Concerted vs stepwise mechanisms in dehydro-Diels-Alder reactions

Article abstract of DOI:10.1021/jo201567d

The Diels-Alder reaction is not limited to 1,3-dienes. Many cycloadditions of enynes and a smaller number of examples with 1,3-diynes have been reported. These "dehydro"-Diels-Alder cycloadditions are one class of dehydropericyclic reactions which have lo

Full text of DOI:10.1021/jo201567d

Article
pubs.acs.org/joc
Concerted vs Stepwise Mechanisms in Dehydro-Diels−Alder
Reactions
Aida Ajaz, Alexander Z. Bradley, Richard C. Burrell, William Hoi Hong Li, Kimberly J. Daoust,
Laura Boddington Bovee, Kenneth J. DiRico, and Richard P. Johnson*
Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, United States
S
* Supporting Information
ABSTRACT: The Diels−Alder reaction is not limited to 1,3-
dienes. Many cycloadditions of enynes and a smaller number of
examples with 1,3-diynes have been reported. These “dehydro”-
Diels−Alder cycloadditions are one class of dehydropericyclic
reactions which have long been used to generate strained cyclic
allenes and other novel structures. CCSD(T)//M05-2X
computational results are reported for the cycloadditions of vinylacetylene and butadiyne with ethylene and acetylene.
Both concerted and stepwise diradical routes have been explored for each reaction, with location of relevant stationary points.
Relative to 1,3-dienes, replacement of one double bond by a triple bond adds 6−6.5 kcal/mol to the activation barrier; a
second triple bond adds 4.3−4.5 kcal/mol to the barrier. Product strain decreases the predicted exothermicity. In every case, a
concerted reaction is favored energetically. The difference between concerted and stepwise reactions is 5.2−6.6 kcal/mol
for enynes but diminishes to 0.5−2 kcal/mol for diynes. Experimental studies on intramolecular diyne + ene cycloadditions
show two distinct reaction pathways, providing evidence for competing concerted and stepwise mechanisms. Diyne + yne
cycloadditions connect with arynes and ethynyl-1,3-cyclobutadiene. This potential energy surface appears to be flat, with only a
minute advantage for a concerted process; many diyne cycloadditions or aryne cycloreversions will proceed by a stepwise
mechanism.
dynamics.33,46 In general, concerted reactions are believed to be
favored by only a few kcal/mol relative to their stepwise
counterparts, which proceed through diradical intermediates.
INTRODUCTION
■
The Diels−Alder cycloaddition is not limited to 1,3-dienes.
Cycloadditions of enynes have been known for over 100
Transition states for enyne cycloadditions (eqs 3 and 4) must
years1−3 with many recent reports of new examples.4−16 Similar
be asynchronous, even if concerted. For 1,3-diynes (eqs 5 and
[2 + 4] reactions of diynes have been described but still are
6), a symmetrical transition state structure is possible, but this
rare.17−21 “Dehydro”-Diels−Alder cycloadditions22 are one
requires substantial deformation of the linear diyne. We
class of dehydropericyclic reactions23 which are derived
recently reported that no concerted transition state exists for
conceptually by systematic removal of hydrogen atom pairs.
the similar [2 + 4] cycloaddition of o-benzyne to 1,3-
These novel processes have long been used to generate strained
butadiyne.47 This highly exothermic reaction is predicted to
cyclic allenes24−28 and other reactive molecules.
favor a stepwise [2 + 2] route. These considerations have led us
Scheme 1 illustrates the dehydropericyclic principle and
summarizes the six most fundamental Diels−Alder cyclo-
additions. Dehydropericyclic variations with an enyne or diyne
(eqs 3−6) lead to a reactive intermediate, either a strained cyclic
cumulene or, in the final example, o-benzyne. In earlier work,
to model both concerted and stepwise pathways for dehydro
variations on the Diels−Alder reactions.
Portions of these reaction surfaces have been described in
earlier computational investigations. We reported MP4SDTQ/
6-31G(d)//MP2/6-31G(d) computations on concerted mech-
anisms, predicting barriers of 30.8, 31.6, 35.8, and 35.5 kcal/mol
we reported intramolecular examples of each Diels−Alder
variation and used MP4//MP2 theory to predict energetics
for eqs 3−6, respectively.17,29 Ananikov48 and Lu49 later used
MP2 and DFT methods to study intramolecular enyne
cycloadditions. Bachrach has reported MP4//MP2 transition
states and energetics for addition of a phosphaenyne and
vinylacetylene to ethylene.50 All of these calculations supported
concerted mechanisms and, for hydrocarbons, yielded activation
barriers within a few kcal/mol of those cited above. Addition of
1,3-diynes to the SiSi bond appears to favor [2 + 2] products;
for concerted reactions.17,29 In the present study, we have
endeavored to provide more accurate energetics and mecha-
nisms for these dehydropericyclic variations on the Diels−Alder
cycloaddition.
The question of concerted vs stepwise mechanisms for the
parent Diels−Alder reaction has been the subject of much
debate,30−44 now convincingly resolved in favor of a concerted
mechanism for the simplest versions. Many cycloaddition
transition states are, however, significantly asynchronous,
depending on polarity and structure.45 The preferred
mechanism is a subtle question of structure and reaction
Received: July 27, 2011
Published: October 6, 2011
© 2011 American Chemical Society
9320
dx.doi.org/10.1021/jo201567d|J. Org. Chem. 2011, 76, 9320−9328

The Journal of Organic Chemistry
Article
Scheme 1. Diels−Alder and Dehydro-Diels−Alder Reactions
DFT computations support a stepwise mechanism.51,52 In
addition to our earlier study,17,29 several groups have viewed eq
6 in reverse, describing computations to model the endothermic
concerted cycloreversion of o-benzyne (11), a reaction of likely
importance in combustion chemistry as a mechanism for
benzene decomposition.53−55 Lower levels of theory (UHF or
B3LYP/6-31G*) predict a stepwise mechanism for benzyne
cycloreversion,55 but as in our initial study, the most recent
calculations favor a concerted process.53
Scheme 2. Selected Examples of Enyne−Ene Reactions
COMPUTATIONAL METHODOLOGY
■
All calculations were carried out with Gaussian 03 Revision
E.01,56 Gaussian 09, Revision B.01,57 Spartan 06, or Spartan
08.58 Structures were optimized and characterized by frequency
analysis at the M05-2X/6-311+G(d,p) level of theory,59−63
followed by single point (U)CCSD(T)/6-311+G(d,p) calcu-
lation. A “broken-symmetry” guess was used for open shell
singlet wave functions. For each transition state, we calculated
the intrinsic reaction coordinate (IRC) to verify connection to
reactants or product. Unscaled DFT zero point vibrational
energy (ZPVE) corrections have been applied to both DFT and
CCSD(T) energies. The M05-2X functional60 was chosen
because it has been shown to provide improved descriptions of
alkyne and cumulene relative energies.64 Benchmark computa-
tions at this same level of theory for the cycloaddition of
butadiene with ethylene and acetylene (eqs 1 and 2) gave
activation barriers of 24.8 and 25.7 kcal/mol, respectively.
