Generation of cyclopentadienones from 2-bromocyclopentenones

Full text of DOI:10.1021/jo015671+

5232
J . Org. Chem. 2001, 66, 5232-5236
Notes
Sch em e 1
Gen er a tion of Cyclop en ta d ien on es fr om
2-Br om ocyclop en ten on es
Michael Harmata,* Charles L. Barnes, J ames Brackley,
Gary Bohnert, Patrick Kirchhoefer, Laszlo Ku¨rti, and
Paitoon Rashatasakhon
Department of Chemistry, University of
MissourisColumbia, Columbia, Missouri 65211
harmatam@missouri.edu
Received April 6, 2001
In tr od u ction
Sch em e 2
The generation of cyclopentadienone (2) from a bro-
mocyclopentenone precursor was first reported by Hafner.1
This report was quickly followed by a paper from DePuy
and co-workers2 who showed that the precursor that was
used by Hafner to generate the reactive intermediate was
4-bromocyclopentenone (1) and not 5-bromocyclopenten-
one as proposed by Hafner. In fact, the latter was shown
to decompose under the reaction conditions that were
used to generate cyclopentadienone from 5-bromocyclo-
pentenone.3 DePuy and co-workers also beautifully dem-
onstrated a number of interesting aspects of the chem-
istry of 2.2b
Cyclopentadienone is highly reactive and dimerizes to
form 3 in virtually quantitative yield (Scheme 1). This
compound can be decarbonylated to produce either 4 or
5 in good yield.1,2,4
While unsubstituted cyclopentadienone and various
substituted analogues dimerize rapidly, reactions of these
compounds as dienes or dienophiles are rather limited
and have seen only a few applications in natural product
synthesis.5,6 However, more-highly substituted cyclopen-
tadienones are isolable, and their ability to function as
dienes is well-known.7
reactions,8 we attempted to brominate 2-bromocyclopen-
tenone and use the resultant tribromide as a precursor
to the oxyallylic cation 8 (Scheme 2). We learned that
the tribromide 7 is difficult to handle. In an attempt to
sort out exactly what occurred during studies involving
cycloaddition reactions with furan, we allowed 6 to stir
in a trifluoroethanol (TFE) solution of furan and triethy-
lamine (TEA) for approximately one week at room
temperature. During this time the slow formation of a
new compound was made evident by TLC. Workup and
chromatographic purification led to the identification of
the compound as the cyclopentadienone dimer 3, which
was formed in 57% yield. To the best of our knowledge,
the generation of cyclopentadienone from a 2-substituted
cyclopentenone has not been reported.9 We thus decided
to optimize the reaction and explore its generality, albeit,
at this stage only to a limited extent.
Resu lts a n d Discu ssion
As part of our program involving the development of
halogenated, cyclic, allylic cations in 4+3 cycloaddition
Table 1 shows the results of some of our work with
2-bromocyclopentenone in which we explored such vari-
ables as solvent, base, and temperature. The data suggest
that relatively high temperatures are preferable to room
temperature in this reaction (Table 1, cf. entries 1, 8, and
9). However, it is clear that prolonged heating could
result in the formation of 1-indanone by thermal decar-
bonylation of 3 followed by isomerization (Table 1, entry
3).
(1) Hafner, D.; Goliasch, K. Angew. Chem. 1960, 72, 781.
(2) (a) DePuy, C. H.; Lyons, C. F. Chem. Ind. 1961, 429-430. (b)
DePuy, C. H.; Isaks, M.; Eilers, K. L.; Morris, G. F. J . Org. Chem. 1964,
29, 3503-3507.
(3) DePuy, C. H.; Ponder, B. W.; Fitzpatrick, J . D. J . Org. Chem.
1964, 29, 3508-3510.
(4) (a) DePuy, C. H.; Lyons, C. E. J . Am. Chem. Soc. 1960, 82, 631-
633. (b) Hafner, K.; Goliasch, K. Chem. Ber. 1961, 94, 2909-2921. (c)
Baggiolini, E.; Herzog, E. G.; Iwasaki, S.; Schorta, R.; Schaffner, K.
Helv. Chim. Acta 1967, 50, 297-306.
(5) (a) Al-Busafi, S.; Whitehead, R. C. Tetrahedron Lett. 2000, 41,
3467-3470. (b) Bird, C. W.; Coffee, E. C. J .; Schmidl, B. W. C. J . Chem.
Soc., Chem. Commun. 1993, 613-620. (c) Nantz, M. H.; Fuchs, P. L.
J . Org. Chem. 1987, 52, 5298-5299. (d) Baraldi, P. G.; Barco, A.;
Benetti, S.; Pollini, G. P.; Polo, E.; Simoni, D. J . Chem. Soc., Chem.
Commun. 1984, 1049-1050. (e) Gavin˜a, F.; Costero, A. M.; Gil, P.; Luis,
S. V. J . Am. Chem. Soc. 1984, 106, 2077-2080. (f) Gavin˜a, F.; Costero,
A. M.; Palazo´n, B.; Luis, S. V. J . Am. Chem. Soc. 1981, 103, 1797-
1798
The best choice for base at this point is triethylamine.
As few as 1.2 equiv of this base produced 3 in high yield
(7) For a review of cyclopentadienone chemistry, see: Ogliaruswo,
M. A.; Romanelli, M. G.; Becker, E. I. Chem. Rev. 1965, 65, 262-367.
(8) (a) Harmata, M.; Shao, L. Synthesis 1999, 1534-1540. (b)
Harmata, M.; Shao, L.; Ku¨rti, L.; Abeywardane, A. Tetrahedron Lett.
