Tandem cyclizations involving carbene as an intermediate: Photochemical reactions of substituted 1,2-diketones conjugated with ene-yne

Article abstract of DOI:10.1021/ja990763q

We have investigated photoreactions of a novel system in which a carbene generator and a carbene trap are contained in the same molecule for studying tandem cyclizations involving carbene. The photocyclization of 1,2-diketones conjugated with ene-yne to (2-furyl)carbene was employed as a carbene- generating system. Upon photoirradiation of 1,2-diketones possessing biphenyl and 2-acetyl-l-cyclopentenyl systems as a carbene trapping unit in aprotic solvents, we observed tandem cyclizations via a carbene intermediate to produce fluorenylfuran and bifuran derivative with nearly quantitative yield, respectively. The solvent dependency for the tandem cyclization clearly indicated that 1,2-diketone is equilibrated with (2-furyl)carbene under the steady state photoirradiation conditions. The results reported here indicated that such compounds containing a carbene generator and a trap within a molecule are extremely useful for studying the sequential carbene addition reaction.

Full text of DOI:10.1021/ja990763q

J. Am. Chem. Soc. 1999, 121, 8221-8228
8221
Tandem Cyclizations Involving Carbene as an Intermediate:
Photochemical Reactions of Substituted 1,2-Diketones Conjugated
with Ene-Yne
Kazuhiko Nakatani,* Kaoru Adachi, Kazuhito Tanabe, and Isao Saito*
Contribution from the Department of Synthetic Chemistry and Biological Chemistry,
Faculty of Engineering, Kyoto UniVersity, and CREST, Kyoto 606-8501, Japan
ReceiVed March 8, 1999. ReVised Manuscript ReceiVed June 22, 1999
Abstract: We have investigated photoreactions of a novel system in which a carbene generator and a carbene
trap are contained in the same molecule for studying tandem cyclizations involving carbene. The photocyclization
of 1,2-diketones conjugated with ene-yne to (2-furyl)carbene was employed as a carbene-generating system.
Upon photoirradiation of 1,2-diketones possessing biphenyl and 2-acetyl-1-cyclopentenyl systems as a carbene
trapping unit in aprotic solvents, we observed tandem cyclizations via a carbene intermediate to produce
fluorenylfuran and bifuran derivative with nearly quantitative yield, respectively. The solvent dependency for
the tandem cyclization clearly indicated that 1,2-diketone is equilibrated with (2-furyl)carbene under the steady
state photoirradiation conditions. The results reported here indicated that such compounds containing a carbene
generator and a trap within a molecule are extremely useful for studying the sequential carbene addition reaction.
Introduction
Tandem or sequential cyclizations involving cations,1a,2
anions,1a radicals,1,3 and metal carbenoids4 as well as those
catalyzed by transition metals5 are well-known. Equation 1
represents a general scheme for such reactions, where alkenes
or alkynes play a key role as a bridge that mediates a transfer
of a reactive intermediate. In contrast, such sequential cycliza-
tions involving a carbene intermediate are not common, although
1,3- and 1,2-carbene migrations are well-known for propargyl6
and alkenyl7 carbenes, respectively.
As a part of our continuing interest for a sequential carbene
cyclization, as exemplified in eq 2, we have examined the design
and synthesis of such molecular systems which contain two
essential molecular units of a carbene generator and a trap. We
previously reported a novel photocyclization of 1,2-diketones
conjugated with ene-yne 1 to furan derivative 3 via carbene
intermediate 2 (eq 3).8,9 In our preliminary studies on the
photocyclization, we proposed an equilibration between 1 and
2 under the steady-state photoillumination conditions.9 Taking
into account the efficiency of the carbene generation from 1,2-
diketones in combination with synthetic accessibility, a carbene-
generating system such as 4 was connected to the peripheral π
systems that can effectively trap the carbene intermediate as
exemplified by 5 and 6. Butadienyl (X ) CH2)10 and 4-oxa-
butadienyl carbenes (X ) O)11 are known to spontaneously
undergo 6π electrocyclization to produce cyclopentadiene and
furan derivatives, respectively (eq 4).
* Address correspondence to these authors. Phone: +81-75-753-5656.
Fax: +81-75-753-5676. E-mail: nakatani@sbchem.kyoto-u.ac.jp and
saito@sbchem.kyoto-u.ac.jp.
(1) (a) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. Engl. 1993, 32,
131. (b) Parsons, P. J.; Penkett. C. S.; Shell, A. J. Chem. ReV. 1996, 96,
195.
(2) (a) Sutherland, J. K. In ComprehensiVe Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 9, pp 341-
377. (b) Bartlett, P. A. In Asymmetric Synthesis; Morrison, J. D., Ed.;
Academic Press: New York, 1984; Vol. 3, p 341.
(3) (a) Molander, G. A.; Harris, C. R. Chem. ReV. 1996, 96, 307. (b)
Snider, B. L. Chem. ReV. 1996, 96, 339.
(4) Padwa, A.; Weingarten, M. D. Chem. ReV. 1996, 96, 223.
(5) Negishi, E.; Cope´ret, C.; Ma, S.; Liou, S,-Y.; Liu, F. Chem. ReV.
1996, 96, 365.
(6) For recent studies on 1,3-shift of a propargyl carbene, see: (a) Noro,
M.; Koga, N.; Iwamura, H. J. Am. Chem. Soc. 1993, 115, 4916. (b) Herges,
R.; Mebel, A. J. Am. Chem. Soc. 1994, 116, 8229. (c) Seburg, R. A.;
McMahon, R. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 2009. (d) Stanton,
J. F.; DePinto, J. T.; Seburg, R. A.; Hodges, J. A.; McMahon, R. J. J. Am.
Chem. Soc. 1997, 119, 429.
We herein describe a novel photoinduced tandem cyclization
of 5 and 6 involving a carbene as an intermediate. Upon
irradiation, both 5 and 6 undergo a tandem cyclization with high
efficiency to produce corresponding fluorenylfuran and bifuran
(8) Nakatani, K.; Maekawa, S.; Tanabe, K.; Saito, I. J. Am. Chem. Soc.
1995, 117, 10635.
(9) Nakatani, K.; Tanabe, K.; Saito, I. Tetrahedron Lett. 1997, 38, 1207.
(7) (a) Wentrup, C. Top. Curr. Chem. 1976, 62, 173. (b) Jones, W. M.
Acc. Chem. Res. 1977, 10, 353.
10.1021/ja990763q CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/25/1999

8222 J. Am. Chem. Soc., Vol. 121, No. 36, 1999
Nakatani et al.
Scheme 1a
Scheme 2a
a Reagents and conditions: (a) Me3SiCtCH, PdCl2(PPh3)2, 2,6-
lutidine, CuI, DMF, 93%; (b) TBAF, AcOH, THF, 73%; (c) 12,
PdCl2(PPh3)2, 2,6-lutidine, CuI, DMF, 36%.
a Reagents and conditions: (a) (2-phenylphenyl)acetylene (for 9b),
trimethylsilylacetylene (for 9d), PdCl2(PPh3)2, 2,6-lutidine, CuI, DMF,
56% (for 9b), 67% (for 9d); (b) TBAF, AcOH, THF, 82%; (c) lithium
hexamethyldisilazide, t-BuPh2SiCl, -78 °C, 87%; (d) 2-acetyl-1-
cyclopenten-1-yl trifluoromethanesulfonate, PdCl2(PPh3)2, 2,6-lutidine,
CuI, DMF, 62%; (e) (1) NaOH, H2O, MeOH, room temperature; (2)
(COCl)2, benzene, then CH3CHN2, 78% (for 10a), 37% (for 10b), 33%
(for 10c); (f) PPh3, ether, then NaNO2, 2 N HCl, THF, 94% (for 11a),
52% (for 5), 46% (for 6), 49%; (g) TBAF, AcOH, THF, 79%.
