Stereochemistry of the thermal isomerizations of trans-1-ethenyl-2-phenylcyclopropane to 4-phenylcyclopentene

Article abstract of DOI:10.1021/ja9613771

The stereochemical course of the thermal isomerization of trans-1-ethenyl-2-phenylcyclopropane to 4-phenylcyclopentene at 216.4°C in the gas phase has been uncovered through syntheses and kinetic studies based on chiral d₉-labeled analogs. This example of the vinylcyclopropane-to-cyclopentene rearrangement takes place with the participation of all four stereochemically distinct paths, the relative contributions (± 3%) being 58% si, 8% ar, 24% sr, and 10% ai. The stereochemical outcome is determined by alternative diradical transition structures of comparable energy, rather than by orbital symmetry control.

Full text of DOI:10.1021/ja9613771

8258
J. Am. Chem. Soc. 1996, 118, 8258-8265
Stereochemistry of the Thermal Isomerizations of
trans-1-Ethenyl-2-phenylcyclopropane to 4-Phenylcyclopentene
John E. Baldwin* and Samuel J. Bonacorsi, Jr.
Contribution from the Department of Chemistry, Syracuse UniVersity, Syracuse, New York 13244
ReceiVed April 26, 1996X
Abstract: The stereochemical course of the thermal isomerization of trans-1-ethenyl-2-phenylcyclopropane to
4-phenylcyclopentene at 216.4 °C in the gas phase has been uncovered through syntheses and kinetic studies based
on chiral d9-labeled analogs. This example of the vinylcyclopropane-to-cyclopentene rearrangement takes place
with the participation of all four stereochemically distinct paths, the relative contributions ((3%) being 58% si, 8%
ar, 24% sr, and 10% ai. The stereochemical outcome is determined by alternative diradical transition structures of
comparable energy, rather than by orbital symmetry control.
Introduction
Scheme 1
The thermal isomerization of trans-1-ethenyl-2-phenylcyclo-
propane (t-1-d0) to 4-phenylcyclopentene (2-d0) is a well-known
vinylcyclopropane rearrangement; it is accompanied by cis, trans
interconversion between t-1-d0 and c-1-d0 (Scheme 1).1
The kinetic situation is more complicated than implied by
the simple outline of Scheme 1, for both cis and trans versions
of 1-d0 occur in enantiomeric forms, and each rate constant for
vinylcyclopropane rearrangement, k and k′, could have four
components corresponding to four stereochemical paths. Thus,
the kinetic situation is one involving 28 rate constants or, less
dauntingly, 13 independent kinetic parameters. Any experi-
mental determination of reaction stereochemistry for the vinyl-
cyclopropane rearrangement would need to employ isotopic
labeling and chiral substrates, and deal with the inherent kinetic
complexities of the situation. This challenge has now been met
using the chiral d9-labeled substrates (1S,2R)-1-E and (1S,2R)-
1-Z.
One substantial technical difficulty inherent in this system is
presented by the fact that the deuterium-labeled 4-phenylcy-
clopentene products cannot be analyzed through GC or chiral
GC, a powerful method we have used to define rection
stereochemistry for other instances of the vinylcyclopropane
rearrangement.3-6 And there is a further complication not
encountered in earlier work with deuterium-labeled vinylcy-
clopropanes7 or trans-1-ethenyl-2-methylcyclopropanes:3,8,9 prod-
ucts may form from cis as well as from trans isomers. Thus,
one must plan on an analytical strategy for the cyclopentene
products independent of GC or chiral GC or, of course,
polarimetry, a strategy able to sort out reaction mixtures
containing four isomeric products, each of which could be
derived from four different vinylcyclopropanes. Further, the
analytical methods employed would have to be sensitive enough
to permit one to acquire stereochemical information on very
small (∼1 mg) samples of the cyclopentenes, for thermal
reactions run to higher conversions form more and more
products from stereorandom reactants, and are stereochemically
less informative.
The thermal stereomutation reactions2 for the vinylcyclopro-
pane (1S,2R)-1-E are shown explicitly in Scheme 2. This chiral
trans starting material may be expected to undergo both cis-
trans isomerization and loss of enantiomeric excess as (1R,2S)-
1-E forms. Each of the four isomers in Scheme 2 would have
time-dependent relative concentrations, and each could react to
give four different isomers of d9-labeled 4-phenylcyclopentene.
The relationships among the immediate precursor, stereo-
chemistry of the cyclopentene product, and reaction stereo-
chemistry (suprafacial or antarafacial, s or a, participation of
the allyl unit; retention or inversion, r or i, at the migrating
carbon, C2) for (1S,2R)-1-E are summarized in Scheme 3.
Similar correlations for other isomers of 1-E and 1-Z reactants
are easily constructed.
In Ghatlia’s stereochemical investigation of the vinylcyclo-
propane rearrangement of (-)-(1R,2R)-1-(2′-(Z)-deuterioethen-
yl)-2-methylcyclopropane,9 cyclopentene products were con-
(3) Baldwin, J. E.; Bonacorsi, S. J. J. Am. Chem. Soc. 1993, 115, 10621-
10627.
(4) Baldwin, J. E.; Bonacorsi, S. J. J. Org. Chem. 1994, 59, 7401-7409.
(5) Asuncion, L. A.; Baldwin, J. E. J. Org. Chem. 1996, 60, 5778-
5784.
(6) Asuncion, L. A.; Baldwin, J. E. J. Am. Chem. Soc. 1995, 117, 10672-
10677.
X Abstract published in AdVance ACS Abstracts, August 15, 1996.
(1) (a) Simpson, J. M.; Richey, H. G. Tetrahedron Lett. 1973, 27, 2545-
2548. (b) Marvell, E. N.; Lin, C. J. Am. Chem. Soc. 1978, 100, 877-883.
(c) Andrist, A. H.; Kalynchuk, D. G. Spectrosc. Lett. 1978, 11, 133-142.
(2) Baldwin, J. E. In The Chemistry of the Cyclopropyl Group; Rappoport,
Z., Ed.; John Wiley & Sons: Chichester, 1995; Vol. 2, pp 469-494.
(7) Baldwin, J. E.; Villarica, K. A.; Freedberg, D. I.; Anet, F. A. L. J.
Am. Chem. Soc. 1994, 116, 10845-10846.
(8) Andrews, G. D.; Baldwin, J. E. J. Am. Chem. Soc. 1976, 98, 6705-
6706.
(9) Baldwin, J. E.; Ghatlia, N. D. J. Am. Chem. Soc. 1991, 113, 6273-
6274.
S0002-7863(96)01377-7 CCC: $12.00 © 1996 American Chemical Society

Isomerizations of trans-1-Ethenyl-2-phenylcyclopropane
J. Am. Chem. Soc., Vol. 118, No. 35, 1996 8259
Scheme 2
Scheme 4
Scheme 5
Scheme 3
methylammonium bromide as a phase transfer catalyst.12 The
extent of deuterium incorporation in the two R positions was
about 99%, judging from the loss of proton NMR absorption
intensity at δ 2.4 and 2.7. Reduction of ketone (3R)-4-d4 with
Red-Al in benzene gave a mixture of diastereomeric alcohols
(3R)-5-d4,13 which were converted to the xanthate esters (3R)-
6-d4 using n-Bu4NHSO4 as a phase transfer catalyst.14,15
The olefins formed through pyrolysis of the xanthates (3R)-
6-d4 at 175 °C were distilled from the reaction vessel as they
formed and collected in a cold trap. The chiral, deuterium-
labeled 4-phenylcyclopentene (4R)-2-d3 was separated from the
isomeric (3R)-phenylcyclopentene-2,5,5-d3 byproduct and puri-
fied by preparative GC. Oxidation with MCPBA converted
(4R)-2-d3 to (4R)-3-d3.
