Photochemical behavior of cyclopropyl-substituted benzophenones and valerophenones

Article abstract of DOI:10.1021/jo102309w

p-Cyclopropylbenzophenone, 20, gives no photoreduction when irradiated in i-PrOH solvent. This is a general phenomenon and a number of cyclopropyl-substituted benzophenones, including 4-(endo-6-bicyclo[3.1.0]hexyl) benzophenone, 19, 4-(cis-2,3-dimethylcyclopropyl)benzophenone, 21, 4-(cis-2-vinylcyclopropyl)benzophenone, 22, and 4-(endo-7-bicyclo[4.1.0]hept-2- enyl)benzophenone, 23, also fail to undergo photoreduction. Instead these latter compounds undergo cis-trans isomerization when irradiated. A mechanism involving formation of an (n, π*) triplet, which subsequently fragments the strained cyclopropane bond to give a lower energy and unreactive open triplet, has been suggested. p-Cyclopropylvalerophenone, 25, and p-(endo-6-bicyclo[3.1.0]hexyl)valerophenone, 24, also undergo photoisomerization and fail to undergo the Norrish Type II photoreactions. Triplet energy dissipation by fragmentation of the cyclopropane bond is also proposed. In addition to the Norrish Type II reaction, p-cyclobutylvalerophenone, 27, undergoes a photofragmentation to give ethylene and p-vinylvalerophenone, 60, by an energy dissipation mechanism involving a 1,4-biradical derived from cyclobutane bond fragmentation.

Full text of DOI:10.1021/jo102309w

ARTICLE
pubs.acs.org/joc
Photochemical Behavior of Cyclopropyl-Substituted Benzophenones
and Valerophenones
Xavier Creary,* Jenifer Hinckley, Casey Kraft, and Madeleine Genereux
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States
S Supporting Information
b
ABSTRACT: p-Cyclopropylbenzophenone, 20, gives no photo-
reduction when irradiated in i-PrOH solvent. This is a general
phenomenon and a number of cyclopropyl-substituted benzo-
phenones, including 4-(endo-6-bicyclo[3.1.0]hexyl)benzophe-
none, 19, 4-(cis-2,3-dimethylcyclopropyl)benzophenone, 21,
4-(cis-2-vinylcyclopropyl)benzophenone, 22, and 4-(endo-7-
bicyclo[4.1.0]hept-2-enyl)benzophenone, 23, also fail to under-
go photoreduction. Instead these latter compounds undergo cis-
trans isomerization when irradiated. A mechanism involving
formation of an (n, π*) triplet, which subsequently fragments
the strained cyclopropane bond to give a lower energy and unreactive open triplet, has been suggested. p-Cyclopropylvalerophenone,
25, and p-(endo-6-bicyclo[3.1.0]hexyl)valerophenone, 24, also undergo photoisomerization and fail to undergo the Norrish Type II
photoreactions. Triplet energy dissipation by fragmentation of thecyclopropane bondis alsoproposed. Inadditionto theNorrishType
II reaction, p-cyclobutylvalerophenone, 27, undergoes a photofragmentation to give ethylene and p-vinylvalerophenone, 60, by an
energy dissipation mechanism involving a 1,4-biradical derived from cyclobutane bond fragmentation.
’ INTRODUCTION
A second major photochemical process that carbonyl-contain-
ing compounds undergo is the Norrish Type II transformation.5
This process is illustrated for the aromatic ketone valerophenone,
8, which, on irradiation, gives the cyclobutanols 9, along with
fragmentation products acetophenone, 10, and propene, 11.
Mechanistically, this process involves intramolecular hydrogen
atom transfer in the triplet 12 to form the 1,4-biradical 13.
Intersystem crossing and ring closure gives the cyclobutanol 9,
while fragmentation of biradical 13 leads to propene and 14, the
enol tautomer of acetophenone.
The fledgling field of organic photochemistry was significantly
advanced in 1900 when Ciamician and Silber exposed a solution
of benzophenone in ethyl alcohol to sunlight.1 The result was the
photoreduction of benzophenone 1 to benzopinacol 2. A mod-
ified version of this photochemical reaction is now the basis of the
Organic Syntheses preparation of benzopinacol.2 The photochem-
istry and photophysics of benzophenone have been thoroughly
investigated.3 The mechanism of this transformation4 involves
formation of the singlet excited state of benzophenone 4,
followed by intersystem crossing to the triplet state 5. This
triplet, which has radical characteristics, abstracts a hydrogen
atom from the isopropyl alcohol to generate radicals 6 and 7.
Coupling of 6 gives benzopinacol. A second source of radical 6 is
hydrogen atom transfer from radical 7 to benzophenone.
Received: November 20, 2010
Published: March 03, 2011
r
2011 American Chemical Society
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Our interest in carbonyl photochemistry stems from our
studies of radical reactions and the methylenecyclopropane
rearrangement.6 During the course of our studies, it was found
that substrates 15 and 17 undergo the thermal rearrangement to
give 16 and 18, respectively. We have also found that under
photochemical conditions, the same rearrangement products are
formed.7 Interestingly, when 15 was irradiated in i-PrOH solvent,
the same rearrangement product 16 was observed, with no trace
of the corresponding pinacol reduction product. The rearranged
product 16 also gave no trace of reduction when irradiated in i-
PrOH. The lack of photoreduction was attributed to fragmenta-
tion of the strained cyclopropane bond of the excited state triplet
derived from 15. This dissipates the triplet energy and renders it
incapable of hydrogen atom abstraction from i-PrOH. The
substrate 17 also rearranges to 18 under photochemical condi-
tions and no trace of Norrish Type II products are observed. The
lack of Norrish Type II products is again attributed to rapid
dissipation of energy of the triplet derived from 17 by fragmenta-
tion of the cyclopropane bond. Hence intramolecular hydrogen
atom transfer never occurs.
Scheme 1. Synthesis of Substituted Benzophenone 19
In view of these findings, it was of interest to examine the
photochemical behavior of other cyclopropane-containing car-
bonyl compounds. The carbonyl-containing substrates 19-25
were therefore prepared. These substrates are less strained than
the previously examined methylenecyclopropanes 15 and 17.
Hence they might be less prone to fragmentation. Additionally,
substrates 22 and 23 are substituted vinylcyclopropanes and
hence they might be prone to further rearrangements. The
cyclobutyl systems 26 and 27 are even less strained (per
methylene) than the cyclopropyl analogues. Would these com-
pounds give photoreduction and Norrish Type II reactions?
Reported here are the results of qualitative photochemical
studies on these substrates.
known 4-benzoylbenzaldehyde 28 to this diazocompound was
accomplished by pyrolysis of the sodium salt of the correspond-
ing tosylhydrazone.8 The p-cyclopropyl-substituted benzophe-
none 19 was then prepared by the Cu(OTf)2-catalyzed reaction
of diazocompound 29 with cyclopentene (Scheme 1). This
major product 19 was separated from the minor exo-isomer by
silica gel chromatography and 1H NMR spectroscopy was used
to establish stereochemistry of these isomers. The endo-isomer
19 shows a larger 8.2 Hz coupling constant between the benzylic
hydrogen and the cis-hydrogens on the cyclopropane ring.
