Rhodium(II)-catalyzed carbocyclization reaction of α-diazo carbonyls with tethered unsaturation

Article abstract of DOI:10.1021/jo991938h

o-Alkynyl-substituted α-diazoketones undergo internal cyclization to produce indenone derivatives upon treatment with catalytic quantities of Rh(II)-carboxylates. A variety of structural influences were encountered by varying the nature of the substituent group attached to the diazo center. The cyclization reaction involves addition of a rhodium-stabilized carbenoid onto the acetylenic π-bond to generate a cycloalkenone carbenoid. The cyclized carbenoid was found to undergo both aromatic and aliphatic C-H insertion as well as cyclopropanation across a tethered π-bond. Subjection of diazo phenyl acetic acid 3-phenylprop-2-ynyl ester to Rh(II) catalysis furnished 8- phenyl-1,8-dihydro2-oxacyclopenta[a]indenone in high yield. The formation of this compound involves cyclization of the initially formed carbenoid onto the alkyne to produce a butenolide which then undergoes C-H insertion into the neighboring aromatic system. When a vinyl ether is added, the initially formed rhodium carbenoid intermediate can be intercepted by the electron-rich π-bond prior to cyclization. Different rhodium catalysts were shown to result in significant variation in the product ratios. The competition between bimolecular cyclopropanation, 1,2-hydrogen migration, and internal cyclization was probed using several enol ethers as well as diazoesters which possess different substituent groups on the ester backbone. The specific path followed was found to depend on electronic, steric, and conformational factors.

Full text of DOI:10.1021/jo991938h

3722
J . Org. Chem. 2000, 65, 3722-3732
Rh od iu m (II)-Ca ta lyzed Ca r bocycliza tion Rea ction of r-Dia zo
Ca r bon yls w ith Teth er ed Un sa tu r a tion
Albert Padwa* and M. David Weingarten
Department of Chemistry, Emory University, Atlanta, Georgia 30322
Received December 17, 1999
o-Alkynyl-substituted R-diazoketones undergo internal cyclization to produce indenone derivatives
upon treatment with catalytic quantities of Rh(II)-carboxylates. A variety of structural influences
were encountered by varying the nature of the substituent group attached to the diazo center. The
cyclization reaction involves addition of a rhodium-stabilized carbenoid onto the acetylenic π-bond
to generate a cycloalkenone carbenoid. The cyclized carbenoid was found to undergo both aromatic
and aliphatic C-H insertion as well as cyclopropanation across a tethered π-bond. Subjection of
diazo phenyl acetic acid 3-phenylprop-2-ynyl ester to Rh(II) catalysis furnished 8-phenyl-1,8-dihydro-
2-oxacyclopenta[a]indenone in high yield. The formation of this compound involves cyclization of
the initially formed carbenoid onto the alkyne to produce a butenolide which then undergoes C-H
insertion into the neighboring aromatic system. When a vinyl ether is added, the initially formed
rhodium carbenoid intermediate can be intercepted by the electron-rich π-bond prior to cyclization.
Different rhodium catalysts were shown to result in significant variation in the product ratios.
The competition between bimolecular cyclopropanation, 1,2-hydrogen migration, and internal
cyclization was probed using several enol ethers as well as diazoesters which possess different
substituent groups on the ester backbone. The specific path followed was found to depend on
electronic, steric, and conformational factors.
Over the past two decades, transition metal based
are the cyclotrimerization of alkynes to alkenes,25 the
coupling of alkynes with carbene ligands in the Do¨tz
reaction6,7 and the Pauson-Khand reaction for the
formation of cyclopentenones from an alkyne, an alkene,
and carbon monoxide.26 Another emerging area of syn-
thesis is the use of transition metal complexes derived
from R-diazo carbonyl compounds to facilitate the con-
struction of various ring systems.27 The role of R-diazo
carbonyl compounds in organic synthesis is well estab-
lished and in recent years much effort has been devoted
to the study of the effect of different transition-metal
catalysts on these substrates.28 In synthetic terms, most
of the work has centered on cyclopropanation29 and C-H
insertion reactions30 of the resulting metallo carbenoids.
Much less attention has been paid to the transition metal
methods have gained considerable importance in organic
synthesis since they allow simultaneous formation of
more than one bond in a single synthetic operation with
high selectivity.1-24 Construction of medium-sized rings
through metal intervention has been a particularly
fruitful area of investigation. Noteworthy among these
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10.1021/jo991938h CCC: $19.00 © 2000 American Chemical Society
Published on Web 05/17/2000

Rhodium(II)-Catalyzed Carbocyclization Reactions
J . Org. Chem., Vol. 65, No. 12, 2000 3723
Sch em e 1. Typ e I In ter n a l Cycliza tion Rou te
Sch em e 2. Typ e II In ter n a l Cycliza tion Rou te
Sch em e 3
mediated carbocyclization of diazo carbonyls that contain
two or more elements of unsaturation.
Several years ago, our group31 as well as Hoye’s32
described a route for producing cycloalkenone carbenoids
which involved the rhodium(II)-catalyzed decomposition
of R-diazoalkynyl-substituted ketones (Scheme 1). Such
diazo carbonyls are appealing as synthetic intermediates
in that they are readily accessible, reasonably robust, and
leave functionality in the cyclized product that is useful
for further synthetic transformation. The cyclization was
interpreted as proceeding by addition of the rhodium
carbenoid 2 onto the acetylenic π-bond to give vinyl
carbenoid 3. The vinyl carbenoid complex was subse-
quently trapped in an intramolecular fashion to give
bicyclohexanes such as 4 when an alkene was tethered
to the alkynyl group.31,32 The potential for many other
chemical pathways exists with these novel cycloalkenone
carbenoids. Two basic structural variations were studied
that differed from each other by altering the point of
attachment of the functional group to the alkyne center.
We refer to these two modes as the type I (Scheme 1)
and type II (Scheme 2) internal cyclization routes. In our
previous studies with type I molecules, we had observed
that the Rh(II)-catalyzed reaction can result in cyclopro-
panation, C-H insertion, onium ylide formation, and
cyclopropenation.31,33 Since chemical reactivity in in-
tramolecular cyclization processes is easily modified by
the choice of substituent group and geometry, we under-
took a related study of the chemistry of type II R-diazo
carbonyl compounds (Scheme 2). In this paper, we report
a full account of our effort with these systems.34
Resu lts a n d Discu ssion
R-Diazo carbonyl compounds are recognized precursors
to carbenoid species when exposed to many transition
metal complexes.27 Intramolecular C-H insertion of the
electrophilic rhodium-carbene complex generally leads
to the preferential formation of five-membered rings in
acyclic, conformationally mobile systems.30 The specific
reaction path followed depends on the nature of the
R-diazo carbonyl compound employed and is often gov-
erned by steric, conformational factors as well as elec-
tronic factors.27 Our initial efforts with type II molecules
focused on the rhodium(II)-catalyzed reaction of R-diazo
ketone 14. This substrate was prepared from ketone 9
as outlined in Scheme 3. The base-catalyzed transfer of
a diazo moiety to a methylene group adjacent to one or
(31) Padwa, A.; Krumpe, K. E.; Zhi, L. Tetrahedron Lett. 1989, 2623.
Padwa, A.; Chiacchio, U.; Gareau, Y.; Kassir, J . M.; Krumpe, K. E.;
Schoffstall, A. M. J . Org. Chem. 1990, 55, 414. Padwa, A.; Krumpe, K.
E.; Gareau, Y.; Chiacchio, U. J . Org. Chem. 1991, 56, 2523. Padwa,
A.; Krumpe, K. E.; Kassir, J . M. J . Org. Chem. 1992, 57, 4940. Padwa,
A.; Austin, D. J .; Xu, S. L. Tetrahedron Lett. 1991, 32, 4103. Padwa,
A.; Gareau, Y.; Xu, S. L. Tetrahedron Lett. 1991, 32, 983.
(32) Hoye, T. R.; Dinsmore, C. J .; J ohnson, D. S.; Korkowski, P. F.
J . Org. Chem. 1990, 55, 4518. Hoye, T. R.; Dinsmore, C. J . J . Am.