Figure 1. Spectral change during the photoirradiation of 5 (6.25 ×
10-5 M) in acetonitrile with 382 nm light obtained from a monochro-
mator (0, 100, 200, 300, 400, 500, and 800 counts of irradiation time).
The photocyclization has completed in 800 counts irradiation.
derivatives, respectively. These studies demonstrated that 1,2-
diketones conjugated with ene-yne are actually equilibrated with
the (2-furyl)carbene under steady state photoillumination condi-
tions, and molecular systems containing carbene generator and
a trap within a molecule are widely applicable to sequential
carbene addition reactions.
enol triflate 8 with (2-phenylphenyl)acetylene12 produced ene-
yne esters 9b. The coupling of 8 with trimethylsilylacetylene
produced 9d, which was desilylated to 9e. Silylation of 9e with
tert-butyldiphenylchlorosilane produced 9a and the cross cou-
pling with 2-acetyl-2-cyclopenten-1-yl trifluoromethanesulfonate
gave 9c. Three-step sequence for an ester hydrolysis of 9a-c,
acid chloride formation, and diazoethane addition afforded
R-diazo ketones 10a-c, which were transformed into 1,2-
diketones 11a, 5, and 6 by treating with triphenylphosphine and
sodium nitrite in aqueous acid, respectively.13 Diketone 4 was
obtained by desilylation of 11a. Similarly, C2 symmetric
diketone 7 was obtained by a sequential coupling of enol triflate
12 with trimethylsilylacetylene (Scheme 2).
Photoreactions in Aprotic Solvents. We carried out pho-
toreactions of 5 and 6 in benzene at 365 nm with a transillu-
minator. The photoreaction of 5 produced a single product in
an almost quantitative yield (eq 5). We observed clear isosbestic
Results
Synthesis of Substituted 1,2-Diketones. We have synthe-
sized 1,2-diketones 4, 5, and 6 and reference compound 7
according to the method previously reported for the synthesis
of 1 (Scheme 1).8,9 The palladium-catalyzed cross coupling of
(10) (a) O’Leary, M.; Wege, D. Tetrahedron 1981, 37, 801. (b) Palik,
E. C.; Platz, M. S. J. Org. Chem. 1983, 48, 963. (c) Padwa, A.; Akiba, M.;
Chou, C. S.; Cohen, L. J. Org. Chem. 1982, 47, 183. (d) Padwa, A.; Austin,
D. J.; Gareau, Y.; Kassir, J. M.; Xu, S. L. J. Am. Chem. Soc. 1993, 115,
2637.
(11) (a) Tomer, K. B.; Harrit, N.; Rosenthal, I.; Buchardt, O.; Kumler,
P. L.; Creed, D. J. Am. Chem. Soc. 1973, 95, 7402. (b) Mukherjee, A. K.;
Margaretha, P.; Agosta, W. C. J. Org. Chem. 1996, 61, 3388 and see also
ref 10c.
points on UV spectral change during the photoirradiation with
382 nm light isolated from a monochromator (Figure 1). The
molecular formula of the product determined by HRMS was
C22H18O2, which was the same as that of starting 5. The H
NMR spectra of the product showed a characteristic singlet at
5.28 ppm (Figure 2) that was directly attached to the carbon
1

Tandem Cyclizations with Carbene as an Intermediate
J. Am. Chem. Soc., Vol. 121, No. 36, 1999 8223
for 6 (Figure 2). It was apparent from the 13C NMR spectra
that two acetylenic carbons and two of three carbonyl carbons
did not exist in the product, but there are eight sp2 carbons in
addition to one carbonyl carbon instead. HRMS of the product
indicated a molecular formula of C17H18O3, which is the same
as that of starting 6. We confirmed the structure of the product
as bifuran 15 by observing long-range C-H correlations in the
HMBC spectra between C9-H7, C10-H7, and C10-H12
(Figure 2). Other 1,2-diketones 1 and 4 were recovered
unchanged under the photoirradiation conditions. Attempts to
trap the intermediate carbene by external alkenes also resulted
in a recovery of starting material. We examined the direct and
triplet-sensitized photoreactions of C2 symmetric diketone 7,
but no significant product was obtained, indicating that the 1,2-
diketone chromophore is indispensable for the carbene genera-
tion.
Figure 2. The key C-H correlations observed in the HMBC spectra
of 14 and 15.
Photoreactions in Protic Solvents. 1,2-Diketone 4 undergoes
a smooth photocyclization in ethanol to produce 16 (eq 7).
Figure 3. Stern-Volmer plot of relative quantum yields for the
photocyclization of 5 in the presence of triplet quencher (E,E)-1,4-
diphenyl-1,3-butadiene. The quantum yield measurements were carried
out with 5 (1 mM) in the presence of the quencher (0, 2.5, 5, 7.5, and
12.5 mM) in acetonitrile at 382 nm. The relative quantum yield (Φo/
Φ) was plotted against quencher concentration [Q].
Protonation of the initially formed (2-furyl)carbene intermediate
followed by a solvent addition to the resulting cation would
rationalize the formation of 16.14,15 With regard to the photo-
reaction of 1,2-diketones 5 and 6, a competition between the
carbene trapping by electrocyclization and the protonation with
solvents may be conceivable. Photoirradiation of 6 in aqueous
acetonitrile produced bifuran 15 as a major product in 47%
isolated yield (eq 6). We could not isolate the product derived
from protonation of the initially formed furylcarbene. In sharp
contrast, photoirradiation of 5 in ethanol produced furan
derivative 17 possessing an ethoxyl group R to the furan ring
in 68% yield together with a trace amount of 14 (eq 8). The
quantum yield for the disappearance of 5 in ethanol was 0.13,
which is about 60% of that observed for the cyclization to 14
in benzene. Protonation of the intermediate carbene with ethanol
is a bimolecular reaction, whereas a carbene trapping by the
internal biphenyl subunit was an unimolecular reaction. There-
fore, the efficiency for the formation of 17 should be dependent
on the ethanol concentration. Actually, photoreactions of 5 in a
mixed solvent of ethanol and benzene produced both 14 and
17 with the ratio being dependent on ethanol concentration
(Table 1). A normalized ratio of the two products was 13:87 in
50% ethanol in benzene, whereas the ratio became 58:42 when
the benzene-ethanol ratio was 32:1.
observed at 47.2 ppm in the 13C NMR spectra. We observed
seven aromatic carbons attached to a hydrogen (sCHd) in 13
C
NMR of 5, but only four of such carbons were detected in the
product, indicating that there is a symmetric structure in the
product with regard to the aromatic rings. On the basis of these
data and the long-range C-H correlations observed in the
HMBC spectra (Figure 2), we identified the product as fluore-
nylfuran 14. The quantum yield for the disappearance of 5 in
acetonitrile at 365 nm was 0.21, and the photocyclization was
quenched by (E,E)-1,4-diphenyl-1,3-butadiene. Stern-Volmer
analysis at 382 nm irradiation showed a linear correlation
between relative quantum yields and quencher concentrations
with a correlation coefficient (r) of 0.985 with a slope (kqτ) of
227 M-1 (Figure 3).
Photoirradiation of 6 for 1.5 h at room temperature also
1
produced a single product (eq 6). The H NMR spectra of the
(12) John, J. A.; Tour, J. M. Tetrahedron 1997, 45, 15515.
(13) Bestmann, H. J.; Klein, O.; Go¨thlich, L.; Buckschewski, H. Chem.
Ber. 1963, 96, 2259.
(14) Kirmse, W. In AdVances in Carbene Chemistry; Brinker, U. H.,
Ed.; JAI Press: Greenwich, CT, 1994; Vol 1, pp 1-57.
(15) (a) Kirmse, W.; Meinert, T.; Modarelli, D. A.; Plats, M. S. J. Am.
