Highly efficient photochemical generation of a triple bond: Synthesis, properties, and photodecarbonylation of cyclopropenones

Article abstract of DOI:10.1021/jo034869m

UV irradiation of alkyl-, aryl-, and heteroatom-substituted cyclopropenones results in the loss of carbon monoxide and the formation of quantitative yields of corresponding alkynes. The quantum yield of the photochemical decarbonylation reaction ranges from 20% to 30% for alkyl-substituted cyclopropenones to above 70% for the diphenyl- and dinaphthylcyclorpopenones. Rapid formation (<5 ns) and then a somewhat slower decay (ca. 40 ns) of an intermediate in this reaction was observed by using laser flash photolysis. The DFT calculations allowed us to identify this intermediate as a zwitterionic species formed by a cleavage of one of the carbon-carbon bonds of the cyclopropenone ring. The latter then rapidly loses carbon monoxide to produce the ultimate acetylenic product. Despite their high photoreactivity, cyclopropenones were found to be thermally stable compounds with the exception of hydroxy- and methoxy-substituted cyclopropenones. The latter undergo rapid solvolysis in hydroxylic solvents even at room temperature. The application of this reaction to the in situ generation of the enediyne strucutre was illustrated by the photochemical preparation of benzannulated enediyne 12.

Full text of DOI:10.1021/jo034869m

High ly Efficien t P h otoch em ica l Gen er a tion of a Tr ip le Bon d :
Syn th esis, P r op er ties, a n d P h otod eca r bon yla tion of
Cyclop r op en on es
Andrei Poloukhtine and Vladimir V. Popik*
Center for Photochemical Sciences, Bowling Green State University, Bowling Green, Ohio 43403
vpopik@bgnet.bgsu.edu
Received J une 20, 2003
UV irradiation of alkyl-, aryl-, and heteroatom-substituted cyclopropenones results in the loss of
carbon monoxide and the formation of quantitative yields of corresponding alkynes. The quantum
yield of the photochemical decarbonylation reaction ranges from 20% to 30% for alkyl-substituted
cyclopropenones to above 70% for the diphenyl- and dinaphthylcyclorpopenones. Rapid formation
(<5 ns) and then a somewhat slower decay (ca. 40 ns) of an intermediate in this reaction was
observed by using laser flash photolysis. The DFT calculations allowed us to identify this
intermediate as a zwitterionic species formed by a cleavage of one of the carbon-carbon bonds of
the cyclopropenone ring. The latter then rapidly loses carbon monoxide to produce the ultimate
acetylenic product. Despite their high photoreactivity, cyclopropenones were found to be thermally
stable compounds with the exception of hydroxy- and methoxy-substituted cyclopropenones. The
latter undergo rapid solvolysis in hydroxylic solvents even at room temperature. The application
of this reaction to the in situ generation of the enediyne strucutre was illustrated by the
photochemical preparation of benzannulated enediyne 12.
In tr od u ction
carbonyl carbon with the formation of acrylic acid deriva-
tives7 and (2) decarbonylation to alkynes under high-
temperature pyrolysis or in the presence of various
catalysts.8 Acetylenes were also observed as intermedi-
ates1,9 or were even isolated7,10 in photolysis of some
cyclopropenones. In this work we report synthesis, prop-
erties, and photochemistry of the series of cycloprope-
nones 1a -n and 12.
The development of enediyne-based photonucleases,
which is underway in our group, requires robust and
efficient methods for the photogeneration of a triple bond.
We have already utilized photochemical decarbonylation
of hydroxycyclopropenones for the generation of short-
lived ynol1 intermediates and decided to explore the
suitability of this reaction for the preparation of stable
acetylenes. The preparation of the first cyclopropenone,
diphenylcyclopropenone, was reported independently in
1959 by Breslow et al.2 and Vol’pin et al.3 Cycloprope-
nones received considerable attention due to their pos-
sible description as aromatic compounds.4 The discovery
of cyclopropenone-containing natural antibiotic penitri-
cin,5 as well as cyclopropenone-based protease inhibitors,6
renewed interest in this class of cyclic ketones. The
chemical reactivity of the cyclopropenone ring is domi-
nated by two processes:4 (1) nucleophilic attack on the
Syn th esis. We have explored three different ap-
proaches to a cyclopropenone structure: (1) alkylation
of aromatic compounds with trichlorocyclopropenium
(1) (a) Chiang, Y.; Kresge, A. J .; Popik, V. V. J . Am. Chem. Soc. 1999,
121, 5930. (b) Chiang, Y.; Kresge, A. J .; Paine, S. W.; Popik, V. V. J .
Phys. Org. Chem. 1996, 9, 361. (c) Chiang, Y.; Kresge, A. J .; Popik, V.
V. J . Am. Chem. Soc. 1995, 117, 9165.
(2) Breslow, R.; Haynie, R.; Mirra, J . J . Am. Chem. Soc. 1959, 81,
247.
(3) Vol’pin, M. E.; Koreshkov, Y. D.; Kursanov, D. N. Dokl. Akad.
Nauk SSSR, Ser. Khim. 1959, 506.
(7) Ciabattoni, J .; Nathan, E. C. J . Am. Chem. Soc. 1969, 91, 4766.
Dehmlow, E. V.; Neuhaus, R.; Schell, H. G. Chem. Ber. 1988, 121, 569.