Chem. Soc. 1991, 113, 4343. Hoye, T. R.; Dinsmore, C. J . Tetrahedron
Lett. 1991, 32, 3755. Hoye, T. R.; Dinsmore, C. J . Tetrahedron Lett.
1992, 33, 169.
(33) Padwa, A.; Kassir, J . M.; Xu, S. L. J . Org. Chem. 1997, 62, 1642.
(34) Mueller, P. H.; Kassir, J . M.; Semones, M. A.; Weingarten, M.
D.; Padwa, A. Tetrahedron Lett. 1993, 34, 4285.

3724 J . Org. Chem., Vol. 65, No. 12, 2000
Padwa and Weingarten
Sch em e 4
more electron-withdrawing groups represents a well-
established protocol for R-diazo ketone synthesis.35-38 The
most commonly used reagents for diazo transfer have
been tosyl35 or mesyl azide,36 though in recent years a
number of other azido compounds and methods have been
proposed.37-39 Recently, McGuiness and Shechter re-
ported on the use of azidotris(diethylamino)phosphonium
bromide (11) as an efficient diazo transfer reagent.39 This
reagent only requires a catalytic amount of base, and the
product diazo compounds have been reported to be easily
separated from the coproduct, hexaethylphosphorimidic
hydrobromide. In our hands, however, the reaction of
ketone 9 with phosphonium bromide 11 afforded only
triazole 13 in 76% yield. The formation of the triazole
ring can be attributed to attack of the initially formed
enolate onto the terminal nitrogen of 11 followed by an
intramolecular Staudinger reaction40 and a subsequent
1,3-hydrogen shift.
Sch em e 5
With simple ketones, the diazo transfer reaction is
often facilitated through a prior formylation step and
subsequent elimination of the activating formyl group
during the course of the actual diazo transfer.41,42 Con-
sequently, we decided to use this protocol to overcome
the diazo transfer difficulty encountered with the Shechter
reagent. Treatment of the keto enolate of 9 (or 10) with
ethyl formate produced a dicarbonyl compound that, upon
reaction with mesyl azide, afforded the desired diazo
ketone 14 in good yield.41 When 14 was allowed to react
with rhodium(II) acetate in benzene, initial cyclization
occurred to produce a rhodium carbenoid that underwent
subsequent insertion onto the neighboring aromatic ring
to ultimately form compound 16 in 75% yield. The
structure of 16 was unequivocally established by an X-ray
crystal structure analysis. When the reaction was carried
out under an atmosphere of argon, it was possible to
isolate 15 (60%) in addition to 16. Compound 15 was
readily oxidized to 16 when allowed to stand open to the
air. The Rh(II)-catalyzed reaction of the homologous
R-diazo ketone 17 was also investigated and was found
to give 18 (70%) as the only isolable product. The
formation of 18 involves insertion into the benzylic C-H
bond, and this is consistent with other Rh(II)-mediated
insertions, which generally exhibit a large preference for
the generation of five-membered rings.43
involves addition of the initially formed rhodium-
stabilized carbenoid onto the acetylenic π-bond to give
vinyl carbenoid 20 which readily undergoes C-H inser-
tion into the aromatic ring. The literature indicates that
these aromatic C-H insertions are facile processes which
can best be counted for by invoking electrophilic addition
of the metal-bound carbene to the adjacent π-bond
followed by a 1,2-hydride migration to complete the
overall substitution process.27-30
As an extension of this methodology, the carbenoid
cyclization reaction of R-diazo ketones 22 and 23 was next
investigated. In both cases it was possible to isolate the
bicycloalkanes derived from intramolecular cyclopropa-
nation44 (i.e., 25 (67%) and 26 (81%)) (Scheme 5). In our
earlier studies, we had found that o-alkynyl-substituted
R-diazoacetophenone derivatives produce vinyl car-
benoids that could be trapped by electron-rich π-bonds
(i.e., ethyl vinyl ether) to give indenyl-substituted cyclo-
propanes in 90% yield.45 With this in mind, we attempted
to bimolecularly trap the cyclized carbenoid intermediate
24, by carrying out the reaction in the presence of a large
excess of ethyl vinyl ether. However, in no case (22, 23)
were we able to detect any signs of the bimolecular
adduct (e.g., 27). This observation indicates that, with
these systems, bimolecular trapping of the cyclized
rhodium carbenoid is significantly slower than either
intramolecular cyclopropanation or insertion.
The success achieved by the Rh(II)-catalyzed transfor-
mation of diazo ketones 14 and 17 was extended to the
simpler diazo phenylethanone derivative 19. Treatment
of this diazo ketone with a catalytic amount of rhodium-
(II) acetate afforded indenone 21 in 93% yield (Scheme
4). The simplest mechanism to rationalize this result
(35) Regitz, M. Angew. Chem., Int. Ed. Engl. 1967, 6, 733.
(36) Taber, D. F.; Schuchardt, J . L. J . Am. Chem. Soc. 1985, 107,
5289. Taber, D. F.; Ruckle, R. E.; Hennessy, M. J . J . Org. Chem. 1986,
51, 4077.
(37) Baum, J . S.; Shook, D. A.; Davies, H. M. L.; Smith, H. D. Synth.
Commun. 1987, 17, 1709.
(38) Koskinen, A. M. P.; Munoz, L. J . Chem. Soc., Chem. Commun.
1990, 652.
(39) McGuiness, M.; Shechter, H. Tetrahedron Lett. 1990, 4987.
(40) Review: Gololobov, Y. G.; Zhmurova, I. N.; Kasukhim, L. F.
Tetrahedron 1981, 37, 437.
(41) Taber, D. F.; Gleave, D. M.; Herr, R. J .; Moody, K.; Hennessy,
M. J . J . Org. Chem. 1995, 60, 2283. Danheiser, R. L.; Miller, R. F.;
Brisbois, R., G.; Park, S. Z. J . Org. Chem. 1990, 55, 1959. Metcalf, B.
W.; J und, K.; Burkhart, J . P., Tetrahedron Lett. 1980, 21, 15.
(42) Benati, L.; Nanni, D.; Spagnolo, P. J . Org. Chem. 1999, 64, 5132
and referenced cited therein.
(43) For leading references, see: Doyle, M. P.; Westrum, L. J .;
Wolthuis, W. N. E.; See, M. M.; Boone, W. P.; Bagheri, V.; Pearson,
M. M. J . Am. Chem. Soc. 1993, 115, 958.
We also attempted to trap the cyclized indenone
carbenoid with an acetylenic π-bond. The insertion of
alkynes into various transition metal carbon bonds is a
well-documented reaction and has been observed in
nearly all of the triads of transition metals.46 Our initial
efforts focused on the rhodium(II) carbenoid catalyzed
(44) For leading references, see: Harvey, D. F.; Lund, K. P.; Neil,
D. A. J . Am. Chem. Soc. 1992, 114, 8424.
(45) Padwa, A.; Austin, D. J .; Chiacchio, U.; Kassir, J . M.; Rescifina,
A.; Xu, S. L. Tetrahedron Lett. 1991, 32, 5923.
(46) For leading references, see: O’Connor, J . M.; J i, H.; Iranpour,
M.; Rheingold, A. L. J . Am. Chem. Soc. 1993, 115, 1586.

Rhodium(II)-Catalyzed Carbocyclization Reactions
J . Org. Chem., Vol. 65, No. 12, 2000 3725
Sch em e 6
Sch em e 7
reaction of R-diazo ketone 28. We found that treatment
of 28 with Rh(II) acetate did not afford the product of
internal attack on the acetylenic π-bond. Instead, only
indenone 30 was obtained in 83% yield (Scheme 6).
Insertion of the rhodium carbenoid into the propargylic
C-H bond is clearly preferred over attack at the acetyl-
enic π-bond. This may be related to conformational
factors that place the propargylic hydrogens within the
reactive environment of the carbenoid center for an easy
C-H insertion reaction.