Chem. Soc. 1993, 115, 8918. (b) Kirmse, W.; Krzossa, B.; Steenken, S.
Tetrahedron Lett. 1996, 37, 1197.
product showed two methyl signals at 2.24 and 2.39 ppm with
a small upfield shift from those observed at 2.40 and 2.48 ppm

8224 J. Am. Chem. Soc., Vol. 121, No. 36, 1999
Nakatani et al.
Table 1. Product Distribution in the Photoreactions of 5 at a
resulting cation with solvent was obtained in the photoreaction
of 1 in deuterium oxide (99.8% D) and acetonitrile. We isolated
deuterated furan derivative 18 with D content of more than 95%.
Different Concentration of Ethanol in Benzenea
ethanol-benzene 14b 17b
ethanol-benzene 14b 17b
1:1
1:2
1:8
1:16
13
16
26
44
87
84
74
56
1:32
1: 64
1:128
58
76
95
42
24
5
a Photoreaction of 5 was carried out in the indicated solvent mixture
1
(2 mL). Product ratio was determined by H NMR. NMR analysis of
the crude products indicated that both 14 and 17 were the predominant
products in all runs. b The ratio of two products was normalized.
Photoirradiation of 1,2-diketones 5 and 6 in the aprotic
solvents produced fluorenylfuran 14 and bifuran 15, respectively,
with high efficiency via 6π electrocyclization of the initially
formed (2-furyl)carbenes 19 and 20 (eqs 5 and 6). It is obvious
that the formation of 14 involves a 1,5-H shift after electrocy-
clization. In sharp contrast to the photoreaction in aprotic
solvents, (2-furyl)carbene species 19 was trapped by protonation
in ethanol to produce 17 (eq 8). The ratio of two products 14
and 17 in the photoirradiation of 5 in a mixed solvent of ethanol
and benzene was dependent on ethanol concentration. With
decreasing ethanol concentration, the amount of 17 decreased
with a concomitant increase of 14, indicating that both products
would be derived from a common carbene intermediate 19.
It has been known that (2-furyl)carbene undergoes rapid ring-
opening rearrangement to cis-2-pent-4-ynal (eq 10).20,21 This
Discussions
Synthetic Accessibility. As illustrated in Scheme 1, 1,2-
diketones conjugated with ene-yne were readily synthesized
from the corresponding R-diazo ketones. A most significant
feature on the synthetic scheme was that various π conjugated
subunits were directly connected to the carbene-forming carbon
by using palladium-catalyzed cross coupling reactions.
Mechanism for the Carbene-Generating Step. The pho-
tocyclizations described here are reminiscent of the cyclization
of the propargyl 1,4-diradicals to produce the cycloalkenyl
carbenes11b,16,17 as well as of the related cyclization producing
nitrenes as we reported earlier (eq 9).18 It was well rationalized
that such cyclizations proceed via triplet diradicals.16 The
photocyclization of 5 in the presence of varying amounts of
(E,E)-1,4-diphenyl-1,3-butadiene (ET ) 177 kJ/mol)19 as a triplet
quencher showed a linear correlation between the relative
quantum efficiency and quencher concentrations with a Stern-
Volmer slope of 227 M-1. However, it was not quenched by
(E)-stilbene with ET of 227 kJ/mol. If we assume that the
quenching by 1,4-diphenyl-1,3-butadiene is diffusion controlled
(∼1010 M-1 s-1), the lifetime of excited triplet 5 is 23 ns. The
fact that C2 symmetric diketone 7 did not cyclize under both
direct and triplet-sensitized conditions indicated that the 1,2-
diketone chromophore is essential for the cyclization. We
concluded that the photocyclization of the 1,2-diketones con-
jugated with ene-yne proceeded from its lowest triplet excited
state. The quantum yields for the disappearance of 5 in both
benzene and ethanol were 0.21 and 0.13, respectively.
Solvent Dependency for the Carbene Reaction. In aprotic
solvents, 1,2-diketones 1 and 4 were photostable, but they
efficiently produced corresponding furan derivatives 3 and 16
in protic solvents by solvent incorporation. Such remarkable
solvent dependency was due to the irreversible trapping of the
intermediate carbene by protic solvents. The direct evidence
for the carbene protonation14,15 followed by trapping of the
reaction has shortened the lifetime of (2-furyl)carbene and,
consequently, the direct determination by spectroscopic method
has not been readily accomplished. The existence of (2-furyl)-
carbene as a distinct intermediate was only recently confirmed
by IR spectra measurement of the N2 matrix isolated carbene
stabilized by chlorine substitution (R ) Cl in eq 10).22
Theoretical studies on the (2-furyl)carbene revealed that it is a
ground-state singlet with the structure being close to the most
suitable conformation to undergo the ring-opening rearrange-
ment. The activation energy for the reaction is as low as 9.6
kcal/mol.23 Taking into account the marked solvent dependency
of the cyclization of 1, 4, and 5 in addition to the efficient ring-
opening rearrangement of (2-furyl)carbenes, it seems very
general that the 1,2-diketones conjugated with ene-yne are
equilibrated with the (2-furyl)carbenes under the steady-state
photoirradiation conditions, i.e., photoproducts are produced
when intermediate carbenes are trapped by protic solvents or
by intramolecular reactions. The mechanism of photoinduced
tandem cyclization of 5 is illustrated in Scheme 3.
Efficiency for the Carbene-Trapping Step. The reaction
rates for protonation and electrocyclization are expressed by
eq 11, where kp and ke are the rate constants for the protonation
(16) Agosta, W. C.; Margaretha, P. Acc. Chem. Res. 1996, 29, 179.
(17) (a) Hussain, S.; Agosta, W. C. Tetrahedron 1981, 37, 3301. (b)
Agosta, W. C.; Caldwell, R. A.; Jay, J.; Johnson, L. J.; Venepalli, B. R.;
Scaiano, J. C.; Singh, M.; Wolff, S. J. Am. Chem. Soc. 1987, 109, 3050.
(c) Rathjen, H.-J.; Margaretha, P.; Wolff, S.; Agosta, W. C. J. Am. Chem.
Soc. 1991, 113, 3904. (d) Margaretha, P.; Reichow, S.; Agosta, W. C. J.
Org. Chem. 1994, 59, 5393. (e) Kisilowski, B.; Agosta, W. C.; Margaretha,
P. J. Chem. Soc., Chem. Commun. 1996, 2065 and references therein.
(18) (a) Saito, I.; Kanehira, K.; Shimozono, K.; Matsuura, T. Tetrahedron
Lett. 1980, 21, 2737. (b) Saito, I.; Shimozono, K.; Matsuura, T. J. Am.
Chem. Soc. 1980, 102, 3948. (c) Saito, I.; Shimozono, K.; Matsuura, T. J.
Org. Chem. 1982, 47, 4356. (d) Saito, I.; Shimozono, K.; Matsuura, T.
Tetrahedron Lett. 1982, 23, 5439.
and the electrocyclization steps, respectively. We assume that
(20) (a) Hoffman, R. V.; Shechter, H. J. Am. Chem. Soc. 1971, 93, 5940.
(b) Hoffman, R. V.; Orphanides, G. G.; Shechter, H. J. Am. Chem. Soc.
1978, 100, 7927. (c) Hoffman, R. V.; Shechter, H. J. Am. Chem. Soc. 1978,
100, 7934.
(21) (a) Albers, R.; Sander, W. Liebigs Ann. 1997, 897. (b) Sander, W.;
Albers, R.; Komnick, P.; Wandel, H. Liebigs Ann. 1997, 901.
(22) Khasanova, T.; Sheridan, R. S. J. Am. Chem. Soc. 1998, 120, 233.
(23) Herges, R. Angew. Chem., Int. Ed. Engl. 1994, 33, 255.