1999, 40, 1075-1078.
(9) For a process that appears to be related, see: Rizzo, C. J .;
Bunlap, N. K.; Smith, A. B., III. J . Org. Chem. 1987, 52, 5280-5283.
(6) Applications in the synthesis of unnatural products are well-
known. For example, see: (a) Eaton, P. E. Angew. Chem., Int. Ed. Engl.
1992, 31, 1421-1436. (b) Carbocyclic Cage Compounds; Osawa, E.,
Yonemitsu, O., Eds.; VCH: New York, 1992.
10.1021/jo015671+ CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/03/2001

Notes
J . Org. Chem., Vol. 66, No. 15, 2001 5233
Ta ble 1. F or m a tion of 3 fr om 6 u n d er Va r iou s
Con d ition s
Ta ble 3. In d a n on e F or m a tion fr om Cyclop en ta d ien on e
Dim er s
solvent,
[M]a
base,
no. of equiv.
temp.
(°C)
yield
time (h) (%)
entry
1
2
TFE, 0.3
TEA, 3
TEA, 3
rt
rt
48
3 min
43
b
ether, 2.4
LiClO4, 0.3
TFE, 0.3
TFE, 0.34
ethanol, 0.35 TEA, 1.2
3
4
5
6
7
8
9
2,6-lutidine, 3 reflux
DBU, 1.2
16
2.25
4
24c
57
21
35
entry educt
R
time (h) adduct yield (%)
reflux
reflux
reflux
1
2
3
4
5
6
3
H
5.25
5.5
5
54
84
65
86
84
77
11a
phenyl
20a
20b
21a
22a
23a
THF, 0.35
TEA, 5
TEA, 1.2
TEA, 2
2.75
11b phenyl
2.5
THFd
rt, reflux 0.33, 10 38
reflux
reflux
13a
15a
17a
3-methoxyphenyl
4-tert-butylphenyl
2,5-dimethylphenyl
4.25
5.5
3.25
TFE, 0.5
TFE, 0.7
1
2.5
90
85
TEA, 1.2
a
b
Concentration of 3 in solvent. Rapid decomposition was
observed. c A 6% yield of 1-indanone was also isolated. Contain-
ing 1 equiv of LiClO4.
d
appeared to proceed somewhat more cleanly and quickly
when the reaction was performed in this way. After the
reaction was shown to be complete by TLC, the mixture
was cooled, the TFE removed, and ethyl acetate or
chloroform was added in an amount that was 7-10 times
the volume of TFE that was used. Extraction with
aqueous acid, bicarbonate, and brine, followed by flash
chromatographic purification (hexanes/ethyl acetate),
afforded the products.
Ta ble 2. Gen er a tion of Cyclop en ta d ien on e Dim er s fr om
2-Br om ocyclop en ten on es
Interestingly, these dimerizations proceeded with rea-
sonable regioselectivity and complete diastereoselectivity.
Before we had definitive structural assignments, we took
11a and treated it with triethylamine in refluxing TFE.
No change was observed, and we concluded that the
isomers that were observed were in fact regioisomers. We
obtained crystal structures of 17a and 17b, and these
data confirmed our assignments.12 The structures of the
other products were assigned on the basis of analogy. The
product distributions that were observed are the result
of kinetic control and can presumably be rationalized on
the basis of FMO interactions, though a larger data set
with a more diverse array of substituents will be useful
in drawing more definitive conclusions.
To demonstrate that these cyclopentadienone dimers
could be converted to products of further synthetic utility,
they were refluxed in quinoline for several hours. This
produced the expected indanones in good to excellent
yields (Table 3).13 The isomer corresponding to 4 (Scheme
1) presumably isomerizes rapidly in the presence of base.
Finally, at the behest of a referee, we carried out the
reaction sequence shown in Scheme 3. Addition of n-
butyllithium to 6 afforded 24 in low yield. Oxidation with
PCC gave the ketone 25 without incident. When 25 was
heated in trifluoroethanol in the presence of triethy-
lamine, crude NMR and IR data suggested the formation
of cyclopentadienone dimers as well as indanones. These
time
yield ratio
entry educt
R
(h) adduct (%) (a:b)a
1
2
3
4
5
10
12
14
16
18
phenyl
2
3.5
3
5
2.5
11
13
15
17
19
72
87
90
97
69
3:1
4.3:1
10.2:1
3-methoxyphenyl
4-tert-butylphenyl
2,5-dimethylphenyl
phenylalkynyl
5.6:1
b,c
Ratio determined by integration of crude 1H NMR data. b Ratio
a
less than 2:1 as determined by 1H and 13C NMR. c Only one isomer
was isolated and characterized.
(Table 1, entry 9). However, we noted that reactions
proceeded more quickly in the presence of larger amounts
of base and prefer to use 2-3 equiv in performing the
reaction. A slight increase in yield was observed when
this was done (Table 1, entry 8).
While too few solvents have been examined to make
generalizations, it seems that a polar, protic solvent such
as TFE is well-suited for the reaction, while ethanol is
surprisingly not. The use of THF resulted in a low yield
of 3. No improvement was observed when 1 equiv of
LiClO4 was included in the reaction mixture. Ethereal
LiClO4, a polar but aprotic medium, destroyed 6 rapidly.
With an acceptable procedure for the transformation
of 6 into 3 in hand, we explored a small number of other
substrates to begin to expand the scope of the reaction.
