Cyclopropyl alkynes as mechanistic probes to distinguish between vinyl radical and ionic intermediates

Article abstract of DOI:10.1021/jo047797n

(Chemical Equation Presented) The reactions of (trans-2-phenylcyclopropyl) ethyne, 1a, (trans,trans-2-methoxy-3-phenylcyclopropyl)-ethyne, 1b, and (trans,trans-2-methoxy-1-methyl-3-phenylcyclopropyl)ethyne, 1c, with either aqueous sulfuric acid or tris(trimethylsilyl)silane (or tributyltin hydride) and AIBN have been investigated. Protonation and addition of the silyl (or stannyl) radical occurred at the terminal position of the alkyne giving an α-cyclopropyl-substituted vinyl cation or radical, respectively. Under both reaction conditions, 1a yielded products derived from ring opening toward the phenyl substituent. Alkynes 1b and 1c, however, gave different products depending on whether radical or cationic conditions were used. When radical conditions were employed, products derived from regioselective ring opening toward the phenyl substituent were obtained. In contrast, when cationic conditions were employed, products derived from selective ring opening toward the methoxy substituent were isolated. The corresponding α-cyclopropyl- substituted vinyllithium derivatives were also synthesized and were found to be stable toward rearrangement. An estimate of the rate constants for ring opening of the α-cyclopropylvinyl cations was also made: values of 10 ¹⁰-10¹² s^-1 were found for the vinyl cations derived from protonation of the terminal carbon of alkynes 1a-c. Based on these results, cyclopropyl alkynes 1a-c can be classified as hypersensitive mechanistic probes for the detection of vinyl radical or cationic intermediates generated adjacent to the cyclopropyl ring and, in the case of 1b and 1c, the distinction between a radical or cationic intermediate is possible.

Full text of DOI:10.1021/jo047797n

Cyclopropyl Alkynes as Mechanistic Probes To Distinguish
between Vinyl Radical and Ionic Intermediates
Stephen E. Gottschling, Tina N. Grant, Kaarina K. Milnes, Michael C. Jennings, and
Kim M. Baines*
Department of Chemistry, University of Western Ontario, London, Ontario, Canada N6A 5B7
kbaines2@uwo.ca
Received December 16, 2004
The reactions of (trans-2-phenylcyclopropyl)ethyne, 1a, (trans,trans-2-methoxy-3-phenylcyclopropyl)-
ethyne, 1b, and (trans,trans-2-methoxy-1-methyl-3-phenylcyclopropyl)ethyne, 1c, with either
aqueous sulfuric acid or tris(trimethylsilyl)silane (or tributyltin hydride) and AIBN have been
investigated. Protonation and addition of the silyl (or stannyl) radical occurred at the terminal
position of the alkyne giving an R-cyclopropyl-substituted vinyl cation or radical, respectively. Under
both reaction conditions, 1a yielded products derived from ring opening toward the phenyl
substituent. Alkynes 1b and 1c, however, gave different products depending on whether radical or
cationic conditions were used. When radical conditions were employed, products derived from
regioselective ring opening toward the phenyl substituent were obtained. In contrast, when cationic
conditions were employed, products derived from selective ring opening toward the methoxy
substituent were isolated. The corresponding R-cyclopropyl-substituted vinyllithium derivatives
were also synthesized and were found to be stable toward rearrangement. An estimate of the rate
constants for ring opening of the R-cyclopropylvinyl cations was also made: values of 1010-1012 s-1
were found for the vinyl cations derived from protonation of the terminal carbon of alkynes 1a-c.
Based on these results, cyclopropyl alkynes 1a-c can be classified as hypersensitive mechanistic
probes for the detection of vinyl radical or cationic intermediates generated adjacent to the
cyclopropyl ring and, in the case of 1b and 1c, the distinction between a radical or cationic
intermediate is possible.
Introduction
the reactivity of R-cyclopropylvinyl and the isomeric
homoallenyl radicals.4 Simple derivatives of the radicals
The rapid ring-opening rearrangement of cyclopropy-
lcarbinyl radicals is the cornerstone of many effective
radical clocks,1 mechanistic probes,2 and diverse synthetic
methodologies.3 Despite the versatility of the cyclopro-
pylcarbinyl radical rearrangement, relatively little is
known about the reactivity of the analogous R-cyclopro-
pylvinyl radicals. Crandall et al. were the first to examine
(2) For examples, see: (a) Flemmig, B.; Kretzschmar, I.; Friend, C.
M.; Hoffmann, R. J. Phys. Chem. A 2004, 108, 2972. (b) Tong, X.;
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* To whom correspondence should be addressed.
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Org. Chem. 1994, 59, 3969. (d) Caldwell, R. A.; Zhou, L. J. Am. Chem.
Soc. 1994, 116, 2271. (e) Engel, P. S.; Lowe, K. L. Tetrahedron Lett.
1994, 35, 2267. (f) Newcomb, M. Tetrahedron 1993, 49, 1151. (g) Adam,
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M. J. Am. Chem. Soc. 1991, 113, 1730. (i) Campredon, M.; Kanabus-
Kaminska, J. M.; Griller, D. J. Org. Chem. 1988, 53, 5393. (j)
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10.1021/jo047797n CCC: $30.25 © 2005 American Chemical Society
Published on Web 03/04/2005
2686
J. Org. Chem. 2005, 70, 2686-2695

Cyclopropyl Alkynes as Mechanistic Probes
SCHEME 2
were generated independently by reaction of the ap-
propriate iodides with tributyltin hydride under various
conditions. The interconversion between the R-cyclopro-
pylvinyl and the homoallenyl radical was confirmed by
the formation of the same products regardless of the
starting iodide (Scheme 1). The results suggested that
SCHEME 1
for rearrangement of the cyclopropylcarbinyl radical is
larger than that of the vinyl analogue.
More recently, Mainetti et al. examined the reactivity
of R-cyclopropylvinyl radicals derived from the intra-
molecular addition of a primary radical, generated by
reaction of a (bromomethyl)dimethylsilyl ether with
tributyltin hydride onto a cyclopropyl-substituted alkyne
(Scheme 3).6 When the R-cyclopropylvinyl radical was
SCHEME 3
the rate constants for the isomerizations are smaller than
those between the unsubstituted cyclopropylcarbinyl and
homoallyl radicals.
Back et al. studied the free-radical selenosulfonation
of cyclopropylacetylene and various vinylcyclopropanes.5
Cyclopropylacetylene was photolyzed in the presence of
Se-phenyl p-toluenesulfonate yielding compounds 2 and
3. The formation of the observed products was proposed
to involve the initial generation of an R-cyclopropylvinyl
radical from the regioselective addition of the ArSO2
radical to the triple bond. The vinyl radical can then
either be trapped directly by the PhSe radical or can
rearrange to the homoallenyl radical before trapping
(Scheme 2). When the analogous vinylcyclopropanes were
subjected to the same reaction conditions, only products
derived from trapping of the ring-opened homoallyl
radical were obtained suggesting that the rate constant
generated in the absence of a nearby π-bond, rearrange-
ment of the radical to the corresponding allene occurred.
However, when the reaction was carried out using a
derivative containing a tethered alkene, radical cycliza-
tion occurred in preference to ring opening (Scheme 4).
(3) For examples, see: (a) Ruedi, G.; Hansen, H.-J. Tetrahedron Lett.
2004, 45, 5143. (b) Cai, Y.; Roberts, B. P. Tetrahedron Lett. 2003, 44,
4645. (c) Bernard, A. M.; Cadoni, E.; Frongia, A.; Piras, P. P.; Secci, F.
Org. Lett. 2002, 4, 2565. (d) Takekawa, Y.; Shishido, K. J. Org. Chem.
2001, 6, 8490. (e) Ogawa, A.; Ogawa, I.; Sonoda, N. J. Org. Chem. 2000,
65, 7682. (f) Takekawa, Y.; Shishido, K. Tetrahedron Lett. 1999, 40,
6817. (g) Lee, P. H.; Lee, B.; Lee, J.; Park, S. K. Tetrahedron Lett. 1999,
40, 3427. (h) Kantorowski, E. J.; Borhan, B.; Nazarian, S.; Kurth, M.
J. Tetrahedron Lett. 1998, 39, 2483. (i) Fagnoni, M.; Schmoldt, P.;
Kirschberg, T.; Mattay, J. Tetrahedron 1998, 54, 6427. (j) Ziegler, F.
E.; Petersen, A. K. Tetrahedron Lett. 1996, 37, 809. (k) Tsunoi, S.; Ryu,
I.; Muraoka, H.; Tanaka, M.; Komatsu, M.; Sonoda, N. Tetrahedron
Lett. 1996, 37, 6729. (l) Boto, A.; Betancor, C.; Suarez, E. Tetrahedron
Lett. 1994, 35, 5509. (m) Batey, R. A.; Harling, J. D.; Motherwell, W.
