Ruthenium-catalyzed cyclization of alkyne-epoxide functionalities through alternation of the substituent and structural skeleton of epoxides

Article abstract of DOI:10.1021/jo048983w

Treatment of 1-(o-ethynylphenyl)-2-alkyl-2-aryl epoxides with TpRuPPh ₃(CH₃CN)₂PF₆ catalyst (10 mol %) in hot toluene (100 °C, 12 h) led to an atypical cyclization and gave 1-aryl-2-alkyl-1H-indene derivatives a

Full text of DOI:10.1021/jo048983w

Ru th en iu m -Ca ta lyzed Cycliza tion of Alk yn e-Ep oxid e
F u n ction a lities th r ou gh Alter n a tion of th e Su bstitu en t a n d
Str u ctu r a l Sk eleton of Ep oxid es
Lin Ming-Yuan, Reniguntala J . Madhushaw, and Rai-Shung Liu*
Department of Chemistry, National Tsing-Hua University, Hsinchu, Taiwan, ROC
rsliu@mx.nthu.edu.tw
Received J une 17, 2004
Treatment of 1-(o-ethynylphenyl)-2-alkyl-2-aryl epoxides with TpRuPPh3(CH3CN)2PF6 catalyst (10
mol %) in hot toluene (100 °C, 12 h) led to an atypical cyclization and gave 1-aryl-2-alkyl-1H-
indene derivatives and carbon monoxide efficiently. The cyclization of 1-cis-enynyl-2-alkyl epoxides
with this catalyst in hot toluene (10 mol %, 100 °C, 12 h) gave 2,5-disubstituted phenols in 45-
72% yields. Under the same conditions, 1-cis-enynyl- 2,2-dialkyl epoxides and 1-cis-enynyl- 2-alkyl-
2-aryl epoxides gave the corresponding 6,6-disubstituted cyclohexa-2,4-dien-1-ones in good yields
(85-91%). Mechanisms for these new cyclization reactions are proposed on the basis of trapping
experiments and isotope labeling experiments. The formation of 1H-indene products likely involves
ruthenium-acyl intermediates whereas cyclohexa-2,4-dien-1-ones are thought to derive from
ruthenium-ketene intermediates.
In tr od u ction
reaction generally requires an excess amount of metal
or Lewis acid reagents. Only a few examples have been
reported for catalytic epoxide-alkyne coupling reaction.4,5
Recently, we reported8 a cascade alkyne-epoxide cy-
clization of (o-ethynyl)phenyl epoxides catalyzed by
TpRuPPh3(CH3CN)2PF6.9 This cyclization led to a com-
plete oxygen transfer from epoxide to terminal alkyne
to give cationic ruthenium ketene-alkene intermediate
(I), further leading to intramolecular cyclization.8 The
reaction products are highly dependent on the epoxide
substituents: 1,2-disubstituted epoxides gave 2-naphthol
product A whereas 1,2,2-trisubstituted epoxides afforded
1-alkylidene-2-indanones B (Scheme 1). These two cy-
clized products arise from attack of the alkene of inter-
mediate I at the tethered ketene functionality via 6-endo-
dig and 5-endo-dig cyclizations, respectively. For such a
cationic cyclization, we envisage that the substituents of
epoxide substrate are crucial for the cyclization chemose-
lectivity because they affect the location of cationic charge
of reaction intermediates I. In this continuing work, we
discovered new patterns of alkyne-epoxide cyclization
Transition-metal-catalyzed cyclization is a powerful
tool for the construction of complex carbocyclic and
heterocyclic molecules.1,2 The reaction generally involves
formation of two or three carbon-carbon bonds among
molecules of π-type such as alkene, alkyne, 1,3-diene,
methylenecyclopropane, carbon monoxide, ketone, alde-
hyde, allene, and imine. Although the hybridization of
an epoxide molecule lies between sp2 and sp3 character,3
metal-mediated coupling reaction on organic epoxides is
less studied.4,5 Several metal salts effect the coupling of
epoxide with alkyne via a one-electron radical process6
or acid-mediated ring opening of epoxides,7 but the
(1) Selected reviews: (a) Lautens, M.; Klute, W.; Tam, W. Chem.
