. Resu lts of th e RCM of Sever a l F u n ction a lized
hinder the tethered alkylidene as it approaches the
disubstituted olefin to form the cyclic product. The
higher conversion observed with alkylidene 2 is believed
to be due to the higher reactivity of this alkylidene, which
overrides the factors inhibiting alkylidene 1 discussed
above.
Dien es
Exposure of the diene 7a to alkylidene 1 or 2 under
standard conditions yielded only dimeric products (Table
1, entry 5). In order to determine if the methyl group
substituent on 7a had prevented productive RCM from
occurring, the analogous diene 8a without olefinic sub-
stituents was synthesized (Table 1, entry 6). Again, only
dimeric products were observed upon exposure to both
alkylidenes. This result is in good agreement with
previous work from these laboratories,46 showing that
formation of eight-membered cyclics through RCM only
occurs in systems where the dienes are conformationally
predisposed for ring formation as in the catechol deriva-
tive shown below. Unconstrained systems failed to yield
eight-membered cyclics through RCM in almost all cases,
and it has been demonstrated for several other cycliza-
tions that formation of eight-membered rings is less
favorable than formation of five-, six-, or seven-membered
rings.47 Clearly, the diester moiety does not provide
enough conformational bias to favor RCM in the cases of
7a and 8a .
1
Numbers in parentheses represent the conversion to product
as measured by 1H NMR.
alkylidene 2 also converted 20a and 21a quantitatively
to the expected cyclic products.
Effect of Olefin Su bstitu tion . Once it had been
established that formation of substituted cyclics with 1
was feasible, attention was turned toward the olefinic
substituent (Table 2, entries 1-3). The steric bulk
tolerated by each alkylidene was examined through the
use of dienes 11a , 12a , and 13a . The cyclization of ethyl-
substituted diene 11a with 1 proceeded in 93% yield over
24 h. Reaction of isopropyl-substituted diene 12a with
1 required 48 h for 98% yield of 12b to be achieved,
presumably due to the presence of additional steric bulk
on the olefin. Alkylidene 1 showed no reaction with tert-
butyl-substituted diene 13a over 5 days, demonstrating
that further increasing the steric bulk on the olefin
inhibits RCM with 1. Due to the more active nature of
In order to demonstrate that this methodology is
general to a variety of substituted dienes, amide 20a and
ether 21a were examined (Table 1, entries 7 and 8).
Alkylidene 1 cyclized amide 20a and ether 21a to the
corresponding heterocycles 20b and 21b in 97% and 98%
yield, respectively. In accordance with previous reports
from this laboratory,1,2 it was found that the molybdenum
(44) Forbes, M. D. E.; Patton, J . T.; Myers, T. L.; Maynard, H. D.;
Smith, D. W.; Schulz, G. R.; Wagener, K. B. J . Am. Chem. Soc. 1992,
114, 10978-10980.
(45) J ung, M. E.; Gervay, J . J . Am. Chem. Soc. 1991, 113, 224-
232, and references contained therein.
(46) Miller, S. J .; Kim, S.-H.; Chen, Z.-R.; Grubbs, R. H. J . Am.
Chem. Soc. 1995, 117, 2108-2109.
(47) Illuminati, G.; Mandolini, L. Acc. Chem. Res. 1981, 14, 95-
102.

7314 J . Org. Chem., Vol. 62, No. 21, 1997
Sch em e 4. P ossible P r od u cts Resu ltin g fr om th e RCM of 19a
Kirkland and Grubbs
alkylidene 2, it was presumed that 2 would be more
active toward the RCM of more hindered dienes such as
12a and 13a . In fact, 2 converts all three of these alkyl-
substituted dienes into the corresponding cyclopentenes
in high yield over 24 h.
do not react productively with alkylidene 1.48 The
explanation for the failure of alkylidene 2 to react with
18a has not been determined.
Due to the failure of alkylidene 1 to effectively cyclize
dienes containing substituents in conjugation with an
olefin, functional groups which do not electronically
deactivate the substrate but could be used to efficiently
derivatize the cyclic olefin after RCM were investigated.
Allylic alcohol 15a was the target molecule for this
approach. Because the alcohol should have only an
inductive effect on the olefin, it was hoped that the diene
would not be deactivated for RCM with 1. The reactivity
of 1 toward 15a was therefore presumed to be similar to
its reactivity toward the ethyl substituted diene 11a . In
fact, both the alcohol 15a and the acetate 14a react with
1 to yield the expected cyclopentenes in excellent yields
(Table 2, entries 7 and 8). As expected, molybdenum
alkylidene 2 decomposes in the presence of the primary
alcohol present in 15a to give no ring-closed product,
although it does convert protected diene 14a to the
cyclized product.
Due to the fact that three olefins are present in
substrate 19a , reaction of 19a with either alkylidene 1
or 2 could yield either cyclopentene 19b or cyclohexene
19c (Scheme 4). On the basis of the kinetic scheme
described previously (Figure 1), it was predicted that
alkylidene 1 would preferentially react with the two less
substituted olefins on 19a to give 19c. This prediction
proved correct, and 19c is formed in 96% yield upon
treatment of 19a with 1.49,50 Due to the lower selectivity
of molybdenum alkylidene 2 for monosubstituted olefins,
it was believed that a mixture of 19b and 19c might be
formed. However, reaction of 19a with 2 also showed
quantitative conversion to cyclohexene 19c with none of
the cyclopentene 19b detected. This result suggests that
while 2 is not as selective for less substituted olefins than
1, it will still preferentially react with the less substituted
olefin when two olefins with different substitution are
present.51 This formation of exo-methylene ring systems
such as 19c represents a complementary diene system
After examining the steric bulk tolerated by these
alkylidenes, several substituents which affect the elec-
tronic nature of the olefin were examined. Previous
reports from this laboratory had shown that enol ethers
did not undergo RCM when exposed to 1.23 For this
reason we turned our attention away from electron-
donating substituents and toward electron-withdrawing
substituents (Table 2, entries 4 and 5). When the phenyl-
substituted 16a was subjected to RCM conditions with
1, only 25% conversion to cyclized product was observed.
In the case of the more electron-deficient diene 17a , 5%
conversion was observed. The failure of 16a and 17a to
yield the desired product in higher yield when exposed
to alkylidene 1 is postulated to be a combination of the
steric effect of the substituent and the electron-with-
drawing effects of the phenyl and methyl ester groups.
Alkylidene 1 is capable of cyclizing substrates which
contain substituents of approximately equal steric de-
mand to these substituents such as the isopropyl group
in diene 12a . Examples have been reported of R,â-
unsaturated carbonyl- and phenyl-substituted acety-
lenes21 and dienes3,19,43 reacting with alkylidene 1 to form
cyclic products. However, when both the steric bulk and
electron-withdrawing character are combined in the same
diene substituent, the rate of RCM with alkylidene 1
becomes so slow that catalyst decomposition is competi-
tive with RCM and high yields are not obtained.