(19) Murov, S. L.; Carmichael, I.; Hug, G. L. In Handbook of
Photochemistry, 2nd ed.; Marcel Dekker: New York, 1993.

Tandem Cyclizations with Carbene as an Intermediate
J. Am. Chem. Soc., Vol. 121, No. 36, 1999 8225
Scheme 3
produce a detectable amount of solvent-incorporated product.
Both compounds 5 and 6 contain carbene-trapping subunits that
are different in their electronic character from each other. The
enone subunit incorporated into 6 is a strong electron-withdraw-
ing group unlike the biphenyl group in the case of 5. An efficient
formation of 15 from 6 via 20 implies that such an electron-
withdrawing substituent does not affect the cyclization rate, but
does drastically retard the protonation rate. It has been shown
that an electron-withdrawing substituent attached to the carbene
center suppressed the carbene protonation due to an increased
singlet-triplet energy gap.14,26 This is likely the reason that we
could not isolate the protonated product of carbene 20 in the
photoreaction of 6 in aqueous solvents. While it is not certain
whether electrocyclization of 19 and 20 proceeds from their
singlet and/or triplet states, kinetic studies of 2-biphenylmeth-
lyene in perfluorinated alkane at 77 K indicated that the carbene
is ground-state triplet and undergoes cyclization to fluorene
under these conditions.27
Implication for the Molecular Design of the Sequential
Reactions Involving Carbenes. We have designed the molec-
ular systems containing a carbene generator and a trap in the
same molecule. The carbene generator 4 can produce furylcar-
bene on photoirradiation, whereas electrocyclizations of 2-bi-
phenyl and 2-acetylcyclopentenylmethylene are used as a trap.
Both carbene generation and trapping steps proceed with high
efficiency as demonstrated by the photoreaction of 5 and 6
giving 14 and 15 in almost quantitative yield, respectively. The
carbene-generating step is unique because the furyl carbene
produced equilibrate with the starting diketone under steady-
state photoillumination conditions. Therefore, reactions of 19
and 20 leading to stable products would compete with the ring-
opening reaction that requires only 9.6 kcal/mol of the activation
energy. Photoreactions of 1 and 4 in benzene resulted in a
complete recovery even in the presence of external alkenes as
a trap. These results suggest that reactions of furylcarbenes with
higher activation energy may be effectively eliminated from a
product-forming pathway by the energy threshold. Apparently
from the efficient formation of 14 and 15, intramolecular
electrocyclizations can compete with the ring opening of
furylcarbenes. These studies clearly demonstrate that a combina-
tion of a furylcarbene generator and a trap by electrocyclization
is a suitable molecular system for tandem cyclizations involving
carbene. Connection of such molecular units with acetylenic
bridges may realize a long-range carbene transfer system as
illustrated in eq 13.
Figure 4. Plots of the ratio of 14 and 17 (17/14) vs the ethanol
concentration [EtOH]. A linear correlation was obtained for the first
five plots with a correlation coefficient (r) of 0.993 (inset).
the protonation and the electrocyclization of 19 are rate
determining for the formation of 14 and 17, respectively.
Accordingly, the relative rate for the two processes would be
proportional to the product ratio. This leads to the following
equation, showing that the ratio of two products (17/14) is
proportional to the ethanol concentration with a slope of kp/ke
(eq 12).
A plot of the product ratio against ethanol concentration listed
in Table 1 showed a linear correlation at low ethanol concentra-
tion (∼1.9 M) (Figure 4). The slope (kp/ke) is 1.44 with a
correlation coefficient (r) of 0.993. It has been reported that
the singlet arylcarbenes such as xanthlidene24 and 3,6-
dimethoxyfluorenylidene25 react with alcohols at a diffusion-
controlled rate.14 Therefore, the value of 1.44 for kp/ke implies
that the 6π electrocyclization of 19 to 14 is also a fast process.
In contrast, the photoirradiation of 6 in protic solvents did not
Experimental Section
General. 1H NMR spectra were measured with Varian Gemini 200
(200 MHz), JEOL JNM R-400 (400 MHz) or JEOL R-500 (500 MHz)
spectrometers. The chemical shifts are expressed in ppm downfield
from residual chloroform (δ ) 7.24) and benzene (δ ) 7.15) as an
internal standard. 13C NMR spectra were measured with Varian Gemini
200 (50 MHz) and JEOL JNM R-400 (100 MHz) spectrometers. IR
spectra were recorded on a Jasco FT-IR-5M spectrophotometer. A Jasco
V-550 UV/VIS spectrophotometer was used for the absorption spectra
measurements. Mass spectra were recorded on a JEOL JMS SX-102A
(24) Lapin, S. C.; Schuster, G. B. J. Am. Chem. Soc. 1985, 107, 4243.
(25) Chuang, C.; Lapin, S. C.; Schrock, A. K.; Schuster, G. B. J. Am.
Chem. Soc. 1985, 107, 4238.
(26) Field, K. W.; Schuster, G. B. J. Org. Chem. 1988, 53, 4000.
(27) Palik, E. C.; Platz, M. S. J. Org. Chem. 1983, 48, 963.

8226 J. Am. Chem. Soc., Vol. 121, No. 36, 1999
Nakatani et al.
or a JEOL HX-100 spectrometer. A Funakoshi TEL-33 transilluminator
was used for irradiation at 365 nm. A Jasco CRM-FD monochromator
was used for irradiation at 365 and 382 nm. A Wakogel C-200 was
used for silica gel chromatography. Precoated TLC plates Merck silica
gel 60 F254 was used for monitoring the reactions and also for
preparative TLC. Tetrahydrofuran (THF) and ethyl ether (Et2O) were
distilled under N2 from sodium/benzophenone ketyl prior to use.
Dichloromethane (CH2Cl2), acetonitrile (CH3CN), and benzene were
distilled from CaH2 at atmospheric pressure. All other reagents and
solvents were used as received.
General Procedures for Palladium-Catalyzed Cross Coupling.
Ethyl 2-(2-(2-Phenylphenyl)ethynyl)cyclopent-1-enecarboxylate (9b).
To a mixture of enol triflate 8 (862 mg, 3.0 mmol), (2-phenylphenyl)-
acetylene12 (705 mg, 4.0 mmol), bis(triphenylphosphine)palladium(II)
chloride (69.4 mg, 0.10 mmol), and 2,6-lutidine (530 mg, 5.0 mmol,
0.58 mL) in deaerated, anhydrous DMF (5 mL) was added cuprous
iodide (37.7 mg, 0.2 mmol). The mixture was stirred at ambient
temperature for 3 h under nitrogen. The resulting mixture was diluted
with saturated NH4Cl and extracted with ethyl acetate. The extract was
washed with brine, dried over anhydrous MgSO4, filtered, and
concentrated in vacuo. The crude product was purified by silica gel
chromatography (5% ethyl acetate/hexane) to give 9b (526 mg, 56%)
as a yellow solid: 1H NMR (400 MHz, CDCl3) δ 1.24 (t, 3 H, J ) 7.1
Hz), 1.83 (quint, 2 H, J ) 7.6 Hz), 2.48 (m, 2 H), 2.65 (m, 2 H), 4.14
(q, 2 H, J ) 7.1 Hz), 7.24-7.37 (6 H), 7.56-7.59 (3 H); 13C NMR
(100 MHz, CDCl3) δ 14.5, 22.2, 33.4, 38.9, 60.2, 88.4, 99.5, 121.2,
126.8, 127.3, 127.7, 128.9, 129.1, 129.3, 133.2, 134.2, 137.3, 140.0,
143.7, 164.3; IR (neat) 3266, 2923, 1699, 1211 cm-1; MS m/e (%)
316 (M+) (27), 287 (88), 243 (100); HRMS calcd for C22H20O2 (M+)
316.1462, found 316.1477.
acetate/hexane) to give 9a (5.25 g, 87%) as a colorless oil: 1H NMR
(500 MHz, CDCl3) δ 1.11 (s, 9 H), 1.20 (t, 3 H, J ) 7.0 Hz), 1.95
(quint, 2 H, J ) 7.6 Hz), 2.74-2.78 (4 H), 4.23 (q, 2 H, J ) 7.0),
7.34-7.39 (6 H), 7.81-7.83 (4 H); 13C NMR (50 MHz, CDCl3) δ 14.3,
18.6, 22.1, 27.0, 33.6, 39.7, 60.4, 100.8, 104.4, 127.7, 129.5, 133.1,
134.8, 135.6, 139.9, 164.5; IR (CHCl3) 3011, 2984, 2143, 1696, 1429,
1112, 752, 702 cm-1; MS m/e (%) 402 (M+) (2), 345 [(M - t-Bu)+]
(100), 301 (80); HRMS calcd for C22H21O2Si [(M - t-Bu)+] 345.1310,
found 345.1303.