The results are shown in Table 2. Our initial course was
a safe one; we used 2-bromocyclopentenones that were
substituted only with substituents bearing no acidic
protons. However, the literature suggests that using
precursors with potentially acidic hydrogens should not
be a problem.10
The general reaction procedure consisted of reacting a
0.3 M trifluoroethanol solution of the starting material11
with 3 equiv of triethylamine and heating to reflux. While
the excess base was, in principle, not needed, reactions
(10) Elliott, M.; Harper, S. H.; Kazi, M. A. J . Sci. Food Agric. 1967,
18, 167-171.
(11) The bromoenones were prepared by the addition of organo-
lithium compounds to 6 followed by PCC oxidation. See the Experi-
mental Section.
(12) A crystal structure was also obtained for 11a and 3. To the best
of our knowledge, X-ray data on 3 have only appeared in the context
of its participation in an inclusion complex. See: Toda, F.; Tanaka,
K.; Marks, D.; Goldberg, I. J . Org. Chem. 1991, 56, 7332-7335.
(13) This type of transformation has also been accomplished by a
metal-mediated process. See: Luh, T.-Y. J . Organomet. Chem. 1979,
174, 169-172.

5234 J . Org. Chem., Vol. 66, No. 15, 2001
Notes
2-Br om o-1-(3-m et h oxyp h en yl)-2-cyclop en t en -1-ol: 1H
NMR (250 MHz, CDCl3) δ 7.29 (t, 1H, J ) 8.0 Hz), 7.03-6.96
(m, 2H), 6.84 (dd, J ) 0.9, 2.5 Hz, 1H), 6.26-6.24 (m, 1H), 3.82
(s, 3H), 2.64 (s, 1H, OH), 2.52-2.37 (m, 4H); 13C NMR (62.9 MHz,
CDCl3) δ 159.6, 146.2, 134.6, 129.3, 128.4, 117.2, 112.5, 110.9,
87.2, 55.1, 40.6, 30.0; HRMS calcd for C12H13BrO2 268.0099,
found 268.0089.
Sch em e 3
2-Br om o-1-(4-ter t-bu tylp h en yl)cyclop en t-2-en -1-ol: 1H
NMR (250 MHz, CDCl3) δ 7.34-1.29 (m, 4H), 6.20 (t, J ) 2.4
Hz, 1H), 2.56 (s, 1H), 2.52-2.31 (m, 4H), 1.31 (s, 9H); 13C NMR
(CDCl3, 62.9 MHz) δ 150.0, 141.3, 134.3, 128.8, 125.2, 124.6, 87.1,
40.3, 34.4, 31.3, 29.9. Anal. Calcd for C15H19BrO: C, 61.03; H,
6.49. Found: C, 61.23; H, 6.55.
2-Br om o-1-(2,5-d im eth ylp h en yl)cyclop en t-2-en -1-ol: mp
72-74 °C; 1H NMR (250 MHz, CDCl3) δ 7.24 (s, 1H), 7.01 (m,
2H), 6.22 (m, 1H), 2.43 (m, 11H); 13C NMR (62.9 MHz, CDCl3)
δ 141.0, 134.8, 134.6, 132.7, 132.3, 128.9, 128.2, 126.9, 87.7, 38.3,
30.1, 21.1, 20.6. Anal. Calcd for C13H15OBr: C, 58.44; H, 5.66.
Found: C, 58.60; H, 5.72.
were not separable. The product mixture was heated in
quinoline to afford the indanones 26a and 26b in 37 and
13% isolated yields, respectively, after two steps.
2-Br om o-1-p h en yleth yn yl-2-cyclop en ten -1-ol: 1H NMR
(250 MHz, CDCl3) δ 7.54-7.42 (m, 2H), 7.38-7.26 (m, 3H), 6.09
(t, 3H, J ) 2.6 Hz), 3.00 (s, 1H), 2.73-2.61 (m, 1H), 2.55-2.37
(m, 3H); 13C NMR (62.5 MHz, CDCl3) δ 134.2, 133.5, 131.8, 131.6,
128.4, 128.1, 126.3, 122.1, 89.4, 85.3, 79.4, 40.1, 39.2, 29.8;
HRMS calcd for C13H11BrO - H+ 260.9915, found 260.9916.
2-Br om o-1-bu tyl-cyclop en t-2-en ol (24): colorless oil; 1H
NMR (250 MHz) δ 5.99 (t, J ) 2.5 Hz, 1H), 2.48-2.34 (m, 1H),
2.29-2.15 (m, 2H), 2.06-1.93 (m, 1H), 1.89 (s, 1H), 1.76-1.51
(m, 2H), 1.41-1.16 (m, 4H), 0.92 (t, J ) 6.84 Hz, 3H); 13C NMR
(62.9 Hz) δ 132.9, 129.1, 85.4, 38.9, 34.5, 29.7, 26.1, 22.9, 14.0.
Gen er a l P r oced u r e for th e Syn th esis of 2-Br om ocyclo-
p en ten on es. To a solution of 2-bromocyclopentenol (0.21 mmol)
in 2.0 mL of CH2Cl2 (0.1M) was added 0.07 g (0.31 mmol, 1.5
equiv) of PCC, and the mixture was stirred at room temperature
for 24 h. The solution was diluted with 5 mL of ether and filtered
through a pad of silica gel. The filtrate was concentrated and
the crude product purified by flash chromatography (silica gel,
10% EtOAc/hexanes).