The chiral deuterium-labeled 1-ethenyl-2-phenylcyclopro-
panes required for this stereochemical investigation were
prepared following well-established precedents (Scheme 5).
Styrene-d8 was condensed with (()-menthyl diazoacetate16 in
the presence of a chiral copper aldimine catalyst derived from
L-alanine to provide a 15:85 mixture of cis and trans isomers
of (()-menthyl 2-phenylcyclopropanecarboxylates, enriched in
the (1R,2R)-7 isomer.17 The corresponding aldehyde, obtained
through a LiAlH4 reduction followed by a pyridinium chloro-
chromate oxidation, was converted to dibromide (1S,2R)-8 with
CBr4 and triphenylphosphine.18,19
verted to cyclopentane oxides, and these oxides were analyzed
by 2H NMR spectroscopy with the aid of an added chiral
lanthanide shift reagent. A similar approach was envisioned
1
for the present work, but for practical reasons, H NMR was
adopted as the spectroscopic tool. The required discrimination
between enantiotopic hydrogens was established, stereochemical
assignments based on a deuterium-labeled 4-phenylcyclopentene
of known absolute stereochemistry were made, and the sub-
strates selected for the study were prepared and isomerized.
Results
Syntheses. Authentic samples of the cis and trans isomers
of 1-ethenyl-2-phenylcyclopropane (c-1-d0, t-1-d0) and of
4-phenylcyclopentene (2-d0) were prepared following published
procedures.1,10 Oxidation of 2-d0 with m-chloroperbenzoic acid
(MCPBA) in CH2Cl2 gave a 1:9 mixture of c-3-d0 and t-3-d0,
Dibromide (1S,2R)-8 was dehydrochlorinated with n-BuLi
in pentane to yield alkyne (1R,2R)-9.18 A distilled sample
(11) (a) Smith, A. B.; Branca, S. J.; Guaciaro, M. A.; Wovkulich, P.
M.; Korn, A. Organic Syntheses; Wiley: New York, 1990; Collect. Vol.
VII, pp 271-275. (b) Hulce, M.; Mallomo, J. P.; Frye, L. L.; Kogan, T. P.;
Posner, G. H. Organic Syntheses Wiley: New York, 1990; Collect. Vol.
VII, pp 495-500 and references therein. (c) Posner, G. H.; Mallamo, J. P.;
Miura, K. J. Am. Chem. Soc. 1981, 103, 2886-2888. (d) Posner, G. H.;
Hulce, M.; Mallamo J. P.; Drexler, S. A.; Clardy, J. J. Org. Chem. 1981,
5246-5248. (e) Posner, G. H.; Mallamo, J. P.; Hulce, M.; Frye, L. L. J.
Am. Chem. Soc. 1982, 104, 4180-4185. (f) Posner, G. H.; Frye, L. L.;
Hulce, M. Tetrahedron 1984, 40, 1401-1407.
a mixture difficult to separate by preparative GC. A sample of
the cis epoxide was secured by treating 2-d0 with an aqueous
solution of N-bromosuccinimide followed by dehydrohaloge-
nation of the intermediate bromohydrin with NaOH.
A chiral deuterium-labeled analog of epoxide t-3-d0, trans-
(4R)-phenylcyclopentene-1,3,3-d3 oxide ((4R)-3-d3), was pre-
pared from (3R)-(+)-phenylcyclopentanone11 as outlined in
Scheme 4. Ketone (3R)-4-d0 was converted to (3R)-4-d4 using
a biphasic system containing K2CO3, D2O, C6H6, and cetyltri-
(12) Krzymien, L. L.; Leitch, L. C. J. Labelled Compd. 1973, 9, 331-
338.
(13) Capka, M.; Chvalosky, V.; Kochloefl, K.; Kraus, M. Collect. Czech.
Chem. Comm. 1969, 34, 118-124.
(14) Lee, A. W. M.; Chan, W. H.; Wong, H. C.; Wong, M. S. Synth.
Commun. 1989, 19, 547-552.
(10) 4-Substituted cyclopentenes usually give a preponderance of the
trans epoxide when oxidized by MCPBA: (a) Crossley, N. S.; Darby, A.
C.; Henbest, H. B.; McCullough, J. J.; Nicholls, B.; Stewart, M. F.
Tetrahedron Lett. 1961, 12, 398-403. (b) Henbest, H. B. Proc. Chem. Soc.
1962, 74-75. (c) Henbest, H. B. Proc. Chem. Soc. 1963, 159-165. (d)
Sohar, P.; Bernath, G. Acta Chim. Acad. Sci. Hung. 1975, 87, 285-291.
(15) Lee, A. W. M.; Chan, W. H.; Wong, H. C. Synth. Commun. 1988,
18, 1531-1536.
(16) Takamura, N.; Mizoguchi, T.; Koga, K.; Yamada, S. Tetrahedron
Lett. 1971, 47, 4495-4498.
(17) (a) Aratani, T. Pure Appl. Chem. 1985, 57, 1839-1844. (b) Baldwin,
J. E.; Carter, C. G. J. Am. Chem. Soc. 1982, 104, 1362-1368.

8260 J. Am. Chem. Soc., Vol. 118, No. 35, 1996
Baldwin and Bonacorsi
containing both alkyne (1R,2R)-9 and some (1R,2S)-9 was
reacted with 1 equiv of DIBAL in pentane.20,21 Reaction of
the organoaluminum intermediate with an excess of D2O
afforded a mixture containing the expected olefins, unreacted
alkynes, and some overreduced compounds. Olefinic products
were isolated by preparative GC on a TCEPE column, and then
(1S,2R)-1-E and (1S,2S)-1-E were separated from each other
by GC on an Apiezon L column. Partially separated samples
of the olefins were chromatographed again to yield analytically
Scheme 6
1
pure (1S,2R)-1-E. The H NMR analysis of a homogeneous
sample of (1S,2R)-1-E indicated 96% deuterium incorporation
at the terminal vinyl position, C2′, with E stereochemistry:9,22
the observed coupling constant between the trans hydrogens on
C1′ and C2′ was 17 Hz.
When alkynes (1R,2R)-9 and (1R,2S)-9 were separated by
preparative GC, and (1R,2R)-9 was reduced with 1.5 equiv of
DIBAL over a longer reaction period, a slightly higher yield of
(1S,2R)-1-E was realized, and it was easily obtained as a
homogeneous sample through a simple GC purification using
a TCEPE column, but 1H NMR spectroscopy revealed a lower
(85%) incorporation of deuterium label. The extended reaction
time may have allowed more d0 olefin to be formed through a
reductive elimination of the organoaluminum intermediate prior
to reaction of that intermediate with D2O.
The (1S,2R)-1-Z substrate was prepared (Scheme 5) from a
sample of GC-purified (1R,2R)-9 by way of the d9 alkyne
(1R,2R)-10 (99% deuterium at the alkynyl position, after two
exchanges), which was reduced with 1.2 equiv of DIBAL for
16 h and then treated with H2O. Olefin (1S,2R)-1-Z was isolated
in pure form from the product mixture by preparative GC. The
1H NMR spectrum showed a coupling constant of 10 Hz
between the two cis vinyl hydrogens on C1′ and C2′. Small
samples of (1S,2R)-1-E and (1S,2R)-1-Z from each synthetic
route were subjected to oxidation with KMnO4 followed by
treatment with diazomethane to yield methyl trans-2-phenyl-
cyclopropanecarboxylates enriched in the (1R,2R) enantiomer.3,4
Chiral GC analyses, utilizing a Cyclodex B column at 100 °C,
revealed the enantiomeric excess values of these samples to be
52%, the (1R,2R) enantiomer eluting first. For analyses of the
methyl cis-2-phenylcyclopropanecarboxylates, the Lipodex E
column was used; the (1R,2S)-(-) enantiomer23 eluted first.