Ethyl 2-(2-(2-Acetylcyclopent-1-enyl)ethynyl)cyclopent-1-enecar-
boxylate (9c). To a mixture of 2-acetylcyclopent-1-enyl trifluo-
romethansulfonate (1.22 g, 4.2 mmol), 9e (764 mg, 4.7 mmol),
bis(triphenylphosphine)palladium(II) chloride (148 mg, 0.2 mmol), and
2,6-lutidine (680 mg, 6.4 mmol) in deaerated, anhydrous DMF (6 mL)
was added cuprous iodide (80.6 mg, 0.4 mmol), and the mixture was
stirred at ambient temperature for 6 h under nitrogen. The resulting
mixture was diluted with saturated NH4Cl and extracted with ethyl
acetate. The extract was washed with brine, dried over anhydrous
MgSO4, filtered, and concentrated in vacuo. The crude product was
purified by silica gel chromatography (67% toluene/hexane) to give
9c (711 mg, 62%) as a yellow solid: 1H NMR (400 MHz, CDCl3) δ
1.28 (t, 3 H, J ) 7.1 Hz), 1.88 (quint, 2 H, J ) 7.6 Hz), 1.96 (quint,
2 H, J ) 7.7 Hz), 2.56 (s, 3 H), 2.67-2.80 (8 H), 4.21 (q, 2 H, J ) 7.1
Hz); 13C NMR (50 MHz, CDCl3) δ 14.3, 21.7, 22.2, 29.5, 33.0, 33.5,
38.8, 40.2, 60.4, 95.4, 97.4, 133.2, 133.4, 139.7, 148.1, 164.2, 196.6;
IR (CHCl3) 3011, 2361, 1697, 1651, 1376, 1247, 762 cm-1; MS m/e
(%) 272 (M+) (10), 243 (100), 227 (10); HRMS calcd for C17H20O3
(M+) 272.1411, found 272.1391.
General Procedures for the Preparation of R-Diazo Ketones. 1-(2-
(4,4-Dimethyl-3,3-diphenyl-3-silapent-1-ynyl)cyclopent-1-enyl)-2-
diazopropane-1-one (10a). To a solution of 9a (5.12 g, 12.7 mmol)
in EtOH (120 mL) and H2O (60 mL) was added NaOH (2.29 g, 57.2
mmol), and the mixture was stirred at 45 °C for 15 h. After
concentration in vacuo, the resulting mixture was diluted with H2O,
washed with ethyl acetate, and acidified with 10% HCl. The mixture
was extracted with ethyl acetate, washed with brine, dried over
anhydrous MgSO4, filtered, and concentrated in vacuo to give crude
carboxylic acid (4.40 g, 92%), which was immediately used in the next
step. Oxalyl chloride (2.19 g, 17.3 mmol) was added to a solution of
the crude carboxylic acid in anhydrous benzene (10 mL), and the
mixture was stirred for 4 h at room temperature. Benzene was removed
under reduced pressure, and the crude acid chloride (995 mg, 2.7 mmol)
was dissolved in 20 mL of anhydrous ether. To a solution of diazoethane
prepared from 3.74 g of nitrosourea was added a solution of acid
chloride at 0 °C, and the mixture was stirred for 2 h. Concentration of
the resulting mixture under reduced pressure gave the crude diazo
ketone, which was purified by silica gel chromatography (5% ethyl
acetate/hexane) (930 mg, 85%) to give pure 10a as a yellow solid: 1H
NMR (400 MHz, CDCl3) δ 1.19 (s, 9 H), 1.39 (quint, 2 H, J ) 7.6
Hz), 1.67 (s, 3 H), 2.28 (tt, 2 H, J ) 7.6, 2.5 Hz), 2.62 (tt, 2 H, J )
7.6, 2.5 Hz), 7.17-7.22 (6 H), 7.90-7.92 (4 H); 13C NMR (100 MHz,
CDCl3) δ 8.6, 18.8, 22.4, 27.3, 35.1, 38.3, 99.0, 104.4, 128.2, 128.5,
123.0, 133.4, 135.9, 136.0, 148.8, 186.2; IR (CHCl3) 2959, 2931, 2080,
1605, 1570, 1429, 1375, 702 cm-1; MS m/e (%) 384 [(M - N2)+]
(50), 327 (100); HRMS calcd for C26H28OSi [(M - N2)+] 384.1908,
found 384.1896.
Ethyl 2-(trimethylsilylethynyl)cyclopentenecarboxylate (9d). 9d
was obtained as a brown oil: 1H NMR (400 MHz, CDCl3) δ 0.21 (s,
9 H), 1.30 (t, 3 H, J ) 7.2 Hz), 1.88 (m, 2 H), 2.60-2.71 (4 H), 4.22
(q, 2 H, J ) 7.2 Hz);13C NMR (100 MHz, CDCl3) δ 0.00, 14.4, 22.3,
33.48, 39.6, 60.5, 100.5, 105.6, 133.5, 139.1, 164.3; IR (neat) 2960,
2141, 1720, 1260, 860 cm-1; MS m/e (%) 236 (M+) (15), 221 [(M -
Me)+] (20), 207 (25); HRMS calcd for C13H20O2Si (M+) 236.1232,
found 236.1224.
Ethyl 2-(2-(2-Acetylcyclopent-1-enyl)ethynyl)cyclopent-1-enecar-
boxylate (9c). 9c was obtained as yellow solids: 1H NMR (400 MHz,
CDCl3) δ 1.28 (t, 3 H, J ) 7.1 Hz), 1.88 (quint, 2 H, J ) 7.6 Hz), 1.96
(quint, 2 H, J ) 7.7 Hz), 2.56 (s, 3 H), 2.67-2.80 (8 H), 4.21 (q, 2 H,
J ) 7.1 Hz); 13C NMR (50 MHz, CDCl3) δ 14.3, 21.7, 22.2, 29.5,
33.0, 33.5, 38.8, 40.2, 60.4, 95.4, 97.4, 133.2, 133.4, 139.7, 148.1, 164.2,
196.6; IR (CHCl3) 3011, 2361, 1697, 1651, 1376, 1247, 762 cm-1
;
MS m/e (%) 272 (M+) (10), 243 (100), 227 (10); HRMS calcd for
C17H20O3 (M+) 272.1411, found 272.1391.