2-Br om o-3-p h en yl-2-cyclop en ten -1-on e (10): mp 99-101
°C; 1H NMR (250 MHz, CDCl3) δ 7.93-7.86 (m, 2H), 7.52-7.47
(m, 3H), 3.11-3.07 (m, 2H), 2.71-2.67 (m, 2H); 13C NMR (62.9
MHz, CDCl3) δ 201.4, 167.3, 133.9, 130.9, 128.5, 127.6, 121.5,
32.4, 30.5. Anal. Calcd for C11H9BrO: C, 55.72; H, 3.83. Found:
C, 55.70; H, 3.69.
2-Br om o-3-(3-m eth oxyp h en yl)-2-cyclop eten -1-on e (12):
mp 58-59 °C; 1H NMR (250 MHz, CDCl3) δ 7.45-7.33 (m, 3H),
7.03-7.00 (m, 1H), 3.83 (s, 3H), 3.03 (t, 2H, J ) 4.8 Hz), 2.63 (t,
2H, J ) 4.8 Hz); 13C NMR (62.9 MHz, CDCl3) δ 201.4, 167.2,
159.4, 135.1, 129.5, 121.6, 119.9, 116.4, 113.2, 55.3, 32.4, 30.6;
HRMS calcd for C12H11BrO2 265.9942, found 265.9963.
2-Br om o-3-(4-t er t -b u t ylp h e n yl)-2-cyclop e n t e n -1-on e
(14): mp 81-83 °C; 1H (250 MHz, CDCl3) δ 7.91 (dt, J ) 2.0,
8.5 Hz, 2H), 7.52 (dt, J ) 2.0, 8.5 Hz, 2H), 3.12-3.08 (m, 2H),
2.70-2.66 (m, 2H), 1.37 (s, 9H); 13C NMR (62.9 MHz, CDCl3) δ
201.6, 167.0, 154.7, 131.1, 127.6, 125.5, 120.8, 35.0, 32.4, 31.0,
30.4. Anal. Calcd for C15H17BrO: C, 61.45; H, 5.84. Found: C,
61.42; H, 5.89.
Con clu sion
In summary, we have shown that several 2-bromocy-
clopentenones give rise to cyclopentadienones upon treat-
ment with base in trifluoroethanol. To expand the scope
of this intermolecular reaction, some of our future goals
include exploring the alkylation chemistry of 2-halocy-
clopentenones and developing the chemistry of the cy-
cloadducts and using the approach to study intramolec-
ular cycloaddition reactions of cyclopentadienones with
dienes and dienophiles. Results will be reported in due
course.
Exp er im en ta l Section
Gen er a l. 2-Bromocyclopentenone was prepared as described
in the literature.14 THF and diethyl ether were distilled over
sodium-benzophenone before use. 2,2,2-Trifluoroethanol was
distilled over anhydrous CaSO4 before use. Melting points were
not corrected. 2-Cyclopentenone, bromine, phenyllithium, n-
butyllithium, 3-bromoanisole, 4-tert-butylbromobenzene, 2,5-
dimethylbromobenzene, phenylacetylene, and quinoline were
used as supplied. Analytical TLC was performed on silica gel
plates with F-254 indicator. 1H NMR spectra were recorded at
250 and 300 MHz as CDCl3 solutions with tetramethylsilane
(0.05 vol %) as the internal reference. 13C NMR spectra were
obtained on the same instruments at 62.9 or 75 MHz with CDCl3
(δ ) 77 ppm) as the internal reference.
Gen er a l P r oced u r e for th e Ad d ition of Or ga n olith iu m s
to 2-Br om ocyclop en ten on e. Into a flame-dried flask were
placed 2-bromo-2-cyclopentenone (0.1 g, 0.62 mmol) and 3.0 mL
of freshly distilled THF. The solution was cooled to -78 °C, and
1.2 equiv of aryllithium was slowly added.15 The mixture ws
stirred at -78 °C for 30 min, and the reaction was quenched
with water (5 mL). The layers were separated, and the aqueous
phase was extracted with Et2O (3 × 10 mL). The combined
organic phases were washed with brine, dried over MgSO4 or
Na2SO4, filtered, and evaporated. The crude product was purified
by flash chromatography (silica gel, hexanes/EtOAc).
2-B r o m o -3-(2,5-d im e t h y lp h e n y l)-c y c lo p e n t -2-e n on e
(16): mp 107-108 °C; 1H NMR (250 MHz, CDCl3) δ 7.15 (m,
2H), 6.93 (s, 1H), 2.98 (m, 2H), 2.72 (m, 2H), 2.35 (s, 3H), 2.23
(s, 3H); 13C NMR (62.9 MHz, CDCl3) δ 201.2, 173.8, 135.4, 135.2,
131.0, 130.4, 129.9, 126.4, 124.4, 33.3, 32.9, 20.8, 19.0. Anal.
Calcd for C13H13BrO: C, 58.89; H, 4.94. Found: C, 58.85; H,
4.98.
2-Br om o-1-p h en yl-2-cyclop en ten -1-ol: 1H NMR (250 MHz,
CDCl3) δ 7.43-7.23 (m, 5H), 6.24 (t, J ) 2.5 Hz, 1H), 2.61-2.32
(m, 5H); 13C NMR (62.5 MHz, CDCl3) δ 144.4, 134.6, 128.6, 128.3,
127.3. 124.9, 87.3, 40.7, 30.0. Anal. Calcd for C11H11BrO: C,
55.26; H, 4.64. Found: C, 55.30; H, 4.51.