Rev. 1996, 96, 49. (b) Aubert, C.; Buisine, O.; Malacria, M. Chem. Rev.
2002, 102, 813. (c) Trost, B. M.; Toste, F. D.; Pinkerton, A. B. Chem.
Rev. 2001, 101, 2067. (d) Schore, N. E. In Comprehensive Organome-
tallic Chemistry; Abel, E. W., Stone, F. G. A., Wilkinson, G., Hegedus,
L. S., Eds.; Pergamon Press: Oxford, 1995; Vol. 12, p 703. (e) Geis, O.;
Schaltz, H. Angew. Chem., Int. Eng. 1998, 37, 911. (f) Fruhauf, H. W.
Chem. Rev. 1997, 97, 523.
(2) For selected examples, see: (a) Brummond, K. M.; Lu, J . J . Am.
Chem. Soc. 1999, 121, 5087. (b) Tobisu, M.; Chatani, N.; Asaumi, T.;
Amako, K.; Ie, Y.; Fukumoto, Y.; Murai, S. J . Am. Chem. Soc. 2000,
122, 12633. (c) Kablaoui, N. M.; Hicks, F. A.; Buchwald, S. L. J . Am.
Chem. Soc. 1996, 118, 5818. (d) Chatani, N.; Morimoto, T,; Fukumoto,
Y.; Murai, S. J . Am. Chem. Soc. 1996, 118, 5335. (e) Chatani, N.;
Tobisu, M.; Asaumi, T.; Murai, S. Synthesis 2000, 925. (f) Shibata, T.;
Toshida, N.; Takagi, K. Org. Lett. 2002, 4, 1619. (g) Seo, J .; Chui, H.
M. P.; Heeg, M. J .; Montgomery, J . J . Am. Chem. Soc. 1999, 121, 476.
(h) Takimoto, M.; Mori, M. J . Am. Chem. Soc. 2002, 124, 10008. (i)
Yamamoto, Y. Takagishi, H.; Itoh, K. J . Am. Chem. Soc. 2002, 124,
6844.
(3) Nicolaou, K. C.; Duggan, M. E.; Huang, C. K.; Somers, P. K. J .
Chem. Soc., Chem. Commun. 1985, 1359.
(4) (a) McDonald, F. E.; Schultz, C. C. J . Am. Chem. Soc. 1994, 116,
9363. (b) Gansauer, A.; Bluhm, H.; Pierobon, M. J . Am. Chem. Soc.
1998, 120, 12849. (c) Lo, C.-Y.; Guo, H.-Y.; Lian, J .-J .; Liu, R.-S. J .
Org. Chem. 2002, 67, 3930
(6) (a) RajanBabu, T. V.; Nugent, W. A. J . Am. Chem. Soc. 1994,
116, 986. (b) Gansauer, A.; Pierobon, M.; Bluhm, H. Angew. Chem.,
Int. Eng. 1998, 37, 101.
(7) (a) Chou, W.-N.; White, J . B. Tetrahedron Lett. 1991, 32, 7637.
(b) Gaebert, C.; Mattaay, I. Tetrahedron Lett. 1997, 53, 14297. (c)
Palomino, E.; Schaap, A. P.; Heeg, M. J . Tetrahedron Lett. 1989, 30,
6801. (d) Madhushaw, R. J .; Li, C.-L.; Shen, K.-H.; Hu, C.-C.; Liu, R.-
S. J . Am. Chem. Soc. 2001, 123, 7427.
(8) Madhushaw, R. J .; Lin, M.-Y.; Abu Sohel, S. M.; Liu, R.-S. J .
Am. Chem. Soc. 2004, 126, 6895.
(9) For catalytic reactions that use this ruthenium catalyst, see: (a)
Yeh, K.-L.; Liu, B.; Lo, C.-Y.; Liu, R.-S. J . Am. Chem. Soc. 2002, 124,
6510. (b) Datta, S.; Chang, C.-L.; Yeh, K.-L.; Liu, R.-S. J . Am. Chem.
Soc. 2003, 125, 9294. (c) Shen, H.-C.; Pal, S.; Lian, J .-J .; Liu, R.-S. J .