In contrast to 1, alkylidene 2 was reported to convert
dienes containing an enol ether to cyclic enol ethers in
high yield.23 Treatment of substrates 16a and 17a with
alkylidene 2 afforded the expected cyclopentenes in good
yield as well (Table 2, entries 4 and 5). The higher
reactivity exhibited by 2 toward olefins containing both
electron-withdrawing and electron-donating substituents
as compared to 1 underscores its generally higher activity
toward gem-disubstituted olefins.
Next, vinyl halide containing dienes were examined.
Exposure of 18a to either alkylidene 1 or 2 afforded no
cyclic product (Table 2, entry 6). In all cases, only 18a
and alkylidene decomposition products were detected
upon examination of the reaction mixtures. The expla-
nation for this lack of reactivity with alkylidene 1 is
presumed to be the same as for dienes 16a and 17a .
Acetylenic halides have been shown to react with alky-
lidene 1 through halide exchange, but will not undergo
RCM.21 It has also been shown that other vinyl halides
(48) Kim, S-H., Unpublished results.
(49) The product of the metathesis of 19a was determined not to be
19b through comparison to the spectral data of 19b as reported.50
(50) Chatani, N.; Morimoto, T.; Muto, T.; Murai, S. J . Am. Chem.
Soc. 1994, 116, 6049-6050.
(51) Although the mechanism presented explains the formation of
19c (Scheme 4), there are two other obvious means by which 19c could
be formed from 19a . If the alkylidene initiates at the conjugated
terminal olefin, the only possible RCM product is 19c. Additionally, it
is possible that cyclopentene 19b is formed initially and undergoes
subsequent reaction to produce the thermodynamically more stable
cyclohexene 19c. However, in NMR experiments formation of 19b is
not observed.

The Ring-Closing Metathesis of Dienes
J . Org. Chem., Vol. 62, No. 21, 1997 7315
Sch em e 5. Rea ction of th e Ru th en iu m Meth ylid en e w ith Su bstitu ted Alk en e a n d Alk yn e Su bstr a tes
Ta ble 3. RCM of Dien es To F or m Tetr a su bstitu ted
Cyclics
mation of tetrasubstituted cyclic olefins through dienes
such as 9a is not feasible using alkylidene 1.
Con clu sion s
We have demonstrated the formation of trisubstituted
and tetrasubstituted olefins via ring-closing metathesis
of gem-disubstituted olefins. This is a general reaction
for the formation of five-, six-, and seven-membered
carbocycles and heterocycles. The reactivities of all
substrates examined supports the general observation
that five-membered ring formation is the most kinetically
favorable and eight-membered ring formation is the least
favorable regardless of the alkylidene used. Ruthenium
alkylidene 1 will cyclize dienes with olefinic substituents
as sterically demanding as isopropyl in good yield, but
will not cyclize a tert-butyl-substituted diene. In addi-
tion, dienes containing an electron-withdrawing olefinic
substituent do not undergo RCM when exposed to 1. The
more active and less selective molybdenum alkylidene 2
does catalyze the RCM of many of the substrates for
which 1 was not active. Both alkylidenes 1 and 2 are
shown to efficiently convert trienes such as 19a to the
exo-methylenecyclohexene 19c. Tetrasubstituted cyclic
olefins can be synthesized from bis-gem-disubstituted
dienes using the more active alkylidene 2, but 1 is
unreactive toward that class of dienes. However, alky-
lidene 1 does perform RCM in excellent yield to form a
carbocycle containing an allylic alcohol.
The differing reactivities of alkylidenes 1 and 2 suggest
that both have a role in the synthesis of complex
molecules through RCM. The more active molybdenum
alkylidene 2 is required for the RCM of highly substituted
dienes. However, RCM using 2 frequently requires a
substantial number of substrate protection and depro-
tection steps which are not required when 1 is used.
Another advantage of ruthenium alkylidene 1 is that
rigorous purification, drying, and degassing of substrates
is not required for RCM. Therefore, total syntheses of
many densely functionalized targets may be more simply
and efficiently carried out using 1.
to the vinyl systems afforded through enyne metathesis
(Scheme 1).
Syn th esis of Tetr a su bstitu ted Olefin s. Having
demonstrated the formation of a variety of trisubstituted
cyclic olefins, formation of tetrasubstituted cyclic olefins
through the RCM of dienes 9a and 10a was investigated.
Formation of cyclopentenes with tetrasubstituted olefins
analogous to 9b with molybdenum alkylidene 2 has been
reported.1,4 Indeed, when 9a was exposed to 2 under
standard RCM conditions, 9b was obtained in 93% yield
(Table 3). Formation of the cyclohexene 10b using
alkylidene 2 proceeded in 61% yield.
Exposure of 9a or 10a to alkylidene 1 afforded no cyclic
product under standard RCM conditions. Even when the
concentration of substrate was increased 10-fold neither
ring-closed product nor dimerization were observed.
However, previous studies in this laboratory have shown
that tetrasubstituted cyclic olefins can be generated
through reaction of 1 with acetylene containing sub-
strates.21 The key difference between these two systems
lies in the initial reaction of alkylidene with the sub-
strate. In acetylene-containing substrates such as 22a ,
the monosubstituted olefin is the site of initiation (Scheme
5). Once the alkylidene has initiated to yield intermedi-
ate 22b, the intramolecular reaction is favored to form
intermediate 22c. The new alkylidene present in 22c
performs another intramolecular reaction with the di-
substituted olefin at the end of the tether to form the
fused bicyclic compound 22d containing a tetrasubsti-
tuted olefin. As discussed earlier, an intramolecular
reaction is also observed in the formation of trisubstituted
dienes through metathesis of gem-disubstituted olefins,
although only at high dilution. Initiation occurs through
the less substituted olefin and the new alkylidene
undergoes the intramolecular reaction providing the
desired product. When no monosubstituted olefin is
present on the RCM substrate, however, reaction with 1
is not observed. In fact, the isolation of disubstituted
alkylidenes of ruthenium which are metathesis active has
not been reported. The low reactivity of 1 with gem-
disubstituted olefins intermolecularly indicates that for-
Exp er im en ta l Section
Gen er a l. NMR spectra were recorded on either a General
Electric QE-300 (300.1 MHz for 1H; 75.49 MHz for 13C) or a
J eol GX-400 (399.65 MHz 1H; 100 MHz 13C) spectrometer.