Dehmlow, S. S.; Dehmlow, E. V. Z. Naturforsch. B 1975, 30b, 404.
Dehmlow, E. V. Leib. Ann. 1969, 729, 64.
(4) Potts, K. T.; Baum, J . S. Chem. Rev. 1974, 74, 189. Halton, B.;
Banwell, M. G. In The Chemistry of the Cyclopropyl Group; Rappoport,
Z., Ed.; Wiley: New York, 1987; pp 1300-1311.
(8) Wadsworth, D. H.; Donatelli, B. A. Synthesis 1981, 4, 285-286.
(9) (a) Wagner, B. D.; Zgierski, M. Z.; Lusztyk, J . J . Am. Chem. Soc.
1994, 116, 6433. (b) Quinkert, G.; Opitz, K.; Wiersdorff, W. W.;
Weinlich, J . Tetrahedron Lett. 1963, 1863. (c) Chapman, O. L.; Gano,
J .; West, R. P.; Regitz, M.; Maas, G. J . Am. Chem. Soc. 1981, 103,
7033. (d) Krebs, A.; Cholcha, W.; Mueller, M.; Eicher, T.; Pielartzik,
H.; Schnoeckel, H. Tetrahedron Lett. 1984, 25, 5027. (e) Murata, S.;
Yamamoto, T.; Tomioka, H. J . Am. Chem. Soc. 1993, 115, 4013. (f)
Sung, K.; Fang, D.-C.; Glenn, D.; Tidwell, T. T. J . Chem. Soc., Perkin
Trans. 2 1998, 2073-2080.
(5) Okuda T.; Yoneyama Y.; Fujiwara A.; Furumai T. J . Antibiot.
1984, 37, 712-7.
(6) (a) Ando, R.; Morinaka, Y.; Tokuyama, H.; Isaka, M.; Nakamura,
E. J . Am. Chem. Soc. 1993, 115, 1515. (b) Ando, R.; Sakaki, T.;
Morinaka, Y.; Takahashi, C.; Tamao, Y.; Yoshii, N.; Katayama, S.;
Saito, K.; Tokuyama, H.; Isaka, M.; Nakamura, E. Bioorg. Med. Chem.
1999, 7, 571.
10.1021/jo034869m CCC: $25.00 © 2003 American Chemical Society
Published on Web 09/09/2003
J . Org. Chem. 2003, 68, 7833-7840
7833

Poloukhtine and Popik
SCHEME 1a
a
Reagents and conditions: (i) acetone-water mixture, 0 °C; (ii) (1) MeOH, (2) HClconc; (iii) diazomethane; (iv) (1) SOCl2, (2) aniline; (v)
(1) ArH, (2) H2O.
SCHEME 2
cation followed by hydrolysis (Scheme 1); (2) dihalocy-
clopropanation of acetylenes and hydrolysis of intermedi-
ate hem-dihalocyclopropenes (Scheme 2); and (3) intro-
duction of substituents into 2- and 3-positions of cyclopro-
penone acetal followed by deprotection of the carbonyl
group (Scheme 3).
The reaction of the arylcyclopropenium salt 2 with the
second equivalent of the aromatic compound results in a
subsequent Friedel-Crafts alkylation to produce sym-
metric4,8 (1j-n ) or nonsymmetric10d (1i and 12) diaryl-
cyclopropenones (Schemes 1 and 5).
Cyclopropanation of acetylenic compounds with
dichloro-14 or fluorochlorocarbenes15 results in the forma-
tion of gem-dihalosubstituted cyclopropenes. The latter
are then hydrolyzed to corresponding cyclopropenones.
Using this method, we were able to conduct a regio-
selective cyclopropanation of o-dialkynyl substituted
benzene 3 to produce cyclopropenone 4 (Scheme 2).
Unfortunately, the conversion in the cyclopropanation
step of this reaction was low and o-alkynylphenylcyclo-
propenone 4 was found to be unstable.
Cyclopropenones are susceptible to a nucleophilic at-
tack, which limits the range of reactions that can be used
to achieve the desired structural modification. Use of
cyclopropenone acetal allows us to mask the reactivity
of the cyclopropenone moiety. Simple dimethyl or diethyl
acetals of cyclopropenones are rather unstable and
undergo a facile hydrolysis even in neutral solution.12 The
neopentyl glycol acetal possesses much higher kinetic
stability and was chosen as the protecting group for the
preparation of alkyl-substituted cyclopropenones. The
1,3-dichloroacetone was converted into acetal 6 by treat-
ing it with neopentyl glycol in the presence of p-toluene-
sulfonic acid. The reaction of 6 with sodium amide in
liquid ammonia results in a cyclization/dehydrohaloge-
nation reaction and formation of the sodium salt of
cyclopropenone acetal 7. The latter can be quenched by
The reaction of tetracholorocyclopropene with anhy-
drous aluminum chloride generates the trichlorocyclo-
propenium cation, which is then used in Friedel-Crafts
alkylation of aromatic compounds to produce an aryldi-
chlorocyclopropenium cation 2 (Scheme 1). Controlled
hydrolysis of the latter in an acetone-water mixture at
0 °C produces arylhydroxycyclopropenone 1e,g in moder-
ate yields.11 Quenching of the salt 2 with methanol
followed by hydrolysis with concentrated hydrochloric
acid allowed us to prepare arylmethoxycyclopropenone
1h . The dimethylacetal of 1h is likely an intermediate
in this reaction. Dialkyl acetals of cyclopropenones are
known to be extremely susceptible to hydrolysis with a
sub-millisecond lifetime in aqueous solution.12 The ester
1h was alternatively prepared by esterification of aryl-
hydroxycyclopropenone 1g with diazomethane (Scheme
1).