These values agree very well with earlier predictions.65,66
reaction as a cycloaddition or a cycloreversion.29,68,69 Addi-
tional examples are cited in the recent review by Wessig and
Muller.22
̈
The results of our calculations on enyne−ene cycloadditions
are presented in Scheme 3, where energetics are summarized
relative to reactants. Figure 1 shows structures for stationary
points. The reaction leading to cyclic allene 8 is predicted to be
moderately exothermic, with a concerted barrier 6 kcal/mol
above diene + alkene cycloaddition at the same level of theory.
Two stepwise pathways are predicted to lie 6−7 kcal/mol above
concerted TS3. Potential diradical intermediates R1 and R2
represent shallow energy minima. Energetics of the two stepwise
routes are surprisingly similar. These results clearly favor a
concerted mechanism for the cycloaddition of vinylacetylene
and ethylene. The 26 kcal/mol diminished exothermicity,
relative to reaction of 1,3-butadiene, is attributed to the 32
kcal/mol of strain in cyclic allene 8. Structures for stationary
points agree well with expectation, with bond lengths for TS3
similar to other Diels−Alder reactions.70 TS2 and TS3 are
“early” transition states, consistent with their high exothermicity.
Enyne−Yne Cycloadditions. Cycloaddition of vinylace-
tylene with acetylene (eq 4) should give 1,2,4-cyclohexatriene
(9). This benzene isomer is a well-known reactive intermediate,
most commonly accessed by Hopf cyclization of dienynes71−73
and estimated to possess an allene strain energy of 34 kcal/
mol.24 Scheme 4 shows selected examples of this synthetically
important cycloaddition.29,74−76 Additional examples are
described in a recent review.22
RESULTS AND DISCUSSION
■
We began by optimizing reactants, products, and concerted
transition states with a closed shell M05-2X/6-311+G(d,p)
wave function, followed by single point CCSD(T)/6-311+G-
(d,p) calculation and correction with the DFT ZPVE. At the
levels of theory investigated, all concerted transition states were
found to be stable, relative to becoming open shell. Stepwise
mechanisms were next examined using open shell DFT
calculations. For eqs 3 and 4, addition to both ends of the
enyne was considered. We did not explore the full conforma-
tional space available for stepwise reactions but only modeled
geometries judged likely to lie along the reaction path and
connected by IRC calculations to the transition state structures.
In every case, the IRC showed a smooth connection between
products and reactants. A summary of results for each
cycloaddition in eqs 3−6 follows.
Scheme 5 and Figure 2 summarize CCSD(T)//DFT results
for the cycloaddition of vinylacetylene and acetylene. Stationary
point structures agree well with expectations. The reaction is
predictably more exothermic because of the higher energy
alkyne component and has a barrier to concerted reaction that
is slightly above vinylacetylene + ethylene. Two stepwise routes
through diradical intermediates R3 and R4 are 4−5 kcal/mol
higher in energy. We conclude that for the parent hydrocarbons
Enyne−Ene Cycloaddition. Enyne−ene cycloadditions
present an expedient route to 1,2-cyclohexadienes, which
have a chiral structure67 and an estimated strain energy of
ca. 32 kcal/mol.24,50 Several examples of cycloreversion have also
been reported. Scheme 2 presents selected examples of this
9321
dx.doi.org/10.1021/jo201567d|J. Org. Chem. 2011, 76, 9320−9328

The Journal of Organic Chemistry
Article
Scheme 3. CCSD(T)//M05-2X Energetics (kcal/mol) of Enyne−Ene Cycloadditions
Figure 1. Stationary points in enyne−ene cycloadditions.
Scheme 4. Selected Examples of Enyne−Yne Cycloadditions
vinylacetylene and acetylene cycloaddition favors a concerted
reaction pathway.
shown that 9 can proceed to benzene by sequential hydrogen
shifts, passing through a carbene intermediate.71−73
Kinetic data for the gas-phase pyrolysis of a mixture of
vinylacetylene + acetylene to give benzene have been reported
by two groups.77,78 The activation energy for formation of
benzene is reported to be 30.1 ± 1.3 kcal/mol.78 If we assume
cycloaddition to be the rate-determining step en route to
benzene, this agrees well with our predicted value. We have
previously noted that cyclic allene 9 should have a very low
C−H dissociation energy to give phenyl radical, which can then
give benzene by hydrogen abstraction.79 Other studies have
Diyne−Ene Cycloaddition. Diyne−ene cycloadditions,
which should generate an intermediate 1,2,3-cyclohexatriene
(10), are the rarest in this ensemble. The sole example we are
aware of was reported by our group in 1996.29 We have shown
that cyclic cumulene 10 is easily generated in solution80 and has a
predicted strain energy of 50 kcal/mol.24 We reported earlier that
flash vacuum pyrolysis of 12 (Scheme 6) gives predominantly 15,
which is presumed to arise from ring-opening of 13, as well as one
unidentified isomer and smaller amounts of indene and indan.