Ethyl 2-Ethynylcyclopent-1-enecarboxylate (9e). To a solution of
9d (653 mg, 2.8 mmol) and acetic acid (829 mg, 13.8 mmol) in THF
(6 mL) was added TBAF (4.1 mL, 1.0 M in THF, 4.1 mmol) at 0 °C,
and the mixture was stirred at ambient temperature for 2 h. The resulting
mixture was diluted with saturated NaHCO3 and extracted with ethyl
acetate. The extract was washed with brine, dried over anhydrous
MgSO4, filtered, and concentrated in vacuo. The crude product was
purified by silica gel chromatography (3% ethyl acetate/hexane) to give
9e (370 mg, 82%) as a brown oil: 1H NMR (400 MHz, CDCl3) δ 1.29
(t, 3 H, J ) 7.1 Hz), 1.91 (m, 2 H), 2.61-2.72 (4 H), 3.51 (s, 1 H),
4.21 (q, 2 H, J ) 7.1 Hz); 13C NMR (100 MHz, CDCl3) δ 14.3, 22.2,
33.3, 39.1, 60.4, 79.4, 87.3, 133.1, 140.0, 164.0; IR (neat) 3270, 2970,
2100, 1710, 1610 cm-1; MS m/e (%) 164 (M+) (64), 136 (65), 119
(100); HRMS calcd for C10H12O2 (M+) 164.0837, found 164.0840.
Ethyl 2-(4,4-Dimethyl-3,3-diphenyl-3-silapent-1-ynyl)cyclopent-
1-enecarboxylate (9a). To a solution of 9e (2.45 g, 14.9 mmol) in
THF (30 mL) was added LHMDS (17.9 mL, 1.0 M in THF, 17.9 mmol)
at -78 °C, and the mixture was stirred at 0 °C for 15 min. To this
mixture was added tert-butylchlorodiphenylsilane (4.92 g, 17.9 mmol)
at -78 °C, and the mixture was stirred at -78 °C for 3 h and at 0 °C
for another 1 h. The resulting mixture was diluted with saturated NH4-
Cl and extracted with ethyl acetate. The extract was washed with brine,
dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The
crude product was purified by silica gel chromatography (2% ethyl
2-Diazo-1-(2-(2-(2-phenylphenyl)ethynyl)cyclopent-1-enyl)propan-
1-one (10b). 10b was obtained as a yellow oil: 1H NMR (400 MHz,
C6D6) δ 1.38 (quint, 2 H, J ) 7.7 Hz), 1.61 (s, 3 H), 2.25 (m, 2 H),
2.65 (m, 2 H), 6.96-7.04 (2 H), 7.12-7.23 (4 H), 7.53-7.60 (3 H);
13C NMR (100 MHz, C6D6) δ 8.8, 22.3, 35.2, 38.4, 88.3, 98.4, 121.7,
126.5, 127.3, 127.8, 128.3, 129.2, 129.5, 130.0, 133.6, 140.7, 144.4,
146.3, 186.1 (one carbon was not observed by peak overlap); IR (neat)
2928, 2848, 2072, 1583, 1373 cm-1; MS m/e (%) 327 [ (M + H)+]
(45), 154 (100); HRMS calcd for C22H19ON2 [(M + H)+] 327.1496,
found 327.1482.
2-Diazo-1-(2-(2-(2-acetylcyclopent-1-enyl)ethynyl)cyclopent-1-
enyl)propan-1-one (10c). 10c was obtained as yellow solids: 1H NMR
(400 MHz, CDCl3) δ 1.88 (quint, 2 H, J ) 7.6 Hz), 1.95 (quint, 2 H,
J ) 7.6 Hz), 2.02 (s, 3 H), 2.47 (s, 3 H), 2.63-2.81 (8 H); 13C NMR
(100 MHz, CDCl3) δ 9.0, 21.7, 22.4, 29.3, 33.2, 35.1, 38.1, 40.3, 94.1,

Tandem Cyclizations with Carbene as an Intermediate
J. Am. Chem. Soc., Vol. 121, No. 36, 1999 8227
96.2, 126.1, 132.8, 147.6, 148.0, 196.2 (we could not observe two
carbons.); IR (CHCl3) 3699, 3022, 3011, 2077, 1653, 1610, 1590, 1571,
1211, 761, 747 cm-1; MS m/e (%) 254 [(M - N2)+] (100), 226 (20),
211 (35); HRMS calcd for C17H18O2 [(M - N2)+] 254.1306, found
254.1310.
1H NMR (400 MHz, CDCl3) δ 0.21 (s, 9 H), 1.83 (quint, 2 H, J ) 7.7
Hz), 2.53 (s, 3 H), 2.63-2.72 (4 H); 13C NMR (100 MHz, CDCl3) δ
-0.4, 21.7, 29.5, 32.9, 40.3, 101.6, 108.5, 133.6, 148.6, 196.7; IR
(CHCl3) 2905, 1651, 1585, 1374, 1252, 742 cm-1; MS m/e (%) 206
(M+) (80), 191 (100), 163 (20); HRMS calcd for C12H18OSi (M+)
206.1126, found 206.1133.
General Procedures for the Preparation of 1,2-Diketones. 1-(2-
(4,4-Dimethyl-3,3-diphenyl-3-silapent-1-ynyl)cyclopent-1-enyl)pro-
pane-1,2-dione (11a). To a solution of 10a (801 mg, 1.9 mmol) in
anhydrous ether (30 mL) was added triphenylphosphine (1.02 g, 3.9
mmol), and the mixture was stirred at ambient temperature for 3 h.
After concentration in vacuo, the resulting mixture was diluted with
THF (30 mL). The THF solution was added to sodium nitrite (402
mg, 5.8 mmol) and cooled to 0 °C. To the mixture was added 2 N HCl
(4.6 mL, 9.1 mmol), and the reaction mixture was stirred at 0 °C for
1 h. The resulting mixture was extracted with ethyl acetate, washed
with brine, dried over anhydrous MgSO4, filtered, and concentrated in
vacuo. The crude product was purified by silica gel chromatography
(3% ethyl acetate/hexane) to give 11a (727 mg, 94%) as a yellow oil:
1H NMR (400 MHz, CDCl3) δ 1.09 (s, 9 H), 1.99 (quint, 2 H, J ) 7.7
Hz), 2.20 (s, 3 H), 2.77 (tt, 2 H, J ) 7.7, 2.4 Hz), 2.85 (tt, 2 H, J )
7.7, 2.4 Hz), 7.35-7.42 (6 H), 7.72-7.74 (4 H); 13C NMR (100 MHz,
CDCl3) δ 18.7, 22.0, 25.8, 27.1, 32.5, 40.7, 102.8, 105.3, 127.9, 129.8,
132.4, 135.6, 138.8, 143.4, 191.5, 200.8; IR (CHCl3) 1712, 1649, 1110,
820, 777, 741 cm-1; MS m/e (%) 400 (M+) (3), 357 [(M - COCH3)+]
(40), 343 (25); HRMS calcd for C24H25OSi [(M - COCH3)+] 357.1673,
found 357.1665.
To a solution of the above ketone (907 mg, 4.4 mmol) and acetic
acid (1.32 g, 22.0 mmol) in THF (7 mL) was added TBAF (6.6 mL,
1.0 M in THF, 6.6 mmol) at 0 °C, and the mixture was stirred at ambient
temperature for 12 h. The resulting mixture was diluted with saturated
NaHCO3 and extracted with ethyl acetate. The extract was washed with
brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo.
The crude product was purified by silica gel chromatography (2% ethyl
acetate/hexane) to give 13 (432 mg, 73%) as a brown solid: 1H NMR
(400 MHz, CDCl3) δ 1.86 (quint, 2 H, J ) 7.7 Hz), 2.53 (s, 3 H),
2.65-2.75 (4 H), 3.64 (s, 1 H); 13C NMR (100 MHz, CDCl3) δ 21.5,
29.4, 32.9, 40.2, 80.2, 89.6, 132.4, 149.0, 196.5; IR (CHCl3) 3302,
3017, 1657, 1589, 1265, 1215, 762, 743 cm-1; MS m/e (%) 134 (M+)
(65), 119 (100), 91 (40); HRMS calcd for C9H10O (M+) 134.0731, found
134.0723.