The treatment of phenylhydroxycyclopropenone 1e
with thionyl chloride converts it into unstable11b aryl-
chlorocyclopropenone. Quenching of the latter with aniline
produces 2-phenyl-3-N-phenylaminocyclopropenone 1f
(Scheme 1).13
(10) (a) Breslow, R.; Altman, L. J .; Krebs, A.; Mohacsi, E.; Murata,
I.; Peterson, R. A.; Posner, J . J . Am. Chem. Soc. 1965, 87, 1326. (b)
Agranat, I.; Barak, A.; Pick, M. P. J . Org. Chem. 1973, 38, 3064. (c)
Eicher, T.; Schmieder, V. Synthesis 1989, 372. (d) Weidner, C. H.;
Wadsworth, D. H.; Knop, C. S.; Oyefesso, A. I.; Hafer, B. L.; Hartman,
R. J .; Mehlenbacher, R. C.; Hogan, S. C. J . Org. Chem. 1994, 59, 4319.
(11) This procedure has been used for the preparation of a series of
arylhydroxycyclopropenones: (a) Chicos, J . C.; Patton, E.; West, R. J .
Org. Chem. 1974, 39, 1647. Also see ref 1. Direct quenching of
arylcyclopropenium cation with water, on the other hand, results in
ring openinig and formation of 2-aryl-3-chloroacrylic acid: (b) West,
R.; Zecher, D. C.; Tobey, S. W. J . Am. Chem. Soc. 1970, 92, 168.
(12) McClelland, R. A.; Ahmad, M. J . Am. Chem. Soc. 1978, 100,
7027.
(13) Several aminocyclopropenones were prepared in
a similar
manner: Chiang, Y.; Grant, A. S.; Kresge, A. J .; Paine, S. W J . Am.
Chem. Soc. 1996, 118, 4366.
(14) Dehmlow, E. V.; Dehmlow, S. S.; Marschner, F. Chem. Ber.
1977, 110, 154.
(15) Dehmlow, E. V.; Winterfeldt, A. Tetrahedron 1989, 45, 2925.
7834 J . Org. Chem., Vol. 68, No. 20, 2003

Cyclopropenones
SCHEME 3a
a
Reagents and conditions: (i) NaNH2 in NH3; (ii) n-C5H11Br or n-C4H9Br, Et2O, -78 °C; (iii) n-BuLi, HMPA, THF, -78 °C; (iv) CH3I,
THF, -78 °C; (v) ZnCl2, THF, -78 °C; (vi) 5% Pd(PPh3)4, PhI; (vii) Amberlist 15, acetone.
TABLE 1. Com p a r ison of Str u ctu r a l P a r a m eter s of P h en yl- a n d Dip h en ylcyclop r op en on es Ca lcu la ted by Usin g th e
DF T B3LYP Hybr id F u n ction a l w ith Cr ysta l Str u ctu r e Da ta
phenylcyclopropenone (R ) H)
diphenylcyclopropenone (R ) Ph)
6-311+G(3df,2p)
parameter
6-31+G(d,p)
6-311+G(3df,2p)
6-31+G(d,p)
X-ray20
C1-O (Å)
1.216
1.430
1.420
1.350
1.440
1.200
1.420
1.410
1.356
1.447
56.6
146.3
145.0
0.0
1.222
1.420
1.211
1.420
1.225 (1.226)a
1.417 (1.409)
C1-C2 (Å)
C1-C3 (Å)
C2-C3 (Å)
C2-Ph (Å)
C2C1C3 (deg)
C3C2Ph (deg)
C1C2H (deg)
φC3C2Ph (deg)
1.370
1.440
57.6
1.360
1.440
57.3
1.349 (1.354)
1.447 (1.452)
56.9 (57.4)
56.8
146.6
145.2
0.0
149.9
149.9
150.6 (149.3)
0.0
0.0
2.2 (6.3)
a
Data in parentheses represent the crystal structure of the diphenylcyclopropenone monohydrate.20b
ammonium chloride and then water to give the acetal of
the parent cyclopropenone.16
cyclopropene itself (1.296 Å).19 This double bond is even
longer in diphenylcyclopropenone (1.349 Å)20 according
to the X-ray data shown in Table 1. This phenomenon is
probably due to the additional conjugation of the double
bond with an aromatic system. We have conducted DFT
geometry optimization of phenylcyclopropenone and diphe-
nylcyclopropenone (1j) using the B3LYP hybrid func-
tional with 6-31+G(d,p) and 6-311+G(3df,2p) basis sets.