B. Tetrahedron 1992, 48, 8031. (n) Clive, D. L.; Daigneault, S. J. Org.
Chem. 1991, 56, 3801. (o) Wong, H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip,
Y.-C.; Tanko, J.; Hudlicky, T. Chem. Rev. 1989, 89, 165. (p) Harling,
J. D.; Motherwell, W. B. J. Chem. Soc., Chem. Commun. 1988, 1380.
(q) Feldman, K. S.; Romanelli, A. L.; Ruckle, R. E., Jr.; Miller, R. F. J.
Am. Chem. Soc. 1988, 110, 3300. (r) Trost, B.; Lee, D. C. J. Am. Chem.
Soc. 1988, 110, 6556. (s) Moiseenkov, A. M.; Czeskis, B. A. Collect.
Czech. Chem. Commun. 1986, 51, 1316. (t) Mariano, P. S.; Bay, E. J.
Org. Chem. 1980, 45, 1763.
SCHEME 4
(4) Crandall, J. K.; Tindell, G. L.; Manmade, A. Tetrahedron Lett.
1982, 23, 3769.
(5) Back, T. G.; Mualidharan, K. R. J. Org. Chem. 1989, 54, 121.
(6) Mainetti, E.; Fensterbank, L.; Malacria, M. Synlett 2002, 6, 923.
J. Org. Chem, Vol. 70, No. 7, 2005 2687

Gottschling et al.
These results provide an upper limit for the rate constant
for ring opening of the R-cyclopropylvinyl radical.7
We have recently examined the reactivity of the
1-(trans-2-phenylcyclopropyl)ethen-1-yl radical, gener-
ated by photolysis of the corresponding vinyl iodide in
the presence of tributyltin hydride (Scheme 5).8 Under
effectively use this rearrangement as the basis of a
mechanistic probe to detect the formation of vinyl radi-
cals. Since the ring opening of R-cyclopropylvinyl cations
to the homoallenyl derivatives and the reverse reaction
are well-known,11 it is necessary to include substituents
on the cyclopropyl framework of the probe to enable the
discrimination between radical and cationic intermedi-
ates. Thus, we now report on the synthesis and reactivity
of (trans-2-phenylcyclopropyl)ethyne, 1a, (trans,trans-2-
methoxy-3-phenylcyclopropyl)ethyne, 1b, and (trans,trans-
2-methoxy-1-methyl-3-phenylcyclopropyl)ethyne, 1c. For
completeness, we have also examined the reactivity of
the R-cyclopropylvinyl anion, as modeled by the lithium
derivative. Furthermore, during the course of these
studies, we were able to estimate rate constants for the
ring opening of the R-cyclopropylvinyl cations.
SCHEME 5
our conditions, we found clean rearrangement of the
radical to the allene; only traces of the unrearranged
alkene were detected. Furthermore, we estimated, for the
first time, the rate constant for the ring-opening rear-
rangement of the radical. As suggested by the early
studies, the rate constant, at (1.6 ( 0.2) × 1010 s-1, is
smaller than that of the analogous carbinyl system (3 ×
1011 s-1)9 by an order of magnitude.
Results and Discussion
Alkynes 1a,12 1b, and 1c were synthesized according
to Scheme 7. Aldehydes 4a,b were prepared by following
Cations often undergo the same rearrangements as
their radical counterparts. This has led to the develop-
ment of cyclopropylcarbinyl-based mechanistic probes
which are capable of distinguishing between a radical and
a cationic intermediate by the judicious placement of
appropriate substituents.10 One strategy, developed by
Newcomb and co-workers, incorporates an alkoxy sub-
stituent at the 3-position of the cyclopropyl ring.9,10b
When a cation is formed adjacent to the cyclopropane
ring, products derived from regioselective ring opening
toward the methoxy group are obtained, whereas when
a radical is generated, products are derived from regi-
oselective ring opening toward the phenyl substituent
(Scheme 6). Thus, by analyzing the structure of the
SCHEME 7
the literature procedures,9,12 and aldehyde 4c was pre-
pared by a similar procedure starting with the reaction
of â-methoxystyrene and ethyl 2-diazopropionate. Since
aldehyde 4c quantitatively rearranges to dihydrofuran
6 (Scheme 8) in less than 24 h under ambient conditions,
SCHEME 6
SCHEME 8
it was used immediately following preparation. Dibro-
moolefins 5a-c were prepared from aldehydes 4a-c via
a Corey-Fuchs reaction. The relative stereochemistry of
5c was confirmed by X-ray crystallography. Dibromoole-
fin 5b isomerizes to cyclopentenone 7 within two weeks
when stored under ambient conditions (Scheme 9). In
light of this instability, compound 5b was stored at -20
°C and used within 24 h of preparation.
products, one can make conclusions regarding the type
of intermediates formed during the course of the reaction.
We are interested in the development of a mechanistic
probe for the detection of vinylic intermediates and
propose to use cyclopropyl alkynes as precursors.8 The
rate constant for the rearrangement of the 1-(trans-2-
phenylcyclopropyl)ethen-1-yl radical is large enough to
(11) (a) Alem, K. V.; Lodder, G.; Zuilhof, H. J. Phys. Chem. A 2002,
106, 10681. (b) Salcedo, R.; Olvera, C. THEOCHEM 1999, 460, 221.
(c) Brennenstuhl, W.; Hanack, M. Tetrahedron Lett. 1984, 25, 3437.
(d) Seihl, H. U. J. Chem. Soc., Chem. Commun. 1984, 10, 635. (e)
Apeloig, Y.; Schleyer, P. V. R.; Pople, J. A. J. Org. Chem. 1977, 18,
3004. (f) Santelli, M.; Bertrand, M. Tetrahedron 1974, 30, 243. (g)
Bergman, R. G.; Sherrod, S. A. J. Am. Chem. Soc. 1971, 93, 1925. (h)
Bergman, R. G.; Kelsey, D. R. J. Am. Chem. Soc. 1971, 93, 1953. (i)
Nishimura, A.; Ohta, M.; Kato, H. Bull. Chem. Soc. Jpn. 1970, 43,
1530. (j) Sharrod, S.; Bergman, R. G. J. Am. Chem. Soc. 1969, 91, 2115.
(k) Hanack, M.; Ha¨ffner, J. Tetrahedron Lett. 1964, 32, 2191.
(12) Charette, A. B.; Giroux, A. J. Org. Chem. 1996, 61, 8718.
(7) The rate constant for cyclization of the 1,5-hexadien-1-yl radical
was reported to be 3.2 × 108 s-1: Beckwith, A. L. J.; O’Shea, D. M.
Tetrahedron Lett. 1986, 27, 4525.
(8) Milnes, K. K.; Gottschling, S. E.; Baines, K. M. Org. Biomol.
Chem. 2004, 2, 3530.
(9) Le Tadic-Biadatti, M.-H.; Newcomb, M. J. Chem. Soc., Perkin
Trans. 2 1996, 1467.
(10) (a) Tian, F.; Battiste, M.-A.; Dolbier, W. R., Jr. Org. Lett. 1999,
1, 193. (b) Newcomb, M.; Chestney, D. L. J. Am. Chem. Soc. 1994,
116, 9753.
2688 J. Org. Chem., Vol. 70, No. 7, 2005

Cyclopropyl Alkynes as Mechanistic Probes
SCHEME 9
observed between the signals at 2.94 and 2.79 ppm in
the 1H dimension and the signals at 138.6 and 129.7 ppm,
assigned to the ipso and ortho phenyl carbons, respec-
tively. Similar results were obtained for 8a and 8c.
The formation of 8a-c can easily be explained. The
generated silyl (or stannyl) radical adds regioselectively
to the terminal end of the alkyne forming an R-cyclo-
propylvinyl radical. The R-cyclopropylvinyl radical
then rearranges to give the benzyl radical, followed
by abstraction of a hydrogen atom yielding 8a-c. The
regioselective addition of the tris(trimethylsilyl)silyl
radical to the terminal end of an alkyne has previously
been reported.14 There was no evidence (by 1H NMR
spectroscopy) for the formation of products derived from
ring opening toward the methoxy substituent or from
direct abstraction of a hydrogen by the putative vinyl
radical.
Dibromoolefins 5a-c were converted to the desired
alkynes by the addition of 2 equiv of BuLi. Although
compound 1a can typically be prepared very cleanly
rendering further purification unnecessary, minor im-
purities were usually present in the crude reaction
mixtures of 1b,c, and thus, silica gel column chromatog-
raphy was utilized to purify the alkynes. Alkyne 1c
continued to be contaminated with minor amounts of
(trans,trans-2-methoxy-1-methyl-3-phenylcyclopropyl)-
ethene (6% by GC analysis) even after chromatography.
Alkyne 1c is relatively stable but does undergo a slow
decomposition under ambient conditions (12% decompo-
sition after 7 months as determined by GC analysis). The
major products of decomposition were identified as ben-
zaldehyde and 5,5-dimethoxy-4-phenylpenta-1,2-diene.