Chemical shifts are reported in parts per million (ppm)
downfield from tetramethylsilane with reference to internal
solvent. In cases where more than one rotamer is observed,
both rotamers are reported. Infrared spectra were obtained
on a Perkin-Elmer Paragon 1000 FT-IR. High-resolution mass
spectra were provided by either the Chemistry and Biology
Mass Spectrometry Facility (Caltech) or the Southern Cali-
fornia Mass Spectrometry Facility (University of California,

7316 J . Org. Chem., Vol. 62, No. 21, 1997
Kirkland and Grubbs
Riverside). Analytical thin-layer chromatography (TLC) was
performed using silica gel 60 F254 precoated plates (0.25 mm
thickness) with a fluorescent indicator. Flash column chro-
matography was performed using silica gel 60 (230-400 mesh)
from EM Science.52 Alkylidenes 1 and 2 were prepared
according to published procedures.13,14
2H), 4.14 (q, J ) 7.1 Hz, 4H), 2.06-1.95 (m, 4H), 1.89-1.83
(m, 4H), 1.68 (s, 3H), 1.23-1.18 (m, 8H); 13C NMR (CDCl3, 75
MHz) δ 171.8, 145.0, 138.2, 115.1, 110.3, 61.2, 57.3, 33.9, 31.7,
31.5, 30.6, 23.6, 23.2, 14.2; IR (neat, cm-1) 3078, 2980, 2938,
1731, 1643, 1447, 1380, 1255, 1181, 1030; HRMS calcd for
C17H29O4 (MH+) 297.2054, found 297.2066.
4,4-Dica r beth oxy-2-m eth yl-1,6-h ep ta d ien e (3a ). To a
suspension of sodium ethoxide (5.09 g, 74.9 mmol) in DMF
(100 mL) was added diethyl allylmalonate (10.0 g, 49.9 mmol).
After 15 min, methallyl chloride was added (4.52 g, 49.9 mmol).
After stirring for 24 h at room temperature, the reaction was
quenched with water (100 mL) and extracted with Et2O (4 ×
50 mL). Purification of the resultant orange oil on silica gel
(10% EtOAc in hexanes) yielded 3a (8.26 g, 65%) as a clear,
colorless oil, as first reported by Doran:27 1H NMR (CDCl3,
300 MHz) δ 5.79-5.68 (m, 1H), 5.05-4.96 (m, 2H), 4.80 (s,
1H), 4.77 (s, 1H), 3.95-3.92 (m, 4H), 2.85-2.80 (m, 4H), 1.59
(s, 3H), 0.93 (t, J ) 7.2 Hz, 6H); 13C NMR (CDCl3, 75 MHz) δ
170.9, 141.1, 133.4, 118.8, 115.9, 61.1, 57.2, 40.6, 37.4, 23.3,
14.0; IR (neat, cm-1) 3079, 2982, 1731, 1644, 1446, 1367;
HRMS calcd for C14H22O4 (M+) 254.1507, found 254.1518.
4,4-Dica r beth oxy-1-m eth ylcyclop en ten e (3b). To a so-
lution of catalyst 1 (16 mg, 0.02 mmol) in dry, degassed
methylene chloride (40 mL) was added diene 3a (102 mg, 0.4
mmol). After stirring at room temperature for 24 h the
reaction was concentrated and purified on silica gel (5% EtOAc
in hexanes) to yield the product 3b (83 mg, 91%) as a clear,
colorless oil. The spectral data are in good agreement with
that first reported by Schweizer.53
5,5-Dica r beth oxy-2-m eth yl-1,7-octa d ien e (4a ). The di-
ester 4a was prepared in a manner similar to 3a using
1-bromo-3-methyl-3-butene.28 Compound 4a was isolated as
a clear, colorless oil (50%) in good agreement with the spectral
data reported by Sato.54
4,4-Dica r beth oxy-1-m eth ylcycloh exen e (4b). Cyclohex-
ene 4b was obtained as a clear, colorless oil (97%) under
conditions analogous to the reaction producing 3b. The
spectral data are in good agreement with those first reported
by Schweizer.53
5,5-Dica r beth oxy-1,9-d eca d ien e (8a ). The diester 8a
was synthesized in a manner similar to that of 3a using 1,1-
dicarbethoxy-4-pentene and 1-bromo-4-pentene. 8a was iso-
lated as a clear, colorless oil (44%): 1H NMR (CDCl3, 300 MHz)
δ 5.76-5.65 (m, 1H), 4.99-4.87 (m, 4H), 4.11 (q, J ) 7.2 Hz,
4H), 2.03-1.80 (m, 8H), 1.25-1.15 (m, 8H); 13C NMR (CDCl3,
75 MHz) δ 171.6, 138.1, 137.7, 115.05, 114.98, 61.1, 57.2, 33.8,
31.7, 31.5, 28.4, 23.3, 14.1; IR (neat, cm-1) 3079, 2980, 2874,
1732, 1642, 1447, 1368, 1260, 1032, 913; HRMS calcd for
C16H27O4 (MH+) 283.1914, found 283.1909.
4,4-Dicar beth oxy-2,6-dim eth yl-1,6-h eptadien e (9a). The
diester 9a was synthesized in a manner similar to that of 3a
using diethyl methallylmalonate. Compound 9a was isolated
as a clear, colorless oil (72%) as first reported by Doran:27 1H
NMR (CDCl3, 300 MHz) δ 4.88-4.85 (m, 4H), 3.95 (q, J ) 7.1
Hz, 4H), 3.01 (s, 4H), 1.68 (s, 6H), 0.91 (t, J ) 7.1 Hz, 6H); 13
C
NMR (CDCl3, 75 MHz) δ 171.3, 141.6, 115.3, 61.1, 57.1, 41.0,
23.7, 13.9; IR (neat, cm-1) 3078, 2981, 2937, 1732, 1446, 1367;
HRMS calcd for C15H25O4 (MH+) 269.1755, found 269.1753.
4,4-Dica r beth oxy-1,2-d im eth ylcyclop en ten e (9b).
A
solution of 9a (107 mg, 0.4 mmol) in dry, degassed benzene (4
mL) was added to alkylidene 2 (12.0 mg, 0.02 mmol) and
heated to 65 °C. After stirring for 24 h the reaction was
concentrated and purified on silica gel (10% EtOAc in hexanes)
to yield 9b as a clear, colorless oil (89 mg, 93%):55 1H NMR
(CDCl3, 300 MHz) δ 4.16 (q, J ) 7.0 Hz, 4H), 2.90 (s, 4H), 1.57
(s, 6H), 1.22 (t, J ) 7.2 Hz, 6H); 13C NMR (CDCl3, 75 MHz) δ
172.8, 128.2, 61.6, 57.2, 45.9, 14.2, 13.5; IR (neat, cm-1) 3468,
2981, 2859, 1732, 1446, 1366, 1253, 1076, 1020; HRMS calcd
for C13H20O4 (M+) 240.1362, found 240.1362.