Both methods produce optimized structural parameters
(shown in Table 1), which are in good agreement with
the X-ray data. The 6-311+G(3df,2p) basis set, however,
gives a better description of the electronic properties, as
the length of the C2-C3 double bond is closer to the
experimental value and the dipole moment calculated by
using the 6-311+G(3df,2p) basis set (5.31 D) is in better
agreement with the experimental value (5.08 D21a and
5.14 D21b) than results obtained with a smaller set (5.42
D). In other words, the DFT method used in the present
work describes the geometry and electronic structure of
Reaction of the sodium salt 7 with n-butyl or n-amyl
bromide produces 2-alkylcyclopropenone acetals 8a and
8b. Acetal 8b was deprotonated with n-BuLi to give salt
9, which in turn reacted with methyl iodide to yield the
acetal of 2-butyl-3-methylcyclopropenone (8c). Lithium
salt 9 can also be transmetalated with zinc chloride to
produce an organozinc derivative. The latter undergoes
palladium-catalyzed coupling with iodobenzene to give
2-butyl-3-phenylcyclopropenone acetal 8d . Cycloprope-
nones are acid-sensitive compounds and deprotection of
acetals 8 should be conducted under mild conditions. We
found that trans-acetalization in acetone catalyzed by the
Amberlist 15 ion-exchange resin gives the best results.
Str u ctu r e. Cyclopropenones are planar compounds
with a potentially “aromatic” character.17 The structural
feature that supports the notion of cyclopropenone aro-
maticity is elongation of the endocyclic double bond in
the parent cyclopropenone (1.332 Å)18 in comparison with
(19) Stigliani, W. M.; Laurie, V. W.; Li, J . C. J . Chem. Phys. 1975,
62, 1890.
(20) (a) Tsukada, H.; Shimanouchi, H.; Sasada, Y. Chem. Lett. 1974,
639. (b) Ammon, H. L. J . Am. Chem. Soc. 1973, 95, 7093.
(21) (a) Takahashi, K.; Nishijima, K.; Takase, K.; Katagiri, S.
Tetrahedron Lett. 1983, 24, 205. (b) Breslow, R.; Eicher, T.; Krebs, A.;
Petersom, R. A.; Posner, J . J . Am. Chem. Soc. 1965, 87, 1320.
(16) Isaka, M.; Ejiri, S.; Nakamura, E. Tetrahedron 1992, 48, 2045.
(17) For a recent review of the subject see: Nguyen, L. T.; De Proft,
F.; Nguyen, M. T.; Geerlings, P. J . Chem. Soc., Perkin Trans. 2 2001,
898 and references cited therein.
(18) Norden, T. D.; Staley, S. W.; Taylor, W. H.; Harmony, M. D. J .
Am. Chem. Soc. 1986, 108, 7912.
J . Org. Chem, Vol. 68, No. 20, 2003 7835

Poloukhtine and Popik
phenyl-substituted cyclopropenones reasonably well, es-
pecially when using the extended triple-ú basis set.
Both phenylcyclopropenone and 1j are predicted by
DFT calculations to be perfectly planar. X-ray data, on
the other hand, show that benzene rings in 1j are slightly
twisted from the plane of the three-membered ring. We
believe that this distortion is a result of a packing
requirement in the crystal lattice. Planarity of phenyl-
cyclopropenone and 1j means that an efficient conjuga-
tion exists between the cyclopropenone ring and the
aromatic system. Such conjugation should exert a strong
influence on photophysical properties of cyclopropenones
with aromatic substituents as discussed below.
Frequency calculations conducted on phenylcyclopro-
penone and 1j allowed us to address the long-standing
confusion about the nature of the major absorbance band
at ca. 1850 cm-1 in the infrared spectra of cycloprope-
nones. On the basis of the solvent dependency, this band
has been originally assigned to the ring vibration, while
the band at ca. 1630 cm-1 has been assigned to the
carbonyl stretching vibration.22 However, the substitution
of carbonyl oxygen with the 18O isotope affected the
shorter wavelength band more strongly, an observation
that suggests reverse assignment.23 B3LYP/6-311+G
(3df,2p) calculations clearly indicate that the absorbance
band at 1850 cm-1 corresponds to the carbonyl stretching
vibration. The band at 1650 cm-1 is due to endocyclic
double bond stretching vibrations, which in our case is
coupled with vibrations of the benzene ring.
F IGURE 1. Decomposition of cyclopropenones 1e (A) and 1h
(B) in methanolic solution at 25 °C. The reaction was followed
at λ ) 250 nm for 1e and at λ ) 280 nm for 1h .
Sta bility. The UV spectra of the aqueous and metha-
nolic solutions of cyclopropenones bearing alkyl (1a ,c)
and aryl (1d ,k ) substituents show no changes over a
period of 12 h at pH 7.0 and 70 °C. This observation
indicates that these cyclopropenones are reasonably
stable under the given conditions. Cyclopropenone (1k )
was quantitatively recovered after heating at 130 °C in
DMSO solution for 5 h. Samples of cyclopropenones (1a -
d ,i-n ) were stored at ca. -10 °C for several months
without detectable decomposition. The aminocycloprope-
none 1f is also stable at ambient temperatures in
aqueous, methanolic, and THF solutions. In contrast, the
oxygen-substituted cyclopropenes 1e and 1h are the
notable exceptions as they undergo a rapid decomposition
in hydroxylic solvents. The lifetime of phenylhydroxycy-
clopropenone 1e in methanol at 25 °C is 83 min, while
methoxy-substituted cyclopropenone 1h shows τ ) 35 min
in methanol at 25 °C and only 17 min at 40 °C (Figure
1).