Am. Chem. Soc. 2003, 125, 15762. (d) Lo, C.-Y.; Guo, H.-Y.; Lian, J .-
J .; Liu, R.-S. J . Org. Chem. 2002, 67, 3930. (e) Chang, C.-L.; Kumar,
M. P.; Liu, R.-S. J . Org. Chem. 2004, 69, 2793.
(5) Molinaro, C.; J amison, T. F. J . Am. Chem. Soc. 2003, 125, 8076.
10.1021/jo048983w CCC: $27.50 © 2004 American Chemical Society
Published on Web 10/05/2004
7700
J . Org. Chem. 2004, 69, 7700-7704

Ru-Catalyzed Cyclization of Alkyne-Epoxide Functionalities
TABLE 1. Ru th en iu m -Ca ta lyzed Cycliza tion of
2,2-Alk yla r yl Ep oxid es
SCHEME 1
entries
1
expoxidesa
indenesb
X ) Y ) H, Ar ) Ph, R ) Et
(1b, E/Z ) 1.3)
X ) Y ) H, Ar ) p-MePh, R ) Me
(1c, E/Z ) 2.5
X ) Y ) H, Ar ) p-FPh, R ) Me
(1d , E/Z ) 2.6)
X ) H, Y ) F, Ar ) Ph, R ) Me
(1e, E-form only)
X ) H, Y ) F, Ar ) p-MePh, R ) Me
(1f, E-form only)
2b (77%)
2
3
4
5
6
2c (76%)
2d (72%)
2e (75%)
2f (71%)
reactions upon modification of the substrate frameworks
and substituents.
X ) F, Y ) H, Ar ) Ph, R ) Me
(1g, E-form only)
2e (80%)
X ) H, Y ) F
Resu lts a n d Discu ssion
a
Conditions: [substrate] ) 0.75 M, 100 °C, 12 h, toluene.
b
Although 2,2-disubstituted epoxides gave 1-alkylidene-
Yields were reported after elution from a silica column.
2-indanones B, treatment of 2-methyl-2-phenyl epoxide
10
1a with TpRuPPh3(CH3CN)2PF6 catalyst (10 mol %) in
TABLE 2.
hot toluene (100 °C, 12 h) gave 1-phenyl-2-methyl-1H-
indene species 2a in 78% yield. GC analysis of the
gaseous mixture above the reaction solution showed the
presence of carbon monoxide. High-resolution mass spec-
tra of compound 2a indicate loss of carbon monoxide
relative to its starting epoxide 1a . The structure is
confirmed by 13C NMR spectra, which shows 14 carbon
peaks with one carbon less than the expectation. The
proposed structure is also supported by the 1H NOE
effect.11
entries
epoxidesa
phenolsb
1
2
3
R1 ) iPr, R2 ) nBu (3a )
R1 ) nBu, R2 ) nC6H13 (3b)
R1 ) Ph, R2 ) nC6H13 (3c)
4a (72%)
4b (65%)
4c (45%)
We prepared various 2-alkyl-2-aryl epoxides 1b-g to
examine the generality of this atypical cyclization. These
epoxides were present as either the E-isomer or a mixture
of E- and Z-isomers. Entries 2-4 (Table 1) show the
suitability of this cyclization to the variation of alkyl and
aryl substituents of epoxides with ethyl, 4-tolyl, and
4-fluorophenyl groups, and the corresponding indene
products 2b-d were obtained in 72-77% yields. Entries
4-6 show the cyclization of epoxides 1e-g bearing a
fluoro substituent at their phenyl C4 or C5 carbons
respectively; the resulting indenes 2e-f were obtained
in 71-80% yields. The regiochemistry of indene 2e (entry
a
Conditions: [substrate] ) 0.75 M, 100 °C, 12 h, toluene.
b
Yields were reported after elution from a silica column.
in the presence of ruthenium catalyst (10 mol %). The
structures of phenols 4a -c were confirmed by H, 13C,
1
and high-resolution mass spectra,11 although the out-
comes of cyclization of epoxides 3a -c are essentially the
same as those observed for o-ethynylphenyl epoxides
(Scheme 1) that gave 2-naphthols A.