1-(2-(2-(2-Acetylcyclopent-1-enyl)ethynyl)cyclopent-1-enyl)ethan-
1-one (7). To a mixture of enol triflate 12 (199 mg, 0.7 mmol), bis-
(triphenylphosphine)palladium(II) chloride (24.2 mg, 0.03 mmol), and
2,6-lutidine (111 mg, 1.0 mmol) in deaerated, anhydrous DMF (4 mL)
were added 13 (102 mg, 0.8 mmol) and cuprous iodide (13.1 mg, 0.07
mmol). The mixture was stirred at ambient temperature overnight under
nitrogen. The resulting mixture was diluted with saturated NH4Cl and
extracted with ethyl acetate. The extract was washed with brine, dried
over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude
product was purified by silica gel chromatography (2% ethyl acetate/
toluene) to give 7 (66.2 mg, 36%) as a yellow oil: 1H NMR (400 MHz,
CDCl3) δ 1.91 (quint, 4 H, J ) 7.5 Hz), 2.51 (s, 6 H), 2.70-2.79 (8
H); 13C NMR (100 MHz, CDCl3) δ 21.8, 29.4, 33.3, 39.9, 97.4, 132.5,
148.5, 196.0; IR (neat) 2921, 2842, 1651, 1605, 1418, 1251 cm-1; MS
m/e (%) 242 (M+) (100), 227 (13), 199 (24); HRMS calcd for C16H18O2
(M+) 242.1307, found 242.1306.
Photoreaction of 5 in Benzene. 1-(3-Fluoren-9-yl-2,4,5,6-tetrahy-
dro-2-oxapentalenyl)ethan-1-one (14). A solution of 5 (31.4 mg, 0.10
mmol) in anhydrous benzene (10 mL) was irradiated with a transillu-
minator (365 nm) through a Pyrex filter at room temperature for 1.1 h.
The solvent was removed under reduced pressure, and the resulting
mixture was purified by silica gel chromatography (10% ethyl acetate/
hexane) to give 14 (30.5 mg, 97%) as yellow solids:1H NMR (400
MHz, CDCl3) δ 1.83 (t, 2H, J ) 7.1 Hz), 2.15 (quint, 2 H, J ) 7.5
Hz), 2.41 (s, 3 H), 2.75 (t, 2 H, J ) 7.0 Hz), 5.28 (s, 1 H), 7.29 (dt, 2
H, J ) 7.5, 1.2 Hz), 7.39 (t, 2 H, J ) 7.5 Hz), 7.56 (dd, 2 H, J ) 7.5,
0.7 Hz), 7.75 (d, 2 H, J ) 7.5 Hz); 13C NMR (100 MHz, CDCl3) δ
23.6, 26.0, 26.5, 31.2, 47.2, 120.0, 125.5, 127.3, 127.9, 130.7, 140.9,
143.0, 143.2, 144.8, 148.4, 185.6; IR (CHCl3) 2925, 2854, 1742, 1666,
1561, 1449, 1396, 738 cm-1; MS m/e (%) 314 (M+) (90), 271 [(M -
COCH3)+] (100); HRMS calcd for C22H18O2 (M+) 314.1306, found
314.1319.
Photoreaction of 6 in Benzene. 1-(3-(2,4,5,6-Tetrahydro-2-oxa-
pentalenyl)-2,4,5,6-tetrahydro-2-oxapentalenyl)ethan-1-one (15). A
solution of 6 (5.6 mg, 0.02 mmol) in anhydrous benzene (2.1 mL) was
irradiated with a transilluminator (365 nm) through a Pyrex filter at
room temperature for 1.5 h. The solvent was removed under reduced
pressure, and the resulting mixture was purified by silica gel chroma-
tography (10% ethyl acetate/hexane) to give 15 (5.3 mg, 95%) as yellow
solids: 1H NMR (400 MHz, CDCl3) δ 2.24 (bs, 3 H), 2.39 (s, 3 H),
2.33-2.40 (2 H), 2.42-2.47 (2 H), 2.48-2.53 (2 H), 2.77-2.82 (4
H), 2.87 (t, 2 H, J ) 7.4 Hz); 13C NMR (50 MHz, CDCl3) δ 12.9,
23.0, 24.3, 24.9, 26.2, 26.2, 31.5, 32.0, 129.4, 130.3, 133.8, 134.5, 141.2,
142.2, 143.2, 145.1, 197.7; IR (CHCl3) 1640, 1627, 1209 cm-1; MS
m/e (%) 270 (M+) (100), 227 [(M - COCH3)+] (65); HRMS calcd for
C17H18O3 (M+) 270.1255, found 270.1220.
1-(2-(2-(2-Phenylphenyl)ethynyl)cyclopent-1-enyl)propane-1,2-di-
one (5). 5 was obtained as yellow solids: 1H NMR (400 MHz, CDCl3)
δ 1.93 (quint, 2 H, J ) 7.5 Hz), 2.31 (s, 3 H), 2.63 (tt, 2 H, J ) 7.7,
2.2 Hz), 2.72 (tt, 2 H, J ) 7.7, 2.4 Hz), 7.30-7.65 (9 H); 13C NMR
(100 MHz, CDCl3) δ 21.9, 26.1, 31.9, 39.8, 87.3, 103.2, 120.3, 127.3,
127.7, 128.0, 129.2, 129.6, 129.9, 133.1, 140.0, 140.6, 141.5, 144.3,
192.0, 202.0; IR (CHCl3) 2924, 2360, 2342, 2331, 1714, 1639 cm-1
;
MS m/e (%) 314 (M+) (32), 271 [(M - COCH3)+] (100); HRMS calcd
for C22H18O2 (M+) 314.1306, found 314.1293.
1-(2-(2-(2-Acetylcyclopent-1-enyl)ethynyl)cyclopent-1-enyl)pro-
pane-1,2-dione (6). 6 was obtained as a yellow oil: 1H NMR (400
MHz, CDCl3) δ 1.90 (quint, 2 H, J ) 7.7 Hz), 2.00 (quint, 2 H, J )
7.7 Hz), 2.40 (s, 3 H), 2.48 (s, 3 H), 2.68-2.81 (8 H); 13C NMR (100
MHz, CDCl3) δ 21.8, 22.1, 26.0, 29.4, 32.5, 33.3, 39.6, 39.7, 95.5,
98.3, 131.8, 138.6, 143.2, 149.4, 190.9, 197.0, 200.9; IR (CHCl3) 3896,
2358, 1713, 1648, 1603, 746 cm-1; MS m/e (%) 270 (M+) (95), 227
(100), 199 (35); HRMS calcd for C17H18O3 (M+) 270.1255, found
270.1243.
1-(2-Ethynylcyclopent-1-enyl)propane-1,2-dione (4). To a solution
of 11a (96.1 mg, 0.2 mmol) and acetic acid (72.0 mg, 1.2 mmol) in
THF (5 mL) was added TBAF (0.5 mL, 1.0 M in THF, 0.5 mmol) at
0 °C, and the mixture was stirred at ambient temperature for 16 h. The
resulting mixture was diluted with saturated NaHCO3 and extracted
with ethyl acetate. The extract was washed with brine, dried over
anhydrous MgSO4, filtered, and concentrated in vacuo. The crude
product was purified by silica gel chromatography (3% ethyl acetate/
hexane) to give 4 (30.7 mg, 79%) as a yellow oil: 1H NMR (400 MHz,
CDCl3) δ 1.96 (quint, 2 H, J ) 7.7 Hz), 2.40 (s, 3 H), 2.74 (t, 4 H, J
) 7.7 Hz), 3.59 (s, 1 H); 13C NMR (100 MHz, C6D6) δ 22.0, 25.8,
32.6, 40.0, 78.9, 90.5, 135.2, 144.5, 191.5, 200.2; IR (CHCl3) 3302,
1715, 1650, 1588, 1349, 1215, 779, 732 cm-1; MS m/e (%) 162 (M+)
(12), 119 (100), 91 (25); HRMS calcd for C10H10O2 (M+) 162.0680,
found 162.0684.