Sch em e 8
Butenolides are widely distributed in nature, and some
of them exhibit interesting biological properties and find
applications as insecticides, herbicides, and seed and
plant growth regulators.47 They have also been reported
to be useful intermediates in organic synthesis.48 Because
of these reasons, they represent a synthetic target of
great interest, and numerous approaches to their prepa-
ration have been reported, with many of them relying
on palladium chemistry.49 Our interest in the synthesis
of five-membered oxygen heterocycles50 and the earlier
studies we carried out using the Rh(II)-catalyzed reaction
of 2-alkynyl 2-diazo-3-oxobutanoates51 prompted us to
examine the possible use of similar chemistry for devel-
oping a new and versatile route to functionalized buteno-
lides. To ascertain whether the intramolecular alkyne
metathesis reaction of R-diazo carbonyls could be used
for a butenolide synthesis, we decided to study the Rh(II)-
catalyzed reaction of R-diazo esters of type 31. These
compounds differ from the earlier model systems (i.e., 19)
in that the aryl ketone backbone is now replaced by a
propargylic ester tether. Trapping the initially formed
rhodium carbenoid with the tethered alkyne group would
represent a unique method for the formation of the
butenolide ring system. Gratifyingly, we found that when
diazo ester 31 (R ) Ph) was exposed to a catalytic
quantity of rhodium(II) acetate in CH2Cl2 at 25 °C,
butenolide 34 was obtained in 92% yield. Its formation
can be rationalized according to the reaction steps
outlined in Scheme 7.
the initially formed carbenoid intermediate 32 prior to
the internal cyclization reaction. Apparently, the rate of
bimolecular cycloaddition of 32 with the external alkene
is faster than intramolecular cyclization to give 33. The
fact that only cyclopropane 37 was obtained is undoubt-
edly related to conformational factors specific to the ester
functionality. The rhodium carbenoid intermediate de-
rived from diazoester 31 exists primarily in the s-trans
conformation about the ester bond (i.e., 32-Z). It is well-
known that esters are more stable in this conformation
for several reasons, one of which is to minimize steric
interactions.52 It has also been recognized for some time
that the E-isomers of esters are destabilized by dipole-
dipole interactions, and this effect also accounts for a
large part of the preference of esters for the Z-conforma-
tion.53 In the Z or s-trans conformation, intramolecular
cyclization of the rhodium carbenoid onto the alkyne
π-bond cannot occur. To cyclize, rotation about the ester
bond must first take place to furnish the E or s-cis
conformer, which can then achieve the necessary geom-
etry for internal cyclization and ultimately, butenolide
formation (Scheme 9).
We also carried out experiments designed to trap the
cyclized carbenoid intermediate 33 by adding an excess
of ethyl vinyl ether to the reaction mixture. On the basis
of our earlier results with type I molecules,31,45 we
expected that the reaction would produce the bimolecular
adduct derived from 33. Interestingly, the reaction of 31
with Rh(II) acetate did not furnish the expected bimo-
lecular adduct 36. Instead, cyclopropyl ester 37 was
obtained as the exclusive product in 93% yield (Scheme
8). Its formation is the result of preferential trapping of
We attempted to determine the conformational energy
differences of carbenoids 32-Z and 32-E by molecular
mechanics calculations (Gajewski’s MMX program54 with
Allinger parameters) using phenylacetic acid 3-phenyl-
prop-2-ynyl as a model system. However, this approach
(47) Pattenden, G. Fortschr. Chem. Org. Naturst. 1978, 35, 133.
(48) Rao, Y. S. Chem. Rev. 1976, 76, 6, 625. Nagao, Y.; Dai, W. M.;
Ochiai, M.; Shiro, M. J . Org. Chem. 1989, 54, 5211.
(49) For some leading references, see: Ali, B. E.; Alper, H. J . Org.
Chem. 1991, 56, 5357.
(50) Padwa, A.; Brodney, M. A.; Satake, K.; Straub, C. S. J . Org.
Chem. 1999, 64, 4617.
(52) Dale, J . Stereochemistry and Conformational Analysis; Verlag
Chemie: New York, 1978; pp 83-85. Testa, B. Principles of Organic
Stereochemistry; Marcel Dekker: New York, 1979; p 105. Eliel, E. L.;
Wilen, S. H. Stereochemistry of Organic Compounds; Wiley-Inter-
science: New York, 1994; pp 618-621.
(51) Kinder, F. R.; Padwa, A. Tetrahedron Lett. 1990, 31, 6835.
Padwa, A.; Kinder, F. R. J . Org. Chem. 1993, 58, 21.
(53) Wiberg, K. B.; Laidig, K. E. J . Am. Chem. Soc. 1987, 109, 5935.
(54) PC Model by Serena Software, Bloomington, IN.

3726 J . Org. Chem., Vol. 65, No. 12, 2000
Padwa and Weingarten
Ta ble 1. Effect of Dih ed r a l An gle on th e HOMO of
Meth yl Vin yl Eth er
Sch em e 9
θ (deg)
HOMO (eV)
θ (deg)
HOMO (eV)
0
15
30
45
60
75
90
-0.339 11
-0.339 36
-0.340 99
-0.343 82
-0.347 93
-0.353 16
-0.356 79
105
120
135
150
165
180
-0.355 11
-0.349 06
-0.342 14
-0.336 15
-0.332 41
-0.331 17
Sch em e 10
F igu r e 1. Dihedral angle vs HOMO (eV) for methyl vinyl
ether.
was terminated after calculations on the propargyl ester
indicated no real preference of the two conformers. For
these reasons, the structures for the s-trans and s-cis
conformers of the propargyl ester were determined using
ab initio theory. Both conformers were optimized at the
HF/6-31G* level of theory using Gaussian 88. The dif-
ference in energy turned out to be 5-8 kcal in favor of
the s-trans conformer, similar but somewhat smaller
than the values determined for methyl acrylate55 for
which ab initio calculations predicted a difference of 9.5
kcal/mol.56
F igu r e 2. . HOMO and dihedral angle θ.
The ease with which R-diazo ester 31 undergoes
cyclization to give butenolide 34 as well as cyclopropa-
nation to furnish 37 suggested that this system might
serve as a tool for determining the facility with which
various enol ethers can undergo reaction with rhodium
carbenoids. We examined the bimolecular reaction of 31
with both dihydrofuran and dihydropyran (5 mol excess)
as the added enol ether and discovered that, in addition
to the expected cyclopropyl esters 38 and 39, varying
amounts of butenolide 34 were also formed (Scheme 10).
However, when a 5 mol excess of ethyl vinyl ether was
used, only the cyclopropyl adduct 37 was obtained (93%),
with no signs of butenolide 34. The implication of these
results is that the rate of cyclopropanation of carbenoid
32 decreases upon changing the trapping agent from
ethyl vinyl ether (fastest) to dihydrofuran and then to
dihydropyran (slowest).
To decipher the factors which influence the rate of
cyclopropanation of this R-diazo ester, we calculated 13
points on the conformational energy surface of ethyl vinyl
ether at the 6-31G*/3-21G level of theory.57 The results
of these calculations are summarized in Table 1. The
value of the CdC-OC dihedral angle θ was held fixed
at the indicated value, and the structure was minimized.
No other constraints were employed. Variation of the Cd
C-OC dihedral angle reveals HOMO maxima near 0 and
180° (Figure 1). The overall preference for planarity is
expected since such arrangements allow the ethoxy
oxygen atom to maximize the effects of conjugation with
the adjacent double bond. It is also worthy to note that
while the HOMO is higher in energy when θ ) 180° as
compared to θ ) 0°, the latter conformation is lower in
energy by approximately 1.4 kcal/mol. This is probably
related to the added stabilization due to hyperconjugation
with the CdC π-bond. Although the HOMO does decrease
in value when the ethoxy group is not coplanar with
respect to the double bond, Figure 1 shows that the effect
is negligible when θ is less the 45°. The calculated “flap”
angle and HOMO energy level for dihydrofuran and
dihydropyran are shown in Figure 2. We found that the
HOMOs of these cyclic enol ethers are actually higher
in energy than ethyl vinyl ether and consequently
interaction with the LUMO of the metallocarbenoid
would be expected to be more pronounced. This should
result in a rate order of dihydrofuran > dihydropyran >
ethyl vinyl ether. However, this predicted reactivity
pattern, which is based on electronic factors, is not
consistent with the actual experimental data observed.
To account for these experimental findings, we assume
that steric factors associated with the cyclopropanation
play an important role in this reaction. As can be seen
from Figure 2, ethyl vinyl ether is the least congested
(55) Blom, C. E.; Gunthard, H. H. Chem. Phys. Lett. 1981, 84, 267.
