Direct measurements of the kinetics of 3-exo radical cyclizations using radical reporter groups

Article abstract of DOI:10.1021/jo990129v

The E and Z isomers of the 4-(2,2-diphenylcyclopropyl)-3-butenyl radical (1), produced by laser flash photolysis of the corresponding PTOC esters in THF, cyclized to the (2,2-diphenylcyclopropyl)(cyclopropyl)methyl radical (2) that rapidly opened to 1,1-diphenyl-4-cyclopropyl-3-butenyl radicals (3). Radicals 3 were monitored by UV spectroscopy, but the observed rate constants were for the initial, relatively slow cyclizations of radicals 1 to radical 2. The Arrhenius functions determined in the temperature range of 20-58°C were log(k/s^-1) = (11.46 ± 0.38) - (9.10 ± 0.54)/θ for (E)-1 and log(k/s^-1) = (12.34 ± 0.32) - (10.10±0.45)/θ for (Z)-1 where θ = 2.3RT in kcal/mol and errors are at 2σ. Radical (Z)-1 cyclizes somewhat faster than radical (E)-1 as a result of a more favorable entropy of activation and despite the fact that the activation energy for cyclization of (Z)-1 through the requisite syn-transition state is greater than that for cyclization of (E)-1 through an anti-transition state.

Full text of DOI:10.1021/jo990129v

4064
J . Org. Chem. 1999, 64, 4064-4068
Dir ect Mea su r em en ts of th e Kin etics of 3-exo Ra d ica l Cycliza tion s
Usin g Ra d ica l Rep or ter Gr ou p s
Eldi Furxhi, J ohn H. Horner,* and Martin Newcomb*
Department of Chemistry, Wayne State University, Detroit, Michigan 48202
Received J anuary 25, 1999
The E and Z isomers of the 4-(2,2-diphenylcyclopropyl)-3-butenyl radical (1), produced by laser
flash photolysis of the corresponding PTOC esters in THF, cyclized to the (2,2-diphenylcyclopropyl)-
(cyclopropyl)methyl radical (2) that rapidly opened to 1,1-diphenyl-4-cyclopropyl-3-butenyl radicals
(3). Radicals 3 were monitored by UV spectroscopy, but the observed rate constants were for the
initial, relatively slow cyclizations of radicals 1 to radical 2. The Arrhenius functions determined
in the temperature range of 20-58 °C were log(k/s-1) ) (11.46 ( 0.38) - (9.10 ( 0.54)/θ for (E)-1
and log(k/s-1) ) (12.34 ( 0.32) - (10.10 ( 0.45)/θ for (Z)-1 where θ ) 2.3RT in kcal/mol and errors
are at 2σ. Radical (Z)-1 cyclizes somewhat faster than radical (E)-1 as a result of a more favorable
entropy of activation and despite the fact that the activation energy for cyclization of (Z)-1 through
the requisite syn-transition state is greater than that for cyclization of (E)-1 through an
anti-transition state.
Sch em e 1
The kinetics of a wide range of alkyl radical reactions
have been determined by indirect methods over the past
few decades.1 Most of these studies ultimately provide
rate constants that are based on the rate constants for
bimolecular reactions of Bu3SnH with alkyl radicals
determined by Ingold’s group by direct laser flash pho-
tolysis (LFP) methods in the early 1980s.2,3 Others relate
to primary kinetic data for reactions of thiols and
nitroxyls.1 The popularity of the indirect method results
from the ability to perform the experiments without
special (and usually expensive) instrumentation and the
absence of useful chromophores in the reactant and
product radicals, which precludes UV detection in the
simplest “special” technique, LFP with UV detection. The
precision of an indirect kinetic determination can be quite
good, but the absolute values of the rate constants thus
determined contain the known uncertainty of the initial
kinetic measurements of the trapping reactions and an
unknown error due to the common requisite assumption
that one radical is an appropriate model for another,
closely related radical.1
temperature7-9 to give benzylic or diphenylalkyl radicals
that are readily detected by UV spectroscopy,10 and
because the follow-up reaction is so fast, only the kinetics
of the initial slow reaction are measured. One attractive
feature of the reporter group approach is that the fast
reporter reaction can divert an inherently reversible
reaction such that the kinetics for a thermodynamically
unfavored step can be measured directly.6 In this work,
we have employed the reporter group approach for direct
measurements of rate constants for 3-exo cyclizations of
3-butenyl radicals to a cyclopropylcarbinyl radical, a
reaction that is inherently unfavorable by more than 5
kcal/mol. Radicals 1, produced photochemically by LFP,
cyclized to radical 2 that rapidly opened to the UV-
detectable radicals 3 (Scheme 1).