Thermolysis of 1a or 1b in the presence of tris-
(trimethylsilyl)silane and a catalytic amount of AIBN
yielded a single compound (8a or b, respectively, Scheme
10), whereas thermolysis of 1c in the presence of tribu-
Hydrolysis of 1a in aqueous acidic THF yielded allene
9 (Scheme 11). The structure of 9 was clearly established
SCHEME 11
SCHEME 10
1
by H, 13C, gCOSY, gHSQC, and gHMBC NMR and IR
spectroscopy and mass spectrometry. Most notably, a
correlation in the 13C-1H gHMBC NMR spectrum of 9
was observed between the triplet (1H) at 4.77 ppm in the
1H dimension and the signals at 125.7 and 143.4 ppm in
the 13C dimension, assigned to the ortho and ipso phenyl
carbons, respectively. The chemical shift and multiplicity
of the 1H signal and the observed correlations to the
phenyl clearly places the hydroxyl and the phenyl sub-
stituents on the same carbon and adjacent to a methylene
group. Furthermore, a correlation was observed between
tyltin hydride and a catalytic amount of AIBN yielded a
1
the pseudo triplet of triplets at 2.46 ppm (2H) in the H
mixture of diastereomers (57:43, 8c). All products were
dimension, assigned to the methylene group and the
signal at 209.2 ppm in the 13C dimension assigned to the
central allenic carbon. These correlations are completely
consistent with the assigned structure. The allene is
likely formed by protonation of the alkyne at the terminal
end to give the R-cyclopropylvinyl cation. Ring-opening
rearrangement toward the phenyl group and subsequent
hydration would give the observed product 9. (trans-2-
Phenylcyclopropyl)ethanone15 was also observed in the
1H NMR spectrum of the crude product, indicating that
hydration of the vinyl cation competes with ring opening
(9/ethanone ) 10.7:1).
1
readily identified by H and 13C NMR spectroscopy and
mass spectrometry. A strong absorption at ∼1930 cm-1
in the IR spectrum of all products as well as a signal at
∼210 ppm in the 13C NMR spectra are consistent with
the presence of an allene moiety. The regiochemistry of
8a-c was established using 1H, 13C, gCOSY, gHSQC, and
1
gHMBC NMR spectroscopy. For example, the H NMR
spectrum of 8b contains two doublets of doublets at 2.94
(J ) 7.6, 13.6 Hz) and 2.79 ppm (J ) 5.6, 13.6 Hz); the
coupling constant of 13.6 Hz as well as the observation
of a correlation in the 13C-1H gHSQC NMR spectrum
between both of these signals and the signal at 42.6 ppm
In contrast, hydrolysis of 1b cleanly afforded a 2:1
1
establishes that the two Hs giving rise to these signals
mixture of 2-phenylcyclopent-2-enone,16 10, and E-2-
are geminal to one other. The chemical shifts of these
1
two H signals (2.94 and 2.79 ppm) are consistent with
(13) The chemical shifts for AH and B/CH2 in (Me3Si)3SiCHdCd
CHCAH(X)CB/CH2Y were calculated using the ACD Inc, I-Lab service.
For XdOMe and YdPh, the chemical shifts were calculated to be 4.14,
2.93, and 2.78 ppm, respectively. For comparison, the chemical shifts
in the regioisomer: XdPh and YdOMe were calculated to be 3.95, 3.94
and 3.77 ppm, respectively.
(14) Kopping, B.; Chatgilialoglu, C.; Zehnder, M.; Giese, B. J. Org.
Chem. 1992, 57, 3994.
(15) Solladie´-Cavallo, A.; Isarno, T. Tetrahedron Lett. 1999, 40, 1579.
(16) Kerr, W. J.; McLaughlin, M.; Pauson, P. L.; Robertson, S. M.
J. Organomet. Chem. 2001, 630, 104.
the presence of a geminal phenyl and a vicinal alkoxy
substituent. These chemical shifts are not consistent with
the regioisomer in which the methoxy and phenyl groups
are interchanged.13 A multiplet at 3.95 ppm (1H) was also
1
observed in the H NMR spectrum of 8b. The chemical
shift is consistent with a 1H geminal to an alkoxy group
and vicinal to an sp2 hybridized carbon.13 In agreement
with the assigned regiochemistry, a correlation was
J. Org. Chem, Vol. 70, No. 7, 2005 2689

Gottschling et al.
phenylpenta-2,4-dienal, 11 (91% recovered yield; Scheme
12). The E configuration of 11 was confirmed by NOESY
oxy-1-methyl-3-phenylcyclopropyl)ethene which contami-
nate alkyne 1c.
Clearly, the presence of the methoxy substituent has
a profound influence on the regiochemistry of the ring-
opening reaction of the vinyl cation produced by proto-
nation of the cyclopropyl alkynes. In the absence of the
methoxy substituent, the R-cyclopropylvinyl cation will
undergo ring opening toward the phenyl substituent, as
in the case of 1a. However, if a methoxy substituent is
present on the ring as in the case of 1b and 1c,
regioselective ring opening toward the methoxy substitu-
ent is observed.
SCHEME 12
The reactivity of the R-cyclopropylvinyl anion was
examined using the corresponding vinyllithium as a
model. Vinyllithium species are readily synthesized by
transmetalation of vinylstannanes with alkyllithium
reagents.19 It was, therefore, envisioned that an R-cyclo-
propylvinyllithium species could be generated from the
corresponding R-cyclopropylvinylstannane. BuLi was
added to a solution of 1-(trans,trans-2-methoxy-3-phe-
nylcyclopropyl)-1-tributylstannylethene,8 14, under vary-
ing conditions (Table 1, Scheme 14). When BuLi was
analysis; a correlation was observed between the alde-
hydic proton and the â-vinylic proton. Apparently, pro-
tonation at the terminal position of the alkyne generates
an R-cyclopropylvinyl cation, which undergoes regiose-
lective ring opening to give the methoxonium ion followed
by addition of water to give the hemiacetal. Hydrolysis
of the hemiacetal would yield the corresponding homoal-
lenic aldehyde which, under the reaction conditions, is
converted to a mixture of 10 and 11.
SCHEME 14
Hydrolysis of 1c under similar conditions yielded a
mixture of 3-methyl-2-phenylcyclopent-2-enone,17 12,
2-methyl-3-phenylcyclopent-2-enone,17 13, in a 80:14
ratio, respectively (Scheme 13). Again, formation of the
SCHEME 13
added to a solution of 14 in THF at -78 °C or at room
temperature (entries 1 and 2), starting material was
recovered in high yield. The addition of the coordinating
cosolvent, TMEDA (Entries 3 and 4), had no effect on
the reaction; starting material was recovered in high
yield even after 17 h of reflux. Attempts to form the
vinyllithium by using the noncoordinating, nonpolar
solvent hexanes were also unsuccessful. When t-BuLi was
used as the reagent, starting material was again recov-
ered in good yield (entries 6 and 7). Beavers and Wilson20
have reported that the addition of BuLi to vinylcyclopro-
pane dissolved in THF and TMEDA resulted in depro-
tonation at several positions on the cyclopropyl ring and
the vinyl substituent. To determine the extent of depro-
tonation (if any) of 14, a portion of one of the reactions
was quenched with D2O (entry 1). 1H NMR spectroscopic
analysis of the recovered 14 showed no decrease in the
intensity of any signals indicating no significant deute-
rium incorporation.
isomeric cyclopentenones 12 and 13 is easily understood
in terms of initial protonation of the alkynyl moiety to
give an R-cyclopropylvinyl cation. In this case, direct
hydration of the vinyl cation effectively competes with
ring opening. Hydration of the cation would yield the
corresponding ketone which could undergo an acid-
catalyzed ring opening to eventually yield the aldehyde.
Finally, an acid-catalyzed aldol condensation followed by
double-bond isomerization would give 13. Alternatively,
ring opening of the vinyl cation would result in the
formation of an allenic oxonium species. Hydrolysis and
double-bond isomerization would yield the conjugated
aldehyde, and finally, an acid-catalyzed cyclization would
yield the observed 12. E- and Z-3-methyl-2-phenylpent-
2-enal18 were also present in the hydrolysis product
mixture in a 1:1 ratio accounting for 6% of the total
product. E- and Z-3-methyl-2-phenyl-pent-2-enal are
likely formed from an acid-catalyzed ring-opening rear-
rangement of the minor amounts of (trans,trans-2-meth-
For comparative purposes, the reaction of 1-(trans-2-
phenylcyclopropyl)-1-tributylstannylethene,8 15, with BuLi
(19) Examples of lithium-tin exchanges can be found in the
following references: (a) Reich, H. J.; Gudmundsson, B. O.; Green, D.
P.; Bevan, M. J.; Reich, I. L. Helv. Chim. Acta 2002, 85, 3748. (b)
Oprunenko, Y. F.; Akhmedov, N. G.; Laikov, D. N.; Malyugina, S. G.;
Mstislavsky, V. I.; Roznyatovsky, V. A.; Ustynyuk, Y. A.; Ustynyuk,
N. A. J. Organomet. Chem. 1999, 583, 136. (c) Beaudet, I.; Launay,
V.; Parrain, J.-L.; Quintard, J.-P. Tetrahedron Lett. 1995, 36, 389. (d)
Kang, K.-T.; Ryu, D. C.; Sung, T. M.; Kim, J. G. Bull. Chem. Soc. Jpn.