Additionally, a B3LYP/6-31G* computational study9 indicates
that endo-6-phenylbicyclo[3.1.0]hexane, 30, adopts a boat-like
conformation, where the endo-phenyl group shields the syn-C3
hydrogen on the cyclopentane ring (Figure 1). This leads to a
GIAO-calculated chemical shift9 of -0.03 ppm for this hydro-
gen. The analogous syn-C3 hydrogen in 19 appears far upfield at
0.02 ppm in the 1H NMR spectrum (C6D6). The syntheses of 21,
’ RESULTS AND DISCUSSION
The diazocompound 29 was the starting material for the
preparation of substrates 19, 21, 22, and 23. Conversion of the
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Figure 1. B3YLP/6-31G* calculated structure of 6-phenylbicyclo[3.1.0]-
hexane.
22, and 23 utilized the same protocol starting with cis-2-butene,
1,3-butadiene, and 1,3-cyclohexadiene, respectively.
Irradiation of a C6D6 solution of the endo-isomer 19 using a
photochemical reactor fitted with lamps emitting light centered
at 350 nm led to isomerization to give the exo-isomer 31. This
wavelength corresponds to the forbidden (n, π*) transition of
aromatic ketones and the substrates described in this paper
weakly absorb in this region of the UV spectrum. A photosta-
tionary state (89% of 31; 11% of 19) was eventually reached.
Figure 2 shows evolving NMR spectra during irradiation of 19 as
a function of irradiation time and Figure 3 shows a plot of the
amount of remaining 19 as a function of time. When the
irradiation was carried out in i-PrOH as solvent, the same
isomerization of 19 to 31 occurred at a comparable rate and
no trace of photoreduction to the corresponding pinacol was
observed. Although quantum yields were not precisely measured,
the reaction is efficient. Thus irradiation of a 0.071 M solution of
benzophenone in i-PrOH for 3 min at 350 nm gave 29%
reduction to benzopinacol. Under identical conditions 15% of
19 isomerized to 31.
Figure 2. Evolving 1H NMR spectra during irradiation (350 nm) of 19
in C6D6.
The photochemical behavior of 19 is reminiscent of the
photoisomerization of cis- and trans-diphenylcyclopropane to
reach a photostationary state.10 A number of additional photo-
chemical rearrangements of carbonyl-containing cyclopropanes,
epoxides, and aziridines have also been studied and radical
mechanisms have been proposed.11 The mechanism in Scheme 2
accounts for the observed isomerization of 19, as well as the lack
of photoreduction in i-PrOH. Standard photoexcitation followed
by intersystem crossing would yield the (n, π*) triplet 32.12
However, it is suggested that the triplet 32, which has spin
density at the para-position, rapidly fragments a cyclopropane
bond and forms a lower energy open triplet 33. This process is
suggested to be faster than hydrogen atom abstraction from
i-PrOH. The new open triplet 33 is not energetic enough to
abstract hydrogen from i-PrOH and hence no photoreduction is
observed. However, 33 can rotate to a different conformation 34.
Intersystem crossing followed by ring closure would generate the
observed product 31.
Figure 3. Plot of remaining 19 after irradiation in C6D6 versus the
irradiation time.
those with low-lying (π, π*) triplet states are less efficiently
reduced (but many are nonetheless reduced to benzopinacols).
While the (n, π*) nature of the lowest triplet state derived from
19 has not been verified, a (π, π*) triplet should still give slow
reduction. The complete lack of reduction of 19 in i-PrOH
suggests that some other factor (i.e., deactivation by ring-open-
ing) prevents reduction.
To determine whether the high strain energy of the bicyclo-
[3.1.0]hexane system 19 was an important feature, the unsub-
stituted p-cyclopropylbenzophenone, 20, was next examined.
Irradiation of 20 in i-PrOH gave no observable reaction
Previous studies have shown that the effect of substituents on
the photochemistry of aromatic ketones can be significant.3a,13
Substituted benzophenones with lowest lying (n, π*) triplet
states are reduced in i-PrOH with high quantum yields. However,
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Scheme 2. Photolysis of Substituted Benzophenone 19:
Mechanistic Analysis
Scheme 4. Photolysis of Cyclopropyl-Substituted Benzo-
phenone 21
Scheme 3. Photolyses of Substituted Benzophenones 20
and 35
biradical 41 offers a convenient explanation for this isomeriza-
tion. The analogous biradical 38 is therefore a reasonable
intermediate during the photolysis of 20 even though this
biradical is “invisible” since 20 lacks a probe for detecting
rotation.
The photochemical behavior of 22 and 23 was of interest in
view of the known thermal vinylcyclopropane to cyclopentene
rearrangement.14 This process is formally a 1,3-sigmatropic shift
that orbital symmetry considerations suggest can be concerted if
inversion occurs at the migrating center.15 The latest mechanistic
thinking is that this rearrangement is a concerted process that
goes through a transition state that has singlet “biradical cha-
racter”.14e-g The substrates 22 and 23 are vinylcyclopropanes
and it was of interest to determine whether triplet biradical
intermediates generated photochemically could lead to the
vinylcyclopropane rearrangement.
Irradiation of both 22 and 23 in C6D6 and i-PrOH led only to
photoisomerization until photostationary states were reached
(Scheme 5). Of note is the fact that the cis-isomer 22 (62%)
predominates over the trans-isomer 42 (38%) once the photo-
stationary state is reached. No benzopinacol reduction products
were formed in i-PrOH. In the case of 22, no vinylcyclopropane
rearrangement to give cyclopentene 43 was observed. No
bicyclo[2.2.1]heptene 45 was formed from 23. This is illustrated
in Figure 4, which shows the clean isomerization of 23 to 44 in
the 1H NMR spectrum.
These results imply that the intermediates in the photoisome-
rizations of 22 and 23 are not involved in the thermal vinylcy-
clopropane rearrangement. In the case of 23, it is suggested that
opening of the initially formed closed triplet followed by rotation
leads to 46. Intersystem crossing and ring closure gives the
observed product 44. Apparently the triplet biradicals derived
from 22 and 23, upon intersystem crossing, do not enter onto the
singlet potential energy surface involved in the thermal rearran-
gements of 22 and 23. The implication is that the singlet biradical
(Scheme 3). This contrasts with p-isopropylbenzophenone, 35,
which gave a high yield of the benzopinacol 36 under the same
conditions. This suggests that there is no problem in forming the
(n, π*) triplet from 20, but that this triplet 37 returns to the
starting ketone without abstracting a hydrogen atom from i-
PrOH. It is proposed that the triplet 37 is deactivated by
fragmentation of the cyclopropane bond. As in the case of 34,
the open triplet 38 simply returns to 20 after intersystem
crossing.