Chemical Shift Assignments for Methylene Protons in 2-d0
and t-3-d0. The proton NMR spectrum of 4-phenylcyclopentene
(2-d0) shows methylene proton absorptions at δ 2.45 and 2.82.10
In the related trans epoxide, t-3-d0, the methylene resonances
come at δ 1.75 and 2.45. Expectations based on chemical shifts
observed for protons in similar compounds provided the tentative
assignments shown in the annotated structures below
Experimental evidence relevant to these assignments was
obtained through NOE and lanthanide shift reagent studies. The
benzylic proton in epoxide 3-d0 is at δ 3.0; NOE difference
spectra24 showed that irradiation of the signal at δ 3.0 resulted
in a positive NOE effect for the δ 2.45 signal and no appreciable
response for the δ 1.75 absorption, thus indicating a cis
relationship between H(benzylic) and H(at δ 2.45). Utilizing
the chiral lanthanide shift reagent tris[3-[(heptafluoropropyl)-
hydroxymethylene]-(+)-camphorato]europium(III), Eu(hfc)3, it
was possible to measure the relative downfield shifts of the
1
signals initially centered at δ 1.75 and 2.45 in the H NMR
spectrum of 3-d0. One would expect that with increased
additions of Eu(hfc)3 the resonances for the proton cis to the
epoxide function would shift downfield faster than the signals
for the other methylene hydrogen.25,26 Plots of increments of
Eu(hfc)3 versus chemical shifts for the two protons initially at
δ 1.75 and 2.45 showed that the δ 2.45 proton moved downfield
more that 50% faster than the absorption originally at δ 1.75,
thus lending further support for an assignment of the proton at
δ 2.45 as the one cis to the epoxide oxygen, and cis to the
benzylic hydrogen. Finally, when labeled 4-phenylcyclo-
pentenes from thermal isomerizations of (1S,2R)-1-E and
(1S,2R)-1-Z were obtained, the proton NMR absorptions at δ
2.45 and 2.82 had unequal intensities, corresponding to the
alternative stereochemical possibilities for the CHD unit. The
related epoxides showed the same inequalities, and confirmed
that the proton at δ 2.45 in the cyclopentene is at δ 1.75 in the
trans epoxide.
Chiral Lanthanide Shift Reagent Studies. Experiments
with several chiral shift reagents and c-3-d0, t-3-d0, and (4R)-
3-d3 were conducted to learn whether an NMR distinction
between enantiotopic hydrogens in 4-phenylcyclopentene could
be made indirectly, by way of the related trans epoxides (Scheme
6).27 The best results were obtained using Eu(hfc)3 that had
been dried under vacuum several days before use. Careful
addition of small quantities of Eu(hfc)3 at the beginning of an
analysis allowed a sure tracking as signals shifted downfield.
Once partial resolution had been attained, larger quantities of
Eu(hfc)3 could be added to resolve the NMR absorptions of
enantiotopic protons fully.
associating the proton cis to phenyl with the signal at δ 2.45 in
the cyclopentene and at δ 1.75 ppm in the epoxide.
When incremental amounts of Eu(hfc)3 were added to a
CDCl3 solution of the achiral trans epoxide 3-d0, the oxirane
hydrogens moved downfield most rapidly, and were resolved,
the benzylic hydrogen moved downfield, the hydrogens cis to
the oxygen of the epoxide function were shilfted downfield and
(18) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 36, 3769-3772.
(19) Posner, G. H.; Loomis, G. L.; Sawaya, H. S. Tetrahedron Lett. 1975,
16, 1373-1376.
(20) Zweifel, G.; Miller, J. A. Org. React. 1984, 32, 375-517.
(21) Gavrilenko, V. V.; Palei, B. A.; Zakharkin, L. I. Bull. Acad. Sci.
USSR, DiV. Chem. Sci. 1968, 872-874.
(22) Gensler, W. J.; Bruno, J. J. J. Chem. Soc. 1963, 1254-1259.
(23) (a) Aratani, T.; Nakanishi, N.; Nozaki, H. Tetrahedron 1970, 26,
1675-1684. (b) Krieger, P. E.; Landgrebe, J. A. J. Org. Chem. 1978, 43,
4447-4452. (c) Doering, W. von. E.; Robertson, L. R.; Ewing, E. E. J.
Org. Chem. 1983, 48, 4280-4286. (d) Scholl, B.; Hansen, H.-J. HelV. Chim.
Acta 1986, 69, 1936-1958. (e) Fritschi, H.; Leutenegger, U.; Pfaltz, H.
HelV. Chim. Acta 1988, 71, 1553-1565.
(24) Derome, A. E. Modern NMR Techniques for Chemistry Research;
Pergamon Press: New York, 1987; pp 97-128.
(25) Manni, P. E.; Howie, G. A.; Katz, B.; Cassady, J. M. J. Org. Chem.
1972, 37, 2769-2771.
(26) Cockerill, A. F.; Davies, G. L. O.; Harden, R. C.; Rackham, D. M.
Chem. ReV. 1973, 73, 553-588.
(27) Yeh, H. J. C.; Balani, S. K.; Yagi, H.; Greene, R. M. E.; Sharma,
N. D.; Boyd, D. R.; Jerina, D. M. J. Org. Chem. 1986, 51, 5439-5443.

Isomerizations of trans-1-Ethenyl-2-phenylcyclopropane
J. Am. Chem. Soc., Vol. 118, No. 35, 1996 8261
Table 1. Relative Concentrations of Vinylcyclopropanes and
Cyclopentenes from Thermal Reactions of c-1-E at 216.4 °C
time (min)
[t-1-E]
[c-1-E]
[2]
0
10
20
45
60
90
10.0
39.6
61.3
78.2
78.9
79.7
90.0
60.4
37.4
19.4
17.8
16.0
0
0
1.3
2.4
3.3
4.3
Table 2. Relative Concentrations of Vinylcyclopropanes and
Cyclopentenes from Thermal Reactions of (1S,2R)-1-E at 216.4 °C
time (min)
[t-1-E]
[c-1-E]
[2]
0
100.0
87.4
83.1
83.7
81.7
81.3
0.0
12.0
15.3
14.3
15.7
15.7
0.0
0.6
1.6
2.0
2.6
3.0
20a
45a
60a
60b
75b
a 96% deuterium incorporation at C2′. b 85% deuterium incorporation
at C2′.
Figure 1. Relative concentrations of t-1-E and c-1-E from thermal
isomerizations of 1-ethenyl-2-phenylcyclopropanes as functions of time
using the data of Tables 1 and 2.
Scheme 7
-λ2t
[t-1-E](t) ) A1(e-λ t) + A2(e
)
(1)
(2)
1
[c-1-E](t) ) B1(e-λ t) + B2(e
)
-λ2t
1
parameters λ1 and λ2 common to all four relative concentration
versus time plots (Figure 1). The coefficients A1 and A2 (and
B1 and B2) are not independent, for the sum must equal the
initial relative concentration of the isomer.
All four calculated functions and the data points are shown
in Figure 1. In each, λ1 ) 9.4 × 10-4 s-1 and λ2 ) 1.0 × 10-5
s-1. The A1 (or B1) parameters and R2 values for the four plots
were -75.1 and 0.998 (t-1-E, Table 1), 74.9 and 0.987 (c-1-E,
Table 1), 15.4 and 0.984 (t-1-E, Table 2), and -16.7 and 0.987
(c-1-E, Table 2).
were resolved, and the related geminal hydrogens (originally
at δ 1.75) moved downfield less quickly, but at high concentra-
tions of shift reagent they too were separated. Some interference
from the aromatic protons in the molecule complicated the
observed resonances for these signals, a complication avoided
with C6D5 in place of C6H5 in the d9-labeled systems used in
the stereochemical experiments. Similar NMR studies with the
cis epoxide c-3-d0 showed that, when enough shift reagent had
been added, NMR signals from it did not overlap with any
signals from protons of t-3-d0; thus, epoxidation reaction
mixtures of reaction products containing c-3-d0 and t-3-d0 in a
1:9 ratio may be analyzed using Eu(hfc)3 and 1H NMR without
The expressions for t-1-E and c-1-E may be integrated and
used to provide an equation for the relative concentration of
the 4-phenylcyclopentenes 2 as a function of time (eq 2):
-λ2t
[2](t) ) k((A1/λ1)(1 - e-λ t) + (A2/λ2)(1 - e )) +
1
1
-λ2t
k′((B1/λ1)(1 - e-λ t) + (B2/λ2)(1 - e )) (3)
1
prior separation of diastereomers, when H NMR enantiotopic
H-cis-to-benzyl-H absorptions have been shifted downfield to
at least δ 13.0.