As shown in Table 3, treatment of 1-cis-ethynyl-2,2-
dialkyl epoxide 5a (E/Z ) 0.9) with ruthenium catalyst
(10 mol %) afforded 6,6-disubstituted cyclohexa-2,4-dien-
1-one 6a with 90% yield. The proposed structure is
1
4) was determined by H NOE spectra.11 Notably, the
indene product generated from epoxide 1g is identical to
that given from epoxide 1e even though these two
epoxides have a fluoro substituent at different phenyl
positions. This information suggests that the cyclizations
of epoxide 1e and 1g proceed through the same inter-
mediate.
With these encouraging results, we further examined
the effects of epoxide skeletons on the cyclization chemose-
lectivity. We prepared various 1,2-disubstituted 3a -c
and 1,2,2-trisubstituted epoxides 5a -h bearing a cis-
enynyl substituent. As shown in Table 2, epoxides 3a -c
gave 2,5-disubstituted phenols 4a -c in 45-72% yields
compatible with its H-NOE11 and 13C NMR spectra and
1
by high-resolution mass spectra. This chemoselectivity
is distinct from what is observed for their o-ethynylphenyl
epoxide analogues that gave 1-alkylidene-2-indanones B
(Scheme 1). We prepared various epoxide analogues with
various E/Z ratios12 to examine the generality of this
cyclization. Entries 2-7 show the suitability of this
cyclization with variation of the R3 and R4 substituents;
the resulting cyclic ketones 6b-g were obtained in 85-
92% yields. We also prepared 2,2-disubstituted epoxide
5h bearing geminal methyl and phenyl groups to examine
a possible alternation of reaction selectivity like those
(10) Chan, W.-C.; Lau, C.-P.; Chen, Y.-Z.; Fang, Y.-Q.; Ng, S.-M.;
J ia, G. Organometallics 1997, 16, 34.
(11) The 1H NOE NMR spectra of key compounds 2a , 2e, and 6a
are shown in either the Experimental Section or the Supporting
Information.
(12) The E/Z ratios of epoxides 3a -c and 5a -h are given in the
Supporting Information.
J . Org. Chem, Vol. 69, No. 22, 2004 7701

Ming-Yuan et al.
TABLE 3. Cycliza tion of 1-cis-En yn yl-2,2-d ia lk yl
Ep oxid es
SCHEME 3
entries
1
epoxidesa
ketonesb
R1 ) nPr, R2 ) Me
R3 ) H, R4 ) Ph (5a )
R1 ) nC5H11, R2 ) Me
R3 ) H, R4 ) Ph (5b)
R1 ) R2 ) Me
6a (90%)
6b (92%)
6c (90%)
6d (85%)
6e (85%)
6f (88%)
6g (92%)
6h (89%)
2
3
4
5
6
7
8
R3 ) H, R4 ) nC6H13 (5c)
R1 ) Et, R2 ) Me
R3 ) H, R4 ) nC6H13 (5d )
R1 ) R2 ) Me
R3 ) H, R4 ) Ph (5e)
R1 ) Me, R2 ) Et
SCHEME 4
R3 ) H, R4 ) Ph (5f)
R1 ) R2 ) Me
R3 ) R4 ) -C4H8- (5g)
R1 ) Ph, R2 ) Me
R3 ) H, R4 ) nC6H13 (5h )
a
Conditions: [substrate] ) 0.75 M, 100 °C, 12 h, toluene.
Yields were reported after elution from a silica column.
b
SCHEME 2
anism of formation of 2,4-cyclohexadien-1-one seems
straightforward because the trapping experiment indi-
cates that ruthenium-ketene species I is likely the
reaction intermediate. The transformation from starting
epoxide to intermediate I has been elucidated in our
previous study.8 As shown in Scheme 4, the 6-endo-dig
cyclization of the terminal alkenyl carbon of species I at
the ketene moiety14 gave ruthenium-π-cyclohexadienone
species II and ultimately afforded the observed cyclic
ketones.