Does the cyclopropane ring of 20 actually fragment during the
irradiation process? The substrate 21 can shed light on this
suggestion. Irradiation of 21 in C6D6 or in i-PrOH led to
complete conversion to a mixture of isomers 39 and 40 in a
75:25 ratio (Scheme 4). Therefore bond rotation must have
occurred about all of the cyclopropane bonds. The open triplet
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Scheme 5. Photolyses of Vinylcyclopropyl-Substituted Ben-
zophenones 22 and 23
Figure 4. Evolving 1H NMR spectra (alkene region) during irradiation
of 23 in C6D6.
structure represented by 47 has no finite lifetime and hence
cannot enter onto the thermal rearrangement energy surface.
Attention was next turned to the Norrish Type II photoreac-
tion. When the cyclopropyl-substituted valerophenone 24 was
irradiated in C6D6, clean isomerization to the exo-isomer 48
occurred (Scheme 6). No traces of the substituted acetophenone
49 or the cyclobutanol 50 were observed, i.e., Norrish Type II
processes are completely bypassed. Intramolecular hydrogen
atom transfer in the triplet 51, which would lead to the Norrish
Type II products 49 and 50, is apparently slow relative to
cyclopropane ring-opening and rotation, which lead to the
observed product 48.
Scheme 6. Photolysis of Substituted Valerophenone 24
The behavior of p-cyclopropylvalerophenone, 25, is analogous
to that of 24 (Scheme 7). Thus irradiation of 25 in C6D6 gave no
apparent reaction, while under the same conditions, valerophe-
none, 8, readily converted to acetophenone and 1-phenyl-2-
methylcyclobutanol. As before, we suggest that the (n, π*) triplet
52 loses it is ability to abstract hydrogen atoms when it dissipates
its energy by cyclopropane ring fragmentation to form 53. This
process is presumably faster than hydrogen atom transfer giving
54. Intersystem crossing and ring closure returns 53 to starting
material.
The photochemistry of the p-cyclobutylbenzophenone, 26,
was next examined in order to determine whether or not the
cyclobutane ring would fragment and allow standard photore-
duction in i-PrOH to be circumvented. When irradiated in this
solvent, facile photoreduction of 26 to the corresponding pinacol
56 resulted (Scheme 8). This is in stark contrast to the
cyclopropyl analogue 20, which gives no observable photoreduc-
tion. The behavior of p-cyclobutylvalerophenone, 27, also con-
trasts with that of “unreactive” p-cyclopropylvalerophenone, 25.
In addition to undergoing the standard Norrish Type II
processes (giving 57 and 58) when irradiated in C6D6, 27 also
fragments to give p-vinylvalerophenone, 59, and ethylene. Ke-
tone 58 is also photolabile, and fragments under the reaction
conditions to give 60, and ethylene.16 Figure 5 shows the
development of these olefinic products 59 and 60 (as well as
propene and ethylene) by 1H NMR spectroscopy during irradia-
tion of 27. A further control experiment shows that ketone 59 is
stable under the photochemical conditions and does not convert
(by a Norrish Type II process) to 60.
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These experiments suggest that (n, π*) triplet state derived
from 26 is “normal” and leads to hydrogen atom abstraction from
i-PrOH. However, it is suggested that the triplet 61 derived from
27 undergoes competing processes. Competing with Norrish
Type II chemistry is opening of the cyclobutane ring of 61 to give
biradical 62, which is the proposed origin of ethylene and the
substituted styrene 59. The fact that triplet biradical 61 can
undergo fragmentation of the cyclobutane ring provides indirect
Scheme 7. Photolysis of p-Cyclopropylvalerophenone, 25:
Mechanistic Analysis
Figure 5. 1H NMR spectrum (alkene region) during irradiation of 27
in C6D6.
Scheme 8. Photolyses of p-Cyclobutylbenzophenone and p-Cyclobutylvalerophenone
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evidence that photoinduced fragmentation of the more strained
cyclopropane rings in 19-25 to give biradical intermediates is
indeed a facile process.
amount of cold methanol. The yield of tosylhydrazone was 2.730 g
(89%).
The crude tosylhydrazone (2.730 g) was placed in a 50 mL flask and
16 mL of freshly prepared 0.50 M NaOCH3 in methanol was added with
stirring. After 20 min, the methanol solvent was removed with a rotary
evaporator and 20 mL of ethylene glycol was then added. The mixture
was warmed in an oil bath at 75 °C to dissolve the salt. The solution was
then heated in the oil bath at 90 °C for 6 min and then recooled to room
temperature. The red-orange mixture was then extracted with ether and
the ether solution of diazocompound 29 was decanted from the ethylene
glycol with use of a pipet. The ethylene glycol residue was then reheated
to 90 °C for 6 min and cooled to room temperature, then the extraction
procedure was repeated. After a third heating and extraction, the
combined ether extracts were washed with cold water and saturated
salt solution, then dried over a mixture of Na2SO4 and MgSO4. After
filtration, the ether solvent was removed with a rotary evaporator leaving
1.460 g (91%) of solid red-orange p-benzoylphenyldiazomethane, 29,
mp 59-62 °C. This diazocompound was stored in the dark at -20 °C.
1H NMR of 29 (CDCl3) δ 7.77 (m, 4 H), 7.57 (t, J = 7.5 Hz, 1 H), 7.47
(t, J = 7.5 Hz, 2 H), 6.98 (d, J = 8.4 Hz, 2 H), 5.08 (s, 1 H). 13C NMR of
29 (CDCl3) δ 195.6, 138.1, 135.9, 132.8, 132.1, 131.4, 129.8, 128.2,
120.6, 48.7.
Preparation of 4-(endo-6-Bicyclo[3.1.0]hexyl)benzophe-
none, 19. Cyclopentene (10 mL) was added to 27 mg of dry Cu(OTf)2
(dried at 70 °C and 0.1 mm pressure). A solution of 205 mg of p-
benzoylphenyldiazomethane 29 in 7 mL of cyclopentene was added
dropwise over a period of 1 h with stirring. The solution was stirred for
an additional 30 min at room temperature and then filtered. The
remaining cyclopentene was removed with a rotary evaporator and
the residue was chromatographed on 6.0 g of silica gel. Elution with 3%
ether in pentane gave a total of 133 mg of 19 and 31 (55% yield). Pure
endo-isomer 19 (71 mg) eluted first followed by fractions containing a
mixture of 19 and 31 (22 mg). Pure exo-isomer 31 eluted last (40 mg).