Here k is the rate constant for all four [1,3] shift paths from the
trans-vinylcyclopropanes, and k′ is the rate constant for all [1,3]
shift paths from the cis-vinylcyclopropanes. Using the data from
Tables 1 and 2, one can plot the concentration of 2 as a function
of time starting with either 90% c-1-E (Table 1) or 100% t-1-E
(Table 2); the data points and calculated functions are shown
in Figure 2. The best fits were found using the parameters k )
When a sample of (4R)-3-d3 of 75% ee (by chiral GC of one
diastereomer of precursor (3R)-5-d4) was investigated with the
aid of Eu(hfc)3, resolved 1H NMR signals for both enantiotopic
versions of both sorts of methylene protons were obtained. In
both cases, the less intense C5-H enantiotopic proton of the
(4S)-phenyl stereoisomer was downfield of the resonance due
to the enantiotopically related proton in the (4R)-phenyl system
(Scheme 7).
Kinetic Data and Rate Constants. The thermal reactions
of (1S,2R)-1-E, (1S,2R)-1-Z and c-1-E at 216.4 °C were run in
the gas phase in sealed ampules. Samples of c-1-E were
obtained from thermal reaction mixtures of (1S,2R)-1-E; they
were purified to 90:10 cis:trans by preparative GC, sealed in
ampules along with a minimun amount of spectral grade
pentane, and isomerized at 216.4 °C. The results of analytical
GC assessments of product mixtures are summarized in Tables
1 and 2.
5.7 × 10-6 s-1 and k′ ) 1.43 × 10-5 s-1
.
With the aid of these best-fit rate constants and eq 3, one
may calculate the relative concentrations and proportions of
4-phenylcyclopentene products derived for cis and trans isomers
of the cyclopropane reactants over any time interval. Some
calculated values for these relative concentrations that will be
convenient to have at hand are gathered in Table 3.
Determinations of enantiomeric excess values for the recov-
ered vinylcyclopropanes (1S,2R)-1-E and (1S,2S)-1-E were made
by chiral GC analyses of the corresponding methyl esters,
obtained through oxidations followed by esterifications with
diazomethane. These observed ee values, relative concentration
differences for the enantiomers of t-1-E, and weighted time-
The data of Tables 1 and 2 can be modeled with integrated
functions (eqs 1 and 2) appropriate for the kinetic situation at
hand (Schemes 1 and 2). A least-squares fit of the data with
the aid of suitable software28 gives optimal values for the
(28) Deltagraph Pro 3, DeltaPoint, Inc., Monterey, CA 93940.

8262 J. Am. Chem. Soc., Vol. 118, No. 35, 1996
Baldwin and Bonacorsi
Figure 2. Relative concentrations of 2 as functions of time from 90%
c-1-E (squares) and 100% (1S,2R)-1-E (filled circles). The data points
were fit with eq 2, using the A, B, and λ parameters found through the
least-squares calculations of Figure 1, to provide the new parameters
Figure 3. 1H NMR spectra in the presence of Eu(hfc)3 for epoxides 3
in 4-phenylcyclopentenes 2 isolated from thermal reaction mixtures:
at top, from 45-min reaction of (1S,2R)-1-Z; at bottom, from 60-min
reaction of (1S,2R)-1-E.
k ) 5.7 × 10-6 s-1 and k′ ) 1.43 × 10-5 s-1
.
Table 3. 4-Phenylcyclopentene Products 2 Derived from Cis and
Trans Isomers of 1-E
time
(min)
[2]
total
[2] from
c-1-E
[2] from
t-1-E
% from
t-1-E
starting material with the single product ratio from c-1-E (Table
5), the rate constant ratios are found to be (ksi + kar)/k ) 0.66
( 0.01 and (k′si + k′ar)/k′ ) 0.52 ( 0.01.
reactant
t-1-E
t-1-E
t-1-E
c-1-E
45
60
75
75
1.77
2.39
3.01
3.76
0.40
0.60
0.80
2.07
1.37
1.80
2.21
1.69
77.3
75.0
73.5
44.9
Samples of d9-labeled 4-phenylcyclopentenes from thermal
reactions of (1S,2R)-1-E and (1S,2R)-1-Z were converted to the
corresponding trans epoxides, which were analyzed by 1H NMR
in the presence of variable proportions of Eu(hfc)3. The
1
observed H NMR signals for enantiotopic protons provided
averaged values of ee for (1S,2R)-1-E at various reaction times
(P(t) values) are recorded in Table 4.
the numerical values summarized in Table 6. Figure 3 displays
segments of Eu(hfc)3 resolved 1H NMR spectra for the epoxides
3 stemming from the 45-min reaction of (1R,2S)-1-Z and the
60-min thermal reaction of (1R,2S)-1-E.
The samples of the cis isomer (1S,2S)-1-E formed through
the stereomutations of (1S,2R)-1-E were found to be racemic,
or nearly racemic. If the cis isomer in reaction mixtures were
always racemic, then one would expect [(1S,2R)-1-E] -
[(1R,2S)-1-E] to follow a single exponential decay; the best
single-exponential-function match to the experimental data was
given by [(1S,2R)-1-E] - [(1R,2S)-1-E] ) 52.2 exp(-3.21 ×
10-4t) (R2 ) 0.997). The weighted time-averaged enantiomeric
excess values (P(t)) for recovered (1S,2R)-1-E were calculated
from the expression P(t) ) (52.2∫exp(-3.21 × 10-4t)(15.4 exp-
(-9.4 × 10-4t) + 84.6 exp(-1 × 10-5t)) dt)/∫(15.4 exp(-9.4
× 10-4t) + 84.6 exp(-1 × 10-5t)) dt. Although the ee values
for recovered (1S,2R)-1-E decrease quite rapidly, the P(t) values
show a more moderate time-dependent diminution.
Table 5 shows the distribution between pairs of cyclopentene
products (4R,5S)-2 + (4S,5R)-2 and (4S,5S)-2 + (4R,5R)-2
formed during thermal isomerizations of (1S,2R)-1-E and of c-1-
E. The percentages of each isomer were estimated by 1H NMR
analyses of preparative GC-purified samples. Fortunately,
isotope-induced chemical shift perturbations were large enough
so that C(5)HD proton absorptions did not overlap with the
minor C(5)H2 resonances. Thus, the relative integrated signal
intensities in Table 5 reflect the d9-labeled systems only; no
“corrections” were needed to adjust for the lack of 100%
deuterium incorporation at C2′ in starting materials.