2-Br om o-3-ph en yleth yn yl-2-cyclopen ten on e (18): 1H NMR
(300 MHz, CDCl3) δ 7.58 (m, 2H), 7.41 (m, 3H), 2.85 (t, 2H, J )
4.5 Hz), 2.62 (t, 2H, J ) 4.5 Hz); 13C NMR (75 MHz, CDCl3) δ
200.9, 153.5, 132.2, 130.2, 128.6, 121.4, 109.0, 84.37, 32.7, 31.3;
HRMS calcd for C13H9BrO 259.9837, found 259.9846.
2-Br om o-3-bu tyl-cyclop en t-2-en on e (25): colorless oil; 1H
NMR (250 MHz) δ 2.70-2.68 (m, 2H), 2.59-2.52 (m, 4H), 1.64-
1.52 (m, 2H), 1.48-1.33 (m, 2H), 0.96 (t, J ) 7.2 Hz, 3H); 13C
NMR (62.9 Hz) δ 201.4, 177.1, 122.7, 33.0, 32.3, 30.2, 28.6, 22.5,
13.6.
(14) Smith, A. B., III; Branca, S. J .; Guaciaro, M. A.; Wovkulich, P.
M.; Korn, A. Org. Synth. 1983, 61, 65-70.
(15) Addition of the bromoketone to the organolithium also produced
good results.
(16) Neither combustion nor HRMS analysis (decarbonylation) was
obtained for this compound.
Gen er a l P r oced u r e for th e Syn th esis of Cyclop en ta d i-
en on e Dim er s. A 10 mL round-bottomed flask was charged
with 1.1 mmol of a bromoketone and 2.5 mL of trifluoroethanol.
(17) Sammour, A.; Elkasaby, M. U. A. R. J . Chem. 1971, 13, 409-
420.

Notes
J . Org. Chem., Vol. 66, No. 15, 2001 5235
To the solution was added 2 or 3 equiv, and the mixture was
refluxed. The reaction was monitored by TLC, and upon comple-
tion, the mixture was cooled and the trifluoroethanol was
removed on a rotary evaporator. To the residue was added 25
mL of a polar solvent (ethyl acetate, chloroform, or dichlo-
romethane). This solution was washed with water, 1 N HCl,
saturated bicarbonate solution, and brine (5 mL each). The
solution was dried (Na2SO4), and the solvent was removed in
vacuo. The product was purified by flash chromatography
(hexanes/EtOAc).
3,5-Diph en yl-3aR*,4S*,7S*,7aS*-tetr ah ydr o-4,7-m eth an o-
1H-in d en e-1,8-d ion e (11a ): mp 196 °C; 1H NMR (250 MHz,
CDCl3) δ 7.49-7.34 (m, 5H), 7.09-6.94 (m, 3H), 6.84-6.81 (m,
2H), 6.66 (dd, J ) 1.4, 3.7 Hz, 1H), 6.54 (d, J ) 1.0 Hz, 1H),
4.21-4.16 (m, 1H), 3.80 (dt, J ) 1.3, 4.8 Hz, 1H), 3.65-3.61 (m,
1H), 3.26 (dd, J ) 4.8, 6.4 Hz, 1H); 13C NMR (62.9 MHz, CDCl3)
δ 205.6, 198.0, 171.7, 140.7, 133.4, 133.2, 132.8, 131.5, 129.0,
128.1, 128.0, 127.2, 125.0, 121.0, 51.4, 50.6, 46.1, 41.0. Anal.
Calcd for C22H16O2: C, 84.59; H, 5.16. Found: C, 84.70; H, 5.29.
3,6-Diph en yl-3aS*,4S*,7S*,7aR*-tetr ah ydr o-4,7-m eth an o-
in d en e-1,8-d ion e (11b): mp 194-196 °C; 1H NMR (250 MHz,
CDCl3) δ 7.68-7.64 (m, 2H), 7.51-7.26 (m, 8H), 6.58 (d, J ) 1.1
Hz, 1H), 6.26 (dd, J ) 1.5, 3.8 Hz, 1H), 4.14-4.10 (m, 1H), 3.86
(dt, J ) 1.4, 4.9 Hz, 1H), 3.60-3.56 (m, 1H), 3.29 (dd, J ) 4.9,
6.3 Hz, 1H); 13C NMR (62.5 MHz, CDCl3) δ 204.6, 197.4, 171.4,
142.3, 133.4, 133.3, 132.4, 131.6, 129.2, 128.5, 127.2, 125.9, 119.8,
52.0, 51.1, 45.1, 42.8. Anal. Calcd for C22H16O2: C, 84.59; H, 5.16.
Found: C, 84.40; H, 5.37.
3,5-Bis(3-m eth oxyph en yl)-3a R*,4S*,7S*,7a S*-tetr ah ydr o-
4,7-m eth a n o-1H-in d en e-1,8-d ion e (13a ): 1H NMR (250 MHz,
CDCl3) δ 7.31 (t, 1H, J ) 7.9 Hz), 7.12 (d, 1H, J ) 7.8 Hz), 7.00-
6.95 (m, 1H), 6.92-6.89 (m, 2H), 6.65-6.61 (m, 2H), 6.51-6.49
(m, 2H), 6.36 (t, 1H, J ) 2.0 Hz), 4.13 (t, 1H, J ) 5.2 Hz), 3.77-
3.75 (m, 4H), 3.63-3.59 (m, 1H), 3.51 (s, 3H), 3.23 (dd, J ) 5.0,
6.2 Hz, 1H); 13C NMR (62.5 MHz, CDCl3) δ 205.6, 197.9, 171.6,
160.0, 159.4, 140.6, 134.7, 134.3, 133.8, 130.0, 129.1, 121.4, 119.5,
117.7, 117.2, 114.3, 112.5, 110.2, 55.3, 54.8, 51.6, 50.6, 46.2, 41.1.