1H NMR of 19 (CDCl3) δ 7.79 (d, J = 7.5 Hz, 2 H), 7.75 (d, J = 8 Hz,
2 H), 7.58 (t, J = 7.5 Hz, 1 H), 7.48 (t, J = 7.5 Hz, 2 H), 7.35 (d, J = 8 Hz,
2 H), 2.00 (t, J = 8.3 Hz, 1 H), 1.84 (m, 2 H), 1.73 (m, 4 H), 1.29 (m,
1 H), -0.03 (m, 1 H). 13C NMR of 19 (CDCl3) δ 196.7, 144.3, 138.0,
135.2, 132.2, 130.3, 130.0, 129.2, 128.2, 25.8, 23.7, 23.1, 22.7. ESI exact
mass (M þ Hþ) calculated for C19H19O 263.1430, found 263.1421. 1H
NMR of 31 (CDCl3) δ 7.76 (d, J = 7 Hz, 2 H), 7.70 (d, J = 8 Hz, 2 H),
7.57 (t, J = 7.5 Hz, 1 H), 7.47 (t, J = 7.5 Hz, 2 H), 7.09 (d, J = 8 Hz, 2 H),
1.95 (d of d, J = 12.4, 8.3 Hz, 2 H), 1.85 (m, 2 H), 1.71 (t, J = 3.1 Hz,
1 H), 1.67 (m, 3 H), 1.30 (m, 1 H). 13C NMR of 31 (CDCl3) δ 196.4,
149.7, 138.2, 134.3, 132.1, 130.4, 129.9, 128.2, 125.1, 31.0, 28.1,
24.2, 20.9.
Preparation of p-Cyclopropylbenzophenone, 20. A solution
of 317 mg of p-cyclopropylbromobenzene19 in 7 mL of anhydrous THF
was cooled to -78 °C and 1.8 mL of 1.6 M n-butyllithium was added.
The solution was warmed to -50 °C for 5 min and recooled to -78 °C.
A solution of 350 mg N,N-dimethylbenzamide in 9 mL of anhydrous
THF was then added dropwise. After the addition was complete, the
solution was slowly warmed to 5 °C. Water (10 mL) was added dropwise
over a 5 min period. The mixture was extracted with ether and the ether
extract was washed with water and saturated NaCl solution. The ether
solution was dried over a mixture of Na2SO4 and MgSO4 and filtered.
The solvent was removed with use of a rotary evaporator and the residue
was chromatographed on 8.8 g of silica gel. The column was eluted with
increasing amounts of ether in hexanes and 210 mg of 2020 (59% yield)
eluted with 4% ether in hexanes. 1H NMR of 20 (CDCl3) δ 7.78 (d, J = 8
Hz, 2 H), 7.72 (d, J = 8 Hz, 2 H), 7.57 (t, J = 8 Hz, 1 H), 7.47 (t, J = 8 Hz,
2 H), 7.15 (d, J = 8 Hz, 2 H), 1.97 (m, 1 H), 1.08 (m, 2 H), 0.80 (m, 2 H).
13C NMR of 20 (CDCl3) δ 196.6, 150.0, 138.2, 134.9, 132.3, 130.6,
130.1, 128.4, 125.4, 15.9, 10.6.
’ CONCLUSIONS
Cyclopropyl-substituted benzophenones are not photore-
duced to benzopinacols when irradiated in i-PrOH solution.
Instead, cyclopropane bond fragmentation occurs, leading to a
lower energy triplet that is incapable of hydrogen atom abstrac-
tion. Evidence for cyclopropane bond fragmentation is the
observation of cis-trans-isomerization of the cyclopropane.
The Norrish Type II photoreaction is also bypassed when
cyclopropyl-substituted valerophenones are irradiated. Fragmen-
tation of the cyclopropane bond again leads to a lower energy
triplet and also accounts for the observed cis-trans-isomeriza-
tion. The photochemical behavior of p-cyclobutylbenzophenone
in i-PrOH is “normal” in that reduction to the benzopinacol is
observed. However, p-cyclobutylvalerophenone fragments to
give ethylene and p-vinylvalerophenone in addition to Norrish
Type II photochemical products. The fragmentation products
provide evidence for a 1,4-biradical intermediate derived from
cleavage of the cyclobutane bond, and further supports the
suggestion of facile cyclopropane bond fragmentation during
photolyses of cyclopropyl-substituted benzophenones and
valerophenones.
’ EXPERIMENTAL SECTION
Preparation of 4-Benzoylbenzaldehyde, 28. A solution of
2.30 g of p-bromobenzaldehyde dimethylacetal17 in 17 mL of THF was
cooled to -78 °C and 7.2 mL of 1.6 M n-BuLi in hexanes was added
dropwise. After 30 min, at -78 °C, the mixture was warmed to -50 °C
for 10 min and then recooled to -78 °C. A solution of 1.505 g of N,N-
dimethylbenzamide in 10 mL of THF was then added over a 10 min
period. The mixture was then slowly warmed to 0 °C and water was
added with stirring. The mixture was then transferred to a separatory
funnel, using ether, and the organic phase was washed with water and
saturated NaCl solution, then dried over a mixture of Na2SO4 and
MgSO4. The solvent was removed with a rotary evaporator and the
residue was distilled. After a lower boiling forrun, 2.11 g (71% yield) of p-
benzoylbenzaldehyde dimethylacetal was collected, bp 150-153 °C
(0.2 mm). 1H NMR (CDCl3) δ 7.81 (m, 4 H), 7.58 (m, 3 H), 7.48 (t, J =
7.6 Hz, 2 H), 5.47 (s, 1 H), 3.36 (s, 6 H). 13C NMR (CDCl3) δ 196.4,
142.4, 137.6, 137.5, 132.5, 130.02, 129.98, 128.3, 126.7, 102.4, 52.7.
A solution of 2.112 g of p-benzoylbenzaldehyde dimethylacetal in
10 mL of THF was stirred as a solution of 400 mg of H2SO4 in 11 mL of
water was added dropwise. The mixture was vigorously stirred for 24 h
and then transferred to a separatory funnel, using about 30 mL of ether.
The ether phase was washed with water, Na2CO3 solution, and saturated
NaCl solution, and dried over a mixture of Na2SO4 and MgSO4. After
filtration, the solvent was removed with a rotary evaporator. On
standing, 1.701 g of 4-benzoylbenzaldehyde, 28,18 mp 65-66 °C,
1
solidified. H NMR (CDCl3) δ 10.14 (s, 1 H), 8.01 (d, J = 9 Hz, 2
H), 7.93 (d, J = 9 Hz, 2 H), 7.82 (d, J = 9 Hz, 2 H), 7.64 (t, J = 9 Hz), 7.52
(t, J = 9 Hz, 2 H). 13C NMR of 28 (CDCl3) δ 195.9, 191.7, 142.6, 138.5,
136.8, 133.2, 130.4, 130.2, 129.5, 128.6.
Preparation of p-Benzoylphenyldiazomethane, 29. A
mixture of 1.701 g of 4-benzoylbenzaldehyde, 28, in 10 mL of methanol
was stirred and 1.550 g of tosylhydrazine was added in one portion. The
tosylhydrazone product immediately began to crystallize and stirring
was continued for 24 h. The mixture was then cooled in an ice bath and
the product was collected on a Buchner funnel and washed with a small
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Preparation of 4-(cis-2,3-Dimethylcyclopropyl)benzophe-
none, 21. Cyclohexane (12 mL) was cooled in an ice/acetone bath
under argon as 8.5 g of cis-2-butene was condensed into the cyclohexane.