4,4-Dicar beth oxy-2,7-dim eth yl-1,7-octadien e (10a). The
diester 10a was synthesized in a manner similar to that of 3a
using diethyl methallylmalonate and 1-bromo-3-methyl-3-
butene. Compound 10a was isolated as a clear, colorless oil
(65%): 1H NMR (CDCl3, 300 MHz) δ 4.79 (s, 1H), 4.68 (s, 1H),
4.62 (s, 2H), 4.17-4.10 (m, 4H), 2.66 (s, 2H), 1.99-1.93 (m, 2H),
1.84-1.79 (m, 2H), 1.65 (s, 3H), 1.59 (s, 3H), 1.19 (t, J ) 7.2
Hz, 6H); 13C NMR (CDCl3, 75 MHz) δ 171.5, 144.9, 140.6,
115.6, 110.3, 61.2, 56.6, 40.0, 32.2, 30.4, 23.1, 22.5, 14.1; IR
(neat, cm-1) 3077, 2981, 2940, 1732, 1650, 1448, 1368, 1259,
1093, 1031; HRMS calcd for C16H27O4 (MH+) 283.1915, found
283.1909.
4,4-Dica r beth oxy-1,2-d im eth ylcycloh exen e (10b). Cy-
clohexene 10b was obtained as a clear colorless oil (61%) under
conditions analogous to the reaction producing 9b: 1H NMR
(CDCl3, 300 MHz) δ 4.16 (q, J ) 7.1 Hz, 4H), 2.43 (s, 2H), 2.11-
2.07 (m, 2H), 1.99-1.97 (m, 2H), 1.63 (s, 3H), 1.57 (s, 3H), 1.22
(t, J ) 7.1 Hz, 6H); 13C NMR (CDCl3, 75 MHz) δ 171.9, 124.7,
123.0, 61.3, 54.0, 36.6, 28.8, 28.2, 19.2, 18.9, 14.3; IR (neat,
cm-1) 2982, 2913, 1732, 1446, 1367, 1297, 1177, 1090, 1031;
HRMS calcd for C14H22O4 (M+) 254.1513, found 254.1518.
5,5-Dica r beth oxy-2-m eth yl-1,8-n on a d ien e (5a ). The di-
ester 5a was prepared in a manner similar to that of 3a using
1-bromo-3-methyl-3-butene and 1,1-dicarbethoxy-4-pentene.
1,1-Dicarbethoxy-4-pentene was also synthesized in a manner
similar to that of 3a using diethyl malonate and 1-bromo-3-
butene. Compound 5a was isolated as a clear, colorless oil
(50%): 1H NMR (CDCl3, 300 MHz) δ 5.77-5.66 (m, 1H), 5.05-
4.89 (m, 2H), 4.80 (s, 1H), 4.74 (s, 1H), 3.95 (q, J ) 7.7 Hz,
4H), 2.32-2.20 (m, 4H), 2.13-2.04 (m, 4H), 1.60 (s, 3H), 0.92
(t, J ) 7.1 Hz, 6H); 13C NMR (CDCl3, 75 MHz) δ 171.3, 145.0,
137.9, 115.1, 110.7, 60.9, 57.4, 32.7, 32.2, 31.4, 28.9, 22.4, 14.0;
IR (neat, cm-1) 3077, 2797, 2939, 1732, 1643, 1454, 1367;
HRMS calcd for C16H27O4 (MH+) 283.1900, found 283.1909.
5,5-Dica r beth oxy-1-m eth ylcycloh ep ten e (5b). To a so-
lution of catalyst 1 (16 mg, 0.02 mmol) in dry, degassed
methylene chloride (40 mL) was added diene 5a (113 mg, 0.4
mmol). After stirring at room temperature for 4 days the
reaction was concentrated and purified on silica gel (5% EtOAc
in hexanes) to yield the product 5b (98 mg, 96%) as a clear,
colorless oil: 1H NMR (CDCl3, 300 MHz) δ 5.40 (s, 1H), 4.15
(q, J ) 7.1 Hz, 4H), 2.19-2.12 (m, 8H), 1.65 (s, 3H), 1.22 (t, J
) 7.9 Hz, 6H); 13C NMR (CDCl3, 75 MHz) δ 172.4, 138.9, 124.9,
4,4-Dica r beth oxy-2-eth yl-1,6-h ep ta d ien e (11a ). The di-
ester 11a was synthesized in a manner similar to that of 3a
using 2-(bromomethyl)-1-butene.30 Compound 11a was iso-
lated as a clear, colorless oil (50%): 1H NMR (CDCl3, 300 MHz)
δ 5.65-5.53 (m, 1H), 5.02-4.97 (m, 2H), 4.80 (s, 1H), 4.70 (s,
1H), 4.14-4.03 (m, 4H), 2.62 (s, 2H), 2.57 (d, J ) 7.4 Hz, 2H),
1.84 (q, J ) 7.4 Hz, 2H), 1.16 (t, J ) 7.1 Hz, 6H), 0.91 (t, J )
7.4 Hz, 3H);
61.3, 58.3, 32.2, 31.1, 29.7, 25.9, 25.9, 23.8, 14.2; IR (neat, cm-1
)
2966, 2853, 1732, 1447, 1367, 1292, 1180, 1035; HRMS calcd
for C14H23O4 (MH+) 255.1588, found 255.1596.
5,5-Dica r beth oxy-2-m eth yl-1,9-d eca d ien e (7a ). The di-
ester 7a was synthesized in a manner similar to that of 3a
using 1,1-dicarbethoxy-4-pentene, which was prepared from
diethyl malonate and 1-bromo-4-pentene. Compound 7a was
isolated as a clear, colorless oil (33%): 1H NMR (CDCl3, 300
MHz) δ 5.78-5.69 (m, 1H), 5.01-4.90 (m, 2H), 4.67-4.66 (m,
13C NMR (CDCl3, 75 MHz) δ 171.2, 146.1, 132.8,
118.9, 113.1, 61.2, 57.1, 38.3, 36.8, 29.3, 14.1, 12.4; IR (neat,
cm-1) 3080, 2982, 2879, 1732, 1642, 1446, 1368, 1288, 1096,
1042; HRMS calcd for C15H25O4 (MH+) 269.1751, found
269.1753.
4,4-Dica r beth oxy-1-eth ylcyclop en ten e (11b). Cyclopen-
tene 11b was obtained as a clear, colorless oil (93%) under
(52) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
(53) Schweizer, E. E.; O’Neill, G. J . J . Org. Chem. 1965, 30, 2082-
2083.
(54) Yamakazi, T.; Kasatkin, A.; Kawanaka, Y.; Sato, F. J . Org.
Chem 1996, 61, 2266-2267.
(55) Grigg, R.; Mitchell, T. R. B.; Ramasubbu, A. J . Chem. Soc.