In Scheme 5, the epoxide 1a is catalyzed by ruthenium
complex to form ruthenium-vinylidenium species III and
further to yield ruthenium-acyl species IV rather than
the ruthenium-ketene I as we failed to trap species I
with isobutyl alcohol. Species C equilibrates with species
V because of the stability of a tertiary benzyl cation. This
species subsequently forms ruthenium-acyl species VI
via intramolecular attack of ruthenium at the tertiary
cationic center. TpRu(IV)-acyl species VI is prone to
decarbonylation reaction; we expect that species VI easily
loses one CO molecule to give ruthenium-cyclohexadiene
intermediate VII and further produces species VIII via
reductive elimination. Addition of H+ or the cationic Ru+
species (M ) H or Ru) to species VIII is expected to yield
benzyl cations IX and IX′. The chemoselectivity in the
described in Scheme 2 and Table 1. Treatment of this
epoxide with ruthenium catalyst in hot toluene (100 °C,
12 h) gave the same ketone 6h in 89% yield (entry 8),
and the electronic effect of the phenyl substituent of
epoxide 5h failed to alter the chemoselectivity in the way
that we observed for their o-(ethynyl)phenyl epoxide
analogues 1a -g.
To examine the nature of reaction mechanism, we
selected isobutyl alcohol as the reaction solvent. Epoxides
1a and 5c were chosen because they gave indene and
cyclohexa-2,4-dien-1-one derivatives, distinct from our
previous observations.8 As shown in Scheme 3, treatment
of epoxide 5c with ruthenium catalyst (10 mol %) in hot
isobutyl alcohol gave the ester 7a in 81% yield. In
contrast, the catalytic reaction of 1a still gave indene 2a
in 72% yield. These results reveal that ruthenium-
ketene intermediate (I) was generated for epoxide 5c but
not for compound 1a . Notably, for the deuterated sample
1a , its alkynyl deuterium was transferred to the C1 and
C3 protons of indene 2a with 42% and 53% deuterium
contents, respectively.13
(13) The deuterium contents of 1H-indene 2a were calculated by
the crude products given from deutertated 1a because purification of
indene 2a on a Et3N-pretreated silica column led to a loss of deuterium
content at the C1 and C3-indene proton. The C1H and C3-H deuterium
contents were estimated to be 30% and 46%, respectively.
(14) (a) Danheiser, R. L.; Brisbois, R. G.; Kowalczyk, J . J .; Miller,
R. T. J . Am. Chem. Soc. 1990, 112, 3093.(b) Merlic, C. A.; Xu, D. J .
Am. Chem. Soc. 1991, 113, 7418. (c) Masamune, S.; Fukumoto, K.
Tetrahedron Lett. 1965, 4647. (d) Mayr, H.; Huisgen, R. J . Chem. Soc.,
Chem. Commun. 1976, 57.
We propose two plausible mechanisms in Schemes 4
and 5, which account for the formation of 2,4-cyclohexa-
dien-1-one and indene products, respectively. The mech-
7702 J . Org. Chem., Vol. 69, No. 22, 2004

Ru-Catalyzed Cyclization of Alkyne-Epoxide Functionalities
SCHEME 5
SCHEME 6
cyclization of fluorophenyl epoxides 1e and 1g depends
on the relative stability of benzyl cations IX and IX′; a
π-donor group such as fluoro prefers cation IX′ through
π-conjugation to induce 1,2-phenyl migration to give
tertiary cation X and ultimately yields the observed
product 2e. Residual water and the acid catalyst TpRu-
PPh3(CH3CN)2PF6 likely generate a small amount of
protons to catalyzed the conversion of species G to indene
2e.
efficiently. The former is proposed to involve TpRu(IV)-
acyl intermediates while the latter likely involves ruthe-
nium-ketene species according to deuterium labeling
and isobutyl alcohol trapping experiments. 6,6-Disubsti-
tuted cyclohexa-2,4-dien-1-ones are a useful building
block in constructing complex molecular framework
through Diels-Alder or Michael reaction.15 This method
has been applied to synthesis of naturally occurring
compounds. Further application of our synthetic method
for the synthesis of complex bioactive molecule is under
current investigation.
Although we obtained no direct evidence for formation
of ruthenium-ketene intermediate I, the loss of CO
indicates the formation of ruthenium(IV)-acyl inter-
mediates.9b In our previous study, the TpRu(IV)-acyl
species was shown to undergo decarbonylation even in
the presence of alcohol or a CO atmosphere under
pressure.9b The symmetric character of species VIII
provides a rationale that both 5-fluoro- and 6-fluoro-
substituted epoxide species 1e and 1g should give the
same product, consistent with our observations (Table
1, entries 4 and 6). This species is also compatible with
the deuterium labeling experiment in Scheme 3 that the
alkynyl deuterium of 1a was transferred equally to the
at C1 and C3 protons of indene 2a .