Our group has developed the use of internal “reporter
groups” for direct LFP kinetic measurements of reactions
of radicals that do not otherwise contain useful chromo-
phores.4-6 The reporter groups are 2-aryl-cyclopropanes
positioned such that the initial radical reactions produce
2-aryl-substituted cyclopropylcarbinyl radical intermedi-
ates. The aryl-substituted intermediate radicals ring open
with rate constants exceeding 1 × 1011 s-1 at ambient
Resu lts a n d Discu ssion
The radical precursors employed were Barton PTOC
esters11 5 prepared from the corresponding carboxylic
acids 4. The diastereomeric acids (E)-4 and (Z)-4 were
obtained by reduction of a mixture of the acids, chro-
matographic separation of the diastereomeric alcohols,
and oxidation of the purified alcohols back to acids 4. The
(E) and (Z) stereochemical assignments were based on
the consistent vinyl coupling constants for the intermedi-
(1) Newcomb, M. Tetrahedron 1993, 49, 1151-1176.
(2) Chatgilialoglu, C.; Ingold, K. U.; Scaiano, J . C. J . Am. Chem.
Soc. 1981, 103, 7739-7742.
(3) J ohnston, L. J .; Lusztyk, J .; Wayner, D. D. M.; Abeywickreyma,
A. N.; Beckwith, A. L. J .; Scaiano, J . C.; Ingold, K. U. J . Am. Chem.
Soc. 1985, 107, 4594-4596.
(7) Newcomb, M.; Manek, M. B. J . Am. Chem. Soc. 1990, 112, 9662-
9663.
(8) Newcomb, M.; J ohnson, C. C.; Manek, M. B.; Varick, T. R. J .
Am. Chem. Soc. 1992, 114, 10915-10921.
(9) Martin-Esker, A. A.; J ohnson, C. C.; Horner, J . H.; Newcomb,
M. J . Am. Chem. Soc. 1994, 116, 9174-9181.
(10) Chatgilialoglu, C. In Handbook of Organic Photochemistry;
Scaiano, J . C., Ed.; CRC Press: Boca Raton, FL, 1989; Vol. 2; pp 3-11.
(11) Barton, D. H. R.; Crich, D.; Motherwell, W. B. Tetrahedron
1985, 41, 3901-3924.
(4) Newcomb, M.; Tanaka, N.; Bouvier, A.; Tronche, C.; Horner, J .
H.; Musa, O. M.; Martinez, F. N. J . Am. Chem. Soc. 1996, 118, 8505-
8506.
(5) Newcomb, M.; Horner, J . H.; Emanuel, C. J . J . Am. Chem. Soc.
1997, 119, 7147-7148.
(6) Horner, J . H.; Tanaka, N.; Newcomb, M. J . Am. Chem. Soc. 1998,
120, 10379-10390.
10.1021/jo990129v CCC: $18.00 © 1999 American Chemical Society
Published on Web 05/13/1999

Kinetics of 3-exo Radical Cyclizations
J . Org. Chem., Vol. 64, No. 11, 1999 4065
Ta ble 1. Ra te Con sta n ts for Cycliza tion s of Ra d ica ls 1
in THF
b
radical
temp (°C)a
10-5 × kobs (s-1
)
(E)-1
19.5
19.7
29.8
30.3
39.2
40.0
48.7
58.2
58.2
0.38 ( 0.04
0.45 ( 0.03
0.84 ( 0.05
0.84 ( 0.03
1.18 ( 0.07
1.30 ( 0.09
1.91 ( 0.07
2.73 ( 0.10
2.76 ( 0.12
0.41 ( 0.03
0.55 ( 0.07
0.75 ( 0.06
0.78 ( 0.06
1.21 ( 0.04
1.29 ( 0.13
1.90 ( 0.10
2.76 ( 0.24
(Z)-1
20.3
29.6
38.9
48.5
0.65 ( 0.06
1.15 ( 0.06
1.77 ( 0.03
2.84 ( 0.21
0.62 ( 0.04
1.04 ( 0.06
1.78 ( 0.09
2.99 ( 0.05
F igu r e 1. Time-resolved spectra from reaction of radical (E)-1
at ambient temperature. The traces are at 4.2, 8.2, 12.2, and
30.2 µs after laser irradiation with data at 2.2 µs subtracted
to give a baseline. Radicals 3 are growing in with λmax at 332
nm, and the 2-pyridinethiyl radical with λmax at 490 nm is
decaying. Symbols on the 30.2 µs spectrum show the wave-
lengths monitored. The inset is the trace observed at 332 nm
where the X-axis is time in µs.