Dry Cu(OTf)2 (18 mg) was then added and a solution of 145 mg of p-
benzoylphenyldiazomethane, 29, in 13 mL of cyclohexane was added
dropwise over 75 min at room temperature. Upon completion of the
addition, the mixture was filtered and the solvents were removed under
vacuum. Chromatography on 5 g of silica gel and elution with 2% ether
in hexanes gave 93 mg (56%) of cis-isomer 21 and trans-isomer 40. Pure
cis-isomer 21 (66 mg; mp 98-99 °C) eluted first followed by a fraction
containing a mixture of 21 and 40 (15 mg). Pure trans-isomer 40 eluted
last (12 mg). 1H NMR of 21 (CDCl3) δ 7.80 (d, J = 8 Hz, 2 H), 7.75 (d, J
= 8 Hz, 2 H), 7.58 (t, J = 8 Hz, 1 H), 7.48 (t, J = 8 Hz, 2 H), 7.33 (d, J = 8
Hz, 2 H), 2.05 (t, J = 9 Hz, 1 H), 1.27 (m, 2 H), 0.96 (m, 6 H). 13C NMR
of 21 (CDCl3) δ 196.7, 143.5, 137.9, 135.0, 132.2, 131.3, 130.02, 129.98,
128.2, 22.9, 13.9, 9.6. ESI exact mass (M þ Hþ) calculated for C18H19O
251.1430, found 251.1447. 1H NMR of 40 (CDCl3) δ 7.76 (d, J = 8 Hz,
2 H), 7.70 (d, J = 8 Hz, 2 H), 7.56 (t, J = 7.5 Hz, 1 H), 7.46 (t, J = 7.5 Hz, 2
H), 7.07 (d, J = 8 Hz, 2 H), 1.26 (m, 3 H), 1.20 (m, 6 H). 13C NMR of 40
(CDCl3) δ 196.4, 150.4, 138.2, 134.2, 132.1, 130.4, 129.9, 128.2, 125.0,
32.5, 23.8, 12.7.
(1.0 mL of 1.6 M) was then added. The solution was warmed to room
temperature and recooled to -78 °C, then 0.25 mL of methanol was
added. The mixture was warmed to room temperature, water was added,
and the mixture was extracted with ether. The ether extract was
vigorously stirred with 5 mL of 3% aqueous HCl solution for 30 min
and then transferred to a separatory funnel. The ether phase was washed
with water and saturated NaCl solution, then dried over a mixture of
Na2SO4 and MgSO4. After filtration, the solvent was removed with a
rotary evaporator. An NMR spectrum showed endo-isomer 24 and exo-
isomer 48 in a 75:25 ratio. This mixture was chromatographed on 8 g of
silica gel and the column was eluted with increasing amounts of ether in
hexanes. A mixture of 24 and 48 (67 mg; 61% yield) eluted with 4% ether
in hexanes. Earlier fractions were enriched in the endo-isomer 24 while
later fractions were enriched in the exo-isomer 48. 1H NMR of
24 (CDCl3) δ 7.88 (d, J = 8.2 Hz, 2 H), 7.32 (d, J = 8.3 Hz, 2 H),
2.95 (t, J = 7.3 Hz, 2 H), 1.97 (t, J = 8.2 Hz, 1 H), 1.83 (m, 2 H), 1.75-
1.68 (m, 6 H), 1.41 (hextet, J = 7.5 Hz, 2 H), 1.26 (m, 1 H), 0.95 (t, J =
7.3 Hz, 3 H), -0.10 (m, 1 H). 13C NMR of 24 (CDCl3) δ 200.7, 144.8,
135.1, 129.6, 128.3, 38.5, 26.8, 26.0, 23.8, 23.3, 22.8, 22.7, 14.2. ESI exact
mass (M þ Hþ) calculated for C17H23O 243.1743, found 243.1734.
1H NMR of 48 (CDCl3) δ 7.83 (d, J = 8.5 Hz, 2 H), 7.06 (d, J = 8.3
Hz, 2 H), 2.91 (t, J = 7.3 Hz, 2 H), 1.93 (m, 2 H), 1.83 (m, 2 H), 1.73-
1.64 (m, 4 H), 1.62 (m, 2 H), 1.40 (hextet, J = 7.5 Hz, 2 H), 1.29 (m,
1 H), 0.94 (t, J = 7.4 Hz, 3 H). 13C NMR of 48 (CDCl3) δ 200.4, 150.1,
134.2, 128.3, 125.5, 38.4, 31.1, 28.2, 26.9, 24.3, 22.8, 21.1, 14.2.
Preparation of p-Cyclopropylvalerophenone, 25. Anhy-
drous ether (2 mL) was cooled to -78 °C and 0.7 mL of 1.6 M
n-butyllithium was added. A solution of 78 mg of p-cyclopropyl-
benzaldehyde21 in 2 mL of ether was then added dropwise. The solution
was warmed to room temperature and 5 mL of water was added. The
ether phase was washed with water and saturated NaCl solution, and
then dried over a mixture of Na2SO4 and MgSO4. After filtration, the
solvent was removed with a rotary evaporator and the residue was
dissolved in 3 mL of CH2Cl2. Pyridinium chlorochromate (215 mg) was
added to the solution and the mixture was stirred at room temperature
for 3 h. Pentane (3 mL) was added and the mixture was filtered through a
small amount of silica gel. The solvent was removed with a rotary
evaporator. The residue was chromatographed on 5 g of silica gel and the
column was eluted with increasing amounts of ether in hexanes. A total
of 62 mg (62% yield) of 25 eluted with 2% ether in hexanes. 1H NMR of
25 (CDCl3) δ 7.85 (d, J = 8 Hz, 2 H), 7.11 (d, J = 8 Hz, 2 H), 2.92 (t, J =
8 Hz, 2 H), 1.94 (m, 1 H), 1.70 (m, 2 H), 1.40 (m, 2 H), 1.05 (m, 2 H),
0.95 (t, J = 7.4 Hz, 3 H), 0.77 (m, 2 H). 13C NMR of 25 (CDCl3) δ
200.3, 150.2, 134.7, 128.5, 125.6, 38.4, 26.9, 22.7, 15.9, 14.2, 10.5. ESI
exact mass (M þ Hþ) calculated for C14H19O 203.1430, found
203.1434.
Preparation of 4-(cis-2-Vinylcyclopropyl)benzophenone,
22. As described above, 6.9 g of 1,3-butadiene was condensed into
12 mL of cyclohexane and 12 mg of dry Cu(OTf)2 was added. Addition
of 165 mg of p-benzoylphenyldiazomethane in 11 mL of cyclohexane
gave, after silica gel chromatography, 84 mg (45% yield) of 22 and 42.
Earlier fractions were enriched in the cis-isomer 22 while later fractions
1
contained mixtures of the cis-isomer 22 and the trans-isomer 42. H
NMR of 22 (CDCl3) δ 7.79 (d, J = 8 Hz, 2 H), 7.74 (d, J = 8 Hz, 2 H),
7.58 (t, J = 8 Hz, 1 H), 7.48 (t, J = 8 Hz, 2 H), 7.30 (d, J = 8 Hz, 2 H), 5.15
(m, 2 H), 4.90 (m, 1 H), 2.41 (m, 1 H), 1.97 (m, 1 H), 1.35 (t of d, J = 8.3,
5.4 Hz, 1 H), 1.15 (q, J = 5.9 Hz, 1 H). 13C NMR of 22 (CDCl3) δ 196.6,
144.5, 138.1, 137.4, 135.4, 132.4, 130.24, 130.16, 129.0, 128.4, 115.2,
24.0, 23.7, 12.3. ESI exact mass (M þ Hþ) calculated for C18H17O
249.1250, found 249.1273.