(56) Wiberg, K. B.; Laidig, K. E. J . Am. Chem. Soc. 1988, 110, 1872.
(57) Force field and quantum calculations were carried out using
the Spartan package, Wavefunction, Inc., 18401 Von Karman Avenue,
Suite 370, Irvine, CA 92715.

Rhodium(II)-Catalyzed Carbocyclization Reactions
J . Org. Chem., Vol. 65, No. 12, 2000 3727
Sch em e 11
Sch em e 12
alkene and thus, the reactivity order encountered is
perfectly consistent with this steric hindrance rationale.
A number of studies in the literature have shown that,
despite their high reactivity, rhodium carbenoid inter-
mediates are often highly chemoselective when two or
more reaction pathways are open to them.58 During the
course of our studies with diazoester 31, we observed that
changing the ligand on the rhodium carboxylate signifi-
cantly altered the product distribution obtained from the
reaction of diazoester 31 with a 1.5 mol excess of the
cyclic enol ether. Rhodium(II) perfluorobutyrate [Rh2-
(pfb)4] was the most efficient catalyst for producing
cyclopropyl esters 38 and 39 (100%), while rhodium(II)
acetate was best for forming butenolide 34 (100%).
Catalysis by rhodium(II) perfluorobutyramide [Rh2(pfm)4]
afforded a 1:1 mixture of both products. The fact that Rh2-
(pfb)4 led to the exclusive formation of the cyclopropyl
esters 38 and 39 is not surprising considering that the
ligands on rhodium are known to exert substantial
control over the reactivity of the carbenoid.59 A strongly
electron-withdrawing ligand will result in a more reactive
carbenoid and lead to cyclopropanation with an electron-
rich π-bond. By changing the ligand from perfluoro-
butyrate to acetate, the reactivity of the carbenoid is
attenuated, thereby allowing the intramolecular cycliza-
tion and insertion pathway to proceed.
As part of our work in this area, we also decided to
probe the competition between the internal cyclization
reaction which occurs with a neighboring alkyne versus
a 1,2-hydrogen shift that can also take place from the
rhodium carbenoid intermediate. These competitive pro-
cesses were evaluated by preparing R-diazoester 40 and
subjecting it to thermolysis in the presence of a rhodium-
(II) catalyst. We found that the reaction of 40 with any
of the aforementioned rhodium(II) catalysts produced the
unsaturated ester 41 as the exclusive product in 92%
yield. There was no indication of any of the rearranged
butenolide 42 in the crude reaction mixture. Clearly, the
1,2-hydrogen migration route proceeds at a much faster
rate than internal cyclization reaction (Scheme 11). With
this diazoester, conformational effects play an important
role in these competitive reactions. The preferential
formation of the thermodynamically less stable Z-isomer
41 is consistent with literature observations and can be
attributed to steric constraints in the transition state for
the 1,2-hydrogen shift.60
Sch em e 13
To determine whether type II diazo carbonyls would
exhibit a similar dependence, we studied the Rh(II)-
catalyzed behavior of diazoester 43. We expected that this
system would also undergo a preferential 1,2-hydrogen
shift as was encountered with diazoester 40. Most
surprisingly, the reaction of 43 with Rh2OAc4 afforded
4-phenyl-3H-isobenzofuranone (45) as the major product
(76%) together with lesser quantities of the Z-pentenynoic
acid ester 44 (16%) (Scheme 12). The fact that 43 gave
mostly 45 is particularly noteworthy and bears some
discussion. This result stands in marked contrast with
the exclusive hydrogen shift that occurred with the
closely related diazoester 40. The facility of hydrogen
migration with 40 is probably a consequence of the fact
that the resulting product (i.e., 41) possesses a double
bond that is in conjugation with both the aromatic ring
and the ester carbonyl group. This arrangement is
thermodynamically favorable and may well facilitate the
rate of the 1,2-hydrogen shift. With diazoester 43,
however, interaction of the alkenyl π-bond with the
alkyne would be of lesser importance from a thermody-
namic stability viewpoint thereby allowing the internal
cyclization reaction of rhodium carbenoid 46 to compete.
What is particularly interesting with this system is that
only the product derived from 6-endo ring closure (i.e.,
47 f 48 f 45) of the cycloalkenone carbenoid is observed
(Scheme 13). No signs of any product derived from the
5-exo-dig cyclization (i.e., 49) could be found in the crude
reaction mixture. In general, the 5-exo vs 6-endo selectiv-
ity in these internal cyclization reactions is derived from
a combination of steric interactions between the R group
on the alkyne and the catalyst (i.e., 50) and the ability
of the substituent group to stabilize the resulting car-
benoid intermediate.31,32 We suggest that, with diazoester
43, the preferred 6-endo vs 5-exo selectivity is due to the
smaller steric interactions that exist between the hydro-
gen substituent on the terminal alkyne and the ligand
groups on the catalyst (i.e., 50; R ) H) (Scheme 14).
In conclusion, the rhodium(II)-catalyzed reaction of
type II R-diazo carbonyl compounds provides a convenient
route to a variety of indenones and substituted buteno-
lides. The tandem cyclization-rearrangement sequence
proceeds with high chemoselectivity that should prove
In our earlier studies with type I diazo ketones (i.e.,
1), a variety of structural influences on the course of the
reaction were encountered by varying the nature of the
substituent group attached to the alkyne carbon atom.31
(58) Miah, S.; Slawin, M. Z.; Moody, C. J .; Sheehan, S. M.; Marino,
J . P., J r.; Semones, M. A.; Padwa, A. Tetrahedron 1996, 52, 1996.
(59) Padwa, A.; Austin, D. J .; Price, A. T.; Semones, M. A.; Doyle,
M. P.; Protopopova, M. N.; Winchester, W. R.; Tran, A. J . Am. Chem.
Soc. 1993, 115, 8669.
(60) Doyle, M. P.; High, K. G.; Oon, S. M.; Osborn, A. K. Tetrahedron
Lett. 1989, 30, 3049. Shankar, B. K. R.; Shechter, H. Tetrahedron Lett.
1982, 23, 2277.

3728 J . Org. Chem., Vol. 65, No. 12, 2000
Padwa and Weingarten
extracts were concentrated under reduced pressure. Silica gel
chromatography of the residue afforded 1.8 g (90%) of 9 as a
crystalline solid: mp 54-55 °C; 1H NMR (300 MHz, CDCl3) δ
3.15 (t, 2H, J ) 7.7 Hz), 3.58 (t, 2H, J ) 7.7 Hz), 7.23-7.48
(m, 12H), 7.67 (d, 1H, J ) 7.6 Hz), 7.76 (d, 1H, J ) 7.5 Hz);
13C NMR (75 MHz, CDCl3) δ 30.4, 44.2, 88.6, 95.0, 121.5, 122.8,
126.2, 128.4, 128.5, 128.8, 131.2, 131.6, 133.9, 140.7, 141.3,
201.8. Anal. Calcd for C23H18O: C, 88.99; H, 5.85. Found: C,
88.85; H, 5.82.
Sch em e 14
4-Ben zyl-5-(2-p h en yleth yn ylp h en yl)-1,2,3-tr ia zole (13).
A solution containing 0.6 g (0.5 mmol) of ketone 9 in 50 mL of
dry THF was cooled to -78 °C. To this solution was added 1.1
mL of a 0.5 M (0.6 mmol) solution of potassium hexamethyl
disilazide. The yellow solution of the anion was allowed to stir
at -78 °C for 1 h. A solution containing 0.2 mg (0.6 mmol) of
azidotris(diethylamino)phosphonium bromide39 in 15 mL of
THF was added dropwise. The solution was allowed to stir at
-78 °C for 1 h and was then left to warm to room temperature
over an additional 60 min before being poured into 30 mL of
10% NaOH. The phases were separated, and the aqueous
portion was extracted with ether. The combined organic
extracts were dried over Na2SO4, and the solvent was removed
under reduced pressure. The crude product was purified by
silica gel flash chromatography to give 0.1 g (62%) of 13 as a
to be useful for further synthetic transformations. We are
continuing to explore the scope and mechanistic details
of these cyclizations and will report additional findings
at a later date.