9322
dx.doi.org/10.1021/jo201567d|J. Org. Chem. 2011, 76, 9320−9328

The Journal of Organic Chemistry
Article
Further studies in our group have now shown that the unidentified
product is 17, whose structure was proven by independent
synthesis. The formation of 17 supports a competitive stepwise
route passing through diradical 14 and then cyclobutene 16, which
undergoes electrocyclic ring-opening. Similar pyrolysis of
homologue 18 at slightly lower temperature resulted in 20 and
21, whose structures were proven by independent synthesis. In
this case, the stepwise reaction product 21 dominates.
spectroscopic evidence for cyclobutenes (23) rather than a cyclic
cumulene (22). Computations supported a stepwise mechanism.51
Computational results for the cycloaddition of butadiyne
with ethylene are summarized in Scheme 7 and Figure 3. We
Scheme 7. CCSD(T)//M05-2X Energetics (kcal/mol) of
Diyne−Ene Cycloadditions
One additional example of diyne + ene reaction has been
reported. In a recent study of surface chemistry, reaction of butadiyne
with Si(100), Ge(100), or Si(111) surfaces (Scheme 6) led to
Scheme 5. CCSD(T)//M05-2X Energetics (kcal/mol) of
Enyne−Yne Cycloaddition
Figure 3. Stationary points in diyne−ene cycloadditions.
find a symmetrical concerted pathway (TS13) that is only
slightly lower than the barrier (TS11) to formation of diradical
R5. In this case, the concerted and stepwise routes are
predicted to have different outcomes. Concerted reaction can
lead directly to cyclic 1,2,3-butatriene 10. Diradical R5 might
also close to 10, but the lower energy and more exothermic
path leads to cyclobutene 24.
Figure 2. Stationary points in enyne−yne cycloaddition.
Scheme 6. Diyne−Ene Cycloadditions
9323
dx.doi.org/10.1021/jo201567d|J. Org. Chem. 2011, 76, 9320−9328

The Journal of Organic Chemistry
Article
Cyclic cumulenes such as 10, 13, and 19 should have low
barriers to electrocyclic ring-opening. For 10, we predict a
CCSD(T)//DFT barrier of 24.9 kcal/mol for ring-opening to
1,5-hexadien-3-yne and a reaction exothermicity of 36.3 kcal/
mol. The reverse cyclization would thus have a barrier of 61.2
kcal/mol, which indicates that 1,2,3-cyclohexatrienes are
unlikely to be accessible by dienyne thermolysis.
Computational results for the cycloaddition of butadiyne
with acetylene are summarized in Scheme 9 and Figure 4. Both
B3LYP and M05-2X functionals, in combination with the 6-
311+G(d,p) basis set, support the existence of a closed-shell
Scheme 9. CCSD(T)//M05-2X Energetics (kcal/mol) of
Diyne−Yne Cycloadditions
For diyne + ene cycloadditions, the concordance between
experiment and theory is striking. Our computations (Scheme 7)
show that the stepwise and concerted mechanisms diverge,
leading either to cyclic cumulene 10 or cyclobutene 24, both of
which should undergo facile secondary reaction. Experimental
results for 12 and 18 show products (Scheme 6) that are
similarly consistent with two divergent pathways.
Diyne−Yne Cycloaddition. This type of cycloaddition or
cycloreversion is of growing mechanistic importance. We showed
in 1997 that flash vacuum pyrolysis of triyne 25 yields products
consistent with intramolecular cycloaddition to produce benzyne
26.17 Beginning in the same year, Ueda and co-workers have
reported many related examples of intramolecular diyne + yne
cycloaddition.18−20,81−89 As one example, cyclization of 27 is
reported to occur under surprisingly mild conditions to yield 29,
believed to come from trapping benzyne intermediate 28. Another
recent example was provided by Tsui and Sterenberg, who showed
that metal templated polyyne 30 undergoes very facile cyclization,
in which the presumed benzyne intermediate 31 is trapped to
afford 32. Several groups have studied the cycloreversion of
benzyne, a species known to arise from sequential loss of hydrogen
atoms from benzene and phenyl radical (33). This process is
believed to play a role in combustion chemistry of aromatic
compounds.53−55
In principle, repetitive aryne + diyne cycloaddition might
provide an efficient route to acynes or acenes. There appear to
be no clear examples of this reaction, however, and we recently
reported computation showing that cycloaddition of o-benzyne
with 1,3-butadiyne should favor a stepwise [2 + 2] route.47
Figure 4. Stationary points in diyne−yne cycloadditions.
Scheme 8. Diyne−Yne Reactions
9324
dx.doi.org/10.1021/jo201567d|J. Org. Chem. 2011, 76, 9320−9328

The Journal of Organic Chemistry
Article
concerted transition state (TS15). Our CCSD(T)//DFT
computations show that the concerted and stepwise routes to
11 have very similar energetics, with only a 0.5 kcal/mol
advantage for concerted reaction.
potential energy surface appears to be flat with only a minute
advantage for a concerted process; many diyne cycloadditions
or aryne cycloreversions will likely proceed by a stepwise
mechanism.
The results in Scheme 9 also suggest an interesting
connection between o-benzyne and ethynyl-1,3-cyclobutadiene
(34). Diradical R6 has a slightly lower barrier for closure to 34,
but this may be reversible at high temperature. This is a
complex and remarkably flat potential energy surface, with four
transition states separated by less than 3 kcal/mol, but spanning
a wide range of molecular geometries. Doering has described
this type of potential surface as a caldera.90,91
EXPERIMENTAL SECTION
Warning. Although we experienced no difficulties with these
compounds, unsubstituted diynes such as 12 and 18 are potentially
explosive and should be handled with care.
■
1-Nonen-6,8-diyne (12). To a solution of 1,4-bis(trimethylsilyl)-
1,3-butadiyne (2.00 g, 10.3 mmol) in THF (20 mL) at −78 °C was
added methyllithium/lithium bromide (6.90 mL, 10.3 mmol). The
mixture was warmed to ambient temperature, stirred for 3.5 h, and
then cooled to −78 °C, and 5-bromo-1-pentene (1.84 g, 12.3 mmol)
in HMPA (20 mL) was added dropwise. After 20 h at ambient
temperature, the reaction was quenched with water and extracted with
pentane (4 × 25 mL). Extracts were washed with water, dried over
MgSO4, and concentrated to give 2.92 g of colorless oil. This was
dissolved in methanol (10 mL), and anhydrous K2CO3 (779 mg, 5.63
mmol) was added. After 17 h at ambient temperature, the mixture was
quenched with water (25 mL) and extracted with pentane (3 × 25
mL). Extracts were dried over MgSO4 and concentrated. Column
chromatography (silica gel, pentane) yielded 1-nonen-6,8-diyne (12)
as a clear oil (595 mg, 48.9% overall). Further purification of 12 was
carried out by preparative gas chromatography (5% SE-30, 130 °C). lH
NMR (CDCl3): δ 5.71−5.83 (ddt, 1 H, J = 17.0, 10.2, 6.6 Hz), 5.03−
5.10 (ddt, 1 H, J = 17.0, 2.0, 1.6 Hz), 4.99−5.03 (ddt, 1 H, J = 10.2,
2.0, 1.3 Hz), 2.26−2.32 (td, 2 H, J = 7.1, 1.3 Hz), 2.13−2.21 (m, 2 H),
1.98 (t, 1 H, J = 1.3 Hz), 1.65 (quintet, 2 H, J = 7.1 Hz). 13C NMR: δ
137.6, 115.8, 78.3, 68.7, 65.2, 64.8, 32.9, 27.3, 18.6. HRMS m/z calcd
for C9H9 (M−H) 117.0704, found 117.0698.