Chem. Comm. 1980, 27-28.

The Ring-Closing Metathesis of Dienes
J . Org. Chem., Vol. 62, No. 21, 1997 7317
conditions analogous to the reaction producing 3b: 1H NMR
(CDCl3, 300 MHz) δ 5.18-5.16 (m, 1H), 4.15 (q, J ) 7.1 Hz,
4H), 2.95 (s, 2H), 2.89 (s, 2H), 2.06-1.99 (m, 2H), 1.23 (t, J )
7.1 Hz, 6H), 1.02 (t, J ) 7.5 Hz, 3H); 13C NMR (CDCl3, 75
MHz) δ 172.6, 143.7, 119.2, 61.6, 59.2, 43.2, 40.7, 23.8, 14.2,
12.2; IR (neat, cm-1) 3057, 2969, 2878, 1732, 1464, 1367, 1252,
1183, 1097, 1015; HRMS calcd for C13H20O4 (M+) 240.1353,
found 240.1362.
4,4-Dica r beth oxy-2-p h en yl-1,6-h ep ta d ien e (16a ). The
diester 16a was synthesized in a manner similar to that of 3a
using R-(bromomethyl)styrene.33 Compound 16a was isolated
as a clear, colorless oil (74%): 1H NMR (CDCl3, 300 MHz) δ
7.32-7.23 (m, 5H), 5.67-5.55 (m, 1H), 5.26 (s, 1H), 5.16 (s,
1H), 5.08-5.02 (m, 2H), 3.96-3.75 (m, 4H), 3.16 (s, 2H), 2.58
(d, J ) 7.3 Hz, 2H), 1.13 (t, J ) 7.1 Hz, 6H); 13C NMR (CDCl3,
75 MHz) δ 170.6, 144.6, 141.7, 132.6, 128.0, 127.5, 127.0, 119.2,
118.7, 61.1, 57.2, 37.2, 36.1, 14.0; IR (neat, cm-1) 3082, 2983,
1732, 1642, 1627, 1601, 1575, 1446, 1368, 1287, 1047; HRMS
calcd for C19H25O4 (MH+) 317.1743, found 317.1753.
4,4-Dica r beth oxy-1-p h en ylcyclop en ten e (16b). Cyclo-
pentene 16b was obtained as a clear, colorless oil (97%) under
conditions analogous to the reaction producing 9b: 1H NMR
(CDCl3, 300 MHz) δ 7.45-7.25 (m, 5H), 6.03 (t, J ) 2.1 Hz,
1H), 4.23 (q, J ) 7.1 Hz, 4H), 3.44-3.42 (m, 2H), 3.24-3.22
(m, 2H), 1.28 (t, J ) 7.1 Hz, 6H); 13C NMR (C6D6, 75 MHz) δ
172.2, 140.2, 136.1, 129.0, 128.0, 126.4, 123.0, 61.9, 59.6, 42.0,
41.9, 14.4; IR (neat, cm-1) 3058, 2982, 2867, 1732, 1600, 1576,
1447, 1367, 1258, 1183, 1073, 1017; HRMS calcd for C17H21O4
(MH+) 289.1431, found 289.1440.
2-Car bom eth oxy-4,4-dicar beth oxy-1,6-h eptadien e (17a).
To a suspension of K2CO3 (1.09 g, 7.91 mmol) in acetone (50
mL) was added 4,4-dicarbethoxy-1,6-heptadiene 2-carboxylic
acid (1.50 g, 5.28 mmol) and CH3I (9.9 mL, 158.3 mmol). After
stirring for 24 h at room temperature, the reaction was
quenched with NaHCO3 (saturated aqueous, 75 mL) and
extracted with Et2O (4 × 60 mL). After concentration, the
yellow oil obtained was purified with silica gel (20% EtOAc in
hexanes). 4,4-Dicarbethoxy-1,6-heptadiene 2-carboxylic acid
4.86 (m, 4H), 4.27 (s, 2H), 4.07-3.96 (m, 4H), 2.57 (s, 2H), 2.51
(d, J ) 7.3 Hz, 2H), 1.92 (s, 3H), 1.09 (t, J ) 7.0 Hz, 6H); 13C
NMR (CDCl3, 75 MHz) δ 170.5, 170.1, 138.9, 132.2, 119.1,
117.2, 66.6, 61.2, 56.9, 37.0, 35.4, 20.7, 13.9; IR (neat, cm-1
)
3082, 2984, 2908, 1732, 1644, 1446, 1368, 1226, 1031, 922;
HRMS calcd for C16H25O6 (MH+) 313.1641, found 313.1651.
1-(Acetoxym eth yl)-4,4-dicar beth oxycyclopen ten e (14b).
Cyclopentene 14b was obtained as a clear, colorless oil (98%)
under conditions analogous to the reaction producing 3b: 1H
NMR (CDCl3, 300 MHz) δ 5.51 (br s, 1H), 4.54 (s, 2H), 4.14 (q,
J ) 7.1 Hz, 4H), 2.98 (s, 2H), 2.95 (s, 2H), 2.02 (s, 3H), 1.20 (t,
J ) 7.1 Hz, 6H); 13C NMR (CDCl3, 75 MHz) δ 171.9, 170.8,
136.3, 125.6, 62.3, 61.7, 59.1, 40.9, 40.5, 20.9, 14.1; IR (neat,
cm-1) 2984, 2909, 1732, 1446, 1367, 1242, 1097, 1022, 972;
HRMS calcd for C14H20O6 (M+) 284.1260, found 284.1260.
4,4-Dica r b et h oxy-2-(h yd r oxym et h yl)-1,6-h ep t a d ien e
(15a ). Lump Na (100 mg, 4.34 mmol) was added to anhydrous
ethanol (50 mL). After the metal was no longer visible, 14a
(1.24 g, 3.95 mmol) was added to the solution. After stirring
for approximately 30 min at room temperature, no starting
material spot was observed by TLC (33% EtOAc in hexanes,
anisaldehyde). The reaction was quenched with NH4Cl (satu-
rated aqueous, 30 mL) and extracted with EtOAc (5 × 30 mL).
After purification on silica gel (33% EtOAc in hexanes) 15a
was obtained as a clear, colorless oil (57%): 1H NMR (CDCl3,
300 MHz) δ 5.65-5.56 (m, 1H), 5.09-5.01 (m, 3H), 4.84 (s,
1H), 4.14-4.06 (m, 4H), 3.90 (s, 2H), 2.73 (s, 1H), 2.63-2.59
(m, 4H), 1.18 (t, J ) 7.1 Hz, 6H); 13C NMR (CDCl3, 75 MHz)
δ 171.3, 144.3, 132.3, 119.4, 114.7, 65.6, 61.5, 57.5, 38.0, 35.8,
14.1; IR (neat, cm-1) 3544, 3080, 2983, 2937, 1738, 1644, 1446,
1418, 1368, 1046, 918; HRMS calcd for C14H22O5 (M+) 270.1469,
found 270.1467.