a
b
(0.2 °C. Errors are 1σ. Rate constants in the two columns
are from independent experiments.
results in a problem in the LFP kinetic measurements.
Specifically, radical-radical and radical-oxygen reac-
tions have pseudo-first-order rate constants that can
approach 1 × 104 s-1 and will contribute to the observed
rate constants for reactions of radicals 1.14 To minimize
the kinetic contribution from radical-radical reactions,
the solutions of precursors employed for kinetic measure-
ments were more dilute than those used for obtaining
time-resolved spectra; the resulting kinetic traces dis-
played significantly less decay than is seen in the inset
in Figure 1. In addition, rate constants for the lower
temperature runs were determined by solving the data
with double exponential functions, for growth and decay;
at higher temperatures, no decay was apparent. These
procedures do not avoid a kinetic contribution from
reactions of radicals 1 with residual oxygen, however, and
kinetic measurements at temperatures below 20 °C
would be increasingly in error. The upper temperature
limit is due to the thermal instability of the PTOC ester
precursors.
The Arrhenius parameters from the kinetic data
(Figure 2) are given in eqs 1 and 2 where θ ) 2.3RT in
kcal/mol and errors are at 2σ. The errors in these
parameters are somewhat larger than those often found
in LFP studies of first-order reactions6 as a result of the
relatively narrow temperature ranges studied. The cal-
culated rate constants at 20 °C are 4.6 × 104 s-1 and 6.2
× 104 s-1 for (E)-1 and (Z)-1, respectively.
ates and PTOC esters 4; J ) 10.4-10.9 Hz for all (Z)
compounds, and J ) 15.2-15.4 Hz for all (E) compounds.
As determined by NMR spectroscopy, the sample of (E)-4
used in preparation of the PTOC ester contained about
5% of the (Z) isomer, and the sample of (Z)-4 contained
<1% of the other isomer.
Carboxylic acids 4 and the intermediate alcohols from
their reduction were characterized by NMR spectroscopy
and HRMS. Because PTOC esters are thermally unstable
and sensitive to visible light, radical precursors 5 were
characterized only by NMR spectroscopy. The samples
of PTOC esters used in the LFP kinetic studies were
judged to be >95% pure on the basis of the 1H NMR
spectra. Impurities in the PTOC ester samples did not
affect the kinetic measurements because the concentra-
tions of precursors used in the LFP studies were only
about 2 × 10-5 M.
PTOC esters are efficiently cleaved by 355 nm light
from a Nd:YAG laser and have been used in a number of
kinetic studies.12 The initial photochemical reactions of
5 gave acyloxyl radicals that decarboxylated “instantly”
on the nanosecond time scale to produce radicals 1. The
byproduct of the photolysis, the 2-pyridinethiyl radical,
has a long wavelength absorbance with λmax ) 490 nm13
but does not absorb appreciably at 330-335 nm, which
was the expected λmax of product radicals 3.10 Figure 1
shows time-resolved spectra obtained following photolysis
of (E)-5. The ultimate product radicals 3 are growing in
with λmax at 332 nm, and decay of the signal from the
2-pyridinethiyl radical is observed (490 nm).