P h otop h ysica l P r op er ties. The UV spectra of alkyl-
and dialkyl-substituted cyclopropenones show only tail
absorbance above 200 nm, similar to the parent unsub-
stituted compound.24 Conjugation of the cyclopropenone
system with the benzene ring in 1c causes the appear-
ance of an intense band at 251 nm (Figure 2, Table 2).
According to the time-dependent DFT B3LYP/6-311+G-
(3df,2p)25 calculation on phenylcyclopropenone, this ab-
F IGURE 2. UV spectra of ca. 10-5 M solutions of cyclopro-
penones 1c,d ,j,k ,l,n in methanol at 25 °C.
TABLE 2. Extin ction Coefficien ts a n d Qu a n tu m Yield s
of P h otolysis of Cyclop r op en on es
λ
max/nm (log ꢀ)a
Φa (λ/nm)
1a
1c
1d
1e
1f
1i
259 (1.57)
254 (1.92)
251 (4.18)
260 (4.30), 252 (4.30)
314 (4.43)
340 (4.20)
0.228 ( 0.006 (254)
0.26 ( 0.01 (254)
0.40 ( 0.01 (350)
0.26 ( 0.02 (300)
0.48 ( 0.02 (350)
0.37 ( 0.02 (350)
1j
1k
∼284 (4.28),b 295 (4.33), ∼307 (4.16)b 0.78 ( 0.07 (350)
∼309 (4.08),b 325 (4.28), 340 (4.28)
0.24 ( 0.01 (350)
0.23 ( 0.01c (350)
0.45 ( 0.02 (350)
0.36 ( 0.01 (350)
0.70 ( 0.02 (350)
1l
1m
1n
347 (4.51), 360 (4.49)
273 (4.25), 322 (4.05)
∼347 (4.16),b 364 (4.33), 383 (4.29)
a
b
Measured in methanol. Shoulder. c Measured in hexane
sorbance band corresponds to the HOMO-1 f LUMO
transition. The HOMO-1 of phenylcyclopropenone is
similar to the HOMO of the styrene26 with additional
involvement of the n-orbital of a carbonyl oxygen. The
LUMO of phenylcyclopropenone, on the other hand, looks
almost identical to the LUMO of styrene (Figure 3). In
fact, the HOMO f LUMO transition of styrene corre-
sponds to the absorbance band at 247 nm (log ꢀ )
(22) Krebs, A.; Schrader, B.; Hoefler, F. Tetrahedron Lett. 1968,
5935. Osawa, E.; Kitamura, K.; Yoshida, Z. J . Am. Chem. Soc. 1967,
89, 3814.
(23) Schubert, R.; Ansmann, A.; Bleckmann, P.; Schrader, B. J . Mol.
Struct. 1975, 26, 429.
(24) Breslow, R.; Oda, M. J . Am. Chem. Soc. 1972, 94, 4787.
(25) The geometry of phenyl- and diphenylcyclopropenones was
optimized at the DFT B3LYP/6-311+G(3df, 2p) level by using the
Gaussian 98W program as discussed in the Experimental Section.
(26) Amatatsu, Y. J . Comput. Chem. 2001, 23, 950.
7836 J . Org. Chem., Vol. 68, No. 20, 2003

Cyclopropenones
F IGURE 3. HOMO-1 and LUMO of S0 of phenylcyclopropenone and diphenylcyclopropenone (1j) by B3LYP/6-311+G (3df,2p).
SCHEME 4
4.17),27 which is similar to the band observed in the UV
spectrum of 1d (Table 2). Substitution of the alkyl group
in 1d with the second phenyl ring in 1j results in a 44-
nm bathochromic shift of the major band in the UV
spectrum (Figure 2, Table 2). TD-DFT calculations
predict that this band in the spectrum of 1j also corre-
sponds to the HOMO-1 f LUMO transition (Figure 3),
No phosphorescence could be detected but a weak
fluorescence can be observed at room temperature in
methanolic solutions of cyclopropenones 1j,k ,n with use
of 300 and 350 nm excitation light. The fluorescence
spectrum is identical in shape to the spectrum of corre-
sponding photoproducts, i.e., diarylacetylenes 9j,k ,n ,
which are intensely fluorescent. We believe that the weak
which closely resembles the HOMO f LUMO transition
of stilbene.28 The red shift of this absorbance band is,
however, more pronounced between 1d and 1j than
between styrene (247 nm in ethanol)27 and stilbene (278
nm in ethanol).29 This difference is apparently due to
different geometry: phenyl- and diphenylcyclopropenones
are planar, as discussed above, while stilbene is twisted
fluorescence of these cyclopropenones is due to their
with the ca. 43° dihedral angles between both benzene
photodecomposition by the excitation source. The absence
rings and the plane of the double bond.30 This distortion
of phosphorescence and fluorescence of diarylcyclopro-
penones indicates a fast nonradiative depopulation of
excited states and is in agreement with the high quantum
substantially reduces conjugation in stilbene.