It is interesting to note the different chemoselectivities
in the cyclization of 1-(o-ethynylphenyl)-2,2-dialkyl
epoxides and 1-(enynyl)-2,2-disubstituted epoxides 5a -h
which gave 1-alkylidene-2-indanones B and 2,4-cyclo-
hexadien-1-ones 6a -h , respectively. This discrimination
is probably due to a higher energy in the transformation
of ketene species I to the ruthenium-dieneone II, which
sacrifices the aromatic energy of species I (Scheme 6).
Exp er im en ta l Section
(1) Typ ica l P r oced u r e for th e Syn th esis of 1-(o-Eth -
yn ylp h en yl)-2-m eth yl-2-p h en yl Ep oxid es (1a ). The syn-
thetic protocol of epoxide 1a is depicted in Scheme 7. To a THF
solution (20 mL) of (R-methylbenzyl)triphenylphosphonium
n
bromide (3.32 g, 7.42 mmol) at 0 °C was added BuLi (2.5 mL,
2.5 M, 6.43 mmol), and the mixture was stirred at 0 °C for
1.0 h. To this solution was added o-(2′-trimethylsilylethynyl)-
benzaldehyde a -1 (1.00 g, 4.95 mmol), and the mixture was
stirred at 28 °C for 4 h. The solution was quenched with water
and concentrated in vacuo. The organic layer was extracted
with diethyl ether, dried over MgSO4, and chromatographed
(hexane, Rf ) 0.75) over a silica column to give the olefination
product a -2 as a colorless oil (1.22 g, 4.20 mmol, 85%). This
silyl compound was then dissolved in THF (10 mL) and added
with Bu4NF (1.0 M, THF, 4.65 mL, 4.60 mmol), and the
mixture was stirred at 26 °C for 8 h before addition of water
(10 mL). The solution was concentrated, extracted with diethyl
ether, and chromatographed on a silica column (hexane, Rf )
Con clu sion s. We report new patterns of the epoxide-
alkyne cyclizations with alternation of the substituent
and structural skeleton of the epoxide substrates. With
TpRuPPh3(CH3CN)2PF6 catalyst, 1-(o-ethynylphenyl)-2-
alkyl-2-aryl epoxides gave 1-aryl-2-alkyl-1H-indene de-
rivatives and carbon monoxide in hot toluene whereas
1-cis-enynyl-2,2-disubstituted epoxides produced the cor-
responding 6,6-disubstituted cyclohexa-2,4-dien-1-ones
(15) Liao, C.-C.; Peddinti, R. K. Acc. Chem. Res. 2002, 35, 856.
J . Org. Chem, Vol. 69, No. 22, 2004 7703

Ming-Yuan et al.
colorless oil. This olefination compound was converted to the
epoxide 3a in an overall 65% yield following the same Bu4-
NF-desilylation and m-CPBA oxidation procedures as de-
scribed in Scheme 7.
SCHEME 7
(4) Sp ectr a l Da ta for 1-(o-Eth yn ylp h en yl)-2-m eth yl-2-
p h en yl Ep oxid es (1a ): IR (Nujol, cm-1): 3330 (s), 3100 (s),
1
3065 (s), 2258 (m), 2119 (s), 1625 (w), 1250 (m). H NMR (400
MHz, CDCl3): (major-E-isomer) δ 7.53-7.44 (m, 3 H), 7.41 (dt,
J ) 8.0, 1.0 Hz, 3 H), 7.38 (dt, J ) 7.5, 1.0 Hz, 2 H), 7.25 (d,
J ) 7.5 Hz, 1 H), 4.20 (s, 1 H), 3.25 (s, 1 H), 1.41 (s, 3 H);
(selected peaks, minor-Z-isomer) δ 7.43 (dt, J ) 7.5, 1.0 Hz, 3
H), 7.18 (dt, J ) 7.5, 1.0 Hz, 2 H), 7.13 (dt, J ) 8.0, 1.0 Hz, 2
H), 4.45 (s, 1 H), 3.42 (s, 1 H), 1.85 (s, 3 H), the remaining
peaks are overlapped with those of the major isomer. 13C NMR
(100 MHz, CDCl3): (major E-isomer) δ 142.5, 139.5, 132.2,
128.6, 128.4, 127.8, 127.6, 126.7, 125.6, 121.5, 82.4, 81.8, 64.9,
64.0, 17.9. MS (75 eV, m/z): 234 (M+). HRMS: calcd for
SCHEME 8
C
17H14O 234.1045, found 234.1042.