(E)-1: log(k/s-1) ) (11.46 ( 0.38) - (9.10 ( 0.54)/θ
(1)
(Z)-1: log(k/s-1) ) (12.34 ( 0.32) - (10.10 ( 0.45)/θ
(2)
The Arrhenius parameters might seem unusual, but
they are readily rationalized. The larger activation
energy for cyclization of radical (Z)-1 results from the
facts that the transition states for the cyclizations of the
two isomers are different and strain energy in the ground
state of the (Z) radical is not necessarily relieved in the
requisite transition state for cyclization.15 The larger log
A term for cyclization of (Z)-1 is due to the loss of one
The kinetics of cyclization of radicals (E)-1 and (Z)-1
were measured over the temperature ranges 20-58 °C
and 20-48 °C, respectively, and the results are in Table
1. These cyclization reactions are relatively slow, which
(14) In our experimental design, radical-radical reactions and
reactions of radicals with residual oxygen have pseudo-first-order rate
constants summing to about 5 × 103 s-1. See: Musa, O. M.; Horner, J .
H.; Shahin, H.; Newcomb, M. J . Am. Chem. Soc. 1996, 118, 3862-
3868.
(12) See refs 4-6 and references therein.
(13) Alam, M. M.; Watanabe, A.; Ito, O. J . Org. Chem. 1995, 60,
3440-3444.

4066 J . Org. Chem., Vol. 64, No. 11, 1999
Furxhi et al.
propyl)methyl radical (9) by the kinetic competency of
the ring opening of 9 and the fact that cyclic radical 9
was trapped in low yields in reactions of 8.20 The
cyclization of 8 to 9 is accelerated by a Thorpe-Ingold
effect of the two methyl groups, but the cyclizations that
ultimately result in deuterium label scrambling in the
homoallyl radicals 1321 and 1422 are quite similar to the
reactions of radicals 1 studied here.
The deuterium label scrambling in radical 13 was
studied over a wide temperature range by ESR and
competition kinetic studies involving trapping by Bu3-
SnH.21 The rate constants for rearrangements deter-
mined from the tin hydride trapping experiments must
be corrected with the now-accepted rate constants for
reactions of alkyl radicals with Bu3SnH.2 When this is
done, the Arrhenius function in eq 3 is obtained for the
cyclization of 13 to 12, where it is assumed that the
isotopic substitution has negligible kinetic effects in the
cyclization of 13 and ring opening of 12. The rate constant
for cyclization of 13 at 20 °C from eq 3 is 6500 s-1, or
only about 10-15% as large as those for cyclizations of
radicals 1. This difference in cyclization rate constants
reflects the steric and electronic effects of the reporter
F igu r e 2. Arrhenius plots for radical (E)-1 (circles) and (Z)-1
(squares).
group substituent in radicals 1. The rate constant for
22
cyclization of radical 14 at 25 °C (k ) 5.5 × 104 s-1
)
is
quite similar to those of radicals 1.
log(k/s-1) ) 12.1-11.1/θ
(3)
The 3-exo cyclizations of radicals 15 and 16 give
thermodynamically favored products as a result of the
radical stabilization of the aryl groups, and these cycliza-
tion reactions are relatively fast. The kinetics of cycliza-
tion of radical 15 were studied by indirect methods
involving tin hydride trapping23 and nitroxyl radical
trapping24 reactions. More recently, the 3-exo cyclizations
of both radicals 15 and 16 were measured directly by LFP
methods that gave highly precise rate constants and
Arrhenius parameters with good precision.25 The rate
constants for cyclization at 20 °C are 5.3 × 106 s-1 for 15
and 1.8 × 107 s-1 for 16, and the Arrhenius log A terms
are (11.41 ( 0.19) and (10.7 ( 0.4) for 15 and 16,
respectively, where the errors are at 2σ.25
The Arrhenius log A parameters are the entropic
terms, and these should be similar for 3-exo cyclizations
of various homoallyl radicals because few conformational
options are available in formation of the small cyclopropyl
ring. In general, this expectation is fulfilled. The values
for the log A terms for radicals 1 are similar to those of
radicals 13 and 15, despite the large differences in rate
constants. Because of the unusual steric demands of the
two phenyl groups in radical 16, it is perhaps not
unexpected that the log A term for cyclization of this
radical is not consistent with those for the other 3-exo
radical cyclizations. It is noteworthy that the log A terms
for the trans-substituted radicals (E)-1 and 15, both of
which were determined with quite good precision, are
F igu r e 3. Radical reactions involving 3-exo cyclizations.