Exp er im en ta l Section
Melting points are uncorrected. Mass spectra were deter-
mined at an ionizing voltage of 70 eV. Unless otherwise noted,
all reactions were performed in flame-dried glassware under
an atmosphere of dry argon. Solutions were evaporated under
reduced pressure with a rotary evaporator, and the residue
was chromatographed on a silica gel column using an ethyl
acetate/hexane mixture as the eluent unless specified other-
wise. All solids were recrystallized from ethyl acetate/hexane
for analytical data.
clear oil: IR (neat) 2214, 1601, 1495, 1454, 1002, 757 cm-1
;
1H NMR (300 MHz, CDCl3) δ 4.18 (s, 2H), 7.09-7.18 (m, 5H),
7.26-7.40 (m, 8H), 7.64 (d, 1H, J ) 7.0 Hz); 13C NMR δ 31.5,
88.2, 93.1, 122.8, 123.1, 126.4, 128.3, 128.4, 128.5, 130.2, 131.5,
132.6, 138.5. Anal. Calcd for C23H17N3: C, 82.35; H, 5.11; N,
12.53. Found: C, 82.28; H, 5.07; N, 12.39.
3-P h en yl-1-(2-p h en yleth yn ylp h en yl)-1-p r op a n on e (9).
To a mixture containing 9.4 g (51 mmol) of 2-bromobenzalde-
hyde and 6.7 g (66 mmol) of phenyl acetylene in 100 mL of
triethylamine was added 0.02 g of bis-triphenylphosphine
palladium(II) chloride, 0.18 g of cuprous iodide, and 0.01 g of
triphenylphosphine. The reaction mixture was heated at reflux
under nitrogen for 48 h and filtered to remove the triethy-
lammonium iodide, and the filtrate was concentrated under
reduced pressure. The residue was taken up in 100 mL of ether
and washed with 5% HCl followed by water. Vacuum distil-
lation of the dark brown oil afforded 8.4 g (80%) of 2-phenyl-
ethynylbenzaldehyde61 as a light yellow oil: bp 123-125 °C
5-P h en yl-5,10-d ih yd r oben zo[b]flu or en -11-on e (15). To
a 100 mL flask of 0.3 g of NaH (60% in mineral oil) in 5 mL of
ether containing two drops of absolute ethanol was added a
solution of 0.7 g (2.4 mmol) of ketone 9, 1 mL of ethyl formate,
and 20 mL of ether. The mixture was stirred at 0 °C for 3 h
and at 25 °C for an additional 12 h. A solution of 0.7 g (5.9
mmol) of mesyl azide in 15 mL of ether was added, and the
mixture was stirred at room temperature for an additional 2
h. The reaction was quenched with 2 mL of water, and the
ether layer was washed with 10% NaOH and extracted with
ether. The combined ether extracts were dried over Na2SO4
and concentrated under reduced pressure. The crude residue
was purified by flash silica gel chromatography to give 0.24 g
(30%) of 2-diazo-3-phenyl-1-(2-phenylethynylphenyl)propanone
(0.15 mm); IR (neat) 2213, 1695, 1266, 1192 cm-1 1H NMR
;
(300 MHz, CDCl3) δ 7.35-7.47 (m, 4H), 7.53-7.67 (m, 4H),
7.96 (m, 1H), 10.68 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 85.0,
96.4, 122.3, 126.8, 127.2, 128.6, 129.1, 131.6, 132.5, 133.2,
133.7, 135.8, 191.5.
(14): IR (neat) 2080, 1613, 1450, 1150 cm-1 1H NMR (300
;
MHz, CDCl3) δ 3.91 (s, 2H), 7.17-7.43 (m, 10H), 7.56 (m, 4H).
This diazo ketone was immediately used in the next step
without further purification.
To a 100 mL flask containing 0.7 g (27 mmol) of magnesium
turnings was added a solution containing 3.6 g (18 mmol) of
2-bromo-1-phenylethane in 50 mL of ether at such a rate so
as to produce a mild exotherm. After the addition was
complete, the reaction was allowed to stir for 1 h and was then
added to a solution containing 2.5 g (12 mmol) of the above
aldehyde in 50 mL ether at room temperature. The mixture
was poured into 50 mL of a saturated NH4Cl solution, the
phases were separated, and the aqueous layer was extracted
with ether. Removal of the solvent under reduced pressure
followed by flash silica gel chromatography gave 2.8 g (74%)
of 3-phenyl-1-(2-phenylethynylphenyl)-1-propanol as a white
To a 50 mL flask containing 0.1 g (0.3 mmol) of diazo ketone
14 in 25 mL of benzene was added 2 mg of rhodium(II) acetate.
The solution was stirred for 12 h at 25 °C. Removal of the
solvent under reduced pressure followed by silica gel chro-
matography of the residue gave 0.07 g (80%) of 15: IR (neat)
3060, 1710, 1490, 780 cm-1; 1H NMR (300 MHz, CDCl3) δ 3.71
(dd, 1H, J ) 5.1, 4.8 Hz), 3.82 (dd, 1H, J ) 5.1, 4.8 Hz), 5.07
(t, 1H, J ) 5.1 Hz), 6.80-7.45 (m, 13H); 13C NMR (75 MHz,
CDCl3) δ 25.2, 45.6, 120.3, 122.1, 123.8, 126.7, 126.9, 127.3,
128.1, 128.5, 129.1, 129.5, 129.8, 131.1, 131.7, 131.9, 133.2,
136.7, 142.5, 143.9, 196.8. On standing in air, this material
was oxidized to a product which was identified as 5-phenyl-
benzo[b]fluoren-11-one (16) on the basis of an X-ray structure
analysis:62 1H NMR (300 MHz, CDCl3) δ 6.32 (m, 1H), 7.22
(m, 3H), 7.45 (m, 4H), 7.60 (m, 3H), 7.73 (m, 1H), 7.93 (m,
1H), 8.24 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 123.8, 124.2,
125.2, 126.8, 127.1, 128.0, 128.3, 128.3, 128.4, 128.9, 129.3,
129.7, 130.7, 131.5, 132.5, 133.4, 134.1, 135.3, 136.5, 136.9,
137.4, 154.1, 193.2. Anal. Calcd for C23H14O: C, 90.17; H, 4.61.
Found: C, 90.03; H, 4.55.
solid: mp 87-88 °C; IR (neat) 3370, 3050, 1430, 1210 cm-1
;
1H NMR (300 MHz, CDCl3) δ 2.11-2.32 (m, 2H), 2.33 (brs,
1H), 2.80-2.99 (m, 2H), 5.35 (dd,1H, J ) 7.7 and 4.7 Hz),
7.21-7.25 (m, 1H), 7.27-7.33 (m, 3H), 7.39-7.42 (m, 4H),
7.49-7.51 (m, 2H), 7.58 (d, 1H, J ) 7.7 Hz), 7.62 (d, 1H, J )
7.7 Hz); 13C NMR (75 MHz, CDCl3) δ 32.4, 39.7, 71.7, 87.2,
94.4, 120.6, 123.1, 125.5, 125.8, 127.2, 128.4, 128.5, 128.5,
128.6, 128.9, 131.6, 132.3, 141.9, 146.6.
A solution containing 2.0 g (6 mmol) of the above alcohol in
30 mL of CH2Cl2 was added to a suspension of 3.0 g (14 mmol)
of PCC and 3.5 g of Celite in 75 mL of CH2Cl2. After the
solution was stirred at 25 °C for 4 h, 100 mL of ether was
added, and the mixture was filtered through a pad of Florisil.
The filter cake was washed with ether, and the combined
4-P h en yl-1-(2-p h en yleth yn ylp h en yl)-1-bu ta n on e (10).
To a 100 mL flask containing 0.8 g (33 mmol) of magnesium
(62) The authors have deposited coordinates for structure 16 with
the Cambridge Crystallographic Data Centre. The coordinates can be
obtained, on request, from the Director, Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge, CB2 1EZ, U.K.