SUMMARY AND CONCLUSIONS
■
The energetics of concerted Diels−Alder reactions are
summarized in Table 1. We compare here the cycloadditions
Table 1. CCSD(T)/6-311+G(d,p)//M052X/6-311+G(d,p) +
ZPVE Energetics (kcal/mol) of Concerted Diels−Alder
Reactions
1-Decene-7,9-diyne (18). The procedure above was carried out
with 1,4-bis(trimethylsilyl)-l,3-butadiyne (1.00 g, 5.15 mmol), MeLi/
LiBr (3.5 mL of a 1.5 M solution in ether, 5.20 mmol), and 6-bromo-l-
hexene (857 mg, 5.26 mmol) to give 1.26 g of oil. Reaction as above
with anhydrous K2CO3 (883 mg, 6.39 mmol), and purification
afforded 1-decene-7,9-diyne (18, 239 mg, 52% overall) as a clear
liquid. Further purification of 18 was carried out by preparative GC
1
(5% SE-30, 110 °C). H NMR (CDCl3): δ 5.80 (ddt, lH, J = 17.1,
10.2, 6.7 Hz), 5.02 (dq, 1H, J = 17.1, 1.7 Hz), 4.97 (dp, 1H, J = 10.2,
1.1 Hz), 2.28 (td, 2H, J = 6.8, 0.9 Hz), 2.07 (q, 2H, J = 6.9. Hz), 1.96
(t, 1H, J = 1.1 Hz), 1.53 (m, 4H). l3C NMR (CDCl3): δ 138.5, 115.0,
78.5, 68.6, 64.9, 64.7, 33.3, 28.1, 27.6, 19.1. HRMS m/z calcd for
C10Hl1 (M−H) 131.0860, found 131.0865.
of butadiene, vinylacetylene, and butadiyne with ethylene and
acetylene. Our results show that replacement of one double
bond with a triple bond adds 6 or 6.5 kcal/mol to the activation
barrier; a second triple bond adds 4.5 or 4.3 kcal/mol to the
cycloaddition barrier. Reaction exothermicity is decreased in
proportion to product strain.24 A notable exception is eq 6,
which generates the aromatic product o-benzyne. Predicted
barriers to concerted reaction agree surprisingly well with
earlier MP4//MP2 results.17,29,50
Dehydropericyclic reactions provide common routes to
reactive intermediates.23 For the Diels−Alder cycloaddition,
dehydro versions have been known for over a century, with
many new examples reported in recent years.4−22 Our
calculations support concerted mechanisms for cycloadditions
of vinylacetylene with ethylene and ethyne to produce highly
strained cyclic allenes as products. In these cases, stepwise
reaction is 5.2−6.6 kcal/mol higher in energy, based on the first
step. Potential diradical intermediates lie in shallow energy
minima. For cycloadditions of 1,3-butadiyne, we are still able to
locate concerted transition states; however, the advantage of
synchrony is small. With diyne + ene cycloaddition, our
experimental studies and computational models for the parent
structures both support well-defined stepwise and concerted
reaction pathways. Diyne + yne cycloadditions connect with
arynes and ethynyl-1,3-cyclobutadiene as products. This
Pyrolysis of l-Nonen-6,8-diyne. 1-Nonen-6,8-diyne (12, 188
mg) was passed during 30 min through a horizontal quartz tube
packed with quartz chips, maintained at 600 °C and 0.07 Torr. The
product was collected in a cold trap (−78 °C), then dissolved in 5 mL
of pentane, filtered through a plug of silica, and concentrated to give
162 mg of oil. Capillary GC indicated conversion to four major
products. Components were isolated by preparative scale gas
chromatography (120 °C) and identified by comparison of spectral
data with those of authentic samples: 1-nonen-6,8-diyne (12, 2.9%,
retention time 7.8 min), 1-(1-methylene-prop-2-ynyl)-cyclopentene
(17, 20.2%, 8.3 min), indan (3.8%, 10.3 min), 1-(3-buten-1-yn-1-yl)-
cyclopentene (15, 64.5%, 10.6 min), indene (2.4%, 11.6 min), three
unidentified minor products (total 6.2%).
Pyrolysis of l-Decen-7,9-diyne. l-Decen-7,9-diyne (18, 65.5 mg)
was passed through a horizontal quartz tube packed with quartz chips,
maintained at 560 °C and 0.025 Torr. The product was collected in a
cold trap (−78 °C) to give 45 mg of a yellow oil. Capillary GC (110 °C)
indicated a 29% conversion. Products were isolated by preparative GC
(15% SE-30, 100 °C) and identified by comparison to authentic
samples: 1-(1-methylene-prop-2-ynyl)-cyclohexene (21, 57%) and 1-(3-
buten-1-yn-1-yl)-cyclohexene (20, 43%).