free internal rotation in this isomer in comparison to
(E)-1 and the corresponding reduced entropy demand for
achieving the transition state.16,17
Although 3-exo cyclizations of simple 3-butenyl radicals
to give cyclopropylcarbinyl radicals are thermodynami-
cally unfavorable, they occur in vinyl migration reactions
or the equivalent (Figure 3).18 Perhaps the most well-
known example is the neophyl radical (6) rearrangement
to the 1,1-dimethyl-2-phenylethyl radical (7).18 Isomer-
ization of the 2,2-dimethyl-3-butenyl radical (8) to the
1,1-dimethyl-3-butenyl radical (10)19,20 was demonstrated
to proceed through the intermediate (2,2-dimethylcyclo-
(15) A similar situation exists in the analogous 3-pentenyl radicals
where computations at the B3LYP/6-31G* level indicated that the anti
transition state for cyclization of the (E)-radical is 0.9 kcal/mol more
stable than the syn transition state for cyclization of the (Z)-radical.6
(16) In radical (Z)-1, steric interactions between the substituents
on the double bond will limit conformational mobility about the C4-
C5 bond (between the vinyl and cyclopropyl groups), leading to a higher
log A value. The difference in log A values for cyclizations of the two
isomers of 1 (0.9) corresponds to a difference in ∆S‡ of 4 eu, which is
in the range of values expected for torsional entropy of rotation of a
C-C single bond.17
(21) Effio, A.; Griller, D.; Ingold, K. U.; Beckwith, A. L. J .; Serelis,
A. K. J . Am. Chem. Soc. 1980, 102, 1734-1736.
(22) Engel, P. S.; Culotta, A. M. J . Am. Chem. Soc. 1991, 113, 2686-
2696.
(17) Page, M. I.; J encks, W. P. Proc. Natl. Acad. Sci. U.S.A. 1971,
68, 1678-1683.
(18) Beckwith, A. L. J .; Ingold, K. U. In Rearrangements in Ground
and Excited States; de Mayo, P., Ed.; Academic: New York, 1980; Vol.
1; pp 161-310.
(23) Bowry, V. W.; Lusztyk, J .; Ingold, K. U. J . Chem. Soc., Chem.
Commun. 1990, 923-925.
(19) Chatgilialoglu, C.; Ingold, K. U.; Tse-Sheepy, I.; Warkentin, J .
Can. J . Chem. 1983, 61, 1077-1081.
(24) Beckwith, A. L. J .; Bowry, V. W. J . Am. Chem. Soc. 1994, 116,
2710-2716.
(20) Newcomb, M.; Glenn, A. G.; Williams, W. G. J . Org. Chem.
1989, 54, 4, 2675-2681.
(25) Halgren, T. A.; Roberts, J . D.; Horner, J . H.; Martinez, F. N.;
Tronche, C.; Newcomb, M. Submitted for publication.

Kinetics of 3-exo Radical Cyclizations
J . Org. Chem., Vol. 64, No. 11, 1999 4067
sure. The crude product (6.7 g, 0.023 mol) was purified by
chromatography on silica gel (2:1, hexanes/EtOAc) to give 4.2
g (72%) of a mixture of the isomeric acids as an oil. The product
was a 75:25 (Z/ E) mixture that was not separable by chro-
matography on silica gel.
statistically indistinguishable; this reinforces the conclu-
sion that an unusual entropic effect is at play in the
cyclization of the cis-substituted radical (Z)-1.16
The similarities of the log A terms for 3-exo cyclizations
of radicals 1 that contain the reporter groups and other
radicals that do not and the similarities in the rate
constants for cyclization of radicals 1, 13, and 14 suggest
that the reporter groups are relatively benign in a
mechanistic sense. The same conclusion was reached
previously in studies of 5-exo cyclizations of radical 174
and of ring openings of several cyclopropylcarbinyl
radicals 186 containing the same reporter group as in
radicals 1. For example, the log A term for the initial
ring opening reactions of radical 18 (R ) R′ ) H) was
nearly equal to that for the parent radical, the cyclopro-
pylcarbinyl radical (12 with R ) H), and the Ea term for
18 was slightly reduced such that at 20 °C radical 18
fragmented five times faster than the cyclopropylcarbinyl
radical.6
(Z)- a n d (E)-5-(2,2-Dip h en ylcyclop r op yl)-4-p en ten -1-ol.