1994, 15, 926. (e) Yang, Y.; Wong, H. N. C. J. Chem. Soc., Chem.
Commun. 1992, 23, 1723.
(17) Kobayashi, T.; Koga, Y.; Narasak, K. J. Organomet. Chem.
2001, 624, 73.
(18) Dana, G.; Gharbi-Benarous, J. Can. J. Chem. 1980, 58, 1451.
(20) Beavers, W. A.; Wilson, S. E. Tetrahedron Lett. 1979, 19, 1678.
2690 J. Org. Chem., Vol. 70, No. 7, 2005

Cyclopropyl Alkynes as Mechanistic Probes
TABLE 1. Addition of Alkyllithium Reagents to 14
entry
RLi
equiv
solvent
time (h)
T (°C)
result
1
2
3
4
5
6
7
BuLi
BuLi
BuLi
BuLi
BuLi
t-BuLi
t-BuLi
1.1
1.1
3.0
3.0
2.0
2.0
2.0
THF
THF
THF/TMEDA (5:1)
THF/TMEDA (5:1)
hexanes
THF
THF
1
1.5
1
-78
rt
no reactiona
recovered 14 (91%)
rt
no reactiona
17
21
2
reflux
rt
-78 °C (1 h) f rt (1 h)
rt
recovered 14 (98%)b
recovered 14 (94%)b
no reactiona
19
recovered 14 (98%)b
1
1
a Based on H NMR spectroscopic analysis of a quenched aliquot after aqueous workup. b Based on H NMR spectroscopic analysis of
isolated material after aqueous workup of entire reaction.
SCHEME 15
was also investigated. When 15 was allowed to react with
BuLi at -78 °C for 1 h followed by the addition of water,
(trans-2-phenylcyclopropyl)ethene was obtained in good
yield (76%). Presumably, the vinyllithium is an interme-
diate in the formation of the alkene (Scheme 14). There
was no evidence for the formation of any ring-opened
products, and thus, it was concluded that the vinyl-
lithium does not rearrange under the reaction conditions.
This result is in agreement with previous reports con-
cerning the reactivity of cyclopropylvinyllithium and
Grignard species.20,21 The difference in reactivity between
vinylstannanes 14 and 15 toward BuLi is puzzling. It
appears to be the result of electronic effects of the
methoxy substituent, although the nature of this elec-
tronic effect is unclear.
Estimation of Rate Constants of Ring Opening of
R-Cyclopropylvinyl Cations. To assess the potential
of alkynes 1a-c to act as mechanistic probes, determi-
nation of the rate constants for rearrangement of the
R-cyclopropylvinyl intermediates was necessary. We have
recently reported the rate constant for the rearrangement
of the 1-(trans-2-phenylcyclopropyl)ethen-1-yl radical.8
The reported value of (1.6 ( 0.2) × 1010 s-1 is only 1 order
of magnitude smaller than the rate constant for ring
opening of the analogous R-cyclopropylcarbinyl radical.9,22
In order for the rearrangement to be used as a mecha-
nistic probe, the rearrangement must be able to compete
effectively with other processes that may take place
during the course of the reaction; with a rate constant
for rearrangement on the order of 1010 s-1, the R-cyclo-
propylvinyl radicals can be considered as hypersensitive
radical probes. We believe that the rate constant for ring
opening of the analogous radicals from 1b and 1c will
be comparable; the remote methoxy and methyl group
will not greatly influence the rate constant of rearrange-
ment.
kinetics, the ratio of the rate constant of rearrangement
of the cation (kR) and trapping of the cation (kT) by
hydration is equal to the ratio of the rearranged product
(RT) and the trapped product (UT) times the concentra-
tion of the trapping agent (T) (eq 1). For this rough
estimate we have assumed that the water trapping
reactions are irreversible. The ratio of the two products
1
formed (12 and 13) was determined by H NMR spec-
troscopy and the concentration of the trapping agent,
water, was known. The rate constant for the competition
reaction, the hydrolysis of a cyclopropyl substituted vinyl
cation (kT), has not been determined. However, even in
the presence of a strong cation-stabilizing substituent
such as the p-methoxyphenyl substituent, vinyl cations
do not persist long enough (<20 ns) to permit an
evaluation of the rate constant for hydrolysis.23 Although
there is some debate in the literature regarding the
relative ability of a cyclopropyl or phenyl substituent to
stabilize a vinyl cation,24 we believe it is reasonable to
assume that the rate constant for hydrolysis of an
R-cyclopropylvinyl cation will approach or be at the
diffusion limit. Using the value of 2.1 × 1010 M-1 s-1
reported by Newcomb25 for the rate constant for diffusion
in THF as the rate constant for the competition reaction
(i.e., hydrolysis of an R-cyclopropylvinyl cation), a value
An approximate rate constant for the ring-opening
rearrangement of the 1-(trans,trans-2-methoxy-1-methyl-
3-phenylcyclopropyl)ethen-1-ylium cation, 16, can also be
estimated if the hydrolysis of 1c (vide supra) is analyzed
by competition kinetics (eq 1). The acid-catalyzed hy-
drolysis of alkyne 1c yielded products from two competing
reactions: the direct hydration of the R-cyclopropylvinyl
cation as well as from ring opening followed by hydrolysis
of the oxonium ion (Scheme 15). According to competition
(21) (a) Emme, I.; Redlich, S.; Labahn, T.; Magull, J.; de Meijere,
A. Angew. Chem., Int. Ed. 2002, 41, 786. (b) Crandall, J. K.; Ayers, T.
A. J. Org. Chem. 1992, 57, 2993. (c) Maerker, A.; Girreser, U. Angew.
Chem. 1990, 120, 718. (d) Mislankar, D. G.; Mugrage, B.; Darling, S.
D. Tetrahedron Lett. 1981, 22, 4619. (e) Richey, H. G., Jr.; Kossa, W.
C., Jr. Tetrahedron Lett. 1969, 9, 2313.
(23) Cozens, F. L.; Kanagasabapathy, V. M.; McClelland, R. A.;
Steenken, S. Can. J. Chem. 1999, 77, 2069.
(24) (a) Allen, A. D.; Chiang, Y.; Kresge, A. J.; Tidwell, T. T. J. Org.
Chem. 1982, 775. (b) Apeloig, Y.; Schleyer, P. v. R.; Pople, J. A. J. Org.
Chem. 1977, 18, 3004. (c) Alem. K. v.; Lodder, G.; Zuilhof, H. J. Phys.
Chem. A 2002, 106, 10681.
(22) Newcomb, M.; Johnson, C. C.; Manek, M. B.; Varick, T. R. J.
Am. Chem. Soc. 1992, 114, 10915.
(25) Newcomb, M.; Manek, M. B. J. Am. Chem. Soc. 1990, 112, 9662.
J. Org. Chem, Vol. 70, No. 7, 2005 2691

Gottschling et al.
of 4 × 1010 s-1 for the rate constant for the ring opening
of cation 16 was estimated.
lated. Based on these data, the rate constant for ring
opening of cation 18 was estimated to be 2 × 1012 s-1
.
In all cases, the rate constant for the rearrangement
of the vinyl cation is estimated to be 1010 s-1 or greater.
Even with due consideration given to the uncertainty in
the rate constant and the assumptions made, at this
magnitude, the rearrangement should effectively compete
with other possible chemical processes, and thus, this
rearrangement can be used as a hypersensitive probe for
the formation of R-cyclopropylvinyl cations.
RT 7T
9
R+ 79k
U
+ 9T 8 UT
kT
R
kR
[RT][T]
[UT]
)
(1)
kT
By similar analysis, the rate constant for the ring
opening of cation 17 can also be estimated. The products
formed in the acid-catalyzed hydrolysis of alkyne 1b, 10
and 11, were derived exclusively from ring opening of the
R-cyclopropylvinyl cation followed by hydrolysis of the
oxonium ion (Scheme 16). No products derived from
Conclusion
Alkynes 1a-c rapidly rearrange when a radical or a
cation is generated adjacent to the cyclopropyl ring.
Compound 1a yields products derived from ring opening
toward the phenyl substituent under both radical and
cationic conditions. Thus, the formation of rearrangement
products indicates the presence of a reaction intermedi-
ate; however, the structure of the product alone does not
allow for the determination of the type of the intermedi-
ate. When an anion is generated adjacent to the cyclo-
propyl ring, no products derived from the opening of the
cyclopropyl ring were observed. In contrast, compounds
1b,c gave different products depending on the nature of
the reaction intermediate formed adjacent to the ring.
Products obtained under radical conditions are derived
from ring opening toward the phenyl substituent, whereas
products obtained under cationic conditions are derived
from ring opening toward the methoxy substituent. The
rearrangement of cations 16, 17, and 18 were examined
using competition kinetics. The rate constants for rear-
rangement of the cations were crudely estimated to be
in the range of 1010-1012 s-1. Thus, based on the results
herein and our previous work,8 we conclude that cyclo-
propyl alkynes 1b,c can indeed act as hypersensitive
mechanistic probes which are capable of distinguishing
between the formation of a cation, radical or anion at the
vinylic position. We believe such versatile probes will find
extensive applications in organic, organometallic, biologi-
cal and materials science. Indeed, we have utilized probe
1c in the investigation of the mechanism of the cycload-
dition of alkynes to disilenes; the results will be reported
in due course.