4,4-Dicar beth oxy-1-(h ydr oxym eth yl)cyclopen ten e (15b).
Cyclopentene 15b was obtained as a clear, colorless oil (97%)
under conditions analogous to the reaction producing 3b: 1H
NMR (CDCl3, 300 MHz) δ 5.45-5.43 (m, 1H), 4.18-4.09 (m,
6H), 2.98-2.95 (m, 4H), 2.46 (br s, 1H), 1.20 (t, J ) 7.1 Hz,
6H), 13C NMR (CDCl3, 75 MHz) δ 172.3, 141.6, 122.2, 61.7,
61.3, 59.2, 40.7, 40.5, 14.1; IR (neat, cm-1) 3462, 2982, 2871,
1732, 1446, 1392, 1368, 1257, 1184, 1072, 1017; HRMS calcd
for C12H18O5 (M+) 242.1148, found 242.1154.
4,4-Dicar beth oxy-2-isopr opyl-1,6-h eptadien e (12a). The
diester 12a was synthesized in a manner similar to that of 3a
using 2-(bromomethyl)-3-methyl-1-butene.31 Compound 12a
was obtained as a clear, colorless oil (33%): 1H NMR (CDCl3,
300 MHz) δ 5.69-5.58 (m, 1H), 5.08-5.01 (m, 2H), 4.86 (s,
1H), 4.70 (s, 1H), 4.18-4.08 (m, 4H), 2.69-2.62 (m, 4H), 2.03-
1.98 (m, 1H), 1.21 (t, J ) 7.1 Hz, 6H), 0.97 (d, J ) 6.8 Hz,
6H); 13C NMR (CDCl3, 75 MHz) δ 171.4, 151.1, 133.0, 119.0,
111.0, 61.4, 57.5, 37.3, 37.3, 37.0, 33.8, 22.1, 14.2; IR (neat,
cm-1) 3082, 2964, 2874, 1732, 1641, 1443, 1366, 1288, 1209,
1050; HRMS calcd for C16H27O4 (MH+) 283.1912, found
283.1909.
was prepared in
a manner similar to that of 3a using
2-(bromomethyl)acrylic acid. Compound 17a was obtained as
a pale yellow, colorless oil (1.02 g, 65%): 1H NMR (CDCl3, 300
MHz) δ 6.17 (s, 1H), 5.67-5.56 (m, 2H), 5.02-4.97 (m, 2H),
4.11-4.01 (m, 4H), 3.62 (s, 3H), 2.87 (s, 2H), 2.49 (d, J ) 7.3
Hz, 2H), 1.15 (t, J ) 7.2 Hz, 6H); 13C NMR (CDCl3, 75 MHz)
δ 170.5, 167.3, 135.9, 132.5, 129.3, 119.2, 61.3, 57.5, 51.8, 37.1,
33.6, 14.0; IR (neat, cm-1) 3080, 2983, 2908, 1732, 1632, 1445,
1368, 1155, 1053, 1008; HRMS calcd for C15H23O6 (MH+)
299.1482, found 299.1495.
1-Ca r bom eth oxy-4,4-d ica r beth oxycyclop en ten e (17b).
Cyclopentene 18b was obtained as a clear, colorless oil (89%)
under conditions analogous to the reaction producing 9b: 1H
NMR (CDCl3, 300 MHz) δ 6.56 (s, 1H), 4.14 (q, J ) 7.1 Hz,
4H), 3.67 (s, 3H), 3.20-3.19 (m, 2H), 3.13-3.12 (m, 2H), 1.20
(t, J ) 7.1 Hz, 6Hz); 13C NMR (CDCl3, 75 MHz) δ 171.4, 164.5,
139.9, 133.5, 61.9, 58.7, 51.7, 41.1, 39.5, 14.1; IR (neat, cm-1
)
4,4-Dica r beth oxy-1-isop r op ylcyclop en ten e (12b). To a
solution of catalyst 1 (16 mg, 0.02 mmol) in dry, degassed
methylene chloride (40 mL) was added diene 12a (113 mg, 0.4
mmol). After stirring at room temperature for 2 days the
reaction was concentrated and purified on silica gel (5% EtOAc
in hexanes) to yield the product 12b (100 mg, 98%) as a clear,
colorless oil: 1H NMR (CDCl3, 300 MHz) δ 5.16-5.14 (m, 1H),
4.20-4.12 (m, 4H), 2.94 (s, 2H), 2.92 (s, 2H), 2.30-2.24 (m,
1H), 1.21 (t, J ) 8.6 Hz, 6H), 1.00 (d, J ) 8.4 Hz, 6H); 13C
NMR (CDCl3, 75 MHz) δ 172.5, 148.2, 118.2, 61.5, 59.3, 41.3,
40.4, 29.6, 21.3, 14.2; IR (neat, cm-1) 3062, 2963, 1732, 1466,
1447, 1367, 1248, 1182, 1097, 1074; HRMS calcd for C14H22O4
(M+) 254.1519, found 254.1518.
2984, 1732, 1644, 1436, 1367, 1246, 1184, 1069, 1015; HRMS
calcd for C13H19O6 (MH+) 271.1180, found 271.1182.
2-(Acet oxym et h yl)-4,4-d ica r b et h oxy-1,6-h ep t a d ien e
(14a ). To a solution of 2-methylene-1,3-propanediol (5.0 g, 56.7
mmol) in CH2Cl2 (150 mL) at 0 °C was added Ac2O (5.8 g, 56.7
mmol) and NEt3 (8.6 g, 85.1 mmol). This solution was allowed
to warm to rt for 5 h and then quenched with water (75 mL)
and washed with NaHCO3 (saturated aqueous, 75 mL). Upon
concentration of the organic portion, a pale yellow oil was
isolated and the crude acetate was used without further
purification. To a solution of this 2-(acetoxymethyl)-3-propen-
1-ol (3.6 g, 27.5 mmol) in CH2Cl2 (60 mL) at 0 °C was added
PPh3 (10.8 g, 41.3 mmol) and CBr4 (13.7 g, 41.3 mmol). After
stirring for 40 min the solvent was removed and the red
viscous oil was eluted through a plug of silica gel with Et2O.
Concentration of the resulting solution gave a clear, colorless
oil, and this crude bromide was used without further purifica-
tion. The triester 14a was synthesized in a manner similar
to that of 3a using this 1-bromo-2-(acetoxymethyl)-2-propene.