The above mixture of acids (2.6 g, 0.009 mol) in ether (20 mL)
was added to a mixture of LAH (0.71 g, 0.019 mol) in ether
(100 mL). The mixture was stirred for 2 h. Water was then
added carefully to quench the excess LAH. The resulting
precipitate was removed by filtration and washed thoroughly
with ether. The filtrate was dried (MgSO4), and the solvent
was removed under reduced pressure to give the desired
alcohols (2.2 g, 90%) as a 3:1 (Z/ E) mixture. Repeated
chromatography on silica gel (3/1 pentane/ethyl ether) gave
1
the purified isomers. The H NMR spectra indicated that the
(E) isomer was 95% pure and the (Z) isomer was >99% pure.
1
(Z)-Alcoh ol. H NMR (500 MHz): δ 1.35 (s, 1 H), 1.45 (dd,
J ) 5.7, 4.7 Hz, 1H), 1.62 (dd, J ) 8.7, 4.8 Hz, 1 H), 1.75
(quintet, J ) 6.6 Hz, 2H), 2.35 (qd, J ) 7.4, 1.5 Hz, 2H), 2.50
(dddd, J ) 9.9, 8.6, 5.8, 1.0 Hz, 1H), 3.73 (t, J ) 6.6 Hz, 2H),
4.64 (ddt, J ) 11.1, 9.9, 1.6 Hz, 1H), 5.40 (dtd, J ) 10.9, 7.3,
1.1 Hz, 1H), 7.2-7.4 (m, 10H). 13C NMR (75 MHz): δ 22.7,
24.0, 25.2, 32.6, 37.1, 62.6, 125.9, 126.4, 127.5, 128.2, 128.3,
128.7, 130.7, 133.1, 141.6, 146.8. MS (EI): m/z (rel int), 278
(M+, 25), 205 (93), 165 (50), 91 (100). HRMS: calcd for C20H22O,
278.1671; found, 278.1668.
(E)-Alcoh ol. 1H NMR (300 MHz): δ 1.55 (m, 5H), 2.01 (qd,
J ) 8.9, 5.8 Hz, 2H), 2.27 (td, J ) 8.9, 5.8 Hz, 1H), 3.54 (t, J
) 6.6 Hz, 2H), 4.80 (ddt, J ) 15.4, 9.0, 1.3 Hz, 1H), 5.61 (dt,
J ) 15.3, 6.9 Hz, 1H), 7.12-7.39 (m, 10H). 13C NMR (75
MHz): δ 22.0, 28.8, 30.0 32.2, 36.6, 61.2, 125.7, 126.4, 127.2,
128.18, 128.22, 129.5, 131.0, 131.2, 141.5, 146.7. MS (EI): m/z
(rel int), 278 (M+, 20), 205 (80), 91 (100). HRMS: calcd for
Exp er im en ta l Section
Gen er a l Meth od s. 1H NMR spectra were obtained in
CDCl3 at 300 or 400 MHz. 13C NMR spectra were obtained at
75 or 100 MHz. High resolution mass spectral analyses were
performed by the Central Instrumentation Facility at Wayne
State University. Commercially available reagents were pur-
chased from either Aldrich Chemical Co. or Arcos Chemical
Co. and were used as received. Ethyl ether and tetrahydro-
furan (THF) were distilled under a nitrogen atmosphere from
sodium-benzophenone ketyl. Benzene was distilled from
CaH2. The sodium salt of N-hydroxypyridine-2-thione was
purified as described previously.26
Kin etic Mea su r em en ts a n d Da ta An a lysis. Kinetic
measurements were carried out with an Applied Photophysics
LK-50 laser kinetic spectrometer using the third harmonic (355
nm) of a Nd:YAG laser (7 ns pulse duration, 40 mJ /pulse).