SCHEME 16
hydration of the R-cyclopropylvinyl cation were observed
1
in the H NMR spectrum of the crude reaction mixture.
Thus, assuming a detection limit of 5% for 1H NMR
spectroscopy, the lower limit of the rate constant for the
ring opening of the 1-(trans,trans-2-methoxy-3-phenyl-
cyclopropyl)ethen-1-ylium cation, 17, is estimated to be
∼4 × 1012 s-1
.
Vinyl cation 18 derived from protonation at the ter-
minal position of alkyne 1a, opens toward the phenyl
substituent. Again, a competition exists between direct
hydrolysis of the R-cyclopropylvinyl cation to give trans-
2-phenylcyclopropylethanone and ring opening toward
the phenyl substituent, followed by hydration of the
benzyl cation to give allene 9 (Scheme 17). The ratio of
Experimental Section
Preparation of 1,1-Dibromo(trans,trans-2-methoxy-3-
phenylcyclopropyl)ethene (5b). A solution of triphenylphos-
phine (11.21 g, 42.8 mmol) dissolved in CH2Cl2 (30 mL) was
added dropwise to a solution of CBr4 (7.10 g, 21.4 mmol)
dissolved in CH2Cl2 (12 mL) at 0 °C. The resulting dark orange
solution was allowed to stir for 5 min. A solution of aldehyde
4b (1.89 g, 10.7 mmol) dissolved in CH2Cl2 (10 mL) was then
added dropwise. The solution was allowed to stir at 0 °C for
1.25 h after which time it had become dark alpine green in
color. The reaction mixture was quenched by the addition of
distilled H2O (50 mL). The organic and aqueous layers were
separated. The aqueous layer was washed with CH2Cl2 (3 ×
50 mL). The organic layers were combined and washed with
H2O (50 mL) and brine (50 mL). The organic layer was dried
over MgSO4 and filtered. The solvent was removed by rotary
evaporation to give a pasty solid. The solid was washed with
Et2O (5 × 150 mL). The washes were combined and concen-
trated to give a yellow jelly, which was then washed with
hexanes (5 × 150 mL). The washes were combined and filtered
through dry silica. The solvent was removed from the filtrate
SCHEME 17
1
the two products was determined by H NMR spectros-
copy; trans-2-phenylcyclopropylethanone was not iso-
2692 J. Org. Chem., Vol. 70, No. 7, 2005

Cyclopropyl Alkynes as Mechanistic Probes
by rotary evaporation. The Et2O and hexanes wash cycle was
repeated as needed to maximize the yield. The final product
was obtained as a clear, yellow oil (2.96 g, 84%). The product
was taken onto the next step without further purification.
Upon sitting for 2 weeks, 5b was found to convert to 1-bromo-
3-phenylcyclopent-3-en-2-one, 7, which was isolated as a
crystalline, white solid after chromatographic purification
(69%, silica gel, 3:1 hexanes/CH2Cl2). Crystals of 7 were grown
from a concentrated CH2Cl2 solution by slow diffusion of
hexanes and then analyzed by X-ray crystallography. Experi-
mental details for the analysis are presented in the Supporting
Information. Bond lengths and angles, atomic coordinates, and
anisotropic parameters are tabulated.26 5b: IR (cm-1) 3032
(w), 2930 (m) 1691 (m), 1603 (m), 1496 (m), 1445 (m), 1409
(w), 1353 (w), 1240 (w), 1122 (m), 1025 (m), 922 (m), 794 (m),
697 (m); 1H NMR (CDCl3) δ 7.19-7.29 (m, 5H, PhH), 6.01 (d,
1H, Br2CdCH, J ) 8.8 Hz), 3.53 (dd, 1H, MeOCH, J ) 3.2,
6.7 Hz), 3.25 (s, 3H, OMe), 2.23 (t, 1H, PhCH, J ) 6.7 Hz),
2.20 (ddd, 1H, Br2CdCHCH, J ) 3.2, 6.7, 8.8 Hz); 13C NMR
(CDCl3) δ 137.5 (Br2CdC), 135.3 (i-PhC), 128.0, 128.0 (o,m-
PhC), 126.2 (p-PhC), 88.1 (Br2C), 65.7 (MeOCH), 58.6 (OMe),
32.1 (PhCH), 30.6 (Br2CdCHCH); MS (m/z) 332 (C12H12O79-
Br81Br, 5), 253 (C12H12O81Br, 42), 251 (C12H12O79Br, 40), 172
(C12H12O, 100); high-resolution MS (CI, isobutane) for C12H13O79-
Br81Br (M + H+) (m/z) calcd 332.9312, found 332.9320. 7: mp
78-79 °C; IR (cm-1) 3066 (w), 1705 (vs), 1297 (m), 1118 (w),
CH, J ) 2.3, 3.2, 6.4 Hz); 13C NMR (CDCl3) δ 135.0 (i-PhC),
128.0, 128.0, 126.4 (o,m,p-PhC), 83.9 (CtCH), 66.2 (MeOCH)
66.0 (CtCH), 58.5 (OMe), 32.9 (PhCH), 14.9 (CHCtCH); MS
(m/z) 172 (M+, 100), 157 (C11H9O, 23), 141 (C11H9, 65); High-
Resolution MS for C12H12O (M+) (m/z) calcd 172.0889, found
172.0889. 5,5-Dimethoxy-4-phenylpenta-1,2-diene: IR (cm-1
)
3062 (m), 3029 (m), 2935 (s), 2831 (m), 1957 (s), 1726 (s), 1625
(m), 1495 (m), 1452 (s), 1116 (s), 1080 (s), 848 (s), 761 (m),
1
701 (vs); H NMR (CDCl3) δ 7.19-7.32 (m, 5H, o,m,p-PhH),
5.43 (q, 1H, CdCdCH, J ) 6.8 Hz), 4.71, 4.77 (dd on AB, 2H,
H2CdCdC, J ) 10.5, 6.7, 2.3 Hz), 4.51 (d, 1H, MeOCH, J )
6.7 Hz), 3.60 (tt, 1H, PhCH, J ) 2.3, 7.0 Hz), 3.39 (s, 3H, OMe),
3.24 (s, 3H, OMe); 13C NMR (CDCl3) δ 208.8 (CdCdC), 140.0
(i-PhC), 128.6, 128.2, 126.8 (o,m,p-PhC), 106.9 (CH(OMe)2),
90.2 (CdCH), 76.0 (H2CdC), 54.5 (OMe), 54.2 (OMe), 48.6
(PhCH); MS (m/z) 204 (M+, 0.5), 189 (M+ - Me, 0.6), 173 (M+
- MeO, 2.8), 140 (M+ - 2MeOH, 9), 74 (C(OMe)2, 100); high-
resolution MS for C13H16O2 (M+) calcd 204.1150, found 204.1147.
Synthesis of Ethyl trans,trans-2-Methoxy-1-methyl-3-
phenylcyclopropanecarboxylate. A solution of ethyl 2-dia-
zopropionate (13.0 g, 0.10 mol) dissolved in benzene (40 mL)
was added dropwise to a refluxing solution of CuSO4 (1.12 g,
7.0 mmol) and cis-â-methoxystyrene (9.1 g, 0.068 mol) dis-
solved in benzene (100 mL). The suspension was allowed to
reflux for 18 h and then quenched by the addition of H2O (100
mL). The organic and aqueous layers were separated. The
aqueous layer was washed with Et2O (3 × 75 mL). The organic
layers were combined and washed with H2O (75 mL), dried
over MgSO4 and filtered. Removal of the solvent by rotary
evaporation yielded a dark yellow oil. After purification by
column chromatography (silica gel, 4:1 hexanes/EtOAc), a pale
yellow oil was obtained (8.91 g, 94% based on reacted â-meth-
oxystyrene, 98% purity by GC analysis). Ethyl trans,trans-
2-methoxy-1-methyl-3-phenylcyclopropanecarbox-
ylate: IR (cm-1) 2976 (w), 2930 (w), 1711 (s), 1450 (w), 1255
(m), 1127 (m), 1025 (m), 707 (m); 1H NMR (CDCl3) δ 7.18-
7.31 (m, 5H, o,m,p-PhH), 4.16 (q, 2H, OCH2CH3, J ) 7.2 Hz),
3.83 (d, 1H, MeOCH, J ) 7.6 Hz), 3.41 (s, 3H, OMe), 2.75 (d,
1H, PhCH, J ) 7.6 Hz), 1.28 (t, 3H, OCH2CH3, J ) 7.2 Hz),
1.10 (s, 3H, CMe); 13C NMR (CDCl3) δ 174.7 (CdO), 134.2 (i-
PhC), 130.6 (o-PhC), 128.0 (m-PhC), 126.5 (p-PhC), 68.0
(MeOCH) 60.8 (OCH2CH3), 59.1 (OMe), 33.5 (PhCH), 28.2
(CMe), 14.3 (OCH2CH3), 8.1 (Me); MS (m/z) 234 (M+, 20), 205
(M+ - Et, 13), 173 (45), 161 (M+ - C3H5O2, 62), 129 (100), 117
(45), 84 (54); high-resolution MS for C14H18O3 (M+) (m/z) calcd
234.1256, found 234.1260.