1-(3-Buten-1-yn-1-yl)-cyclopentene (15). This substance and
the alcohol precursor below have been prepared earlier by a different
synthetic route.92 To a solution of vinyl bromide (2.91 g, 27.2 mmol) in
diethylamine (30 mL) at 0 °C was added tetrakis(triphenylphosphine)
9325
dx.doi.org/10.1021/jo201567d|J. Org. Chem. 2011, 76, 9320−9328

The Journal of Organic Chemistry
Article
1
palladium(0) (l.00 g, 0.87 mmol) and copper(I) iodide (329.9 mg, l.73
mmol). The mixture was warmed to ambient temperature, and 1-
ethynylcyclopentanol (2.00 g, 18.0 mmol) was added dropwise. After
6.5 h at ambient temperature, the reaction was quenched with water (25
mL) and extracted with diethyl ether. Extracts were washed with 5%
HCl (3 × 15 mL), saturated NaHCO3 (20 mL), water (20 mL), dried
over MgSO4, and concentrated under reduced pressure. Column
chromatography (silica gel, pentane/diethyl ether 5:1) yielded 1-(3-
buten-1-yn-1-yl)-cyclopentanol as a brown oil (1.67 g, 12.3 mmol,
l-cyclopent-l-enyl-3-trimethylsilanylpropynone as a clear oil. H NMR
(CDCl3): δ 7.09−7.11 (m, 1H), 2.53−2.63 (m, 4H), 1.96−2.03 (m,
2H), 0.25 (s, 9H). 13C NMR (CDCl3): δ 175.7, 151.3, 147.3, 101.3,
96.9, 34.2, 29.9, 23.4, −0.4. IR: 2175, 1620 cm−1.
n-BuLi (2.5 mL, 2.5 M in THF, 6.3 mmol) was added in dropwise
to an ice-cooled solution of methyltriphenylphosphonium bromide
(3.7 g, 6.2 mmol) in THF (20 mL). After 45 min, the above-prepared
ketone (1.0 g, 5.2 mmol) in THF was added dropwise. The reaction
was stirred overnight, then quenched with water, extracted with diethyl
ether (3 × 100 mL), dried over MgSO4, and concentrated. Without
further purification, the product was dissolved in methanol (30 mL),
and K2CO3 (1.1 g) was added. After stirring overnight and quenching
with water, the product was isolated by pentane extraction. Purification
by chromatography over silica gel gave 1-(1-methylene-2-propyn-1-yl)-
cyclopentene (17) as a colorless oil (0.40 g, 65%). 1H NMR (CDCl3):
δ 6.16 (s, 1H), 5.51 (s, 1H), 5.35 (s, 1H), 2.95 (s, 1H), 2.44−2.49 (m,
4H), 1.95−1.99 (m, 2H). 13C NMR (CDCl3, 90.56 MHz, center peak
of CDCl3 set to 77.17 ppm): δ 141.8, 132.6, 126.8, 121.3, 82.5, 76.9,
33.3, 31.7, 23.7. IR (neat): 3310, 2980, 2930, 2840 cm−1. HRMS m/z
calcd for C9H10 (M+) 118.0783, found 118.0777.
1
68.3%). H NMR (CDCl3): δ 5.77−5.87 (dd,1H, J = 17.4, 11.0 Hz),
5.57−5.64 (dd,1H, J = 17.4, 2.1 Hz), 5.43−5.47 (dd, 1H, J = 11.0 Hz),
2.51 (s,1H), 1.93−1.98 (m, 4H), 1.70−1.89 (m, 2H). 13C NMR: δ
126.7, 116.9, 93.7, 81.7, 74.7, 42.3, 23.4.
A mixture of the above-prepared alcohol (624 mg, 4.58 mmol) and
p-toluenesulfonic acid (1.74 g, 9.17 mmol) in THF (30 mL) was
refluxed for 15 h. Water was added, and the mixture was extracted with
pentane (3 × 25 mL). Extracts were washed with saturated Na2CO3,
dried over MgSO4, and concentrated. Column chromatography (silica
gel, pentane) yielded 15 as a clear oil (446 mg, 84.2%). Further
1
purification of 15 was carried out by preparative GC (120 °C). H
1-(1-Methylene-2-propyn-1-yl)-cyclohexene (21). The proce-
dure above was repeated with cyclohexen-1-carboxaldehyde to obtain
l-cyclohex-l-enyl-3-trimethylsilanyl-prop-2-yn-l-ol (95% yield) as a
NMR (CDCl3): δ 6.08 (quintet, 1 H, J = 2.1 Hz), 5.90−5.98 (dd, 1 H,
J = 17.4, 11.0 Hz), 5.59−5.65 (dd, 1H, J = 17.4 Hz), 5.44−5.49 (dd, 1
H, J = 11.0 Hz), 2.41−2.50 (m, 4 H), 1.92 (quintet, 2 H, J = 7.3 Hz).
13C NMR: δ 138.3, 126.2, 124.4, 117.3, 89.2, 87.4, 36.3, 33.4, 23.3.
HRMS m/z calcd for C9H10 118.0783, found 118.0786.
1
clear liquid; bp 73 °C (0.04 Torr). H NMR (CDCl3): δ 5.91 (s,
1H), 4.71(d, 4.9 Hz, 1H), 2.16−2.19 (m, 1H), 2.06−2.08 (m, 4H),
1.65−168 (m, 2H), 1.58−1.59 (m, 2H), 0.20 (s, 9H); 13C NMR δ
136.7, 125.1, 104.8, 90.6, 67.2, 25.0, 24.1, 22.5, 22.2, −0.2. IR (neat):
3360, 2940 cm−1. Oxidation as above with CrO3/pyridine yielded 1-
cyclohex-1-enyl-3-trimethylsilanylpropynone (80% yield) as a clear oil;
bp 62 °C (0.04 Torr). 1H NMR (CDCl3): δ 7.26−7.38 (m,1H), 2.31−
2.34 (m, 2H), 2.21−2.24 (m, 2H), 1.62−1.64 (m, 4H), 0.24 (s, 9H).
13C NMR (CDCl3): δ 179.5, 148.2, 140.6, 100.5, 97.8, 26.8, 22.5, 21.8,
21.4, −0.6. Wittig olefination and deprotection of the ketone, as
described above, followed by column chromatography, yielded the
1-(3-Buten-1-yn-1-yl)-cyclohexene (20). This substance and
the alcohol precursor below have been prepared earlier by a different
route.93 The procedure above was carried out with vinyl bromide and
1-ethynyl-1-cyclohexanol to give 1-(3-buten-1-yn-1-yl)-cyclohexanol
1
(98% yield). H NMR (CDCl3): δ 5.78 (dd, 1H, J = 17.5, 11.0 Hz),
5.56 (dd, 1H, J = 17.5, 2.2 Hz), 5.40 (dd,1H, J = 11.0, 2.2 Hz), 2.71 (s,
1H), 1.87 (m, 2H), 1.46−1.66 (m,7H), 1.21 (m, 1H). 13C NMR
(CDCl3): δ 126.8, 116.9, 93.7, 82.9, 68.9, 39.9, 25.2, 23.3.