(5) Sp ect r a l Da t a for 2-Met h yl-1-p h en yl-1H -in d en e
(2a ). IR (Nujol, cm-1): 3030 (s), 3008 (s), 3065 (s), 2258 (m),
1
1625 (m), 1685 (s). H NMR (500 MHz, CDCl3): δ 7.27-7.25
(m, 3 H), 7.20 (dt, J ) 7.5, 1.5 Hz, 2 H), 7.10 (d, J ) 8.0 Hz, 1
H), 7.04 (d, J ) 7.5 Hz, 1 H), 7.01(d, J ) 7.5 Hz, 2 H), 6.53 (s,
1 H), 4.28 (s, 1 H), 1.91 (s, 3 H). 13C NMR (125 MHz, CDCl3):
δ 149.9, 148.5, 144.7, 139.7, 128.6, 128.1, 127.1, 127.0, 126.6,
124.1, 123.7, 119.7, 59.3, 15.1. HRMS: calcd for
206.1096, found 206.1098.
C16H14
0.86) to give an enyne a -3 (0.83 g, 3.78 mmol, 90%) as colorless
oil. To a CH2Cl2 solution (15 mL) of this enyne (0.50 g, 2.29
mmol) was added m-chloroperbenzoic acid (0.52 g, 3.02 mmol),
and the mixture was stirred for 3 h at 28 °C. The resulting
solution was quenched with an aqueous NaHCO3 solution,
extracted with diethyl ether, and dried over anhydrous MgSO4.
The resulting solution filtered through a small basic Al2O3 bed,
concentrated, and eluted through a Et3N-pretreated silica
column (diethyl ether-hexane, 1:1) to afford epoxide 1a as a
colorless oil (0.47 g, 2.00 mmol, 87%).
(2) Exp er im en ta l P r oced u r e for Cycliza tion of (o-
Eth yn yl)p h en yl Ep oxid e (1a ) to In d en e 2a . A long tube
containing TpRuPPh3(CH3CN)2PF6 (32 mg, 0.042 mmol) was
dried in vacuo for 2 h before it was charged with epoxide 1a
(100 mg, 0.42 mmol) and toluene (0.56 mL). The mixture was
heated at 100 °C for 12 h before cooling to room temperature.
The solution was concentrated and eluted through a silica
column (hexane/diethyl ether ) 5/1) to afford indene 2a (68
mg, 3.32 mmol, 78%) as a yellow oil.
(3) Typ ica l p r oced u r e for th e Syn th esis of 1-cis-
En yn yl-2-(isop r op yl) Ep oxid e (3a ). As shown in Scheme 8,
to a diethylamine solution (30 mL) of Z-3-iodohept- 2-en-1-ol
(b-1) (2.00 g, 8.33 mmol) were added trimethylsilylacetylene,
PdCl2(PPh3)2 (110 mg, 0.16 mmol), and CuI (15 mg, 0.80
mmol); the mixture was stirred for 28 °C for 12 h. The solution
was concentrated and eluted through a silica column to afford
an enynyl alcohol b-2 as an oil (1.56 g, 7.42 mmol). To a
dichloromethane solution of this alcohol (1.00 g, 4.75 mmol)
were added oxalic chloride (0.50 mL, 5.9 mmol) and dimethyl
sulfoxide (0.80 mL, 11.2 mmol) at -78 °C, and the mixture
was stirred for 1 h before addition of Et3N (6.6 mL, 47.6 mmol).