1
775 (w), 706 (m); H NMR (CDCl3) δ 7.76 (t, 1H, J ) 2.8 Hz,
CHdCPh), 7.67-7.72 (m, 2H, o-PhH), 7.32-7.42 (m, 3H, m,
p-PhH), 4.52 (dd, 1H, J ) 2.4, 6.7 Hz, CHBr), 3.43 (ddd, 1H,
J ) 2.9, 6.7, 20.0, CH(Htrans)), 3.01 (dt, 1H, J ) 20.0, 2.9, CH-
(Hcis)); 13C NMR (CDCl3) δ 200.1 (C)O), 154.9 (CHdCPh),
140.8 (CPh), 130.5 (i-PhC), 128.9, 128.44 (m, p-PhC) 126.9 (o-
PhC), 42.5 (CHBr), 38.0 (H2C); MS (m/z) 236 (M+, 24), 157
(C11H9O, 65), 129 (C10H9O, 100), 128 (75), 102 (40); high-
resolution MS for C11H9O79Br (M+) (m/z) calcd 235.9838, found
235.9837.
Preparation of (trans,trans-2-Methoxy-3-phenylcyclo-
propyl)ethyne (1b). BuLi (11.1 mL, 17.8 mmol) was added
dropwise to a solution of 5b (2.96 g, 8.9 mmol) dissolved in
THF (30 mL) at -78 °C. The orange solution was allowed to
stir at -78 °C for 2 h, after which time it had become dark
brown in color. The solution was allowed to warm to rt and
then quenched by the addition of distilled H2O (30 mL). The
resulting pale orange, biphasic solution was diluted with Et2O
(30 mL). The organic and aqueous layers were separated. The
aqueous layer was washed with Et2O (3 × 30 mL). The organic
layers were combined and then washed with brine (30 mL).
The organic layer was dried over MgSO4 and then filtered. The
resulting yellow solution was concentrated by rotary evapora-
tion to give a dark, orange oil (1.46 g, 96%). The oil was
purified by column chromatography (silica gel, 1:1 CH2Cl2/
hexanes) to yield a pale yellow oil identified as (trans,trans-
2-methoxy-3-phenylcyclopropyl)ethyne, 1b (1.24 g, 81%, 99%
pure by GC). Alkyne 1b is relatively stable but does undergo
decomposition under ambient atmosphere and temperature
over time (12% decomposition after 7 months as determined
by GC analysis). The major products of decomposition identi-
fied were benzaldehyde and 5,5-dimethoxy-4-phenylpenta-1,2-
diene which was isolated as a pale yellow oil after chroma-
tography (silica gel, CH2Cl2) (28% and 36%, respectively, as
determined by GC analysis). 1b: IR (cm-1) 3288 (s), 3027 (w),
2930 (w), 2822 (w), 2105 (m), 1603 (m), 666 (s); 1H NMR
(CDCl3) δ 7.19-7.31 (m, 5H, PhH), 3.63 (dd, 1H, MeOCH, J
) 3.1, 6.8 Hz), 3.29 (s, 3H, OMe), 2.35 (t, 1H, PhCH, J ) 6.6
Hz), 1.94 (d, 1H, CtCH, J ) 2.2 Hz), 1.82 (ddd, 1H, CHCt
Synthesis of (trans,trans-2-Methoxy-1-methyl-3-phe-
nylcyclopropyl)methanol. A solution of ethyl trans,trans-
2-methoxy-1-methyl-3-phenylcyclopropanecarboxylate (1.65 g,
7.0 mmol) dissolved in Et2O (20 mL) was added dropwise to a
suspension of LAH (797 mg, 21.0 mmol) in Et2O (30 mL). The
reaction mixture was allowed to stir at rt for 4 h, was cooled
to 0 °C, and then quenched by the slow addition of H2O (25
mL). The organic and aqueous layers were separated. The
aqueous layer was washed with Et2O (3 × 25 mL). The organic
layers were combined and washed with H2O (25 mL). The
organic layer was dried over MgSO4 and filtered. Concentra-
tion of the filtrate by rotary evaporation yielded a cloudy,
colorless oil (1.34 g, 99%, 97% pure by GC analysis). (tran-
s,trans-2-Methoxy-1-methyl-3-phenylcyclopropyl)metha-
nol: IR (cm-1) 3384 (bs), 2932 (m), 1599 (w) 1493 (m), 1448
1
(w) 1236 (m), 1138 (m), 1028 (s), 698 (m); H NMR (CDCl3) δ
7.14-7.31 (m, 5H, PhH), 3.54, 3.47 (AB, 2H, CH2OH, J ) 10.9
Hz), 3.38 (s, 3H, OMe), 3.32 (d, 1H, MeOCH, J ) 7.1 Hz), 1.90
(d, 1H, PhCH, J ) 7.1 Hz), 1.23 (broad s, 1H, OH) 1.05 (s, 3H,
CMe); 13C NMR (CDCl3) δ 136.2 (i-PhC), 130.1, 127.9 (o,
m-PhC), 125.7 (p-PhC), 70.5 (CH2OH), 65.7 (COCH3), 58.9
(OMe), 28.6 (PhCH), 27.7 (CMe), 9.8 (Me); MS (CI, Isobutane)
(m/z (%)) 193 (M + H+, 4), 175 (M + H+ - H2O, 55), 161 (M +
H+ - CH3OH, 100), 143 (M + H+ - CH3OH - H2O, 98); high-
resolution MS (CI, Isobutane) for C12H17O2 (M + H+) (m/z)
calcd 193.1228, found 193.1223.
(26) CCDC 257338 contains the supplementary crystallographic data
for compound 7 and CCDC 257339 contains the supplementary
crystallographic data for compound 5c. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crys-
tallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K.;
fax: +44 1223 336033.
J. Org. Chem, Vol. 70, No. 7, 2005 2693

Gottschling et al.
Synthesis of trans,trans-2-Methoxy-1-methyl-3-phe-
nylcyclopropanecarbaldehyde (4c). A solution of DMSO
(5.2 mL, 73 mmol) and CH2Cl2 (40 mL) was added dropwise
to a solution of oxalyl chloride (3.2 mL, 37 mmol) dissolved in
CH2Cl2 (120 mL) at -78 °C. The mixture was allowed to stir
for 10 min. A solution of (trans,trans-2-methoxy-1-methyl-3-
phenylcyclopropyl)methanol (5.5 g, 29 mmol) and NEt3 (28 mL,
203 mmol) dissolved in CH2Cl2 (80 mL) was added dropwise
to the cold solution. The reaction mixture was then allowed
to warm to rt and stirred for 2 h. The reaction was quenched
by the addition of H2O (100 mL), and the organic and aqueous
layers were separated. The aqueous layer was washed with
CH2Cl2 (3 × 100 mL), and the combined organic layers were
washed with H2O. The organic layer was dried over MgSO4,
filtered, and then concentrated by rotary evaporation to yield
a orange-yellow oil. Et2O (100 mL) was added to the oil to
induce precipitation of the NEt3HCl salt. The precipitate was
removed by filtration, and the filtrate was once again concen-
trated to yield a orange-yellow oil (5.1 g, 94%). Aldehyde 4c is
unstable and rearranges in near quantitative yield to 6 over
several days. The rearrangement is accelerated in chloroform
and is complete in less than 12 h. It was difficult to obtain a
clean sample of 4c as contamination with dihydrofuran 6 was
unavoidable. For this reason, aldehyde 4c was used without
further purification. 4c: IR (cm-1) 2935 (m), 2827 (m), 2735
(m) 1701 (s) 1603 (m), 1445 (m) 1245 (m), 1091 (m), 1030 (m),
922 (m) 697 (m); 1H NMR (C6D6) δ 9.06 (s, 1H, CHO) 7.0-
7.25 (m, 5H, o,m,p-PhH), 3.38 (d, 1H, MeOCH, J ) 7.6 Hz),
2.83 (s, 3H, OMe), 2.64 (d, 1H, PhCH, J ) 7.6 Hz), 1.02 (s,
3H, CMe); 13C NMR (C6D6) δ 200.6 (CHO), 140.0 (i-PhC), 130.9
(o-PhC), 128.2 (m-PhC), 126.9 (p-PhC), 69.0 (MeOCH), 58.5
(OMe), 37.3 (CMe), 33.5 (PhCH), 6.8 (Me); MS (m/z) 190 (M+,
100), 161 (M+ - HCO, 78), 129 (M+ - HCO - CH3OH, 92),
115 (53), 91 (41); high-resolution MS for C12H14O2 (M+) (m/z)
5H, o,m,p-PhH), 3.62 (d, 1H, MeOCH, J ) 7.6 Hz), 3.45 (s,
3H, OMe), 2.35 (d, 1H, PhCH, J ) 7.6 Hz), 1.96 (s, 1H, Ct
CH), 1.10 (s, 3H, CMe); 13C NMR (CDCl3) δ 134.3 (i-PhC), 130.5
(o-PhC), 128.0 (m-PhC), 126.4 (p-PhC), 90.3 (CtCH), 67.9
1
(MeOCH) 64.2 (CtCH, JC-H ) 264 Hz), 59.0 (OMe), 33.4
(PhCH), 15.8 (CCtCH), 12.4 (CMe); MS (m/z)186 (M+, 69), 171
(M+ - CH3, 67), 155 (M+ - OCH3, 22), 128 (62), 84 (M+
-
PhCtCH, 100); high-resolution MS for C13H14O (M+) (m/z)
calcd 186.1045, found 186.1046. (trans,trans-2-Methoxy-1-
methyl-3-phenylcyclopropyl)ethene: 1H NMR (C6D6) δ
7.41-7.43 (m, 2H, o-PhH), 5.47 (dd, 1H, HCdCH2, J ) 17.0,
12.5 Hz), 4.97 (dd, 1H, HCdCH(Htrans), J ) 1.0, 17.0 Hz), 4.91
(dd, 1H, HCdCH(Hcis), J ) 1.0, 10.5 Hz), 3.12 (d, 1H, MeOCH,
J ) 7.0 Hz), 3.05 (s, 3H, OMe), 1.99 (d, 1H, PhCH, J ) 7.0
Hz), 1.09 (s, 3H, CMe).