Reaction Stereochemistry. From the experimental evidence
summarized above one may calculate rate constants for each
of the four stereochemically distinct paths leading from one
enantiomer of a d9-labeled trans-1-ethenyl-2-phenylcyclopro-
pane to a d9-labeled 4-phenylcyclopentene. The logic and
method for these calculations follow precedents detailed in
earlier publications.3,4,6-9 One only has to correct the observed
preferences for one enantiomer (Table 6) for the contributions
from racemic d9-labeled cis-1-ethenyl-2-phenylcyclopropane and
for the P(t) of the trans reactant. For example, for the 60-min
product mixture, referring to Tables 3 and 4, 19.5% (100 ×
(25 × 0.48)/(25 × 0.48 + 75 × 0.66)) of the pair of enantiomers
(4R,5R)-3 and (4S,5S)-3 comes from racemic cis reactants, and
80.5% from t-1-E having a weighted time-averaged ee (P(t))
of 31.5%. Thus, the ratio of enantiomers formed directly from
the enantiomeric trans substrates is (59 - 0.5 × 19.5):(41 -
0.5 × 19.5) ) 61.2:38.8. The fraction ksi/(ksi + kar), say f, may
then be calculated simply, for (100 + P(t))f + (100 - P(t))(1
- f) ) 2 × 61.2; from the value of f found, the relative value
of ksi follows: 0.855 × 0.66 ) 0.564, the value recorded (in
percentage terms) along with the other calcluated krel values in
Table 7.
From the product ratios of Table 5, one may calculate the
rate constant ratios (ksi + kar)/k and (k′si + k′ar)/k′, since one
already has values for k and k′ and may calculate the relative
concentrations of 4-phenylcyclopentene products formed from
t-1-E and from c-1 E over the given reaction times (Table 4).
Using each of the three product ratios from (1S,2R)-1-E as
The average values of relative rate constants in Table 7 show
consistency, but the calculated standard deviations underestimate
the likely uncertainties; when the estimated uncertainty in the
(ksi + kar)/k ratio is included, all relative rate constants are
estimated to be reliable to ( 3%, and the values used in the
following discussion, 58% si, 8% ar, 24% sr, and 10 ai, are

Isomerizations of trans-1-Ethenyl-2-phenylcyclopropane
J. Am. Chem. Soc., Vol. 118, No. 35, 1996 8263
Table 4. Observed, Calculated, and Time-Averaged Enantiomeric Excess Values for Recovered (1S,2R)-1-E and (1S,2S)-1-E after Thermal
Reactions at 216.4 °C
time
(min)
(1S,2R)-1-E
ee (obs, %)
[(1S,2R)-1-E] -
[(1R,2S)-1-E]a
[(1S,2R)-1-E] -
[(1R,2S)-1-E]b
(1S,2S)-1-E
ee (obs, %)
P(t)c
0
20
45
60
75
52.2
40.0
28.0
19.0
14.4
52.2
35.4
23.4
15.6
11.7
52.2
35.5
21.9
16.4
12.3
52.2
43.5
35.3
31.5
28.2
8
4
0
0
a (ee (%) of (1S,2R)-1-E/100) [t-1-E]. b Calculated with [(1S,2R)-1-E] - [(1R,2S)-1-E] ) 52.2 exp(-3.21 × 10-4t). c See text.
Table 5. Observed Relative Percentages of Cyclopentene Products
2 Formed During the Thermal Reactions of (1S,2R)-1-E and c-1-E
conclude that this vinylcyclopropane-to-cyclopentene rearrange-
ment is not controlled by any conservation-of-orbital-symmetry
consideration.
time
(min)
[(4R,5S)-2 +
(4S,5R)-2]a
[(4S,5S)-2 +
(4R,5R)-2]b
reactant
Comparisons with the stereochemical characteristics of related
substituted vinylcyclopropane-to-cyclopentene rearrangements
provide further insight. There are now seven examples (sum-
marized in Table 8) of vinylcyclopropane rearrangements that
have been studied in sufficient detail to learn the relative
importance of all four paths, and these examples establish a
clear pattern. Over a substantial range of substituents at trans-
C2 and E-C2′ positions, all four possible reaction paths
participate. The pattern emerges from stereochemical results
obtained for different systems representing a range of kinetic
complexities, studied with different analytical methods by
different experimentalists, utilizing several different data reduc-
tion strategies. The essential result, the fairly consistent pattern
of stereochemical outcomes, does not at this stage seem
vulnerable to some undetected and unsuspected systematic error
in one or another of these experimental efforts.30,31
Just why this pattern of stereochemical proclivities should
be so generally maintained is another question, one that presently
remains elusive. Further experimental and theoretical work
seems required before a fully developed mechanistic under-
standing of the vinylcyclopropane-to-cyclopentene isomerization
may be gained, and investigations designed to contribute toward
that goal are in progress.
(1S,2R)-1-E
(1S,2R)-1-E
(1S,2R)-1-E
c-1-E
45c
60d
75e
75e
63
37
61.3
60.6
56
38.7
39.4
44
a 1H NMR relative intensity at 2.45 ppm. b 1H NMR relative intensity
at 2.82 ppm. c 96% deuterium incorporation at C2′ in the starting
material. d 85% deuterium at C2′. e 90% cis isomer; 91% deuterium
C2′, recovered from thermal product mixtures starting from (1S,2R)-
1-E of 85% or 96% deuterium at C2′.
Table 6. Relative Concentrations of Stereoisomeric Epoxides 3
Derived from 4-Phenylcyclopentene-d9 Thermal Rearrangement
Products
time
(min)
[(4R,5R)-3]:
[(4S,5S)-3]
[(4S,5R)-3]:
[(4R,5S)-3]
reactant
(1S,2R)-1-Za
(1S,2R)-1-Eb
(1S,2R)-1-Ec
(1S,2R)-1-Ec
45
45
60
75
43:57
60:40
59:41
59:41
38:62
56:44
54:46
52:48
a 99% deuterium incorporation at C2′ for (1S,2R)-1-Z. b 96% deu-
terium incorporation at C2′. c 85% deuterium incorporation at C2′.
understood to be associated with such uncertainties. The rate
constants themselves may be calculated, for k ) (ksi + kar + ksr
+ kai) ) 5.7 × 10-6 s-1
.
Experimental Section
General Procedures. Tetrahydrofuran was freshly distilled from
benzophenone and sodium as required. Methylene chloride, pentane,
and hexanes were stored over dried 4A molecular sieves for several
days before use. Pyridine and DMSO were freshly distilled from CaH2
and stored over dry 4A molecular sieves. Diethyl ether was either
distilled from LiAlH4 and stored over molecular sieves or used directly
from a newly opened container. Carbon disulfide was stored over 4A
molecular sieves for several weeks before use. Dry benzene was
secured through distillation.
Measurements of enantiomeric excess values by chiral GC employed
a HP 5890A gas chromatograph with a FID detector interfaced to an
HP 3396 Series II or a HP 3392A integrator. All chiral GC analyses
were done using either a fused silica Cyclodex B capillary column
(methylated â-cyclodextrin as the stationary phase; J & W Scientific,
30 m × 0.26 mm i.d.) or a fused silica Lipodex E capillary GC column
(octakis(2,6-di-O-pentyl-3-O-butyryl)-γ-cyclodextrin as the stationary
phase; Macherey-Nagel, 50 m × 0.25 mm i.d.). The injection port
temperatures were maintained at 160 × °C and the detector block at
300 °C. Optimal GC separations were achieved on the Cyclodex B
column with a column head pressure of 25 psi.
Discussion and Conclusion
Through syntheses of labeled chiral 1-ethenyl-2-phenylcy-
clopropane reactants and a reference compound for establishing
absolute stereochemical assignments for enantiotopic protons
in 4-phenylcyclopentenes, and through exercising suitable
analytical methods, this kinetic and stereochemical study arrived
at experimentally based values for the rate constants for the
four paths leading from (1S,2R)-1-E or (1S,2R)-1-Z to four
stereoisomers of 2.