The solution was continued to stir for 1 h before treatment
with H2O, and the organic layer was extracted with diethyl
ether and chromatographed over a silica column to give
aldehyde b-3 as an oil (0.86 g, 4.14 mmol, 87%). To a THF
solution (25 mL) of isobutyltriphenyl phosphonium bromide
(2.30 g, 5.76 mmol) was added BuLi (2.0 mL, 2.5 M, 5.0 mmol)
at 0 °C, and the mixture was stirred for 1 h before treatment
with aldehyde b-3. The mixture was stirred for 12 h before it
was added excess hexane (30 mL) to precipitate more triphen-
ylphosphine oxide. The solution was filtered, and the filtrate
was concentrated and eluted through a silica column to give
the olefination product b-4 (840 mg, 3.38 mmol, 88%) as a
(6) Sp ectr a l Da ta for 2-(2-Eth yn ylh ex-1-en yl)-3-isop r o-
p yloxir a n e (3a ). IR (Nujol, cm-1): 2256 (m), 1620 (w), 1225
1
(m). H NMR (400 MHz, CDCl3): (major trans-isomer) δ 5.36
(d, J ) 8.7 Hz, 1 H), 3.17 (s, 1 H), 2.77 (dd, J ) 8.6, 4.3 Hz, 1
H), 2.63 (dd, J ) 6.8, 1.2 Hz, 1 H), 2.13 (t, J ) 7.6 Hz, 2 H),
1.60-1.54 (m, 1 H), 1.52-1.44 (m, 2 H), 1.32-1.25 (m, 2 H),
0.96 (d, J ) 6.8 Hz, 3 H), 0.90 (d, J ) 6.8 Hz, 3 H), 0.86 (t,
J ) 6.5 Hz, 3 H); (minor cis-isomer) δ 5.54 (d, J ) 8.7 Hz, 1
H), 3.89 (dd, J ) 8.7, 4.3 Hz, 1 H), 3.63 (dd, J ) 8.7, 1.4 Hz,
1 H), 3.17 (s, 1 H), 2.16 (t, J ) 7.4 Hz, 2 H), 1.60-1.54 (m, 1
H), 1.52-1.44 (m, 2 H), 1.32-1.25 (m, 2 H), 1.09 (d, J ) 6.7
Hz, 3 H), 1.00 (d, J ) 6.7 Hz, 3 H), 0.86 (t, J ) 6.5 Hz, 3 H).
13C NMR (150 MHz, CDCl3): (major trans-isomer) δ 135.6,
128.8, 82.9, 81.2, 65.4, 55.5, 36.9, 36.6, 30.5, 30.0, 21.9, 20.2,
18.3; (minor cis-isomer) δ 132.6, 127.6, 82.5, 81.1, 64.8, 55.4,
36.9, 36.6, 30.0, 28.1, 21.8, 18.9, 13.8. MS (75 eV, m/z): 192
(M+). HRMS: calcd for C13H20O 192.1514, found 192.1520.
(7) Sp ectr a l Da ta for 5-Bu tyl-2-isop r op yl-p h en ol (4a ).
IR (Nujol, cm-1): 3610 (s), 1580 (m), 1625 (w), 1225 (m). 1H
NMR (400 MHz, CDCl3): δ 7.08 (d, J ) 8.0 Hz, 1 H), 6.73 (d,
J ) 8.0 Hz, 1 H), 6.57 (s, 1 H), 4.84 (bs, OH), 3.19-3.12 (m, 1
H), 2.51 (t, J ) 7.6 Hz, 2 H), 1.58-1.53 (m, 2 H), 1.37-1.32
(m, 2 H), 1.24 (s, 3 H), 1.23 (s, 3 H), 0.91 (t, J ) 7.4 Hz, 3 H).
13C NMR (150 MHz,CDCl3): δ 152.5, 141.6, 131.4, 126.1, 120.9,
115.2, 35.0, 33.4, 26.7, 22.7, 22.6, 22.3, 13.9. HRMS: for
C
13H20O calcd 192.1514, found 192.1518.
Ack n ow led gm en t. We thank the National Science
Council, Taiwan, for supporting this work.
Su p p or tin g In for m a tion Ava ila ble: Spectral data of
compounds 1a -g, 2b-f, 3b,c, 4b,c, 5a -h , 6a -h , and 7a in
repetitive experiments; 1H and 13C NMR spectra of key
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O048983W
7704 J . Org. Chem., Vol. 69, No. 22, 2004