1-(2-Ethynylcyclopentenyl)ethan-1-one (13). To a mixture of
2-acetyl-1-cyclopent-1-enyl trifluoromethanesulfonate (12) (2.77 g, 9.63
mmol), bis(triphenylphosphine)palladium(II) chloride (203 mg, 0.3
mmol), and 2,6-lutidine (1.54 g, 14.5 mmol) in deaerated, anhydrous
DMF (6 mL) were added ethynyltrimethylsilane (1.04 g, 10.6 mmol)
and cuprous iodide (110 mg, 0.6 mmol). The mixture was stirred at
ambient temperature for 15 h under nitrogen. The resulting mixture
was diluted with saturated NH4Cl and extracted with ethyl acetate. The
extract was washed with brine, dried over anhydrous MgSO4, filtered,
and concentrated in vacuo. The crude product was purified by silica
gel chromatography (3% ethyl acetate/hexane) to give 1-(2-(trimeth-
ylsilylethynyl)cyclopentenyl)ethan-1-one (1.85 g, 93%) as a red oil:
Photoreaction of 4 in Ethanol. 1-(3-(Ethoxymethyl)-2,4,5,6-
tetrahydro-2-oxapentalenyl)ethan-1-one (16). A solution of 4 (18.1
mg, 0.11 mmol) in ethanol (6 mL) was irradiated with a transilluminator
(365 nm) through a Pyrex filter at room temperature for 1.5 h. The
solvent was removed under reduced pressure, and the resulting mixture

8228 J. Am. Chem. Soc., Vol. 121, No. 36, 1999
Nakatani et al.
was purified by silica gel chromatography (13% ethyl acetate/hexane)
to give 16 (10.0 mg, 43%) as a colorless oil: 1H NMR (400 MHz,
CDCl3) δ 1.20 (t, 3 H, J ) 7.0 Hz), 2.37 (s, 3 H), 2.41 (quint, 2 H, J
) 7.1 Hz), 2.64 (t, 2 H, J ) 7.5 Hz), 2.84 (t, 2 H, J ) 7.3 Hz), 3.53
(q, 2 H, J ) 7.0 Hz), 4.42 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ
15.1, 23.4, 26.2, 26.5, 31.7, 66.3, 67.3, 133.9, 143.3, 143.7, 146.5, 186.5;
IR (CHCl3) 2971, 1669, 1569, 1360, 1093 cm-1; MS m/e (%) 208 (M+)
(90), 193 (14), 179 (15), 163 (100), 137 (98); HRMS calcd for C12H16O3
(M+) 208.1099, found 208.1100.
vacuo. The crude product was purified by silica gel chromatography
(20% ethyl acetate/hexane) to give 18 (6.4 mg, 61%) as a colorless
oil: 1H NMR (200 MHz, C6D6) δ 2.01-2.33 (4 H), 2.35 (s, 3 H), 2.78
(t, 2 H, J ) 7.5 Hz), 7.27-7.45 (5H); IR (CHCl3) 3738-3334, 1663,
1656, 1221, 763, 736 cm-1; MS m/e (%) 257 (M+) (100), 240 [(M -
OH)+] (45), 214 [(M - COCH3)+] (80); HRMS calcd for C16H15O3D
(M+) 257.1160, found 257.1161.
Photoreaction of 7. A solution of 4 (10.0 mg, 0.04 mmol) in benzene
(4.1 mL) was irradiated with a transilluminator (365 nm) for 3 h. In
another experiment, the same solution of 7 containing Michler’s ketone
(11.4 mg, 0.04 mmol) was photoirradiated for 1 h. A 1H NMR spectrum
of the crude photolysate obtained from both experiments showed
complete recovery of 7.
Quantum Yield Measurements. An acetonitrile solution (2 mL)
of 5 (1 mM) in a Pyrex flask containing benzene as an internal standard
was illuminated at 365 nm obtained from the monochromator for 25
counts by an integrator equipped with the monochromator. The
monochromator was calibrated by the chemical actinometer of phe-
nylglyoxylic acid (Φ ) 0.72 at 365 nm)19 under identical conditions.
The amount of produced 14 was measured by HPLC analysis. Under
these conditons, diketone 5 was converted to 14 in 7.7%, whereas
phenylglyoxylic acid was transformed to benzaldehyde in 26.1%. The
quantum yield for the photocyclization of 5 to 14 was calculated as
0.21. Similary, the quantum yields for the disappearance of 5 in ethanol
and 6 in benzene at 365 nm irradiation were measured as 0.13 and
0.19, respectively.
Photoreaction of 5 in Ethanol. 1-(3-(Ethoxy(2-phenylphenyl)-
methyl)-2,4,5,6-tetrahydro-2-oxapentalenyl)ethan-1-one (17). A solu-
tion of 5 (31.4 mg, 0.10 mmol) in ethanol (10 mL) was irradiated with
a transilluminator (365 nm) through a Pyrex filter at room temperature
for 2 h. The solvent was removed under reduced pressure, and the
resulting mixture was purified by silica gel chromatography (13% ethyl
acetate/hexane) to give 17 (24.4 mg, 68%) as a colorless oil and a
trace amount of 14: 1H NMR (400 MHz, CDCl3) δ 1.14 (t, 3 H, J )
7.0 Hz), 2.13 (m, 1 H), 2.20-2.31 (5 H), 2.32 (s, 3 H), 2.75-2.81 (2
H), 3.33-3.41 (2 H), 5.37 (s, 1 H), 7.14-7.42 (8 H), 7.66 (dd, 1 H, J
) 7.7, 1.5 Hz); 13C NMR (100 MHz, CDCl3) δ 15.2, 23.8, 25.9, 26.4,
31.4, 64.6, 73.7, 127.2, 127.4, 127.7, 127.8, 128.1, 129.1, 129.9, 133.7,
136.2, 140.4, 141.7, 143.2, 143.4, 148.3, 186.7; IR (CHCl3) 2924, 2359,
1669, 1071 cm-1; MS m/e (%) 360 (M+) (52), 331 (58), 317 (62), 271
(100); HRMS calcd for C24H24O3 (M+) 360.1724, found 360.1736.
Photoreaction of 6 in Aqueous Acetonitrile. A solution of 6 (8.1
mg, 0.03 mmol) in acetonitrile (1.5 mL) and H2O (1.5 mL) was
irradiated with a transilluminator (365 nm) through a Pyrex filter at
room temperature for 2 h. The solvent was removed under reduced
pressure, and the resulting mixture was purified by silica gel chroma-
tography (10% ethyl acetate/hexane) to give 15 (3.8 mg, 47%).
Photoreaction of 1 in Deuterium Oxide To Give 18. A solution
of 1 (9.8 mg, 0.04 mmol) in CH3CN (2.1 mL) and deuterium oxide
(2.1 mL) was irradiated with a transilluminator (365 nm) through a
Pyrex filter at room temperature for 40 min. After concentration in
vacuo, the resulting mixture was extracted with ethyl acetate, washed
with brine, dried over anhydrous MgSO4, filtered, and concentrated in
Triplet Quenching. Triplet quenching for the photocyclization of
5 (1 mM) was carried out in the presence of (E,E)-1,4-diphenyl-1,3-
butadiene (0, 2.5, 5.0, 7.5, and 12.5 mM) in acetonitrile at 382 nm
obtained from the monochromator. Photoirradiation was carried out
for 50 counts by an integrator equipped with the monochromator.
Relative quantum yields (Φo/Φ) for the cyclization in the presence of
the quencher were 1.33 (2.5 mM), 1.84 (5.0 mM), 2.83 (7.5 mM), and
3.92 (12.5 mM). The Stern-Volmer slope was 227 M-1
.
JA990763Q