Anal. Calcd for C24H20O4: C, 77.40; H, 5.41. Found: C, 77.28;
H, 5.42.
3,6-Bis(3-m eth oxyph en yl)-3a S*,4S*,7S*,7a R*-tetr ah ydr o-
4,7-m eth a n o-1H-in d en e-1,8-d ion e (13b): 1H NMR (250 MHz,
CDCl3) δ 7.39 (t, 1H, J ) 7.9 Hz), 7.25-7.21 (m, 3H), 7.13 (t,
1H, J ) 2.3 Hz), 7.06-6.97 (m, 2H), 6.93 (t, 1H, J ) 2.3 Hz),
6.83 (ddd, J ) 0.8, 2.5, 8.2 Hz, 1H), 6.56 (d, 1H), 6.26 (dd, 1.4,
3.8 Hz, 1H), 4.09 (t, 1H, J ) 5.0 Hz), 3.85 (s, 3H), 3.83 (m, 1H),
3.82 (s, 3H), 3.59-3.55 (m, 1H), 3.27 (dd, 1H, J ) 5.0, 6.3 Hz);
13C NMR (62.5 MHz, CDCl3) δ 204.0, 197.3, 171.3, 160.1, 159.7,
142.3, 134.8, 134.3, 133.7, 130.2, 129.6, 120.3, 119.7, 118.5, 117.0,
114.5, 112.8, 111.3, 55.4, 55.3, 52.1, 51.4, 45.1, 42.9; HRMS calcd
for C24H20O4 372.1361, found 372.1341.
135.6, 134.9, 133.9, 133.3, 132.9, 131.6, 131.2, 130.8, 129.2, 128.4,
128.0, 126.0, 52.9, 50.9, 45.5, 43.4, 22.1, 20.9, 20.8, 20.6. Anal.
Calcd for C26H24O2: C, 84.75; H, 6.57. Found: C, 85.00; H, 6.71.
3,6-Bis(2,5-d im eth ylp h en yl)-3a S*,4S*,7S*,7a R*-tetr a h y-
d r o-4,7-m eth a n o-in d en e-1,8-d ion e (17b): mp 163-165 °C; 1H
NMR (250 MHz, CDCl3) δ 7.26 (s, 1H), 7.23-7.19 (m, 2H), 7.08-
7.00 (m, 2H), 7.01 (m, 1H), 6.43 (d, J ) 1.0 Hz, 1H), 6.06 (dd, J
) 1.4, 3.8 Hz, 1H), 4.20-4.16 (m, 1H), 3.81-3.78 (m, 1H), 3.37-
3.34 (m, 1H), 3.25 (dd, J ) 5.0, 6.3 Hz, 1H), 2.39 (s, 3H), 2.36 (s,
3H), 2.34 (s, 3H), 2.30 (s, 3H); 13C NMR (62.9 MHz, CDCl3) δ
205.2, 197.8, 173.0, 142.9, 138.2, 136.0, 135.6, 133.5, 133.3, 132.5,
131.7, 131.0, 130.8, 130.0, 128.7, 128.0, 124.8, 53.7, 51.5, 45.2,
44.7, 21.2, 21.2, 20.99, 20.96. Anal. Calcd for C26H24O2: C, 84.75;
H, 6.57. Found: C, 85.00; H, 6.71.
3,5-Bis(ph en yleth yn yl)-3a,4,7,7a-tetr ah ydr o-4,7-m eth an o-
1H-in d en e-1,8-d ion e (19):16 1H NMR (250 MHz, CDCl3) δ
7.49-7.42 (m, 2H), 7.39-7.31 (m, 3H), 7.21-7.09 (m, 6H), 6.55
(d, 1H, J ) 3.6 Hz), 6.51 (s, 1H), 3.72 (t, 1H, J ) 5.0 Hz), 3.57
(d, 1H, J ) 4.4 Hz), 3.53 (t, 1H, J ) 3.9 Hz), 3.09 (dd, 1H, J )
5.0 Hz); 13C NMR (62.5 MHz, CDCl3) δ 205.4, 197.2, 154.5, 141.2,
132.4, 132.1, 131.7, 131.5, 130.0, 129.4, 128.6, 128.5, 128.1, 124.0,
122.2, 121.4, 106.7, 95.1, 84.0, 83.8, 53.8, 51.1, 44.5, 44.3.
Gen er a l Deca r bon yla tion P r oced u r e: Syn th esis of In -
d a n on es. In a flame-dried flask, 15-40 mg of the diketone was
dissolved in 1 mL of quinoline. The reaction mixture was stirred
at 150-160 °C and monitored by TLC until the starting material
was consumed. The reaction mixture was cooled to room tem-
perature, diluted with ether, and added to a separatory funnel.
The mixture was washed three times with 3 N HCl, and then
twice with water to remove the quinoline. The organic phase
was dried with MgSO4, and the solvent was removed under
reduced pressure. The crude product was purified by column
chromatography (5-15% EtOAc/hexanes) to yield a clean prod-
uct.
3,5-Dip h en yl-1-in d a n on e (20a ):17 mp 153-155 °C; 1H NMR
(300 MHz, CDCl3) δ 7.87 (d, J ) 8.0 Hz, 1H), 7.66-7.64 (m, 1H),
7.56-7.52 (m, 2H), 7.44-7.22 (m, 7H), 7.18-7.15 (m, 2H), 4.62
(dd, J ) 3.9, 8.0 Hz, 1H), 3.28 (dd, J ) 8.0, 19.2 Hz, 1H), 2.74
(dd, J ) 3.9, 19.2 Hz, 1H); 13C NMR (75.5 MHz, CDCl3) δ 205.4,
158.6, 148.2, 143.6, 140.0, 135.7, 129.0, 128.9, 128.4, 127.7, 127.5,
127.3, 127.0, 125.3, 123.8, 47.2, 44.6; HRMS calcd for C21H16
284.1201, found 284.1190.