Conjugation of cyclopropenone with extended aromatic
systems, such as in bis-R-naphthylcyclopropenone (1n ),
yield of photodecarbonylation (Table 2). This observation
produces an even stronger effect, shifting λmax another
70 nm versus diphenylcyclopropenone (1j). The absorp-
tion envelope for diaryl-substituted cyclopropenones usu-
ally contains two peaks and a shoulder (Figure 2, Table
2), which can be attributed to a coupling of the aromatic
ring vibrations to the electronic transition. Introduction
of donor p-methoxy substituents into benzene rings (1k )
of diphenylcyclopropenone results in the red shift of ca.
30 nm (Table 1). This effect is similar to the one observed
in the stilbene family (e.g., 4,4′-dimethoxystilbene, 296
nm in ethanol)31 but is much stronger. Additional electron-
donating substituents in bis-(2,4-dimethoxyphenyl)-
cyclopropenone (1l) increase the red shift by another 20
nm.
is in sharp contrast with styrene32 and stilbene,33 which
are strongly luminescent.
P h otoch em istr y. Photolysis of cyclopropenones stud-
ied in this work resulted in a remarkably clean decar-
bonylation reaction. The irradiation of cyclopropenones
1a ,c,d ,i-n with UV light produced a quantitative yield
of corresponding alkynes (Scheme 4).
It should be noted that diaryl-substituted acetylenes
produced in the photolysis of cyclopropenones 1i-n are
also photoreactive and can undergo secondary photore-
actions. However, the high quantum yield of cycloprope-
none photolysis allowed us to terminate the irradiation
before significant contamination of the reaction mixtures
occurs.
The quantum efficiency of photochemical decarbony-
lation of cyclopropenones 1a ,c-f,i-n was determined by
using ferrioxalate chemical actinometry. This reaction
was found to be very efficient with quantum yields in
the range from 23% to almost 80%. Alkyl-substituted
cyclopropenones have the lowest quantum efficiency,
while conjugation of the cyclopropenone system with
unsubstituted aromatic systems results in the highest
While the position and the structure of the major UV
band strongly depends on the nature of the aromatic
substituent, cyclopropenones 1d , 1j, 1k , 1l, 1m , and 1n
show similar extinction coefficients (Table 2).
(27) J iang, X.-K.; J i, G.-Z.; Wang, D. Z. J . Phys. Org. Chem. 1995,
8, 143.
(28) Molina, V.; Merchan, M.; Roos, B. O. Spectrochim. Acta A 1999,
55, 433.
(29) DeTar, D. F.; Carpino, L. A. J . Am. Chem. Soc. 1956, 78, 475.
(30) Traetteberg, M.; Frantsen, E. B. J . Mol. Struct. 1975, 26, 69.
Han, W.-G.; Lovell, T.; Liu, T.; Noodleman, L. Chem. Phys. Chem. 2002,
3, 167.
(32) Condirston, D. A.; Laposa, J . D. Chem. Phys. Lett. 1979, 63,
313.
(31) Greene, F. D.; Adam, W.; Cantrill, J . E. J . Am. Chem. Soc. 1961,
83, 3461.
(33) Saltiel, J .; Waller, A. S.; Sears, D. F., J r. J . Am. Chem. Soc.
1993, 115, 2453.
J . Org. Chem, Vol. 68, No. 20, 2003 7837

Poloukhtine and Popik
F IGURE 4. B3LYP/6-31+G(d,p) geometries corresponding to
the local minima on the potential energy surface of decarbo-
nylation of phenyl- and diphenylcyclopropenones.
quantum yield. Interestingly, substituents at the benzene
rings reduce the quantum yield, e.g., 1j versus 1i, 1k , or
1l. This effect is apparently due to increased efficiency
of the vibronic deactivation of the excited state.
Theoretical analysis of the reactivity of the parent
cyclopropenone with density functional,17,34 as well as the
reactivity of several alkyl or heteroatom-substituted
F IGURE 5. Absorbance change at 320 nm produced by laser
flash photolysis of an ca. 10-4 M solution of 1n in methanol.
λexcit ) 355 nm. The solid line represents the least-squares
fitting to a single-exponential expression. The insert shows
spectra of the starting material (1n , solid line) and the product
(bis-R-naphthylacetylene, dashed line) in methanol.
structures lies in the orthogonal plane to the vinyl anion/
carbene system. This observation is in sharp contrast
with structures of other singlet carbenes where the
phenyl group always lies in the plane of the carbene
stabilizing the vacant p-orbital.36 In addition, it is known
that singlet carbenes react with methanol at a rate close
to the diffusion control limit. We have conducted photo-
chemical decarbonylation of cyclopropenones in neat
methanol but were unable to detect any O-H insertion
products or other products that could be derived from
carbene or ketene functionality.
cyclopropenones using Hartree-Fock calculations with
or without Møller-Plesset correlation energy correction
(MP2),35 predict an intermediate in the decarbonylation
reaction. The structure of this intermediate is described
as having both ketenylcarbene and zwitterion fea-
tures.17,35
We have conducted a relaxed scan of the potential
energy surface (PES) relevant to decarbonylation of
phenylcyclopropenone in terms of C2-C1 and C3-C1 bond
length at the B3LYP/6-31+G(d,p) level. In agreement
with previous results, we found that the simultaneous
elongation of both bonds results in a rapid rise in
potential energy and corresponds to a maximum on PES.