The mechanistic significance or interpretation of these results
depends in part on theory, in part on related stereochemical
findings. According to the Woodward-Hoffmann theory,29 if
the vinylcyclopropane-to-cyclopentene isomerization were con-
certed and controlled by the constraints and the energetic
benefits of orbital symmetry control, it should take place
exclusively through the “allowed” si and ar paths. The reaction
stereochemistry favors these paths, but only very modestly; the
(ksi + kar):(ksr + kai) ratio is 66:34, corresponding to a ∆∆Gq
of only 0.65 kcal/mol. (The (k′si + k′ar):(k′sr + k′ai) ratio for
the isomerizations from the cis isomer is estimated to be 52:
48, corresponding to no appreciable energetic preference at all.)
Since the ksr + kai components are very much in evidence, and
the ksi + kar components do not enjoy any substantial energy-
of-concert advantage over the “forbidden” paths, one must
The 1H NMR and 13C NMR spectra were recorded for CDCl3
solution containing 0.1% Me4Si on a General Electric 300 MHz QE-
300 or 500 MHz spectrometers. Other instrumentation used in this
work has been detailed elsewhere.3,4
(30) Vinylcyclopropanes substituted with a tert-butyl group at C1′ appear
to react with other stereochemical characteristics; see: (a) Gajewski, J. J.;
Warner, J. M. J. Am. Chem. Soc. 1984, 106, 802-803. (b) Gajewski, J. J.;
Squicciarini, M. P. J. Am. Chem. Soc. 1989, 111, 6717-6728. (c) Gajewski,
J. J.; Olson, L. P. J. Am. Chem. Soc. 1991, 113, 7432-7433. (d) Gajewski,
J. J.; Olson, L. P.; Willcott, M. R. J. Am. Chem. Soc. 1996, 118, 299-306.
(31) Compare Carpenter, B. K. Acc. Chem. Res. 1992, 25, 520-528.
(29) (a) Woodward, R. B.; Hoffmann, R. Angew. Chem., Int. Ed. Engl.
1969, 8, 781-853. (b) Woodward, R. B.; Hoffmann, R. The ConserVation
of Orbital Symmetry; Verlag Chemie: Weinheim, 1971; pp 120-122.

8264 J. Am. Chem. Soc., Vol. 118, No. 35, 1996
Baldwin and Bonacorsi
Table 7. Relative Rate Constants (%) for Distinct Paths Followed in the Thermal Isomerizations of (1S,2R)-1-Z and (1S,2R)-1-E to
4-Phenylcyclopentenes-d9 at 216.4 °Ct
time
(min)
reactanta
ksi
kar
7.3
10.3
9.6
ksr
24.8
25.4
23.5
20.7
kai
9.2
8.6
10.5
13.3
45
45
60
75
(1S,2R)-1-Z
(1S,2R)-1-E
(1S,2R)-1-E
(1S,2R)-1-E
58.7
55.7
56.4
59.6
6.4
av 57.6 ( 1.8
8.4 ( 1.8
23.6 ( 2.1
10.4 ( 2.1
Table 8. Complete Stereochemical Studies of Thermal
Rearrangements of Chiral
trans-1-((E)-2′-R′-Ethenyl)-2-R-cyclopropanes to
3-R′-4-R-Cyclopentenes
benzylic hydrogen, indicative of nearly 100% deuterium labeling R to
the carbonyl group. The GC retention time of the d4 product was
identical with that of (3R)-4-d0. (Preparative GC of this ketone using
a Carbowax 20M on Chromosorb W column resulted in some loss of
deuterium and the appearance of H NMR absorptions at δ 2.68 and
2.4 ppm.)
1
R
R′
ref T (°C) si (%) ar (%) sr (%) ai (%)
D
D
D
CH3
C6H5
D
7
9
8
3
300
40
55
65
60
58
44
67
13
15
8
10
8
20
12
23
18
22
19
24
25
17
24
13
5
11
10
11
4
(4R)-Phenylcyclopentene-1,3,3-d3 ((4R)-2-d3). A 60-mg (0.37
mmol) sample of ketone (3R)-4-d4 in 10 mL of dry benzene was cooled
to 0 °C under N2, and 0.11 mL of 3.4 M sodium bis(2-methoxyethoxy)-
aluminum hydride (Red-Al) in toluene was added. The cold bath was
removed, and the reaction mixture was stirred for 1 h. It was then
quenched with 5 mL of water, and the products were extracted with
three 15-mL portions of ether. The ether extracts were combined, dried
over Na2SO4, filtered, and concentrated. The two diastereomeric
products were purified together on a 20% Carbowax 20M column. 1H
NMR for the mixture: δ 7.26 (m, 10H), 4.54 (s, 1H), 4.46 (s, 1H),
3.41 (t, J ) 9 Hz, 1H), 3.1 (t, 9 Hz, 1H), 2.26 (dd, J ) 8 and 12.7 Hz,
1H), 2.1 (dd, J ) 7.5 and 12.5 Hz, 1H), 1.9 (t, J ) 11.5 Hz, 1H), 1.64
(t, J ) 12 Hz, 1H), 1.56 (br s, 2H). The later eluting diastereomer
was resolved into separate enantiomers by chiral GC on a Lipodex E
column: it had an ee of 75%, the dominant (3R) enantiomer eluting
first. The mixture of crude d4 alcohols was converted into the
corresponding xanthate esters, and they were pyrolyzed at 175 °C to
provide a mixture of cyclopentenes (4R)-2-d3 and (3R)-phenylcyclo-
pentene-2,5,5-d3. These olefins were separated and purified on a 20%
Carbowax 20M on Chromosorb W column. Data for (4R)-2-d3: 1H
NMR δ 7.26 (m, 5H), 5.77 (s, 1H), 3.45 (t, J ) 8 Hz, 1H), 2.82 (ddd,
J ) 1.9, 9, 16.4 Hz, 1H), 2.44 (ddd, J ) 2.3, 7, 16.4 Hz, 1H). Data
for the (3R) isomer: 1H NMR δ 7.23 (m, 5H), 5.93 (d, J ) 2 Hz, 1H),
3.89 (d of t, J ) 2.1 and 7.7 Hz, 1H), 2.39 (dd, J ) 9, 12.8 Hz, 1H),
1.71 (dd, J ) 6.6 and 13 Hz, 1H); 13C NMR δ 142.8, 133.3, 130.9,
127.4, 126.2, 125, 50.3, 32.8, 31.5.
trans-(4R)-Phenylcyclopentene-1,3,3-d3 Oxide ((4R)-3-d3). Fol-
lowing the procedure used to synthesize epoxide t-3-d0, (4R)-2-d3 was
converted to (4R)-3-d3, which was purified on a 15% SE-30 column;
GC-MS: 169 (M+, 1), 158 (20), 157 (20), 156 (55), 141 (32) 139 (100),
111 (49). 1H NMR δ 7.27 (m, 5H), 2.98 (t, J ) 9 Hz, 1H), 2.45 (dd,
J ) 7.8 and 14 Hz, 1H), 1.75 (dd, J ) 10.31 and 14 Hz).
Resolution of Enantiotopic Proton NMR Absorptions of (4R)-3-
d3 With Eu(hfc)3. The 1H NMR spectrum of a GC purified sample of
(4R)-3-d3 in CDCl3 was recorded, and then small amounts of dry
tris[3-[(heptafluoropropyl)hydroxymethylene]-(+)-camphorato]-
europium(III) (Eu(hfc)3) were added, recording the NMR spectrum after
each addition. After several additions of Eu(hfc)3 the 1H NMR signals
for C2 and both C5 hydrogens of (4R)-3-d3 and of (4S)-3-d3 became
apparent. The dominant signals for the (4R) isomer could be seen at
δ 13.5 and 6.7 ppm. The resolved signals for the minor (4S) enantiomer
were seen at δ 14.0 and slightly downfield from δ 6.7.