(61) Sakamoto, T.; Kondo, Y.; Miura, N.; Hayashi, K.; Yamanaka,
H. Heterocycles 1986, 24, 2311.

Rhodium(II)-Catalyzed Carbocyclization Reactions
J . Org. Chem., Vol. 65, No. 12, 2000 3729
metal was added a solution of 3.7 g (19 mmol) of 3-bromo-1-
phenylpropane in 50 mL of ether at such a rate so as to produce
a mild exotherm. After the addition was complete, the reaction
was allowed to stir for 1 h at room temperature and was then
added to a solution of 2.5 g (12 mmol) of 2-phenylethynylbenz-
aldehyde in 50 mL of ether at 25 °C. The solution was poured
into an ice-cold saturated NH4Cl solution, the ether layer was
separated, and the aqueous layer was extracted with ether.
The combined ether extracts were dried over Na2SO4 and
concentrated under reduced pressure. Flash silica gel chro-
matography afforded 3.4 g (86%) of 4-phenyl-1-(2-phenylethy-
nyl)phenyl-1-butanol: IR (neat) 3375, 3061, 2211, 1596, 1061
cm-1; 1H NMR (300 MHz, CDCl3) δ 1.76-1.84 (m, 1H), 1.85-
1.91 (m, 1H), 1.91-2.01 (m, 2H), 2.52 (brs, 1H), 2.72 (t, 2H, J
) 7.0 Hz), 5.33 (dd, 1H, J ) 6.5, 5.0 Hz), 7.20-7.25 (m, 2H),
was added 3.1 g (18 mmol) of benzyl bromide in 50 mL of ether
at a rate so as to produce a mild exotherm. After the addition
was complete, the reaction was allowed to stir for 1 h at room
temperature, and the mixture was added to a solution of 2.5
g (12 mmol) of 2-phenylethynylbenzaldehyde in 50 mL ether
at 25 °C over a 1.5 h interval. The solution was poured into a
saturated NH4Cl solution, the ether layer was separated, and
the aqueous layer was extracted with ether. Removal of the
solvent under reduced pressure followed by flash silica gel
chromatography of the residue afforded 3.2 g (89%) of 2-phen-
yl-1-(2-phenylethynyl)phenyl-1-ethanol: IR (neat) 3061, 2207,
1
1673 cm-1; H NMR (300 MHz, CDCl3) δ 2.17 (d, 1H, J ) 3.4
Hz), 2.89 (dd, 1H, J ) 13.8, 9.0 Hz), 3.28 (dd, 1H, J ) 13.8,
3.4 Hz), 5.48 (dt, 1H, J ) 9.0, 3.4 Hz), 7.24-7.30 (m, 6H), 7.36-
7.40 (m, 4H), 7.54-7.61 (m, 4H); 13C NMR (75 MHz, CDCl3) δ
45.1, 73.3, 87.1, 94.5, 120.3, 123.1, 125.2, 126.5, 127.1, 128.4,
128.7, 129.5, 131.5, 132.1, 138.4, 145.7.
7.27-7.34 (m, 3H), 7.41-7.46 (m, 3H), 7.57-7.62 (m, 3H); 13
C
NMR (75 MHz, CDCl3) δ 27.9, 35.8, 38.0, 72.3, 87.4, 94.4,
120.6, 123.3, 125.5, 125.8, 127.1, 128.3, 128.5, 128.5, 128.5,
128.9, 131.5, 132.3, 142.4, 146.8.
A solution containing 3.0 g (10 mmol) of the above alcohol
in 25 mL of CH2Cl2 was added to a suspension of 4.3 g (20
mmol) of pyridinium chlorochromate (PCC) and 4.5 g of Celite
in 75 mL of CH2Cl2. After the solution was stirred for 4 h,
ether was added, and the mixture was filtered through a pad
of Florisil. The filter cake was washed with ether, and the
combined extracts were concentrated under reduced pressure.
Silica gel chromatography of the residue afforded 2.1 g (31%)
of the titled compound as a clear oil: IR (neat) 3059, 2212,
A solution of 2.5 g (7.7 mmol) of the above alcohol in 25 mL
of CH2Cl2 was added to a stirring suspension containing 3.4 g
(16 mmol) of PCC and 4.5 g of Celite in 75 mL of CH2Cl2. After
the solution was stirred for 4 h, 100 mL of ether was added,
and the mixture was filtered through a pad of Florisil. The
filter cake was washed with ether, and the combined ether
extracts were concentrated under reduced pressure. Silica gel
chromatography of the residue afforded 2.0 g (81%) of ketone
10 as a pale yellow oil: IR (neat) 2215, 1690, 1591, 1495, 1219,
1
1686, 1591 cm-1; H NMR (300 MHz, CDCl3) δ 4.52 (s, 2H),
7.28-7.45 (m, 10H), 7.54-7.56 (m, 2H), 7.64 (m, 2H); 13C NMR
(75 MHz, CDCl3) δ 48.6, 88.2, 94.9, 121.2, 122.7, 126.9, 128.3,
128.5, 128.8, 129.7, 131.0, 131.6, 133.7, 134.4, 141.1, 200.8.
Anal. Calcd for C22H16O: C, 89.16; H, 5.44. Found: C, 89.05;
H, 5.35.
1
756 cm-1; H NMR (300 MHz, CDCl3) δ 2.11 (tt, 2H, J ) 7.5,
7.3 Hz), 2.71 (t, 2H, J ) 7.5 Hz), 3.18 (t, 2H, J ) 7.3 Hz), 7.15-
7.17 (m, 2H), 7.23-7.39 (m, 5H), 7.41-7.47 (m, 2H), 7.49-
7.53 (m, 3H), 7.62-7.66 (m, 2H); 13C NMR (75 MHz, CDCl3) δ
26.0, 35.3, 41.4, 88.2, 94.6, 121.2, 122.9, 125.9, 128.2, 128.3,
128.3, 128.5, 128.7, 130.9, 131.6, 133.7, 141.4, 141.6, 203.3.
Anal. Calcd for C24H20O: C, 88.85; H, 6.22. Found: C, 88.71;
H, 6.19.
10-P h en yl-10H-in d en o[2,1-a ]in d en -5-on e (21). To a 200
mL flask equipped with a stirring bar and nitrogen inlet was
added a solution of 1.4 g (4.7 mmol) of the above ketone and
1.9 g (6 mmol) of azidotris(diethylamino)phosphonium bromide
(11) in 100 mL of dry THF. The reaction mixture was stirred
at -78 °C for 20 min, and then 0.2 g of NaH (60% in mineral
oil) was added in one portion. After being stirred for 1 h at 25
°C, the reaction mixture was washed with a 10% solution of
NH4Cl and the aqueous layer was extracted with ether. The
combined ether extracts were dried over Na2SO4 and concen-
trated under reduced pressure. The crude diazoketone was
purified by flash chromatography to give 0.8 g (53%) of 2-diazo-
2-phenyl-1-(2-phenylethynylphenyl)-1-ethanone (19) as a labile
pale yellow oil that was immediately used in the next step
without further purification: IR (neat) 2962, 2217, 2080, 1627
tr a n s-2,3-Dih ydr o-2,3-diph en ylcyclopen t[a ]in den -8(3H)-
on e (18). To a dry 50 mL flask containing 0.3 g of NaH (60%
in mineral oil) was added 5 mL of ether containing two drops
of absolute ethanol. The flask was cooled to 0 °C, and a solution
of 0.7 g (2 mmol) of ketone 10, 1 mL of ethyl formate, and 5
mL of ether was added dropwise. The mixture was stirred at
0 °C for 3 h and at 25 °C for an additional 12 h. A solution of
0.7 g (6 mmol) of mesyl azide in 10 mL of ether was added,
and the reaction mixture was stirred at room temperature for
an additional 2 h. The mixture was quenched by the addition
of 2 mL of water, the ether layer was separated and washed
with 10% NaOH, and the aqueous layer was extracted with
ether. The combined ether extracts were dried over Na2SO4
and concentrated under reduced pressure. The crude diazoke-
tone was purified by flash silica gel chromatography to give
0.3 g (37%) of 2-diazo-4-phenyl-1-(2-phenylethynylphenyl)-1-
butanone (17) as a pale yellow oil: IR (neat) 2211, 2076, 1654,
1617, 1493 cm-1; 1H NMR (300 MHz, CDCl3) δ 2.75-3.85 (m,
2H), 2.80-3.00 (m, 2H), 7.15-7.25 (m, 6H), 7.26-7.38 (m, 5H),
7.40-7.55 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 25.1, 33.5,
69.4, 86.5, 94.0, 120.4, 122.7, 126.5, 128.3, 128.4, 128.4, 128.5,
128.7, 129.7, 131.0, 131.0, 132.5, 139.8, 140.7, 189.4. This diazo
ketone was immediately used in the next step without further
purification.