Two saddle points found on the PES correspond to the
geometry where one bond is elongated to ca. 2.1 Å, while
the other remains virtually unchanged. Cleavage of the
C2-C1 cyclopropenone bond, i.e., next to phenyl, requires
somewhat less energy and leads to the local minimum.
The B3LYP/6-31+G(d,p) optimized geometry correspond-
ing to this minimum on the reaction pathway of phenyl-
and diphenylcyclopropenones is shown in Figure 4.
It is interesting to note that cleavage of the C1-C2 bond
resulting in the formation of intermediates 10 and 11 is
also accompanied by a change in the relative position of
phenyl and R (Ph or H) substituents at the double bond.
In the starting cyclopropenone these groups are locked
in the cis position by a cyclic structure, while in the
intermediate, the C2-C3 double bond has trans geometry.
In fact, according to DFT calculations, there are no
energy minima corresponding to cis isomers of 10 and
11. The structure of intermediates 10 and 11, in our
opinion, is better described by the zwitterionic rather
than the ketenylcarbene form. The ESP calculations
predict that C2 atoms in both molecules carry a substan-
tial negative charge (ca. -0.7), while C1 is positively
charged (ca. +0.4). The phenyl ring at C2 in optimized
Results of nanosecond laser flash photolysis (λexcit
)
355 nm) of bis-R-naphthyl-cyclopropenone 1n in methanol
support the formation of the intermediate in the decar-
bonylation reaction. We observed an instant (on the time
scale of the instrument) rise in absorbance following the
laser pulse and then somewhat slower decay, which fits
first-order rate law well. Changes of absorbance at 320
nm after the laser pulse are shown in the Figure 5.
The intermediate has a lifetime of ca. 40 ns and a broad
absorbance spectrum. The latter observation is also more
in agreement with the zwitterionic structure of the
intermediate rather than ketenylcarbene. Saturation of
the methanolic solution of cyclopropenone 1n with oxygen
prior to photolysis did not quench the formation of the
transient or acetylenic product and did not affect the
lifetime of the former. This observation allows us to
conclude that photodecarbonylation of cyclopropenone 1n
proceeds via the singlet exited state and that the inter-
mediate also has a singlet multiplicity. Decay of this
intermediate results in the formation of a residual
absorbance, which does not change in time (Figure 5).
At this wavelength (320 nm) the acetylenic product 9n
absorbs stronger than the starting cyclopropenone 1n
(see insert in Figure 5) and the residual absorbance
apparently corresponds to the acetylene 9n formed in the
reaction.
(34) Nguyen, L. T.; De Proft, F.; Nguyen, M. T.; Geerlings, P. J . Org.
Chem. 2001, 66, 4316.
(35) Sung, K.; Fang, D. C.; Glenn, D.; Tidwell, T. T. J . Chem. Soc.,
Perkin Trans. 2 1998, 2073.
(36) Zhu, Z. D.; Bally, T.; Stracener, L. L.; McMahon, R. J . J . Am.
Chem. Soc. 1999, 2863. Xie, Y.; Schreiner, P. R.; Schleyer, P. v. R.;
Schaefer, H. F. J . Am. Chem. Soc. 1997, 1370 and references therein.
7838 J . Org. Chem., Vol. 68, No. 20, 2003

Cyclopropenones
SCHEME 5
in a quartz vessel equipped with an immersible cooling finger.
The consumption of starting material was followed by TLC.
After the irradiation solvent was removed in a vacuum,
products were analyzed by NMR spectroscopy. Determination
of a quantum yield was performed with a ferrioxalate chemical
actiniometer.37 The laser flash photolysis experiments were
carried out with use of a frequency tripled (355 nm) output of
a Q-switched Nd:YAG laser as the excitation source. The setup
of the laser system and time-resolved UV spectrometer was
described previously.38
SCHEME 6
P h otoch em ica l Gen er a tion of th e En ed iyn e Sys-
tem . To test the applicability of the photochemical
decarbonylation of cyclopropenones to the in situ genera-
tion of the enediyne structure, we explored the photo-
chemistry of 2-(4′-methoxy-2′-(1-pentynyl)phenyl)-3-phe-
nylcyclopropenone 12. This photoactivatable precursor of
benzannulated enediyne 13 was prepared by using the
tetrachlorocyclopropene route. One equivalent of benzene
was alkylated with trichlorocyclopropenium cation to give
phenyldicholorocyclopropenium cation. The latter was
used to alkylate 1-(3-methoxyphenyl)-pentyne-1. After
hydrolysis of the reaction mixture in aqueous acetone,
we have isolated cyclopropenone 12 and the product of
addition of hydrogen chloride across the triple bond of
the former (Scheme 5).
Th er m a l r ea ction s of cyclopropenones were monitored
with a UV-vis spectrometer equipped with a thermostatable
cell holder. Substrate concentrations in the reacting solutions
were ca. 10-4 M, and the temperature of these solutions was
controlled with 0.05 °C accuracy. Observed first-order rate
constants were calculated by least-squares fitting of a single-
exponential function.