CH3
CH3
CH3
C6D5
C6H5 CH3
C6H5 C6H5
284.6
296.5
250
216.4
234.4
160
4
6
trans-4-Phenylcyclopentene Oxide (t-3-d0). To a 15-mg (0.1 mmol)
sample of 4-phenylcyclopentene (2-d0) in 2 mL of CH2Cl2 was added
90 mg (0.25 mmol) of 50% MCPBA. The reaction mixture was stirred
overnight under N2, and then subjected to a conventional workup.
Analytical GC of the concentrate indicated two new products in a 1:9
ratio. Data for the major isomer, t-3-d0, after purification by GC on a
15% SE-30 on Chromosorb W column: GC-MS, m/z (relative
abundance) 160 (M+, 29), 142 (29), 131 (28), 117 (100), 115 (76),
104 (37), 103 (28), 91 (44), 77 (36), 51 (28), 39 (26); 1H NMR δ 7.35
(m, 5H), 3.62 (s, 2H), 3.01 (quintet, J ) 8.9 Hz, 1H), 2.48 (dd, J )
7.5, 14 Hz, 2H), 1.77 (dd, J ) 10.3, 14 Hz, 2H); 13C NMR δ 148.5,
128.4, 127.3, 126.2, 56.6, 37.7, 35.7.
cis-4-Phenylcyclopentene Oxide (c-3-d0). To 80 mg (0.56 mmol)
of 4-phenylcyclopentene (2-d0) and 1 mL of water cooled to 0 °C was
added 100 mg (0.56 mmol) of NBS with stirring. The reaction mixture
was warmed to 40 °C for 2 h and then transferred to a separatory funnel.
The resulting halohydrin was extracted from the aqueous solution with
three 10-mL portions of ether. The ether extracts were washed with
brine, dried, filtered, and concentrated, and the concentrate was
combined with 1 mL of 30% NaOH. The reaction mixture was stirred
for 20 h at rt and then extracted with two 25-mL portions of pentane.
The pentane solution was dried over Na2SO4, filtered, and concentrated
by distillation. Epoxide c-3-d0 was purified on a 15% SE-30 on
Chromosorb W column for analysis: GC-MS, m/z (relative abundance)
160 (22, M+), 117 (40), 116 (24), 115 (26), 104 (17), 40 (100); H
NMR δ 7.21 (m, 5H), 3.56 (s, 2H), 3.47 (tt, J ) 3.1 and 10.3 Hz, 1H),
2.32 (dd, J ) 10.3 and 14.9 Hz, 2H), 2.13 (dd, J ) 3.1 and 14.9 Hz,
2H).
(3R)-(+)-Phenylcyclopentanone ((3R)-4-d0), prepared following a
published route,11 was purified on a 20% Carbowax 20M on Chro-
mosorb W column; analytical GC showed but a single component: [R
1
]
) + 51.2° (c 0.205, CDCl3);32 1H NMR δ 7.3 (m, 5H), 3.43 (m,
D
1H), 2.68 (dd, 7.7 and 18.3 Hz, 1H), 2.4 (m, 4H), 2.0 (m, 1H); 13C
NMR δ 218.4, 143.0, 128.6, 126.7 (2 signals), 45.8, 42.2, 38.8, 31.2.33
(3R)-Phenylcyclopentanone-2,2,5,5-d4 ((3R)-4-d4). To a solution
of ketone (3R)-4-d0 (60 mg, 0.38 mmol) in 10 mL of dry benzene were
added 5 mL of D2O, 20 mg of K2CO3, and 5 mg of cetyltrimethylam-
monium bromide. The biphasic mixture was magnetically stirred and
heated to reflux under a N2 atmosphere for 24 h. The reaction mixture
was then cooled to rt and extracted with several portions of benzene.
The combined extracts were dried, filtered, and concentrated. Analysis
(1R,2R)-trans-2-(Phenyl-d5)cyclopropanecarboxaldehyde-2,3,3-
d3. Condensation of 10 g of styrene-d8 (Aldrich) with (()-menthyl
diazoacetate in the presence of a chiral copper catalyst derived from
L-alanine was accomplished following a well-established precedent. 17
Reduction of the ester or the corresponding carboxylic acid with LiAlH4
and then oxidation using PCC afforded the trans (1R,2R) aldehyde:
GC-MS, m/z (relative abundance) 154 (19), 152 (18), 126 (12), 125
(100), 124 (29), 123 (12), 122 (24), 121 (43), 98 (12), 97 (28), 54
(13), 42 (12), 40 (25).
1
of a small sample of the product by H NMR showed the presence of
only two upfield hydrogens relative to the integrated absorption of the
trans-1-(2′,2′-Dibromoethenyl)-2-(Phenyl-d5)cyclopropane-2,3,3-
d3-((1S,2R)-8). The aldehyde prepared immediately above (6.9 g, 44.8
mmol) dissolved in 500 mL of dry benzene was added to 62.1 g (237
mmol) of PPh3 and 39.8 g (120 mmol) of CBr4. The reaction mixture
was heated to reflux for 24 h under N2, cooled to rt, and filtered through
(32) From this rotation, one may conclude that the ee of the ketone is at
least 56-58%; see: (a) Taber, D. F.; Raman, K. J. Am. Chem. Soc. 1983,
105, 5935-5937, note 13. (b) Taura, Y.; Tanaka, M.; Wu, X.-M.; Funakoshi,
K.; Sakai, K. Tetrahedron 1991, 47, 4879-4888.
(33) Fairlie, D. P.; Bosnich, B. Organometallics 1988, 7, 936-945.

Isomerizations of trans-1-Ethenyl-2-phenylcyclopropane
J. Am. Chem. Soc., Vol. 118, No. 35, 1996 8265
a sintered glass funnel. Concentration of the filtrate gave a red oil
which was triturated with pentane; the resulting PPh3 was removed by
filteration. Several repetitions of this procedure served to remove most
of the PPh3. Final purification was achieved by Kugelrohr distillation
(0.5 mmHg) to yield 10 g (70%) of a mixture of dibromide (1S,2R)-8
along with some cis isomer. Data for (1S,2R)-8: GC-MS, m/z (relative
abundance) 312:310:308 (M+ for C11H2Br2D8, 0.2:0.4:0.2), 231 (15),
229 (15), 150 (100), 149 (21), 148 (28), 121 (12).
each with distilled water. All bulbs were dried immediately before
use in an oven heated to 160 °C. About 65 mg of a GC-purified olefin
((1S,2R)-1-E (85% or 96% D at C2′) or (1S,2R)-1-Z (99% D at C2′))
and 5 mg of hydroquinone were placed in each of a set of 90 cm3
reaction bulbs; the bulbs were subjected to three freeze-pump-thaw
cycles, and then sealed under vacuum.
All thermal reactions were conducted in a thermally regulated oil
bath heated to 216.4 °C; the temperature was monitored with a
calibrated digital platinum resistance thermometer (Hewlett-Packard
2802A with a HP 34740A display) and regulated to (0.2 °C using a
Bayley 253 temperature controller. Following each run, the bulb was
removed from the oil bath and allowed to cool to rt; it was then cooled
to -78 °C, opened, and rinsed out with dry pentane. Capillary GC
analyses of the product mixtures were performed on a HP 5% phenyl
methyl silicone 25 m × 0.20 mm × 0.33 mm film thickness ultra-
high-performance capillary column. The GC analyses of the product
mixtures from the thermal reactions of (1S,2R)-1-E are summarized in
Table 2.
(1R,2S)-trans-1-Ethynyl-2-(phenyl-d5)cyclopropane-2,3,3-d3 ((1R,2S)-
9). To 5 g (16 mmol) of dibromide (1S,2S)-8 in 100 mL of dry pentane
under N2 at -78 °C was added with rapid stirring 20.2 mL (40.4 mmol)
of 2.0 M n-BuLi in pentane. The reaction mixture was stirred at -78
°C for 1 h and then warmed to rt and stirred for an additional 1 h. It
was then cooled to 0 °C, and 25 mL of water was added cautiously.