Thermolysis of (trans-2-Phenylcyclopropyl)ethyne (1a)
with (Me3Si)3SiH. A solution of 1a (100 mg, 0.70 mmol), (Me3-
Si)3SiH (346 mg, 1.40 mmol), and AIBN (20 mg, 0.12 mmol)
dissolved in toluene (5 mL) was refluxed. The progress of the
reaction was monitored by 1H NMR spectroscopy. The solvent
was then removed by rotary evaporation to give a pale, yellow
oil (150 mg, 55%), identified as 1-tris(trimethylsilyl)silyl-5-
phenylpenta-1,2-diene, 8a. All attempts to purify 8a resulted
in decomposition. 8a: IR (cm-1) 3320 (w), 3088 (w), 3065 (w),
3030 (w), 2967 (s), 2897 (s), 1934 (s, CdCdC), 1731 (m), 1263
(s), 1062 (s), 835 (s); 1H NMR (CDCl3) δ 7.15-7.25 (m, 5H,
o,m,p-PhH), 4.84 (dt, 1H, SiCHdCdCH, J ) 3.5, 7.2 Hz), 4.71
(pseudo-q, 1H, SiCHdCdCH, J ) 6.7 Hz), 2.70 (t, 2H, PhCH2,
J ) 8.0 Hz), 2.23-2.32 (m, 2H, PhCH2CH2), 0.18 (s, 27H,
SiMe3); 13C NMR (CDCl3) δ 210.3 (SiCHdCdCH) 141.9 (i-
PhC), 128.3, 128.2, 125.7 (o,m,p-PhC), 81.9 (SiCHdCdCH),
74.1 (SiCHdCdCH), 36.2 (PhCH2), 30.6 (PhCH2CH2), 0.8
(SiMe3); MS (CI, Isobutane) (m/z) 389 (M+ - H, 100), 317 (M+
- SiMe3, 43); high-resolution MS for C20H37Si4 (M+ - H) (m/
z) calcd 389.2026, found 389.1966.
1
calcd 190.0994, found 190.0994. 6: H NMR (CDCl3) δ 7.17-
Thermolysis of (trans,trans-2-Methoxy-3-phenylcyclo-
propyl)ethyne (1b) with (Me3Si)3SiH. The thermolysis of
1b was performed as described for 1a. Specific experimental
details can be found in the Supporting Information. 8b: IR
(cm-1) 2951 (s), 2894 (m), 1932 (s), 1257 (m), 1244 (s), 1100
(m), 837 (vs); 1H NMR (CDCl3) δ 7.19-7.27 (m, 5H, o,m,p-
PhH), 4.76 (dd, 1H, SiCHdCdCH, J ) 6.4, 2.0 Hz), 4.70 (t,
1H, SiCHdCdCH, J ) 7.2 Hz), 3.92-3.97 (m, 1H, MeOCH),
3.30 (s, 3H, OMe), 2.94 (dd, 1H, PhCH2, J ) 7.6, 13.6 Hz),
2.79 (dd, 1H, PhCH2, J ) 5.6, 13.6 Hz), 0.17 (s, 27H, SiMe3);13C
NMR (CDCl3) δ 209.3 (SiCHdCdCH), 138.6 (i-PhC), 129.7 (o-
PhC), 128.0, 126.0 (m,p-PhC), 84.4 (SiCHdCdCH), 80.6
(MeOCH), 75.4 (SiCHdCdCH), 56.7 (OMe), 42.6 (PhCH2), 0.6
(SiMe3); MS (CI, isobutane) (m/z) 477 (M+ + 57, 3), 421 (M +
H+, 9), 389 (M + H+ - MeO, 100); high-resolution MS for
C21H41OSi4 (M + H+) (m/z) calcd 421.2235, found 421.2230.
Thermolysis of (trans,trans-2-Methoxy-1-methyl-3-
phenylcyclopropyl)ethyne (1c) in the Presence of Tribu-
tyltin Hydride. The thermolysis of 1c was performed as
described for 1a, using Bu3SnH in place of (Me3Si)3SiH. The
specific experimental details can be found in the Supporting
Information. 8c: IR (cm-1): 2955 (s), 2925 (s), 2873 (m), 2848
(m), 1936 (m), 1460 (m), 1378 (w), 1260 (m), 1096 (m), 805
7.40 (m, 5H, o,m,p-PhH), 6.29 (m, 1H, CHdCMe), 5.46 (d, 1H,
MeOCH, J ) 7.6 Hz), 3.99 (broad dq, 1H, PhCH, J ) 7.6, 1.4
Hz), 3.33 (s, 3H, OMe), 1.48 (t, 3H, CMe, J ) 1.6 Hz); 13C NMR
(CDCl3) δ 139.2 (OCdC), 135.5 (i-PhC), 130.1, 127.8, 126.9
(o,m,p-PhC), 112.8 (CdCMe), 107.3 (MeOCH), 56.5 (OMe), 55.8
(PhCH), 9.9 (CMe); MS (m/z) 190 (M+, 100), 161 (M+ - HCO,
65), 129 (M+ - HCO - CH3OH, 97), 115 (52), 91 (30); high-
resolution MS for C12H14O2 (M+) calcd 190.0994, found 190.0994.
Synthesis of 1,1-Dibromo(trans,trans-2-methoxy-1-
methyl-3-phenylcyclopropyl)ethene (5c). Compound 5c
was prepared as described for 5b. Specific experimental details
can be found in the Supporting Information. Single crystals
of 5c were grown from a concentrated methylene chloride
solution by slow diffusion of acetonitrile and then analyzed
by X-ray crystallography. Experimental details for the analysis
are presented in the Supporting Information. Bond lengths
and angles, atomic coordinates, and anisotropic parameters
are tabulated.26 5c: mp 67-69 °C; IR (cm-1) 2928 (s), 2822 (w),
1607 (m), 1497 (s), 1444 (m), 1138 (s), 1077 (m), 698 (s); 1H
NMR (CDCl3) δ 7.36 (pseudo-d, 2H, o-PhH, J ) 7.8 Hz), 7.26
(pseudo-t, 2H, m-PhH, J ) 7.2 Hz), 7.19 (pseudo-t, 1H, p-PhH,
J ) 7.2 Hz), 6.65 (s, 1H, Br2CdCH), 3.48 (d, 1H, MeOCH, J )
7.2 Hz), 3.44 (s, 3H, OMe), 2.18 (d, 1H, PhCH, J ) 7.2 Hz),
1.12 (s, 3H, CMe); 13C NMR (CDCl3) δ 141.9 (Br2CdC), 135.4
(i-PhC), 130.4 (o-PhC), 127.9 (m-PhC), 126.1 (p-PhC), 92.4
(Br2C), 67.0 (MeOCH), 59.0 (OMe), 32.6 (PhCH), 28.5 (Br2Cd
CHC), 10.8 (CMe); MS (CI, isobutane) (m/z) 347 (M + H+, 25),
1
(m), 692 (m); H NMR (C6D6) δ major diasteromer 7.31-7.32
(m, 2H, o-PhH), 7.19-7.22 (m, 2H, m-PhH), 7.07-7.09 (m, 1H,
p-PhH), 5.17 (dq, 1H, SnCHdCdC, J ) 0.4, 3.8 Hz, 2J119/117Sn-H
) 24.6 Hz), 4.05 (ddd, 1H, MeOCH, J ) 0.9, 5.3, 8.2 Hz), 3.18
(s, 3H, OMe), 3.11 (dd, 1H, PhCH2, J ) 8.2, 13.8 Hz), 2.90
(dd, 1H, PhCH2, J ) 5.3, 13.8 Hz), 1.75 (d, 3H, Me, J ) 3.8
315 (M+ - CH3OH, 64), 267 (M+
- -
79Br, 100), 236 (M+ 79Br
- OMe, 36), 186 (M+
-
79Br - 81Br, 98); high-resolution MS
5
Hz, J119/117Sn-H ) 19.9 Hz), 1.52-1.59 (SnCH2CH2),27 1.29-
(CI, Isobutane) for C13H15O79Br2 (M + H+) (m/z) calcd 344.9489,
found 344.9495.