O
3,6-Dip h en yl-1-in d a n on e (20b): mp 126-128 °C; 1H NMR
(250 MHz, CDCl3) δ 8.24 (d, J ) 1.7 Hz, 1H), 7.81 (dd, J ) 1.9,
8.0 Hz, 1H), 7.64-7.59 (m, 2H), 7.49-7.22 (m, 7H), 7.19-7.14
(m, 2H), 4.61 (dd, J ) 3.8, 8.0 Hz, 1H), 3.29 (dd, J ) 8.1, 19.2
Hz, 1H), 2.75 (dd, J ) 3.9, 19.2 Hz, 1H); 13C NMR (75.5 MHz,
CDCl3) δ 205.9, 156.8, 143.6, 141.3, 139.9, 137.4, 134.2, 129.0,
127.9, 127.7, 127.2, 127.0, 121.5, 47.2, 44.2; HRMS calcd for
C21H16O 284.1201, found 284.1206.
3,5-Bis(4-ter t-bu tylph en yl)-3aR*,4S*,7S*,7aS*-tetr ah ydr o-
4,7-m eth a n o-1H-in d en e-1,8-d ion e (15a ): mp 213-217 °C dec;
1H NMR (250 MHz, CDCl3) δ 7.37 (s, 4H), 6.91-6.93 (m, 2H),
6.68-6.71 (m, 2H), 4.17-4.20 (m, 1H), 3.77-3.79 (m, 1H), 3.62-
3.58 (m, 1H), 3.23 (dd, J ) 5.1, 6.2 Hz, 1H), 1.36 (s, 9H), 1.19 (s,
9H); 13C NMR (CDCl3, 62.9 MHz) δ 205.7, 198.3, 171.8, 155.2,
151.0, 140.6, 132.6, 130.5, 130.0, 127.2, 125.7, 124.8, 124.7, 119.7,
51.3, 50.5, 46.0, 41.0, 34.9, 34.3, 31.04, 30.97. Anal. Calcd for
C30H32O2: C, 84.87; H, 7.60. Found: C, 84.64; H, 7.60.
3,6-Bis(4-ter t-bu tylph en yl)-3aS*,4S*,7S*,7aR*-tetr ah ydr o-
4,7-m eth a n o-1H-in d en e-1,8-d ion e (15b): mp 213-215 °C dec;
1H NMR (250 MHz, CDCl3) δ 7.59 (dt, J ) 1.6, 7.1 Hz, 2H), 7.48
(dt, J ) 1.6, 7.1 Hz, 2H), 7.35 (s, 4H), 6.55 (d, J ) 0.8 Hz, 1H),
6.23 (dd, J ) 1.1, 3.2 Hz, 1H), 4.11-4.07 (m, 1H), 3.83 (dt, J )
1.1, 4.1 Hz, 1H), 3.57 (dt, J ) 0.9, 3.4 Hz, 1H), 3.27 (dd, J ) 4.2,
5.3 Hz, 1H), 1.36 (s, 9H), 1.30 (s, 9H); 13C NMR (CDCl3, 62.9
MHz) δ 204.8, 197.7, 171.3, 155.5, 151.7, 142.2, 132.6, 130.6,
130.2, 127.2, 126.2, 125.7, 125.5, 119.1, 52.2, 51.2, 45.2, 42.9,
35.1, 34.6, 31.2, 31.1. Anal. Calcd for C30H32O2: C, 84.87; H, 7.60.
Found: C, 84.70; H, 7.60.
3,5-Bis(3-m et h oxyp h en yl)-1-in d a n on e (21a ): mp 97-99
1
°C; H NMR (250 MHz, CDCl3) δ 7.85 (d, J ) 8.0 Hz, 1H), 7.63
(dd, J ) 1.3, 8.1 Hz, 1H), 7.46 (s, 1H), 7.36-7.20 (m, 2H), 7.14-
7.11 (m, 1H), 7.08-7.06 (m, 1H), 6.91 (dd, J ) 2.5, 8.2 Hz, 1H),
6.80-6.69 (m, 3H), 4.58 (dd, J ) 3.8, 8.0 Hz, 1H), 3.84 (s, 3H),
3.76 (s, 3H), 3.26 (dd, J ) 8.0, 19.2 Hz, 1H), 2.73 (dd, J ) 3.9,
19.2 Hz, 1H); 13C NMR (62.9 MHz, CDCl3) δ 205.3, 160.0, 159.9,
158.3, 148.0, 145.2, 141.5, 135.7, 130.0, 129.9, 127.3, 125.3, 123.7,
120.0, 119.9, 113.7, 113.5, 113.4, 112.0, 55.3, 55.2, 47.0, 44.5;
HRMS calcd for C23H20O3 344.1412, found 344.1416.