Dilute solutions of the PTOC esters were placed in a jacketed
addition funnel attached to a UV cuvette via a short length of
Teflon tubing. The solutions were deoxygenated with helium
sparging. The temperature of the sample in the funnel was
adjusted to the desired temperature by circulating fluid from
a constant temperature circulating bath. Sample temperatures
were measured by means of a copper-constantan thermo-
couple wire inserted into the interior of the cuvette through
the sample outflow opening. Data were digitized using a
Hewlett-Packard 54522 oscilloscope. Each kinetic trace con-
tained 500 points. Two sets of data, each containing 14 kinetic
traces, typically were collected at one temperature. Each set
was summed to improve the signal/noise ratio.
5-(2,2-Dip h en ylcyclop r op yl)-4-p en ten oic Acid (4). n-
Butyllithium (20 mL, 2.5 M in hexanes, 0.05 mol) was added
to a solution of hexamethyldisilazane (10.5 mL, 0.05 mol) in
THF (40 mL). After 10 min of stirring (3-carboxypropyl)-
triphenylphosphonium bromide (8.58 g, 0.02 mol) was added
slowly via a solids addition funnel. The dark red solution was
stirred at 0 °C for 1.5 h. A solution of 2,2-diphenylcyclopro-
panecarboxaldehyde27 (4.45 g, 0.02 mol) in THF (10 mL) was
added via syringe, and the mixture was stirred at 0 °C for 3
h. The solution was washed with 10% aqueous HCl solution,
which was back-extracted with ether (200 mL). After drying
over MgSO4, the solvents were removed under reduced pres-
C
20H22O, 278.1671; found, 278.1675.
(Z)-5-(2,2-Dip h en ylcyclop r op yl)-4-p en ten oic Acid ((Z)-
4). J ones reagent was added dropwise to a stirred solution of
the above (Z)-alcohol (0.40 g, 1.4 mmol) in acetone (50 mL) at
0 °C until an orange color persisted. The mixture was stirred
for 5 min and then added to water, and the mixture was
extracted with ether. The ethereal solution was dried (MgSO4),
and the solvent was removed under reduced pressure. The
crude product was purified by chromatography on silica gel
(2:1, hexanes/ethyl acetate) to yield (Z)-4 (0.18 g, 43%). 1H
NMR (300 MHz): δ 1.48 (t, J ) 5.2, 1H), 1.63 (dd, J ) 8.5, 4.7
Hz, 1H), 2.50 (m, 3 H), 2.62 (m, 2H), 4.70 (t, J ) 10.7 Hz, 1H),
5.35 (dt, J ) 11.0, 7.0 Hz, 1 H), 7.20-7.40 (m, 10 H). 13C NMR
(75 MHz): δ 22.7, 23.0, 25.1, 34.2, 37.3, 125.9, 126.5, 126.8,
127.5, 128.27, 128.34, 130.7, 132.1, 141.4, 146.6, 179.6. MS
(EI): m/z (rel int), 292 (M+, 25), 205 (100), 91 (77). HRMS:
calcd for C20H20O, 292.1463; found, 292.1463.
(E)-5-(2,2-Dip h en ylcyclop r op yl)-4-p en ten oic a cid ((E)-
4) was prepared from the above (E)-alcohol by the same
procedure as used for preparation of (Z)-4. (E)-Alcohol (0.38
1
g, 1.4 mmol) gave (E)-4 (0.16 g, 40%). H NMR (300 MHz): δ
1.50 (t, J ) 5.8, 1H), 1.61 (dd, J ) 8.5, 4.9 Hz, 1H), 2.32 (m, 5
H), 4.85 (dd, J ) 15.3, 9.2 Hz, 1 H), 5.65 (dt, J ) 15.3, 6.7 Hz,
1 H), 7.20-7.40 (m, 10 H). 13C NMR (75 MHz): δ 22.1, 27.4,
29.8, 34.0, 36.6, 125.7, 126.4, 127.1, 127.5, 128.2, 130.9, 132.2,
141.2, 146.6, 179.2. MS (EI): m/z (rel int), 292 (M+, 32), 205
(100), 183 (71), 91 (79). HRMS: calcd for C20H20O, 292.1463;
found, 292.1457.