After 30 min at rt, the mixture was acidified with 10% HCl and the
products were extracted with three 50-mL portions of pentane. These
extracts were combined, dried, filtered, and concentrated. Further
purification was achieved by Kugelrohr distillation (0.5 mmHg, bp 60-
80 °C) to give 966 mg (40%) of crude alkyne. Data for (1R,2R)-9:
GC-MS, m/z (relative abundance) 150 (58, M+), 149 (56), 148 (100),
After capillary GC analysis of the thermolysis products, the mixture
of components was subjected to preparative GC on a 14% Apiezon L
column. Samples of (1S,2R)-1-E and c-1-E were recovered together
and oxidized with KMnO4 in benzene containing the crown ether 18-
C-6.3,4 The resulting acids were treated with CH2N2, and the methyl
esters formed were analyzed by chiral GC on a Cyclodex B chiral GC
column. The enantiomeric excesses of the recovered vinylcyclopro-
panes found in this indirect manner are reported in Table 4.
The cyclopentene products 2 from the thermal reactions of (1S,2R)-
1-E and (1S,2R)-1-Z were isolated by preparative GC. Samples of the
1
122 (12), 121 (36), 120 (27), 54 (13); H NMR δ 1.89 (d, J ) 2 Hz,
1H),1.48 (s, 1H); 13C NMR δ 64.7, 10.6.
(1S,2R)-trans-(2′-(E)-Deuterioethenyl)-2-(phenyl-d5)cyclopropane-
2,3,3-d3 ((1S,2R)-1-E). The 966-mg sample (6.44 mmol) of alkyne
(1R,2S)-9 dissolved in 100 mL of dry pentane in a flame-dried flask
was cooled to 0 °C, and 6.66 mL (6.44 mmol) of 1.0 DIBAL in hexanes
was added slowly over 15 min. The reaction mixture was stirred rapidly
and allowed to warm to rt. Stirring was continued for 18 h, and the
reaction was again cooled to 0 °C. Slowly, 10 mL of D2O was added
to the cooled reaction solution. The mixture was stirred rapidly for 3
h at rt, and then enough 10% HCl was added to the mixture to dissolve
the gelantinous mass that had formed. The contents of the reaction
flask were transferred to a separatory funnel, and the aqueous layer
was extracted with three 25-mL portions of pentane. The combined
organic extracts were washed with saturated NaHCO3, dried, filtered,
concentrated, and Kugelrohr distilled to yield 734 mg (75%) of olefin
(1S,2R)-1-E along with some unreacted alkyne and some overreduced
products. Preparative GC using first a 20% TCEPE and then a 14%
Apiezon L column gave the olefin (1S,2R)-1-E as a homogeneous
sample (analytical GC): GC-MS, m/z (realtive abundance) 153 (M+,
38), 152 (20), 151 (18), 137 (52), 136 (100), 135 (78), 134 (50), 133
(26), 122 (17), 121 (27), 97 (17), 82 (18), 70 (28), 69 (28), 54 (23), 42
1
cyclopentenes as small as 0.5 mg were first analyzed by H NMR to
secure the information summarized in Table 5. Data for 2: GC-MS,
m/z (relative abundance) 153 (M+, 68), 152 (33), 151 (21), 137 (49),
136 (100), 135 (77), 134 (77), 133 (23), 121 (26), 70 (26), 69 (30), 54
1
(19); H NMR δ 5.8 (s), 2.45 (s), 2.8 (s). The cyclopentenes were
then dissolved in CH2Cl2 and epoxidized with an excess of MCPBA.
The resulting epoxides were isolated by extracting the CH2Cl2 solution
with pentane and washing the organic phase with aqueous Na2CO3.
Pure samples of the epoxides 3 were secured by preparative GC on a
15% SE-30 on Chromosorb W column. Data for the epoxides 3: 1H
NMR δ 3.59 (s), 2.43 (s), 1.73 (s). The CDCl3 solutions of the epoxides
from each run were treated with enough Eu(hfc)3 to shift the 1H NMR
signals originally at δ 2.47 and 1.73 downfield to approximately δ 14.0
and 9.3. The 1H NMR signals for the separate enantiotopic hydrogens
were well resolved in these regions of the spectrum and uncomplicated
from nearby impurities (Figure 3). The relative integrated absorption
intensities are summarized in Table 6.
1
(19); H NMR δ 5.52 (dd, J ) 8.5 and 17 Hz, 1H), 5.09 (d, J ) 17
Hz), 1.68 (d, J ) 8.5 Hz).
(1S,2R)-trans-(2′-(Z)-Deuterioethenyl)-2-(phenyl-d5)cyclopropane-
2,3,3-d3 ((1S,2R)-1-Z). A GC-purified sample of alkyne (1R,2R)-9 (206
mg,1.37 mmol) was dissolved in dry pentane and reacted with 1.03
mL (2.06 mmol) of 2.0 M n-BuLi in pentane at -78 °C. The flask
was warmed briefly to rt and then cooled again. To the cooled solution
was added 1 mL of D2O (99.9% D), and the reaction mixture was stirred
rapidly for 30 min while being warmed to rt. The reaction solution
was extracted with pentane, and the pentane extracts were dried, filtered,
and concentrated to yield 185 mg (1.23 mmol) of alkyne (1R,2R)-10.
After a second exchange reaction, 1H NMR analysis of the alkyne
indicated greater then 99% deuterium incorporation at the terminal
alkynyl position. The labeled alkyne was placed in a reaction flask
under a N2 atmosphere and cooled to 0 °C; it was treated with 2.06
mL (2.06 mmol) of 1.0 M DIBAL in hexanes. The reaction mixture
was warmed to room temperature and stirred for 18 h. The reaction
flask was then cooled to 0 °C, and 3 mL of 99.9% D2O was added
with rapid stirring. The aqueous solution was extracted with two 25-
mL portions of pentane. The pentane extracts were dried over Na2-
SO4, filtered, and concentrated; purification of the concentrate on a
20% TCEPE on Chromosorb P column gave 75 mg of the pure alkene
(1S,2R)-1-Z): 1H NMR δ 5.53 (ddd, J ) 2.3, 8.4, 10.5 Hz, 1H), 4.91
(d, J ) 10.3 Hz, 1H), 1.68 (d, J ) 8.4 Hz, 1H).
Samples of c-1-E recovered from thermal isomerizations of (1S,2R)-
1-E were GC purified to 90:10% cis/trans (capillary GC). Ap-
proximately 5 mg of c-1-E was dissolved in 50 µL of pentane to provide
a stock solution; small samples of the stock solution, approximately
10 µL, were sealed in 65-mL cleaned reaction bulbs. At the completion
of each reaction the cooled reaction bulbs were scored, broken open,
and rinsed out with a minimum amount of solvent. The GC analyses
of the thermolysis mixtures are summarized in Table 1.
A larger scale thermolysis of c-1-E was conducted using 20 mg of
the GC-purified olefin (90:10% cis/trans by analytical GC). The bulb
containing the olefin was treated in the same manner as described above.
The bulb was placed in an oil bath heated to 216.5 °C for 75 min. The
bulb was allowed to cool to rt and was broken open. The contents of
the bulb were dissolved in pentane, analyzed by GC, and then purified
by GC. The 1H NMR analysis of the cyclopentene products revealed
that the downfield signal at δ 2.82 was larger than the signal at δ 2.45,
the relative absorption intensities being 56:44 (Table 5).
Acknowledgment. This paper is dedicated to Professor
Nelson J. Leonard on the occasion of his 80th birthday. We
thank the National Science Foundation for support of this work
through Grant CHE 91-00246.
Thermal Isomerizations. Kinetic bulbs were prepared and soaked
in 12 M HCl for 24 h, rinsed with distilled water, soaked for 2 days in
concentrated NH4OH saturated with EDTA, and then rinsed 20 times
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