3,5-Bis(4-ter t-bu tylp h en yl)-1-in d a n on e (22a ): mp 203-
1
205 °C; H NMR (250 MHz, CDCl3) δ 7.85 (d, J ) 8.0 Hz, 1H),
7.64 (dd, J ) 1.0, 8.0 Hz, 1H), 7.53-7.43 (m, 5H), 7.34-7.25 (m,
2H), 7.11-7.06 (m, 2H), 4.59 (dd, J ) 3.8, 8.0 Hz, 1H), 3.25 (dd,
J ) 8.0, 19.2 Hz, 1H), 2.73 (dd, J ) 3.9, 19.2 Hz, 1H), 1.34 (s,
9H), 1.30 (s, 9H); 13C NMR (62.9 MHz, CDCl3) δ 205.7, 158.8,
151.6, 149.8, 147.9, 140.5, 137.2, 135.4, 127.3, 127.2, 127.0, 125.9,
125.8, 125.1, 123.7, 47.2, 44.0, 34.6, 34.5, 31.3, 31.2; HRMS calcd
for C29H32O 396.2453, found 396.2479.
3,5-Bis(2,5-d im eth ylp h en yl)-3a R*,4S*,7S*,7a S*-tetr a h y-
d r o-4,7-m eth a n o-in d en e-1,8-d ion e (17a ): mp 163-165 °C; 1H
NMR (250 MHz, CDCl3) δ 7.11-6.96 (m, 4H), 6.87 (d, J ) 8.8
Hz, 1H), 6.53 (dd, J ) 1.7, 3.6 Hz, 1H), 6.40 (d, J ) 0.9 Hz, 1H),
6.33 (s, 1H), 4.23-4.18 (m, 1H), 3.68-3.64 (m, 2H), 3.25-3.20
3,5-Bis(2,5-d im eth ylp h en yl)-1-in d a n on e (23b): mp 47-49
°C; 1H NMR (250 MHz, CDCl3) δ 7.56 (d, J ) 7.91 Hz, 1H), 7.41-
7.37 (m, 1H), 7.37 (d, J ) 7.2 Hz, 1H), 7.15-6.93 (m, 5H), 6.66
(s, 1H), 4.82 (dd, J ) 4.0, 8.0 Hz, 1H), 3.27 (dd, J ) 8.1, 19.1
Hz, 1H), 2.61 (dd, J ) 4.0, 19.1 Hz, 1H), 2.36 (s, 3H), 2.32 (s,
3H), 2.19 (s, 3H), 2.17 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ
205.7, 158.0, 149.2, 140.7, 136.0, 135.7, 135.4, 132.7, 131.9, 130.5,
(m, 1H), 2.31 (s, 3H), 2.26 (s, 3H), 1.97 (s, 3H), 1.93 (s, 3H); 13
C
NMR (62.9 MHz, CDCl3) δ 206.2, 198.5, 172.7, 141.2, 137.7,

5236 J . Org. Chem., Vol. 66, No. 15, 2001
Notes
130.1, 129.2, 128.7, 127.6, 127.5, 123.2, 46.1, 20.9, 20.8, 19.8,
19.4; HRMS calcd for C25H24O 340.1827, found 340.1811.
3,5-Dibu tyl-in d a n -1-on e (26a ): yellow oil; 1H NMR (250
MHz) δ 7.64 (d, J ) 7.8 Hz, 1H), 7.29 (s, 1H), 7.19 (d, J ) 7.8
Hz, 1H), 3.33-3.26 (m, 1H), 2.83 (dd, J ) 7.5, 19.0 Hz, 1H), 2.70
(t, J ) 7.6 Hz, 2H), 2.34 (dd, J ) 3.30, 19.0 Hz, 1H), 1.95-1.88
(m, 1H), 1.70-1.30 (m, 9H), 0.97-0.90 (m, 6H); 13C NMR (62.9
Hz) δ 206.0, 159.2, 150.7, 134.7, 128.1, 125.2, 123.4, 43.3, 38.1,
36.2, 35.8, 33.4, 29.8, 22.7, 22.4, 14.0, 13.9; IR (neat) 3018, 2958,
Ack n ow led gm en t. This work was supported by the
National Science Foundation, to whom we are grateful.
We thank the National Science Foundation for partial
support of the NMR (PCM-8115599) facility at the
University of MissourisColumbia and for partial fund-
ing for the purchase of a 500 MHz spectrometer (CHE-
89-08304). We thank Dr. Dmitri Zagorevski for mass
spectral data and the University of Missouri Research
Board for its continued support of the Mass Spectrom-
etry Facility.
2930, 2858, 1710, 1609, 756 cm-1; HRMS calcd for C17H24
244.1827, found 244.1830.
O
3,6-Dibu tyl-in d a n -1-on e (26b): yellow oil; 1H NMR (250
MHz) δ 7.54 (s, 1H), 7.45-7.38 (m, 2H), 3.34-3.26 (m, 1H), 2.85
(dd, J ) 7.4, 19.0 Hz, 1H), 2.66 (t, J ) 7.5 Hz, 2H), 3.35 (dd, J
) 3.2, 19.0 Hz, 1H), 1.92-1.86 (m, 1H), 1.67-1.26 (m, 9H), 0.95-
0.89 (m, 6H); 13C NMR (62.9 Hz) δ 206.7, 159.7, 142.4, 136.9,
135.3, 125.3, 122.8, 43.5, 37.9, 35.9, 35.2, 33.5, 29.8, 22.8, 22.2,
Su p p or t in g In for m a t ion Ava ila b le: X-ray data for 3,
11a , 17a , and 17b, and copies of proton and carbon spectra
for the alcohol precursors of the 2-bromocyclopentenones and
of 10-26. This material is available free of charge via the
Internet at http://pubs.acs.org.
14.0, 13.9; IR (neat) 3020, 2963, 2932, 2862, 1703, 1216 cm-1
HRMS calcd for C17H24O 244.1827, found 244.1834.
;
J O015671+