Preparation of 4-(endo-7-Bicyclo[4.1.0]hept-2-enyl)ben-
zophenone, 23. Using a procedure analogous to the preparation of
19, reaction of p-benzoylphenyldiazomethane with Cu(OTf)2 in 1,3-
cyclohexadiene gave a mixture of 23 and 44 in 46% yield. 1H NMR of 23
(CDCl3) δ 7.78 (d, J = 7.5 Hz, 2 H), 7.70 (d, J = 8 Hz, 2 H), 7.57 (t, J =
7.5 Hz, 1 H), 7.47 (t, J = 7.5 Hz, 2 H), 7.37 (d, J = 8 Hz, 2 H), 6.10 (m, 1
H), 5.39 (d of d of d, J = 10, 6, 2.5 Hz, 1 H), 2.34 (t, J = 8.7 Hz, 1 H), 1.97
(m, 1 H), 1.80-1.70 (m, 3 H), 1.64 (m, 1 H), 0.59 (m, 1 H). 13C NMR
of 23 (CDCl3) δ 196.9, 144.2, 138.2, 135.4, 132.4, 130.4, 130.2, 130.1,
128.4, 126.5, 124.9, 29.0, 22.3, 18.5, 17.3, 14.6. ESI exact mass (M þ
Hþ) calculated for C20H19O 275.1430, found 275.1415. 1H NMR of 44
(CDCl3) δ 7.77 (m, 2 H), 7.72 (d, J = 8.3 Hz, 2 H), 7.57 (t, J = 7.5 Hz, 1
H), 7.47 (t, J = 7.5 Hz, 2 H), 7.12 (d, J = 8.2 Hz, 2 H), 6.13 (m, 1 H), 5.57
(m, 1 H), 2.19 (t, J = 4.2 Hz, 1 H), 2.15-2.07 (m, 2 H), 1.96 (m, 1 H),
1.82 (m, 1 H), 1.72 (m, 1 H), 1.64 (m, 1 H). 13C NMR of 44 (CDCl3) δ
196.5, 148.7, 138.3, 134.8, 132.3, 130.7, 130.1, 128.4, 127.1, 125.3, 124.1,
28.8, 26.7, 24.1, 21.0, 18.3.
Preparation of p-(endo-6-Bicyclo[3.1.0]hexyl)valerophe-
none, 24. Cyclopentene (15 mL) was added to 26 mg of dry Cu(OTf)2
and a solution of 378 mg of p-cyanophenyldiazomethane7 in 20 mL of
cyclopentene was added dropwise over a 2 h period. The solution was
then warmed to 30 °C for 30 min. The solution was then filtered and the
cyclopentene was removed under vacuum. The residue was chromato-
graphed on 7 g of silica gel and the column was eluted with increasing
amounts of ether in hexanes. A mixture of endo- and exo-4-(6-bicyclo-
[3.1.0]hexyl)benzonitrile (83 mg; 17% yield) eluted with 3% ether in
hexanes.
Preparation of 1-Bromo-4-cyclobutylbenzene. A solution of
844 mg of Et3SiH and 1.318 g of (4-bromophenyl)cyclobutanol22 in
18 mL of CH2Cl2 was cooled to -78 °C and a solution of 1.045 g of
boron trifluoride diethyl etherate in 5 mL of CH2Cl2 was added
dropwise over 5 min. The mixture was warmed slowly to 0 °C and
1.83 g of K2CO3 was added followed by 10 mL of water. The solution
was transferred with ether to a separatory funnel and the aqueous phase
was separated. The organic phase was washed with water and saturated
NaCl solution, then dried over a mixture of NaSO4 and MgSO4. After
filtration, the solvent was removed with a rotary evaporator and the
crude residue was chromatographed on 5 g of silica gel. The product
eluted with pentane and the solvent was removed with a rotary
evaporator. The residue was distilled by using a short-path distillation
head to give 845 mg (69% yield) of 1-bromo-4-cyclobutylbenzene, bp
85 °C (0.8 mm).23 1H NMR (CDCl3) δ 7.40 (d, J = 8.4 Hz, 2 H), 7.08
(d, J = 8.4 Hz, 2 H), 3.49 (quintet, J = 8.8 Hz, 1 H), 2.33 (m, 2 H), 2.10
(m 2 H), 2.02 (m, 1 H), 1.85 (m, 1 H). 13C NMR (CDCl3) δ 145.2,
131.2, 128.1, 119.3, 39.8, 29.7, 18.2.
The mixture of nitriles obtained above was dissolved in 5 mL of
anhydrous ether and the solution was cooled to -78 °C. n-Butyllithium
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Preparation of p-Cyclobutylbenzophenone, 26. A solution
of 358 mg of 1-bromo-4-cyclobutylbenzene in 6 mL of THF was
cooled to -78 °C and 1.1 mL of 1.6 M n-butyllithium was added. After
20 min at -78 °C, a solution of 294 mg of N,N-dimethylbenzamide in
2 mL of THF was added dropwise. After the addition was complete, the
solution was slowly warmed to room temperature. Water was added
dropwise and the mixture was then extracted into ether. The ether extract
was washed with water and saturated NaCl solution, then dried over a
mixture of Na2SO4 and MgSO4. After filtration, the solvent was removed
with a rotary evaporator, the residue was chromatographed on 7 g of silica
gel, and the column was eluted with increasing amounts of ether in
hexanes. The product 26 (251 mg; 63% yield) eluted with 3% ether in
hexanes. 1H NMR of 26 (CDCl3) δ 7.79 (d, J = 8 Hz, 2 H), 7.76 (d, J = 8
Hz, 2 H), 7.58 (t, J = 7.5 Hz, 1 H), 7.47 (t, J = 7.5 Hz, 2 H), 7.31 (d, J = 8
Hz, 2 H), 3.63 (quintet, J = 8.9 Hz, 1 H), 2.40 (m, 2 H), 2.19 (m, 2 H), 2.7
(m, 1 H), 1.90 (m, 1 H). 13C NMR of 26 (CDCl3) δ 196.5, 151.4, 138.0,
135.1, 132.2, 130.3, 130.0, 128.2, 126.2, 40.3, 29.6, 18.3. ESI exact mass
(M þ Hþ) calculated for C17H17O 237.1274, found 237.1265.