1.38 (SnCH2CH2CH2),27 0.85-1.0 (SnCH2),27 0.93 (t, CH2CH3,
J ) 7.8 Hz); minor diastereomer 7.24-7.25 (m, 2H, o-PhH),
7.15-7.18 (m, 2H, m-PhH), 7.06-7.08 (m, 1H, p-PhH), 5.04
Synthesis of (trans,trans-2-Methoxy-1-methyl-3-phe-
nylcyclopropyl)ethyne (1c). Compound 1c was prepared as
described for 1b. Specific experimental details can be found
in the Supporting Information. 1c: IR (cm-1) 3283 (s), 2935
(s), 2105 (m), 1603 (m), 1496 (s), 1445 (m), 1199 (m), 1143 (s),
1081 (s), 907 (s), 697 (s); 1H NMR (CDCl3) δ 7.17-7.32 (m,
(27) Some of the signals corresponding to the tributylstannyl 1Hs
of one diastereomer were overlapped by signals of the other diastere-
omer. Therefore, the chemical shift ranges of both diastereomers have
been listed for these signals.
2694 J. Org. Chem., Vol. 70, No. 7, 2005

Cyclopropyl Alkynes as Mechanistic Probes
(dq, 1H, SnCHdCdC, J ) 1.2, 3.8 Hz, 2J119/117Sn-H ) 24.9 Hz),
4.07 (ddd, 1H, MeOCH, J ) 0.9, 6.2, 7.6 Hz), 3.24 (s, 3H, OMe),
7.41 (m, 3H, m, p-PhH), 7.19-7.21 (m, 2H, o-PhH), 7.05 (d,
1H, CHCHdCH2, J ) 11.4 Hz), 6.70 (ddd, 1H, CHdCH2, J )
10.0, 11.4, 17.0 Hz), 5.81 (ddd, 1H, CHdCH(Htrans), J ) 0.8,
1.6, 17.0 Hz), 5.59 (ddd, 1H, CHdCH(Hcis), J ) 0.8, 1.6, 10.0
Hz); 13C NMR (CDCl3) δ 193.2 (CHO), 149.2 (CHCHdCH2),
141.9 (CdCHCHdCH2), 132.8 (CdCHCHdCH2), 132.1 (i-PhC),
129.7 (o-PhC), 128.2, 128.1 (m, p-PhC), 127.7 (CH2); MS (m/z)
158 (M+, 36), 129 (C10H9, 100), 115 (C9H9, 40); high-resolution
MS for C11H10O (M+) (m/z) calcd 158.0782, found 158.0727.
Hydrolysis of (trans,trans-2-Methoxy-1-methyl-3-phe-
nylcyclopropyl)ethyne (1c). The hydrolysis of 1c was
performed as described for 1a. Specific experimental details
can be found in the Supporting Information.
Addition of BuLi to 1-(trans-2-Phenylcyclopropyl)-1-
tributylstannylethene. BuLi (150 µL of a 1.6 M solution,
0.24 mmol) was added to a solution of stannylethene 15 (53
mg, 0.12 mmol) in THF (5 mL) at -78 °C. The solution was
allowed to stir at -78 °C for 1 h 45 min. The reaction mixture
became yellow in color with the intensity of the color increasing
with time. The cold reaction mixture was quenched by the
addition of H2O (3 mL). The organic and aqueous layers were
separated. The organic layer was dried over MgSO4, filtered,
and concentrated by rotary evaporation to yield a clear,
colorless oil (55 mg). The crude reaction mixture was purified
by preparative thin-layer chromatography (silica gel, 2:1
hexanes/CH2Cl2) to give (trans-2-phenylcyclopropyl)ethene30
(13 mg, 76%).
3.12 (dd, 1H, PhCH2, J ) 7.6, 13.8 Hz), 2.89 (dd, 1H, PhCH2,
5
J ) 6.2, 13.8 Hz), 1.75 (d, 3H, Me, J ) 3.8 Hz, J119/117Sn-H
)
19.6 Hz) 1.52-1.59 (SnCH2CH2),27 1.29-1.38 (SnCH2CH2CH2),27
0.85-1.0 (SnCH2),27 0.90 (t, CH2CH3, J ) 7.8 Hz); 13C NMR
(C6D6) δ: 208.0, 207.7 (CdCdC), 139.9, 139.7 (i-PhC), 129.8,
129.7 (o-PhC), 128.5, 128.4 (m-PhC), 126.3, 126.3 (p-PhC), 87.7,
87.7 (SnCHdCdC), 85.3, 85.0 (MeOCH), 75.9, 75.5 (SnCHd
CdC), 56.1, 55.8 (OMe), 41.2, 41.2 (PhCH2), 29.4, 29.4
(SnCH2CH2), 27.6, 27.6 (SnCH2CH2CH2), 14.0, 13.9 (CH2CH3),
12.8, 12.5 (Me), 10.7 (SnCH2); MS (m/z) 478 (M+, 5), 421 (M+
- Bu, 41), 291 (Bu3Sn+, 64), 265 (100), 235 (55), 179 (49); high-
resolution MS for C25H42O120Sn (M+) (m/z) calcd 478.2260,
found 478.2263.
Hydrolysis of (trans-2-Phenylcyclopropyl)ethyne (1a).
Sulfuric acid (0.75 mL of a concentrated (18 M) solution) was
added to a solution of 1a (105 mg, 0.69 mmol) in THF/H2O (5
mL, 4:1). The solution was heated to reflux and allowed to stir
for 83 h. After cooling to rt, Et2O (5 mL) was added to the
reaction mixture and the organic and aqueous layers were
separated. The organic layer was dried over MgSO4 and
filtered. The solvent was then removed by rotary evaporation
to yield a yellow oil which was identified as 1-phenyl-penta-
3,4-dien-1-ol, 9 (0.64 mmol, 93%).28,29 (trans-2-Phenylcyclopro-
pyl)ethanone15 was always present (9/ethanone ) 10.7:1). 9:
IR (cm-1) 3400 (s, br, OH), 3063 (s), 3032 (s), 2914 (s), 1956 (s,
CdCdC), 1685 (s), 1598 (s), 1495 (s); 1H NMR (CDCl3) δ 7.25-
7.36 (m, 5H, o,m,p-PhH), 5.11 (pseudo-quint, 1H, H2CdCd
CH, J ) 6.8 Hz), 4.77 (t, 1H, CHOH, J ) 6.4 Hz), 4.71 (dt, 2H,
H2CdCdCH, J ) 6.8, 2.4 Hz), 2.46 (tt, 2H, CdCHCH2, J )
2.4, 6.4 Hz); 13C NMR (CDCl3) δ 209.2 (H2CdCdCH) 143.4
(i-PhC), 128.3 (m-PhC), 127.5 (p-PhC), 125.7 (o-PhC), 86.1
(H2CdCdCH), 75.1 (H2CdCdCH), 73.6 (CHOH), 38.6 (Cd
CHCH2); MS (m/z) 160 (M+, 24), 145 (13), 117 (M+ - C3H7,
100), 115 (55); high-resolution MS for C11H12O (M+) (m/z) calcd
160.0888, found 160.0894.
Acknowledgment. We thank the University of
Western Ontario, the NSERC (Canada), and the Cana-
dian Foundation for Innovation for financial support.
Supporting Information Available: NMR spectra and
GC chromatograms, where applicable, for all new compounds.
General experimental details and the preparation of com-
pounds 5c, 1c, 8b-c, and 10. Experimental details for the
X-ray crystallographic analyses including bond lengths and
angles, atomic coordinates, and anisotropic parameters for
compounds 5c and 7. This material is available free of charge
via the Internet at http://pubs.acs.org.
Hydrolysis of (trans,trans-2-Methoxy-3-phenylcyclo-
propyl)ethyne (1b). The hydrolysis of 1b was performed as
described for 1a. Specific experimental details can be found
in the Supporting information. 11: IR (cm-1) 2961 (s), 2920
(s), 1731 (s), 1691 (s), 1445 (m), 1260 (s), 1091 (s), 1025 (s),
799 (s), 679 (m); 1H NMR (CDCl3) δ 9.67 (s, 1H, CHO), 7.34-
JO047797N
(28) Brown, P. A.; Jenkins, P. R. Tetrahedron Lett. 1982, 23, 3733.
(29) Wada, E.; Kanemasa, S.; Fujiwara, I.; Tsuge, O. Bull. Chem.
Soc. Jpn. 1985, 58, 1942.
(30) Theberge, C. R.; Verbicky, C. A.; Zercher, C. A. J. Org. Chem.
1996, 61, 8792.
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