Phosphorus tribromide (1.9 g, 7.0 mmol) was added dropwise to a
cooled (0 °C) solution of the alcohol (528 mg, 3.5 mmol) in pyridine
(20 mL). A heavy white precipitate formed immediately. The dark red
mixture was warmed to ambient temperature, stirred for 4 h, and then
was poured over cracked ice and extracted with pentane (5 × 20 mL).
Extracts were washed with 5% HCl, then water, dried over MgSO4,
and concentrated. Column chromatography (silica gel, pentane)
yielded 1-(3-buten-1-yn-1-yl)-cyclohexene (20) as a clear liquid (221
mg, 48%). Further purification by preparative GC (column C, 110 °C)
1
desired product 21 as a colorless oil (58% yield for the final step). H
NMR (CDCl3): δ 6.43 (s, 1H), 5.47 (s, 1H), 5.44 (s, 1H), 3.00 (s,
1H), 2.16−2.19 (m, 4H), 1.68−171 (m, 2H), 1.54−1.60 (m,2H). l3C
NMR (CDCl3): δ 134.0, 131.5, 130.0, 118.8, 77.9, 77.2, 26.0, 24.8,
22.8, 22.2. IR (neat): 3400, 2940, 2830 cm−1. HRMS m/z calcd for
C10H12 (M+) 132.0939, found 132.0941.
ASSOCIATED CONTENT
■
1
was performed. H NMR (CDCl3): δ 6.10 (septet, 1H), 5.89 (dd,1H,
S
* Supporting Information
J = 17.5, 11.1 Hz), 5.56 (dd, 1H, J = 17.5, 2.2 Hz), 5.39 (dd, 1H, J =
11.1, 2.2 Hz), 2.11 (m, 4H), 1.60 (m,4H). 13C NMR (CDCl3): δ
135.2, 125.7, 120.7, 117.5, 92.0, 85.7, 29.2, 25.8, 22.4, 21.6; HRMS m/
z calcd for C10H12 (M+) 132.0939, found 132.0938.
General experimental procedures, summary table of total
energies and Cartesian coordinates for stationary points,
NMR spectra for the pyrolytic chemistry of 12 and 18,
complete Gaussian references. This material is available free of
charge via the Internet at http://pubs.acs.org.
1-(1-Methylene-2-propyn-1-yl)-cyclopentene (17). To a sol-
ution of trimethylsilylacetylene (6.1 g, 63 mmol) in THF (100 mL) at
−78 °C was added dropwise a 2.5 M solution of n-BuLi in THF (25
mL, 63 mmol). After 30 min, cyclopenten-1-carboxaldehyde (3.0 g, 31
mmol) in THF was added, and the mixture was warmed to ambient
temperature and stirred 12 h. The product was isolated by quenching
with saturated aqueous ammonium chloride and extraction with
diethyl ether (3 × 100 mL). Extracts washed with brine, dried over
Na2SO4, and concentrated to a yellow oil. Vacuum distillation at (0.03
Torr, 63 °C) afforded the intermediate alcohol l-cyclopent-l-enyl-3-
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: Richard.Johnson@unh.edu.
ACKNOWLEDGMENTS
■
1
trimethylsilanyl-prop-2-yn-l-ol (5.9 g, 88%) as a clear liquid. H NMR
We are grateful for generous support from the National Science
Foundation (CHE-0910826 and CHE-9616388).
(CDCl3): δ 5.81 (s, lH), 4.94 (s, 1H), 2.35−2.46 (m, 4H), 1.88−1.98
(m, 2H), 0.18 (s, 9H); 13C NMR (CDCl3) δ 143.2, 128.3, 104.8, 90.0,
62.2, 32.5, 31.6, 23.6, 0.06. IR (neat): 3320 cm−1
.
REFERENCES
■
Solid CrO3 (17 g, 17 mmol) was added in portions into a
mechanically stirred mixture of CH2Cl2 (100 mL) and pyridine (27
mL). After 90 min, the above-prepared alcohol (5.0 g, 28 mmol) in
CH2Cl2 was added slowly. After 4 h, the organic layer was decanted,
and the remaining solid was washed with CH2Cl2 (2 × 50 mL).
Organic fractions were combined, washed with 1 M NaOH (3 × 50
mL), water (50 mL), 5% HCl (3 × 50 mL), and NaHCO3 (75 mL),
then dried over Na2SO4, and concentrated to give a dark oil. Vacuum
distillation (0.015 Torr, 62 °C) afforded 3.4 g (59% yield) of
(1) Michael, A.; Bucher, J. E. Ber. 1895, 28, 2511−2512.
(2) Bucher, J. E. J. Am. Chem. Soc. 1908, 30, 1244−1264.
(3) Butz, L. W.; Gaddis, A. M.; Butz, E. W. J.; Davis, R. E. J. Org.
Chem. 1940, 5, 379−388.
(4) Eghbali, N.; Eddy, J.; Anastas, P. T. J. Org. Chem. 2008, 73,
6932−6935.
(5) Liu, B.; Wang, H.; Xie, H.; Zeng, B.; Chen, J.; Tao, J.; Wen, T. B.;
Cao, Z.; Xia, H. Angew. Chem., Int. Ed. 2009, 48, 5430−5434.
9326
dx.doi.org/10.1021/jo201567d|J. Org. Chem. 2011, 76, 9320−9328

The Journal of Organic Chemistry
Article
(6) Nieto-Oberhuber, C.; Perez-Galan, P.; Herrero-Gomez, E.;
Lauterbach, T.; Rodriguez, C.; Lopez, S.; Bour, C.; Rosellon, A.;
Cardenas, D. J.; Echavarren, A. M. J. Am. Chem. Soc. 2008, 130, 269−
279.
(7) Martinez-Esperon, M. F.; Rodriguez, D.; Castedo, L.; Saa, C.
Tetrahedron 2008, 64, 3674−3686.
(8) Barluenga, J.; Fernandez-Rodriguez Manuel, A.; Garcia-Garcia,
P.; Aguilar, E. J. Am. Chem. Soc. 2008, 130, 2764−2765.
(9) Wessig, P.; Mueller, G.; Pick, C.; Matthes, A. Synthesis 2007,
464−477.