Compound 14a was isolated as a clear, colorless oil (28%, 3
steps): 1H NMR (CDCl3, 300 MHz) δ 5.56-5.46 (m, 1H), 5.04-
4,4-Dicar beth oxy-2-ter t-bu tyl-1,6-h eptadien e (13a). The
diester 13a was synthesized in a manner similar to that of 3a
using 2-(bromomethyl)-3,3-dimethyl-1-butene.32 Compound
13a was obtained as a clear, colorless oil (75%): 1H NMR
(CDCl3, 300 MHz) δ 5.70-5.61 (m, 1H), 5.09-5.03 (m, 2H),
4.92 (s, 1H), 4.62 (s, 1H), 4.17 (q, J ) 7.2 Hz, 4H), 2.80 (d, J
) 7.5 Hz, 2H), 2.72 (s, 2H), 1.23 (t, J ) 7.1 Hz, 6H), 1.06 (s,
9H); 13C NMR (CDCl3, 75 MHz) δ 171.6, 152.2, 132.9, 118.9,
107.0, 61.4, 56.7, 36.8, 36.7, 32.8, 29.4, 14.2; IR (neat, cm-1
)

7318 J . Org. Chem., Vol. 62, No. 21, 1997
Kirkland and Grubbs
3080, 2970, 2873, 1732, 1639, 1466, 1445, 1365, 1298, 1220,
918; HRMS calcd for C17H29O4 (MH+) 297.2058, found 297.2066.
4,4-Dica r beth oxy-1-ter t-bu tylcyclop en ten e (13b). Cy-
clopentene 13b was obtained as a clear, colorless oil (96%)
under conditions analogous to the reaction producing 9b: 1H
NMR (CDCl3, 400 MHz) δ 5.16 (br s, 1H), 4.16 (q, J ) 7.0 Hz,
4H), 2.92 (s, 4H), 1.21 (t, J ) 7.0 Hz, 6H), 1.02 (s, 9H); 13C
NMR (CDCl3, 100 MHz) δ 172.3, 151.0, 117.5, 61.4, 59.6, 40.2,
39.8, 32.7, 28.9, 14.1; IR (neat, cm-1) 2964, 2870, 1732, 1464,
1392, 1365, 1249, 1185, 1062; HRMS calcd for C15H25O4 (MH+)
269.1747, found 269.1753.
5,5-Dicar beth oxy-3-m eth ylen e-1,7-octadien e (19a). The
diester 19a was synthesized in a manner similar to that of 3a
using 2-(bromomethyl)-1,3-butadiene.34-36 Compound 19a was
isolated as a clear, colorless oil (54%): 1H NMR (CDCl3, 300
MHz) δ 6.25-6.16 (m, 1H), 5.64-5.55 (m, 1H), 5.20-5.10 (m,
2H), 5.03-4.91 (m, 3H), 4.11-3.98 (m, 4H), 2.76 (s, 2H), 2.57
(d, J ) 7.2 Hz, 2H), 1.15 (t, J ) 6.9 Hz, 6H); 13C NMR (C6D6,
75 MHz) δ 170.7, 142.1, 139.5, 133.5, 118.91, 118.89, 113.8,
61.1, 57.6, 37.3, 34.0, 14.0; IR (neat, cm-1) 3085, 2982, 1732,
1641, 1595, 1446, 1367, 1296, 1207, 907; HRMS calcd for
C15H23O4 (MH+) 267.1607, found 267.1596.
2938, 1732, 1643, 1446, 1368, 1262, 1196, 1027; HRMS calcd
for C16H27O4 (MH+) 283.1911, found 283.1909.
6,6-Dica r beth oxy-1-m eth ylcycloh ep ten e (6b). Cyclo-
heptene 6b was obtained as a clear, colorless oil (96%) under
conditions analogous to the reaction producing 9b: 1H NMR
(CDCl3, 300 MHz) δ 5.55 (br s, 1H), 4.14 (q, J ) 7.5 Hz, 4H),
2.61 (s, 2H), 2.18-2.14 (m, 2H), 2.04-2.00 (m, 2H), 1.72 (s,
3H), 1.61-1.58 (m, 2H), 1.21 (t, J ) 7.1 Hz, 6H); 13C NMR
(CDCl3, 75 MHz) δ 172.0, 135.2, 127.7, 61.2, 55.7, 37.6, 36.9,
28.0, 26.8, 22.9, 14.2; IR (neat, cm-1) 2937, 2862, 1732, 1446,
1367, 1311, 1224, 1033, 857; HRMS calcd for C14H23O4 (MH+)
255.1601, found 255.1596.
2-Br om o-4,4-d ica r beth oxy-1,6-h ep ta d ien e (18a ). The
diester 18a was synthesized in a manner similar to that of 3a
using 2,3-dibromopropene. Compound 18a was obtained as a
clear, colorless oil (96%): 1H NMR (CDCl3, 300 MHz) δ 5.61-
5.50 (m, 3H), 5.04-5.01 (m, 2H), 4.15-4.07 (m, 4H), 3.05 (s,
2H), 2.67 (d, J ) 7.4 Hz, 2H), 1.17 (t, J ) 7.2 Hz, 6H); 13C
NMR (CDCl3, 75 MHz) δ 169.9, 132.1, 127.2, 122.0, 119.5, 61.5,
56.7, 42.8, 35.9, 14.0; IR (neat, cm-1) 3081, 2983, 2938, 1732,
1641, 1626, 1445, 1367, 1287, 1218, 1149, 1041; HRMS calcd
for C13H20O4Br (M+) 319.0545, found 319.0545.
5,5-Dica r beth oxy-3-m eth ylen ecycloxen e (19c). Cyclo-
hexene 19c was obtained as a clear, colorless oil (96%) under
conditions analogous to the reaction producing 3b: 1H NMR
(CDCl3, 300 MHz) δ 6.11 (d, J ) 9.8 Hz, 1H), 5.78-5.73 (m,
1H), 4.88 (br s, 2H), 4.19-4.08 (m, 4H), 2.82 (t, J ) 1.5 Hz,
2H), 2.65-2.63 (m, 2H), 1.19 (t, J ) 7.1 Hz, 6H); 13C NMR
(CDCl3, 75 MHz) δ 171.0, 139.2, 129.0, 126.6, 113.6, 61.6, 54.0,
36.0, 31.1, 14.1; IR (neat, cm-1) 3083, 2982, 1732, 1642, 1603,
1446, 1367, 1299, 1187, 1074, 1016; HRMS calcd for C13H18O4
(M+) 238.1206, found 238.1205.