in hexanes was added. After 10 min at -78 °C, a solution of 45 mg of
2-methylcyclobutanone25 in 2 mL of anhydrous ether was added
dropwise. The solution was then warmed slowly to room temperature,
quenched with water, and then transferred to a separatory funnel with
use of ether. The ether extract was washed with water and saturated
NaCl solution, then dried over a mixture of Na2SO4 and MgSO4. After
filtration, the solvent was removed with a rotary evaporator. The residue
was chromatographed by using a 4.2 g silica gel column packed with
pentane. The column was eluted with increasing amounts of ether in
pentane to give 96 mg (82%) of alcohols 57. The major product was
1-(4-cyclobutylphenyl)-2-methylcyclobutanol, 57, with the 4-cyclobu-
tylphenyl group trans to the 2-methyl group, while the minor product
was the cis-isomer. 1H NMR of 57 (CDCl3) δ 7.36 (d, J = 8 Hz, 2 H),
7.21 (d, J = 8 Hz, 2 H), 3.54 (quintet, J = 8.8 Hz, 1 H), 2.73 (hextet, J =
7.5 Hz, 1 H), 2.42 (m, 1 H), 2.34 (m, 2 H), 2.17 (m, 3 H), 1.99 (m, 2 H),
1.85 (m, 1 H), 1.77 (m, 1 H), 1.16 (d J = 7.5 Hz, 3H). 13C NMR of 57
(CDCl3) δ 145.1, 144.5, 126.3, 124.7, 78.4, 40.1, 40.0, 33.9, 29.8, 23.2,
18.3, 14.1. ESI exact mass (M þ Naþ) calculated for C15H20NaO
239.1406, found 239.1395.
Preparation of p-Cyclobutylacetophenone, 58. The pre-
paration of 61 was analogous to the preparation of p-cyclobutylvaler-
ophenone, 27. Thus, reaction of 261 mg of 1-bromo-4-cyclobutylben-
zene in 5 mL of THF at -78 °C with 0.75 mL of 1.6 M n-butyllithium
followed by addition of 70 mg of acetaldehyde in 2 mL of ether gave the
crude alcohol product. This product was dissolved in 5 mL of CH2Cl2
and 379 mg of pyridinium chlorochromate was added. After dilution
with 5 mL of pentane and filtration through a small amount of silica gel,
chromatography on 6 g of silica gel and elution with 3% ether in pentane
gave 126 mg (40% yield) of pure 58.26 1H NMR of 58 (CDCl3) δ 7.90
(d, J = 8 Hz, 2 H), 7.29 (d, J = 8 Hz, 2 H), 3.60 (quintet, J = 8.8 Hz, 1 H),
2.58 (s, 3 H), 2.38 (m, 2 H), 2.17 (m, 2 H), 2.05 (m, 1 H), 1.88 (m, 1 H).
13C NMR of 58 (CDCl3) δ 197.9, 152.0, 134.9, 128.4, 126.5, 40.2, 29.5,
26.6, 18.3.
Preparation of p-Vinylvalerophenone, 59. The preparation of
p-vinylvalerophenone, 59, was analogous to the preparation of p-
cyclobutylvalerophenone, 27. Thus reaction of 350 mg of p-bromostyr-
ene in 7 mL of THF with 1.2 mL of 1.6 M n-butyllithium at -78 °C,
followed by addition of 186 mg of valeraldehyde in 3 mL of ether,
followed by oxidation with 625 mg of pyridinium chlorochromate in
8 mL of CH2Cl2, gave, after chromatography on 7 g of silica gel, 218 mg
(61% yield) of 59.27 1H NMR of 59 (CDCl3) δ 7.93 (d, J = 8.4 Hz, 2 H),
7.48 (d, J = 8.4 Hz, 2 H), 6.76 (d of d, J = 17.6, 10.9 Hz, 1 H), 5.87 (d of d,
J = 17.6, 0.7 Hz, 1 H), 5.39 (d of d, J = 10.9, 0.7 Hz, 1 H), 2.95 (t, J = 7.4
Hz, 2 H), 1.72 (quintet, J = 7.4 Hz, 2 H), 1.41 (sextet, J = 7.4 Hz, 2 H),
0.95 (t, J = 7.4 Hz, 1 H). 13C NMR of 59 (CDCl3) δ 200.1, 141.9, 136.3,
136.0, 128.5, 126.3, 116.6, 38.4, 26.6, 22.5, 14.0.
Preparation of p-Vinylacetophenone, 60. The preparation of
p-vinylacetophenone, 60, was analogous to the preparation of p-cyclo-
butylvalerophenone, 27. Thus reaction of 349 mg of p-bromostyrene in
7 mL of THF with 1.2 mL of 1.6 M n-butyllithium at -78 °C, followed
by addition of 90 mg of acetaldehyde in 2 mL of ether, followed by
oxidation with 614 mg of pyridinium chlorochromate in 8 mL of
CH2Cl2, gave, after chromatography on 7 g of silica gel, 152 mg (55%
yield) of 60.28 1H NMR of 60 (CDCl3) δ 7.92 (d, J = 8.3 Hz, 2 H), 7.48
(d, J = 8.3 Hz, 2 H), 6.75 (d of d, J = 17.6, 10.9 Hz, 1 H), 5.88 (d of d, J =
17.6, 0.7 Hz, 1 H), 5.40 (d of d, J = 10.9, 0.7 Hz, 1 H), 2.59 (s, 3 H). 13C
NMR of 60 (CDCl3) δ 197.6, 142.1, 136.3, 135.9, 128.7, 126.3,
116.7, 26.6.
Preparation of p-Cyclobutylvalerophenone, 27. A solution
of 207 mg of 1-bromo-4-cyclobutylbenzene in 5 mL of THF was cooled
to -78 °C and 0.7 mL of 1.6 M n-butyllithium was added. After 20 min
at -78 °C, a solution of 110 mg of distilled valeraldehyde in 2 mL of
ether was added dropwise. After the addition was complete, the solution
was slowly warmed to room temperature. Water was added dropwise
and the mixture was then extracted into ether. The ether extract was
washed with water and saturated NaCl solution, dried over a mixture of
Na2SO4 and MgSO4, and filtered, then the solvent was removed with a
rotary evaporator.
The crude residue was dissolved in 5 mL of CH2Cl2 and 427 mg of
pyridinium chlorochromate was added. The mixture was stirred at room
temperature for 2.5 h, 5 mL of pentane was added, and the mixture was
filtered through a small amount of silica gel. After solvent removal with a
rotary evaporator, the residue was chromatographed on 6 g of silica gel
and the column was eluted with increasing amounts of ether in hexanes.
The product 27 (187 mg; 80% yield) eluted with 2% ether in hexanes.
1H NMR of 27 (CDCl3) δ 7.90 (d, J = 8 Hz, 2 H), 7.29 (d, J = 8 Hz, 2 H),
3.60 (quintet, J = 8.9 Hz, 1 H), 2.94 (t, J = 7.5 H, 2 H), 2.37 (m, 2 H),
2.16 (m, 2 H), 2.05 (m, 1 H), 1.88 (m, 1 H), 1.71 (quintet, J = 7.5 Hz, 2
H), 1.41 (hextet, J = 7.5 Hz, 2 H), 0.95 (t, J = 7.5 Hz, 3 H). 13C NMR of
27 (CDCl3) δ 200.3, 151.7, 134.8, 128.2, 126.5, 40.3, 38.3, 29.6, 26.7,
22.6, 18.3, 14.0. ESI exact mass (M þ Hþ) calculated for C15H21O
217.1587, found 217.1578.