(10) Sato, K.; Menggenbateer.; Kubota, T.; Asao, N. Tetrahedron
2007, 64, 787−796.
(42) Storer, J. W.; Raimondi, L.; Houk, K. N. J. Am. Chem. Soc. 1994,
116, 9675−9683.
(43) Houk, K. N.; Li, Y.; Storer, J.; Raimondi, L.; Beno, B. J. Chem.
Soc., Faraday Trans. 1994, 90, 1599−1604.
(44) Houk, K. N.; Lin, Y. T.; Brown, F. K. J. Am. Chem. Soc. 1986,
108, 554−556.
(45) Alajarin, M.; Cabrera, J.; Pastor, A.; Sanchez-Andrada, P.;
Bautista, D. J. Org. Chem. 2008, 73, 963−973.
(46) Thomas, J. B.; Waas, J. R.; Harmata, M.; Singleton, D. A. J. Am.
Chem. Soc. 2008, 130, 14544−14555.
(47) Cahill, K. J.; Ajaz, A.; Johnson, R. P. Aust. J. Chem. 2010, 63,
1007−1012.
(48) Ananikov, V. P. J. Phys. Org. Chem. 2001, 14, 109−121.
(49) Lu, Y.-X.; Yu, Q.-S.; Zou, J.-W. THEOCHEM 2005, 731, 207−
211.
(50) Bachrach, S. M. J. Org. Chem. 1997, 62, 5801−5803.
(51) Lu, X.; Zhu, M.; Wang, X.; Zhang, Q. J. Phys. Chem. B 2004,
108, 4478−4484.
(52) Huang, H. G.; Lu, X.; Xiang, C. L.; Teo, T. L.; Lai, Y. H.; Xu, G.
Q. Chem. Phys. Lett. 2004, 398, 11−14.
(11) Dai, M.; Sarlah, D.; Yu, M.; Danishefsky, S. J.; Jones, G. O.;
Houk, K. N. J. Am. Chem. Soc. 2007, 129, 645−657.
(12) Gonzalez-Cantalapiedra, E.; de Frutos, O.; Atienza, C.; Mateo,
C.; Echavarren, A. M. Eur. J. Org. Chem. 2006, 1430−1443.
(13) Nieto-Oberhuber, C.; Lopez, S.; Echavarren, A. M. J. Am. Chem.
Soc. 2005, 127, 6178−6179.
(14) Martinez-Esperon, M. F.; Rodriguez, D.; Castedo, L.; Saa, C.
Org. Lett. 2005, 7, 2213−2216.
(53) Zhang, X.; Maccarone, A. T.; Nimlos, M. R.; Kato, S.; Bierbaum,
V. M.; Ellison, G. B.; Ruscic, B.; Simmonett, A. C.; Allen, W. D.;
Schaefer, H. F. III J. Chem. Phys. 2007, 126, 044312/044311−044312/
044320.
(15) Hayes, M. E.; Shinokubo, H.; Danheiser, R. L. Org. Lett. 2005,
7, 3917−3920.
(16) Rodriguez, D.; Martinez-Esperon Maria, F.; Navarro-Vazquez,
A.; Castedo, L.; Dominguez, D.; Saa, C. J. Org. Chem. 2004, 69, 3842−
3848.
(54) Moskaleva, L. V.; Madden, L. K.; Lin, M. C. Phys. Chem. Chem.
Phys. 1999, 1, 3967−3972.
(17) Bradley, A. Z.; Johnson, R. P. J. Am. Chem. Soc. 1997, 119,
(55) Deng, W.-Q.; Han, K.-L.; Zhan, J.-P.; He, G.-Z. Chem. Phys. Lett.
1998, 288, 33−36.
9917−9918.
(18) Kawano, T.; Suehiro, M.; Ueda, I. Chem. Lett. 2006, 35, 58−59.
(19) Miyawaki, K.; Kawano, T.; Ueda, I. Tetrahedron Lett. 1998, 39,
6923−6926.
(56) Frisch, M. J.;et al. Gaussian 03, Revision E.01; Gaussian Inc.:
Wallingford, CT, 2004.
(57) Frisch, M. J.;et al. Gaussian 09, Revision B.01; Gaussian Inc.:
Wallingford, CT, 2010.
(58) Spartan 06 and Spartan 08; Wavefunction Inc.: Irvine, CA.
(59) Zhao, Y.; Truhlar Donald, G. J. Phys. Chem. A 2008, 112, 1095−
1099.
(20) Miyawaki, K.; Suzuki, R.; Kawano, T.; Ueda, I. Tetrahedron Lett.
1997, 38, 3943−3946.
(21) Tsui, J. A.; Sterenberg, B. T. Organometallics 2009, 28, 4906−
4908.
(22) Wessig, P.; Mueller, G. Chem. Rev. 2008, 108, 2051−2063.
(23) Johnson, R. P. J. Phys. Org. Chem. 2010, 23, 283−292.
(24) Daoust, K. J.; Hernandez, S. M.; Konrad, K. M.; Mackie, I. D.;
Winstanley, J. Jr.; Johnson, R. P. J. Org. Chem. 2006, 71, 5708−5714.
(25) Christl, M. Mod. Allene Chem. 2004, 1, 243−357.
(26) Balci, M.; Taskesenligil, Y. Adv. Strained Interesting Org. Mol.
2000, 8, 43−81.
(27) Johnson, R. P. Chem. Rev. 1989, 89, 1111−1124.
(28) Strained Hydrocarbons: Beyond the van’t Hoff and Le Bel
Hypothesis; Johnson, R. P., Konrad, K. M., Eds.; Wiley: New York,
2009.
(29) Burrell, R. C.; Daoust, K. J.; Bradley, A. Z.; DiRico, K. J.;
Johnson, R. P. J. Am. Chem. Soc. 1996, 118, 4218−4219.
(30) Domingo, L. R.; Chamorro, E.; Perez, P. Org. Biomol. Chem.
2010, 8, 5495−5504.
(31) Hirao, H. J. Comput. Chem. 2008, 29, 1399−1407.
(32) Sakai, S.; Okumura, T. J. Mol. Struct.: THEOCHEM 2004, 685,
89−95.
(33) Kraka, E.; Wu, A.; Cremer, D. J. Phys. Chem. A 2003, 107,
9008−9021.
(60) Zhao, Y.; Truhlar, D. G. Acc. Chem. Res. 2008, 41, 157−167.