1
cm-1; H NMR (300 MHz, C6D6) δ 6.77-7.07 (m, 8H), 7.16-
7.27 (m, 4H), 7.50 (m, 2H); 13C NMR (75 MHz, C6D6) δ 86.4,
93.6, 120.6, 122.6, 124.9, 125.9, 126.3, 127.4, 128.1, 128.3,
128.7, 129.7, 131.5, 132.0, 141.3, 187.2.
To a 25 mL flask containing 0.1 g (0.3 mmol) of R-diazo
ketone 19 in 10 mL of CH2Cl2 was added 2 mg of rhodium(II)
acetate. The solution was stirred at 25 °C for 1 h and was
concentrated under reduced pressure. Silica gel chromatog-
raphy of the crude reaction mixture afforded 0.08 g (93%) of
21 as a colorless oil: IR (neat) 3062, 1721, 1598, 1494 cm-1
;
1H NMR (300 MHz, C6D6) δ 4.93 (s, 1H), 7.36 (m, 5H), 7.63
(m, 4H) and 7.81 (m, 4H); 13C NMR (75 MHz, C6D6) δ 64.2,
124.2, 124.4, 126.3, 127.3, 127.6, 128.0, 128.1, 128.3, 128.8,
129.3, 132.7, 134.1, 137.3, 138.7, 143.8, 144.7, 147.5, 192.7.
Anal. Calcd for C22H14O: C, 89.76; H, 4.80. Found: C, 89.65;
H, 4.73.
To a 50 mL flask containing 0.16 g (0.46 mmol) of R-diazo
ketone 17 in 25 mL of CH2Cl2 was added 2 mg of rhodium(II)
acetate. The solution was stirred at 25 °C for 12 h, the solvent
was removed, and the residue was subjected to silica gel
chromatography to give 0.1 g (70%) of 18 as a yellow solid:
1-(2-P h en yleth yn ylp h en yl)-4-p en ten -1-ol. To a mixture
containing 0.7 g (30 mmol) of magnesium turnings was added
a solution of 4.0 g (30 mmol) of 4-bromo-1-butene in 50 mL of
anhydrous ether at a rate sufficient to maintain a mild
exotherm. After the addition was complete, the solution was
allowed to stir for 2 h and was then added to a solution of 3.8
g (18 mmol) of 2-phenylethynylbenzaldehyde in 50 mL of ether
at 0 °C. The solution was stirred at 25 °C for 2 h and was
quenched by the addition of a saturated NH4Cl solution. The
ether layer was separated, the aqueous extracts were extracted
with ether, and the combined extracts were dried with Na2-
SO4. Concentration under reduced pressure followed by flash
mp 172-173 °C; IR (neat) 1690, 1600, 1500, 1440 cm-1 1H
;
NMR (300 MHz, CDCl3) δ 2.94 (d, 2H, J ) 8.2 Hz), 4.36 (dt,
1H, J ) 8.4, 8.2 Hz), 4.50 (d, 1H, J ) 8.4 Hz), 6.57-6.59 (m,
1H), 6.82-6.89 (m, 6H), 7.02-7.06 (m, 4H), 7.13-7.15 (m, 2H),
7.40-7.43 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 30.4, 52.6,
54.6, 119.9, 122.4, 126.2, 126.7, 127.7, 128.4, 128.5, 128.8,
132.9, 136.0, 136.5, 139.8, 139.8, 143.4, 171.1, 192.9. Anal.
Calcd for C24H18O: C, 89.40; H, 5.63. Found: C, 89.27; H, 5.54.
2-P h en yl-1-(2-p h en yleth yn ylp h en yl)-1-eth a n on e. To a
100 mL flask containing 0.8 g (33 mmol) of magnesium metal

3730 J . Org. Chem., Vol. 65, No. 12, 2000
Padwa and Weingarten
1
silica gel chromatography afforded 4.1 g (85%) of 1-(2-phenyl-
1-ol as a pale oil: IR (neat) 1640, 1602, 1573, 1027 cm-1; H
ethynylphenyl)-4-penten-1-ol as a white solid: mp 56-57 °C;
NMR (300 MHz, CDCl3) δ 1.43-1.58 (m, 1H), 1.60-1.75 (m,
1H), 1.80-1.97 (m, 2H), 2.13 (dd, 2H, J ) 7.2, 7.0 Hz), 2.71
(brs, 1H), 4.96 (d, 1H, J ) 10.5 Hz), 5.02 (dd, 1H, J ) 17.3,
1.5 Hz), 5.28 (dd, 1H, J ) 7.4, 5.3 Hz), 5.78-5.87 (m, 1H), 7.26
IR (neat) 2215, 1642, 1573, 1027 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 1.89-2.02 (m, 2H), 2.21-2.31 (m, 2H), 4.98 (d, 1H,
J ) 10.0 Hz), 5.08 (dd, 1H, J ) 17.0 and 1.5 Hz), 5.28 (m, 1H),
5.88 (m, 1H), 7.23-7.29 (m, 1H), 7.36-7.39 (m, 4H), 7.51-
7.56 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 30.3, 37.4, 71.7,
87.3, 94.4, 115.0, 120.5, 123.2, 123.5, 127.1, 128.5, 128.8, 128.8,
131.5, 132.2, 138.4, 146.7. Anal. Calcd for C19H18O: C, 86.98;
H, 6.92. Found: C, 86.84; H, 6.83.
1-(2-P h en yleth yn ylp h en yl)-4-p en ten -1-on e. A solution
containing 3.3 g (12 mmol) of the above alcohol in 50 mL of
CH2Cl2 was added to a suspension containing 5.3 g (24 mmol)
of PCC and 6 g of Celite in 150 mL of CH2Cl2. After the solution
was stirred at room temperature for 4 h, 100 mL of ether was
added, and the mixture was filtered through a pad of Florisil.
The filter cake was washed with ether, and the combined
extracts were concentrated under reduced pressure. Silica gel
chromatography afforded 3.3 g (93%) of the titled compound
as a pale yellow oil: IR (neat) 1692, 1592, 756 cm-1; 1H NMR
(300 MHz, CDCl3) δ 2.52 (dt, 2H, J ) 7.4, 7.0 Hz), 3.26 (t, 2H,
J ) 7.0), 5.03 (dd, 1H, J ) 10.0, 1.0 Hz), 5.16 (dd, 1H, J )
17.3, 1.0 Hz), 5.90 (ddt, J ) 17.3, 10.0, 7.0 Hz), 7.33-7.44 (m,
5H), 7.53-7.68 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 28.4,
41.2, 88.4, 94.7, 115.4, 121.2, 122.9, 128.3, 128.3, 128.5, 128.8,
131.0, 131.6, 133.8, 137.2, 141.1, 202.2. Anal. Calcd for
(t, 1H, J ) 7.5 Hz), 7.34-7.41 (m, 4H), 7.53-7.58 (m, 4H); 13
C
NMR (75 MHz, CDCl3) δ 25.4, 33.7, 37.9, 72.2, 87.3, 94.3,
114.7, 120.6, 123.2, 125.4, 127.0, 128.5, 128.5, 128.8, 131.5,
132.2, 138.7, 146.8.