Photolyses in C6D6: General Procedures. The following pro-
cedure is representative. Benzene-d6 was deoxygenated by briefly bubbling
N2 through the stock sample. A solution of 4.0 mg of 19 in 270 mg of C6D6
was placed in a 3 mm NMR tube under N2 or argon. The NMR tube was
sealed and then placed in a Rayonet Photochemical Reactor fitted with
350 nm lamps.24 The tube was irradiated for various time periods at
ambient temperature (22 °C) using the air-cooling provided by the reactor
fan. The tube was periodically analyzed by 600 MHz 1H NMR spectros-
copy and typical spectra are shown in Figure 2. Spectra and data for
compounds 21, 22, and 24 are given as Supporting Information.
Photolysis of p-Cyclobutylvalerophenone, 27, in C6D6. A
solution of 4.0 mg of 27 in 320 mg of C6D6 was placed in a 3 mm NMR
1
tube under argon and the solution was irradiated for 2 h. H NMR
analysis, as shown in the Supporting Information, showed 57, 58, 59,
and 60 in an 11:31:11:4 ratio, along with 43% of unreacted 27. Further
analysis of the olefinic region of the spectrum (Figure 5) showed the
presence of ethylene and propene. These products were all identified by
spectral comparison in C6D6 with authentic samples prepared as
described below.
Preparation of 1-(4-Cyclobutylphenyl)-2-methylcyclobu-
tanol, 57. A solution of 115 mg of 1-bromo-4-cyclobutylbenzene in
2 mL of THF was cooled to -78 °C and 0.36 mL of 1.6 M n-butyllithium
Photolyses in i-PrOH: General Procedures. The following
procedure is representative. A solution of 4.6 mg of 21 in 295 mg of
nitrogen-purged i-PrOH was sealed in a 3 mm NMR tube under nitrogen
or argon. The NMR tube was then irradiated with 350 nm lamps for
various time periods at ambient temperature (22 °C), using the air-
cooling provided by the reactor fan. The tube was periodically analyzed
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The Journal of Organic Chemistry
ARTICLE
by 600 MHz 1H NMR spectroscopy by using No-D NMR techniques29
and typical spectral data showing isomerizations of 21, 22, and 23, as well
as photoreduction of 26, are given as Supporting Information.
(13) (a) Pitts, J. N., Jr.; Johnson, H. W.; Kuwana, T. J. Phys. Chem.
1962, 66, 2456. (b) Schuster, D. I.; Goldstein, M. D.; Bane, P. J. Am.
Chem. Soc. 1977, 99, 187. (c) Filipescu, N.; Kindley, L. M.; Minn, F. L. J.
Org. Chem. 1971, 36, 861. (d) Wagner, P. J.; Kemppainen, A. E. J. Am.
Chem. Soc. 1968, 90, 5898. (e) Yang, N. C.; Dusenbery, R. L. J. Am.
Chem. Soc. 1968, 90, 5899.
(14) (a) Overberger, C. G.; Borchert, A. E. J. Am. Chem. Soc. 1960,
82, 1007. (b) Hudlicky, T.; Price, J. D. Chem. Rev. 1989, 89, 1467.
(c) Baldwin, J. E. In Chemistry of the Cyclopropyl Group; Rappoport, Z.,
Ed., Wiley: New York,1995; Vol. 2, pp 4690-4694. (d) Baldwin, J. E.;
Villarica, K. A.; Freedberg, D. I.; Anet, F. A. L. J. Am. Chem. Soc. 1994,
116, 10845. (e) Davidson, E. R.; Gajewski, J. J. J. Am. Chem. Soc. 1997,
119, 10543. (f) Houk, K. N.; Nendel, M.; Wiest, O.; Storer, J. W. J. Am.
Chem. Soc. 1997, 119, 10545. (g) Baldwin, J. E. J. Comput. Chem. 1998,
19, 222.
Photolysis of p-Isopropylbenzophenone, 35, in i-PrOH. A
solution of 45 mg of 35 in 2.5 mL of i-PrOH was placed in a 5 mm NMR
tube under argon. The NMR tube was then irradiated with 350 nm
lamps for 70 min at ambient temperature. The solvent was then removed
by using a rotary evaporator and the solid residue was slurried with a
small amount of pentane. The pentane was decanted and the product 36
(42 mg; 93% yield; 50:50 mixture of meso and threo diastereomers) was
dried under vacuum. 1H NMR of 36 (CDCl3) δ 7.40 (m, 2 H), 7.30 (m,
2 H), 7.16 (m, 8 H), 7.08 (m, 2 H), 7.03 (m, 2 H), 3.00 (br s, 2 H), 2.84
(m, 2 H), 1.21 (d, J = 7 Hz, 3 H), 1.20 (d, J = 7 Hz, 3 H), 1.19 (d, J = 7 Hz,
6 H). 13C NMR of 36 (CDCl3) δ 147.6, 147.4, 144.53, 144.49, 141.5,
141.3, 128.7, 128.6, 128.5, 128.4, 127.17, 127.16, 126.8, 126.6, 125.34,
125.32, 83.0, 33.52, 33.51, 23.93, 23.91, 23.99, 23.87. ESI exact mass
(M þ Naþ) calculated for C32H34NaO2 473.2451, found 473.2443.
(15) Woodward, R. B.; Hoffmann, R. The Conservation of Orbital
Symmetry; Academic Press: New York, 1970; p 120.
(16) p-Cyclobutylbenzophenone, 27, is also photolabile in C6D6,
and fragments in an inefficient process to give p-vinylbenzophenone and
ethylene along with other unidentified products.
’ ASSOCIATED CONTENT
(17) Creary, X.; Aldridge, T. J. Org. Chem. 1991, 4280.
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(19) (a) Levina, R. Y.; Loim, N. M.; Gembitskii, P. A. Russ. J. Gen.
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Chem. Soc. 1987, 109, 3739.
S
Supporting Information. Complete ref 9, the B3LYP/6-
b
31G* calculated structure, energy, and Cartesian coordinates of
32, 1H and 13C NMR spectra of compounds 19, 21, 22, 23, 24, 25,
26, 27, 36, 56, 57, 58, 59, and 60, evolving1H NMR spectra during
irradiation of 21, 22, and 24 inC6D6, the 1H NMR spectrumof the
1
aromatic region during photolysis of 27 in C6D6, evolving H
NMR spectra during irradiation of 21, 22, 23, and 26 in i-PrOH, as
well as UV spectra of 20, 21, 25, and 35. This material is available
free of charge via the Internet at http://pubs.acs.org.
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’ AUTHOR INFORMATION
Corresponding Author
*Email: creary.1@nd.edu.
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(12) While we have assumed that the lowest triplet is the (n, π*)
triplet, the p-cyclopropyl group could result in a low-lying (π, π*) triplet.
2071
dx.doi.org/10.1021/jo102309w |J. Org. Chem. 2011, 76, 2062–2071