(61) Wodrich, M. D.; Corminboeuf, C.; Schreiner, P. R.; Fokin,
A. A.; Von Schleyer, P. Org. Lett. 2007, 9, 1851−1854.
(62) Zhao, Y.; Truhlar, D. G. Org. Lett. 2006, 8, 5753−5755.
(63) Zhao, Y.; Schultz, N. E.; Truhlar, D. G. J. Chem. Theory Comput.
2006, 2, 364−382.
(64) Zhao, Y.; Truhlar, D. G. J. Phys. Chem. A 2006, 110, 10478−
10486.
(65) Ess, D. H.; Houk, K. N. J. Phys. Chem. A 2005, 109, 9542−9553.
(66) Guner, V.; Khuong, K. S.; Leach, A. G.; Lee, P. S.; Bartberger,
M. D.; Houk, K. N. J. Phys. Chem. A 2003, 107, 11445−11459.
(67) Angus, R. O. Jr.; Schmidt, M. W.; Johnson, R. P. J. Am. Chem.
Soc. 1985, 107, 532−537.
(68) Butz, L. W.; Joshel, L. M. J. Am. Chem. Soc. 1942, 64, 1311−
1313.
(69) Runge, A.; Sander, W. Tetrahedron Lett. 1986, 27, 5835−5838.
(70) Houk, K. N.; Li, Y.; Evanseck, J. D. Angew. Chem., Int. Ed. 1992,
31, 682−708.
(71) Prall, M.; Kruger, A.; Schreiner, P. R.; Hopf, H. Chem.Eur. J.
2001, 7, 4386−4394.
(34) Isobe, H.; Takano, Y.; Kitagawa, Y.; Kawakami, T.; Yamanaka,
S.; Yamaguchi, K.; Houk, K. N. J. Phys. Chem. A 2003, 107, 682−694.
(35) Sakai, S. J. Phys. Chem. A 2000, 104, 922−927.
(36) Bradley, A. Z.; Kociolek, M. G.; Johnson, R. P. J. Org. Chem.
2000, 65, 7134−7138.
(37) Telan, L. A.; Firestone, R. A. Tetrahedron 1999, 55, 14269−
14280.
(38) Diau, E. W. G.; De Feyter, S.; Zewail, A. H. Chem. Phys. Lett.
(72) Roth, W. R.; Hopf, H.; Horn, C. Chem. Ber. 1994, 127, 1781−
1795.
(73) Hopf, H.; Musso, H. Angew. Chem., Int. Ed. 1969, 8, 680.
(74) Wills, M. S. B.; Danheiser, R. L. J. Am. Chem. Soc. 1998, 120,
9378−9379.
(75) Danheiser, R. L.; Gould, A. E.; de la Pradilla, R. F.; Helgason, A.
L. J. Org. Chem. 1994, 59, 5514−5515.
(76) Rodriguez, D.; Martinez-Esperon, M. F.; Navarro-Vazquez, A.;
Castedo, L.; Dominguez, D.; Saa, C. J. Org. Chem. 2004, 69, 3842−
3848.
1999, 304, 134−144.
(39) Houk, K. N.; Beno, B. R.; Nendel, M.; Black, K.; Yoo, H. Y.;
Wilsey, S.; Lee, J. THEOCHEM 1997, 398−399, 169−179.
(40) Firestone, R. A. Tetrahedron 1996, 52, 14459−14468.
(41) Houk, K. N.; Gonzalez, J.; Li, Y. Acc. Chem. Res. 1995, 28,
81−90.
(77) Colket, M. B. III Symp. (Int.) Combust., [Proc.] 1988, 21st, 851−
864.
(78) Chanmugathas, C.; Heicklen, J. Int. J. Chem. Kinet. 1986, 18,
701−718.
9327
dx.doi.org/10.1021/jo201567d|J. Org. Chem. 2011, 76, 9320−9328

The Journal of Organic Chemistry
Article
(79) Mackie, I. D.; Johnson, R. P. J. Org. Chem. 2009, 74, 499−503.
(80) Shakespeare, W. C.; Johnson, R. P. J. Am. Chem. Soc. 1990, 112,
8578−8579.
(81) Torikai, K.; Otsuka, Y.; Nishimura, M.; Sumida, M.; Kawai, T.;
Sekiguchi, K.; Ueda, I. Biorg. Med. Chem. 2008, 16, 5441−5451.
(82) Kawano, T.; Inai, H.; Miyawaki, K.; Ueda, I. Bull. Chem. Soc. Jpn.
2006, 79, 944−949.
(83) Kawano, T.; Inai, H.; Miyawaki, K.; Ueda, I. Tetrahedron Lett.
2005, 46, 1233−1236.
(84) Ueda, M.; Tomita, I. Polym. Bull. (Heidelberg, Ger.) 2004, 51,
359−364.
(85) Miyawaki, K.; Ueno, F.; Ueda, I. Heterocycles 2001, 54, 887−
900.
(86) Ueda, I.; Miyawaki, K.; Sugane, T.; Sakurai, Y.; Wada, Y.; Futai,
M. Pharmazie 2000, 55, 192−195.
(87) Miyawaki, K.; Kawano, T.; Ueda, I. Tetrahedron Lett. 2000, 41,
1447−1451.
(88) Miyawaki, K.; Kawano, T.; Ueda, I. Polycyclic Aromat. Compd.
2000, 19, 133−154.
(89) Ueda, I.; Sakurai, Y.; Kawano, T.; Wada, Y.; Futai, M.
Tetrahedron Lett. 1999, 40, 319−322.
(90) von Doering, W.; Ekmanis, J. L.; Belfield, K. D.; Klaerner, F. G.;
Krawczyk, B. J. Am. Chem. Soc. 2001, 123, 5532−5541.
(91) Klarner, F.-G.; Jones, M.; Magid, R. M. Acc. Chem. Res. 2008,
̇
̇
42, 169−181.
(92) Nazarov, I. N.; Burmistrova, M. S. Izv. Akad. Nauk SSSR, Ser.
Khim. 1947, 51−62.
(93) Nazarov, I. N.; Pinkina, L. N. Izv. Akad. Nauk SSSR, Ser. Khim.
1946, 633−646.
9328
dx.doi.org/10.1021/jo201567d|J. Org. Chem. 2011, 76, 9320−9328