N-Allyl-N-m eth a llylben za m id e (20a ). To a solution of
allyl amine (0.89 g, 15.5 mmol) in CH2Cl2 (50 mL) was added
benzoyl chloride (2.2 g, 15.5 mmol). After 7 h, the reaction
was quenched with water (30 mL) and washed with NH4Cl
(saturated aqueous, 30 mL). After concentration, a pale yellow
oil was isolated and the crude amide was used without further
purification. To a suspension of NaH (0.26 g, 10.9 mmol) in
DMF (35 mL) was added this N-allylbenzamide (1.6 g, 9.9
mmol). After stirring for 15 min, methallyl chloride (0.98 mL,
9.9 mmol) was added. Once the reaction had stirred for 2 h,
it was quenched with water (50 mL) and extracted with Et2O
(3 × 30 mL). After purification on silica gel (25% EtOAc in
hexanes), 20a was obtained as a clear, colorless oil (78%): 1H
NMR (CDCl3, 300 MHz, rt, not coalesced) δ 7.33-7.23 (m, 5H),
5.84-5.76, 5.64-5.55 (2m, 1H), 5.13-5.00 (m, 2H), 4.86-4.75
(m, 2H), 4.04 (s, 2H), 3.70-3.64 (m, 2H), 1.68, 1.48 (2s, 3H);
13C NMR (CDCl3, 75 MHz, rt, not coalesced) δ 171.6, 140.3,
140.0, 136.1, 132.9, 132.6, 129.3, 128.2, 126.3, 117.4, 112.1,
53.7, 50.2, 49.0, 46.8, 19.9; IR (neat, cm-1) 3648, 3496, 3082,
2977, 2918, 1634, 1578, 1495, 1293, 1263, 1152, 923; HRMS
calcd for C14H16NO (M+) 214.1230, found 214.1232.
Meth a llyl 1-P h en yla llyl Eth er (21a ). To a solution of
benzaldehyde (1.6 g, 14.9 mmol) in THF (100 mL) at 0 °C was
added vinylmagnesium bromide (1 M in THF, 15 mL). After
3 h, the reaction was quenched with water (100 mL) and
extracted with Et2O (3 × 75 mL). After concentration, a pale
yellow oil was isolated and the crude alcohol was used without
further purification. To a suspension of NaH (0.22 g, 9.10
mmol) in DMF (25 mL) was added this 1-phenyl-2-propen-1-
ol (1.11 g, 8.27 mmol). After this mixture had stirred for 15
min, methallyl chloride (0.90 mL, 9.10 mmol) was added. After
stirring for 2 h at room temperature, the reaction was
quenched with water (25 mL) and extracted with Et2O (3 ×
30 mL). After purification on silica gel (25% toluene in
hexanes), 21a was obtained as a clear, colorless oil (21%, two
steps): 1H NMR (CDCl3, 300 MHz) δ 7.36-7.28 (m, 5H), 6.00-
5.89 (m, 1H), 5.31-5.18 (m, 2H), 4.99 (s, 1H), 4.90 (s, 1H), 4.77
(d, J ) 6.6Hz, 1H), 3.89 (s, 2H), 1.75 (s, 3H); 13C NMR (CDCl3,
75 MHz) δ 142.4, 141.3, 139.1, 128.6, 127.7, 127.0, 116.2, 112.2,
81.9, 72.2, 19.8; IR (neat, cm-1) 3078, 3030, 2977, 2918, 2856,
1657, 1452, 1092, 1070, 991, 925, 900, 701; HRMS calcd for
C13H16O (M+) 188.1202, found 188.1201.
4-Meth yl-2-p h en yl-2,5-d ih yd r ofu r a n (21b). Dihydrofu-
ran 21b was obtained as a clear, colorless oil (98%) under
conditions analogous to the reaction producing 21b:56 1H NMR
(C6D6, 300 MHz) δ 7.27-7.24 (m, 2H), 7.17-7.03 (m, 3H),
5.76-5.74 (m, 1H), 5.16-5.14 (m, 1H), 4.49-4.41 (m, 2H), 1.31
(s, 3H); 13C NMR (CDCl3, 75 MHz) δ 142.8, 136.6, 128.6, 127.8,
126.5, 124.2, 88.6, 78.6, 12.4; IR (neat, cm-1) 3064, 3030, 2837,
2630, 1668, 1491, 1453, 1258, 1061, 970, 760, 699; HRMS calcd
for C11H11O (M-H+) 159.0806, found 159.0810.
Ack n ow led gm en t. The authors would like to thank
Dr. Soong-Hoon Kim for providing a sample of 19b for
comparison, Dr. Peter Schwab for providing alkylidene
1 and Dr. Osamu Fujimura and Mr. Delwin Elder for
providing alkylidene 2. We wish to thank Dr. Nathan
Dallesko and Dr. Peter Kondrat for providing mass
spectral data. This work was supported by the NIH.
N-Ben zoyl-3-m eth yl-3-p yr r olin e (20b). Pyrroline 20b
was obtained as a clear, colorless oil (97%) under conditions
analogous to the reaction producing 12b: 1H NMR (CDCl3,
300 MHz, rt, not coalesced) δ 7.46 (br s, 2H), 7.34 (br s, 3H),
5.45, 5.29 (2s, 1H), 4.36, 4.28 (2s, 2H), 4.10, 4.02 (2s, 2H), 1.76,
1.65 (2s, 3H); 13C NMR (CDCl3, 75 MHz, rt, not coalesced) δ
169.8, 136.8, 135.6, 134.8, 129.9, 128.4, 126.9, 119.6, 119.0,
59.1, 56.5, 56.3, 53.8, 14.34, 14.26; IR (neat, cm-1) 3545, 3062,
2914, 2858, 1674, 1634, 1576, 1418, 1334, 1226, 1149, 1025,
967; HRMS calcd for C12H13NO (M+) 187.0997, found 187.0997.
4,4-Dica r beth oxy-2-m eth yl-1,8-n on a d ien e (6a ). The di-
ester 6a was synthesized in a manner similar to that of 3a
using 1,1-dicarbethoxy-5-pentene. Compound 6a was isolated
as a clear, colorless oil (68%): 1H NMR (CDCl3, 300 MHz) δ
5.72-5.62 (m, 1H), 4.94-4.83 (m, 2H), 4.75 (s, 1H), 4.64 (s,
1H), 4.12-4.05 (m, 4H), 2.62 (s, 2H), 1.96 (q, J ) 7.1 Hz, 2H),
1.83-1.77 (m, 2H), 1.56 (s, 3H), 1.26-1.14 (m, 8H); 13C NMR
(CDCl3, 75 MHz) δ 171.6, 140.7, 138.1, 115.4, 114.9, 61.1, 56.8,
40.1, 33.8, 31.6, 23.5, 23.2, 14.0; IR (neat, cm-1) 3078, 2981,
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
5b, 6a ,b, 11-21a , 10-20b (24 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
J O970877P
(56) Kunishima, M.; Hioki, K.; Tani, S.; Kato, A. Tetrahedron Lett.
1994, 35, 7253-7254.