(Z)-5-(2,2-Diph en ylcyclopr opyl)-4-pen ten oic Acid 2-Th i-
oxo-2H-p yr id in -1-yl Ester ((Z)-5). A mixture of (Z)-4 (0.14
g, 0.46 mmol), one drop of DMF, and oxalyl chloride (0.16 mL,
1.8 mmol) in dry benzene (20 mL) was stirred for 30 min.
Excess oxalyl chloride and benzene were removed under
reduced pressure. The residue was dissolved in benzene (10
mL), and the solution was added to a suspension of N-hy-
droxypyridine-2-thione sodium salt (0.11 g, 0.72 mmol) and
DMAP (0.007 g, 0.056 mmol) in benzene (10 mL) in a ice-cooled
bath. The mixture was shielded from light during this reaction
and all subsequent workup steps. The mixture was allowed
to warm to room temperature. After 2 h, the reaction mixture
was washed with NaHCO3 (sat, aq), KHSO4 (10%, aq), and
(26) Esker, J . L.; Newcomb, M. J . Org. Chem. 1993, 58, 4933-4940.
(27) Walborsky, H. M.; Braish, L.; Young, A. E.; Impastato, F. J . J .
Am. Chem. Soc. 1961, 83, 2517-2525.

4068 J . Org. Chem., Vol. 64, No. 11, 1999
Furxhi et al.
brine. After drying over MgSO4, the solvent was removed
under reduced pressure. The crude product was chromato-
graphed rapidly on silica gel (2:1, hexanes/ethyl acetate) to
Hz, 1H), 2.28 (td, J ) 8.9, 6.0 Hz, 1H), 2.45 (m, 2H), 2.71 (t, J
) 7.3, 2H). 4.8 (ddt, J ) 15.4, 9.1, 1.4 Hz, 1H), 5.6 (dt, J )
15.2, 6.9 Hz, 1H), 6.64 (td, J ) 6.9, 1.6 Hz, 1H) 7.14-7.38 (m,
11H), 7.51 (dd, J ) 6.9, 1.4 Hz, 1 H), 7.74 (dd, J ) 8.9, 1.8 Hz,
1 H). 13C NMR (100 MHz): δ 22.1, 27.1, 29.8, 31.7, 36.8, 112.5,
125.8, 126.5, 126.7, 127.1, 128.22, 128.24, 130.9, 132.9, 133.5,
137.4, 137.6, 141.2, 146.5, 168.3, 175.8.
1
give (Z)-5 (0.13 g, 68%) as a yellow oil. H NMR (400 MHz):
δ 1.52 (dd, J ) 5.8, 4.8, 1H), 1.67 (dd, J ) 8.7, 4.8 Hz, 1H),
2.48 (tdd, J ) 9.3, 5.7, 0.8 Hz, 1H), 2.82 (m, 2H), 2.90 (m, 2H).
4.74 (tt, J ) 10.4, 1.3 Hz, 1H), 5.41 (tdd, J ) 10.8, 7.1, 0.8 Hz,
1H), 6.63 (td, J ) 6.9, 1.8 Hz, 1H), 7.2-7.4 (m, 11H), 7.58 (dd,
J ) 6.7, 1.1 Hz, 1H), 7.74 (dd, J ) 9.0, 1.2 Hz, 1H). 13C NMR
(100 MHz): δ 22.66, 22.74, 25.2, 31.8, 37.3, 112.5, 125.9, 126.0,
126.6, 127.5, 128.3, 128.3, 130.6, 132.8, 133.4, 137.4, 137.6,
141.2, 146.4, 168.5, 175.8.
Ack n ow led gm en t. This work was supported by a
grant from the National Science Foundation (CHE-
9614968).
(E)-5-(2,2-Diph en ylcyclopr opyl)-4-pen ten oic Acid 2-Th i-
oxo-2H-p yr id in -1-yl Ester ((E)-5). The same procedure used
for the preparation of (Z)-5 was followed; (E)-4 (0.16 g, 0.55
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
1
mmol) gave (E)-5 (0.12 g, 55%) as a yellow oil. H NMR (400
MHz): δ 1.51 (dd, J ) 5.9, 5.1 Hz 1H), 1.62 (dd, J ) 8.7, 4.9
J O990129V