Ma ter ia ls. Moisture- and oxygen-sensitive reactions were
carried out in flame-dried glassware under an argon atmo-
sphere. Tetrahydrofuran and diethyl ether were distilled from
sodium, and dichloromethane was distilled from phosphorus
pentoxide under argon immediately before use. Hexanes used
in column chromatography was distilled from sodium, and
ethyl acetate and acetone were distilled from anhydrous
calcium chloride. HMPA was distilled from calcium hydride
and stored under argon. Diphenylcyclopropenone (1j) was
obtained from Aldrich and recrystalized from ethanol. All other
reagents were used as purchased. Purification of products by
column chromatography was performed with use of 40-63 µm
silica gel. 2-Butylcyclopropenone (1b),16 phenylhydroxycyclo-
propenone (1e),9a and 1,3-dichloroacetone acetal (6)16 were
prepared according to previously reported procedures. Prepa-
ration of compounds 1a -n , 8a , 12, and 13 is described in the
Supporting Information.
Th eor etica l P r oced u r es. Density functional theory cal-
culations were carried out with the Gaussian 98 program.39
Geometries were pre-optimized, using the B3LYP hybrid
functional and 6-31+G(d,p) basis set, and then reoptimized
(in the case of phenyl- and diphenylcyclopropenones) with the
extended triple-ú basis at the B3LYP/6-311+G(3df,2p) level.
Zero-point vibrational energy (ZPVE) corrections, required to
correct the raw relative energies to 0 K, were obtained from
B3LYP/6-311+G(3df,2p) frequency calculations. Analytical
second derivatives were computed to confirm each stationary
point to be a minimum by yielding zero imaginary vibrational
frequencies. These frequency analyses are known to overes-
The 350-nm irradiation of 12 results in the quantita-
tive formation of enediyne 13 (Scheme 6). The photode-
carbonylation of 12 is an efficient reaction with a
quantum yield of 0.56.
Con clu sion s. We have shown that alkyl- or aryl-
substituted cyclopropenones are thermally stable com-
pounds but undergo photochemical decarbonylation to
acetylenes with high quantum and chemical yield. The
decarbonylation reaction is a stepwise process where
cleavage of one bond in the cyclopropenone structure
results in the formation of a short-lived zwitterionic
intermediate, which then loses carbon monoxide to
produce the ultimate acetylenic product. Aryl-substituted
and especially diaryl-substituted cyclopropenones can be
activated with a 350 nm or longer wavelength light and
can be used for the development of photonucleases. The
applicability of cyclopropenone photochemistry to the
generation of the enediyne system has been illustrated
with the example of photochemical preparation of benz-
annulated enediyne 13.
(37) Murov, S. L.; Carmichael, I.; Hug, G. L. In Handbook of
Photochemistry; Marcel Dekker: New York, 1993; p 299.
(38) Serguievski, P.; Ford, W. E.; Rodgers, M. A. J . Langmuir 1996,
12, 348.
(39) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J . R.; Zakrzewski, V. G.; Montgomery, J . A.,
J r.; Stratmann, R. E.; Burant, J . C.; Dapprich, S.; Millam, J . M.;
Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J .;
Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo,
C.; Clifford, S.; Ochterski, J .; Petersson, G. A.; Ayala, P. Y.; Cui, Q.;
Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;
Foresman, J . B.; Cioslowski, J .; Ortiz, J . V.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.;
Fox, D. J .; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; J ohnson, B. G.; Chen,
W.; Wong, M. W.; Andres, J . L.; Head-Gordon, M.; Replogle, E. S.;
Pople, J . A. Gaussian 98; Gaussian, Inc.: Pittsburgh, PA, 1998.
Exp er im en ta l Section
P h otolytic Exp er im en ts. Analytical photolyses were per-
formed by irradiation of ca. 10-4 M solutions of cycloprope-
nones in a 1 cm quartz cell, using a RMR-600 Rayonet
photochemical reactor equipped with a carousel and three sets
of eight lamps with λmax of emission at 254, 300, and 350 nm.
Reaction mixtures were then analyzed by HPLC. Preparative
photolyses were conducted by the irradiation of methanolic
solutions of ca. 100 mg of cyclopropenones, using a 16 lamp
(with λemission ) 254 or 350 nm) Rayonet photochemical reactor
J . Org. Chem, Vol. 68, No. 20, 2003 7839

Poloukhtine and Popik
timate the magnitude of the vibrational frequencies. Therefore,
we scaled the frequencies by 0.9772.40 The vertical excitation
energies were evaluated by using the Random Phase Ap-
proximation for a time-dependent DFT calculation method,41
at the TD-B3PW91/6-311++G(3df,2p) level.
Institutes of Health (grant CA91856-01A1) and Ohio
Cancer Research Associates for the support of this
project. A.P. thanks the McMaster Endowment for a
research fellowship.
Su p p or tin g In for m a tion Ava ila ble: Preparation of cy-
clopropenones 1a -n and, 12; spectroscopic data for compounds
1a -n , 9d -n , 12, and 13; 1H, 13C NMR, and IR spectra of
unknown compounds (1a ,c,d ,g,h ,i,n ); Gaussian 98 output files
for DFT calculations. This material is available free of charge
via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. Authors would like to thank N.
Urdabaev for conducting quantum yield determination
for cyclopropenone 1j. We are grateful to the National
(40) Scott, A. P.; Radom, L. J . Phys. Chem. 1996, 100, 16502.
(41) Casida, M. E.; J amorski, C.; Casida, K. C.; Salahub, D. R. J .
Chem. Phys. 1998, 108, 4439.
J O034869M
7840 J . Org. Chem., Vol. 68, No. 20, 2003