A solution containing 1.8 g (6.3 mmol) of the above alcohol
in 25 mL of CH2Cl2 was added to a stirring suspension of 2.7
g (13 mmol) of PCC and 3 g of Celite in 75 mL of CH2Cl2. After
the solution was stirred for 4 h, 100 mL of ether was added,
and the mixture was filtered through a pad of Florisil. The
filter cake was washed with ether, and the combined extracts
were concentrated under reduced pressure. Silica gel chroma-
tography of the residue afforded 1.6 g (91%) of 1-(2-phenyl-
ethynylphenyl)-5-hexen-1-one as a pale yellow oil: IR (neat)
3064, 2215, 1690, 1642, 1443 cm-1; 1H NMR (300 MHz, CDCl3)
δ 1.86 (tt, 2H, J ) 7.4, 7.0 Hz), 2.13 (dt, 2H, J ) 7.0, 7.0 Hz),
3.13 (t, 2H, J ) 7.4 Hz), 4.94 (dd, 1H, J ) 10.0, 1.0 Hz), 4.99
(dd, 1H, J ) 17.3, 1.0 Hz), 5.78 (ddt, J ) 17.3, 10.0, 7.0 Hz),
7.30-7.44 (m, 5H), 7.51-7.67 (m, 4H); 13C NMR (75 MHz,
CDCl3) δ 23.3, 33.0, 41.0, 88.1, 94.2, 115.0, 120.9, 122.6, 127.9,
128.0, 128.2, 128.4, 130.6, 131.3, 133.5, 138.0, 142.0, 203.0.
Anal. Calcd for C20H18O: C, 87.55; H, 6.62. Found: C, 87.42;
H, 6.65.
C
19H16O: C, 87.65; H, 6.20. Found: C, 87.54; H, 6.08.
1a ,7c-Dih yd r o-7c-1H-cyclop r op a [3,4]cyclop en ta [1,2-a ]-
1,1a ,2,3-Tet r a h yd r o-8c-cyclop r op a [c]flu or en -4(8cH )-
on e (26). A dry 50 mL flask equipped with a stirring bar and
nitrogen inlet was charged with 0.3 g (6.3 mmol) of NaH (60%
mineral oil) in 5 mL of ether containing two drops of absolute
ethanol. To this mixture was added a solution of 0.6 g (2.0
mmol) of the above ketone, 1 mL of ethylformate, and 10 mL
of dry THF at 0 °C. The mixture was stirred at 25 °C for 12 h,
a solution containing 0.7 g (6.0 mmol) of mesyl azide in 10
mL of ether was added, and the mixture was stirred at 25 °C
for an additional 2 h. The solution was quenched with 2 mL
of water, the ether layer was washed with 10% NaOH, and
the aqueous layer was extracted with ether. The combined
ether extracts were dried over Na2SO4 and concentrated under
reduced pressure. The crude oil was purified by flash silica
gel chromatography to give 0.23 g (37%) of 2-diazo-1-(2-
phenylethynylphenyl)-5-hexen-1-one (23) as a pale yellow oil
that was immediately used in the next step: IR (neat) 3066,
in d en e-3(2H)-on e (25). To a dry 50 mL flask of 0.24 g (6.0
mmol) of NaH (60% in mineral oil) was added 5 mL of dry
ether containing two drops of absolute ethanol. The flask was
cooled to 0 °C, and a solution of 0.5 g (2.0 mmol) of the above
ketone, 1 mL of ethyl formate, and 10 mL of dry THF was
o
added dropwise. The mixture was stirred at 0 C for 1 h and
at 25 °C for 12 h. A solution of 0.7 g (6.0 mmol) of mesyl azide
in 10 mL ether was added, the reaction was stirred for an
additional 2 h, and the mixture was quenched by the addition
of 2 mL of water. The ether layer was washed with 10% NaOH,
and the aqueous layer was extracted with ether. The combined
ether extracts were dried over Na2SO4 and concentrated under
reduced pressure. The crude diazoketone was purified by flash
silica gel chromatography to give 0.2 g (34%) of 2-diazo-1-(2-
phenylethynylphenyl)-3-buten-1-one (22) as a pale yellow oil
that was immediately used in the next step: IR (neat) 2217,
2082, 1729, 1617, 756 cm-1; 1H NMR (300 MHz, CDCl3) δ 3.25
(brs, 2H), 5.13 (d, 1H, J ) 10.0 Hz), 5.22 (d, 1H, J ) 17.5 Hz),
5.78-5.91 (m, 1H), 7.34-7.36 (m, 4H), 7.40-7.45 (m, 2H),
7.46-7.51 (m, 2H), 7.55-7.59 (m, 1H); 13C NMR (75 MHz,
CDCl3) δ 27.4, 69.3, 86.3, 93.0, 118.2, 120.4, 122.7, 127.4, 128.4,
128.7, 128.7, 130.0, 131.7, 132.0, 132.5, 140.6, 188.9.
2216, 2073, 1614, 1342 cm-1 1H NMR (300 MHz, CDCl3) δ
;
2.25-2.41 (m, 2H), 2.60-2.73 (m, 2H), 4.95 (d, 1H, J ) 10.0
Hz), 5.12 (d, 1H, J ) 17.5 Hz), 5.78-5.91 (m, 1H), 7.34-7.36
(m, 4H), 7.40-7.45 (m, 2H), 7.46-7.51 (m, 2H), 7.55-7.59 (m,
1H); 13C NMR (75 MHz, CDCl3) δ 22.7, 31.4, 69.6, 86.3, 92.9,
116.5, 120.4, 122.8, 127.2, 128.4, 128.4, 128.6, 128.7, 129.9,
131.6, 132.6, 136.2, 189.6.
To a 50 mL flask containing 0.1 g (0.35 mmol) of diazoketone
22 in 25 mL of CH2Cl2 was added 2 mg of rhodium(II) acetate,
and the solution was stirred for 12 h at 25 °C. Removal of the
solvent followed by silica gel chromatography of the crude
reaction mixture gave 25 (57%) as a pale oil: IR (neat) 1702,
To a 50 mL flask containing 0.05 g (0.2 mmol) of diazoketone
23 in 25 mL of CH2Cl2 was added 2 mg of rhodium(II) acetate.
The solution was stirred for 12 h at 25 °C, the solvent was
removed under reduced pressure, and the crude mixture was
subjected to silica gel chromatography to give 0.04 g (81%) of
1
1605, 1391, 698 cm-1; H NMR (300 MHz, CDCl3) δ 1.00 (dd,
1H, J ) 5.2, 4.8 Hz), 2.06 (dd, 1H, J ) 8.0, 4.8 Hz), 2.26 (ddd,
1H, J ) 8.0, 6.5, 5.2 Hz), 2.66 (d, 1H, J ) 18.2 Hz), 2.88 (dd,
1H, J ) 18.2, 6.5 Hz), 6.49-6.52 (m, 1H), 7.09-7.12 (m, 2H),
7.28-7.35 (m, 6H); 13C NMR (75 MHz, CDCl3) δ 23.1, 28.9,
34.1, 36.1, 104.9, 120.1, 121.8, 127.0, 128.6, 132.5, 136.4, 138.1,
138.9, 139.4, 148.6, 176.0, 192.9. Anal. Calcd for C19H14O: C,
88.34; H, 5.47. Found: C, 88.31; H, 5.29.
26 as a clear pale oil: IR (neat) 1680, 1600, 1450, 1370 cm-1
;
1H NMR (300 MHz, CDCl3) δ 1.42 (dd, 1H, J ) 6.2 and 5.4
Hz), 1.68-1.74 (m, 1H), 1.89 (d, 1H, J ) 8.4 Hz), 1.91 (d, 2H,
J ) 8.8 Hz), 2.17-2.29 (m, 1H), 2.59 (d, 1H, J ) 12.4 Hz),
5.76 (d, 1H, J ) 7.3 Hz), 6.91 (dd, 1H, J ) 7.4, 7.3 Hz, 7.00
(dd, 1H, J ) 7.4, 7.4 Hz), 7.28-7.38 (m, 6H); 13C NMR (75
MHz, CDCl3) δ 15.5, 18.9, 19.4, 26.2, 28,6, 121.3, 121.4, 127.2,
127.7, 128.5, 128.6, 129.7, 132.3, 132.7, 141.9, 143.6, 196.2.
Anal. Calcd for C20H16O: C, 88.20; H, 5.93. Found: C, 88.08;
H, 5.76.
1-(2-P h en yleth yn ylp h en yl)-5-h exen -1-on e. A solution of
2.4 g (16 mmol) of 5-bromo-1-pentene in 50 mL of anhydrous
ether was added to 0.5 g (21 mmol) of magnesium turnings.
The resulting Grignard reagent was allowed to stir for 2 h and
was then added to a solution of 2.1 g (10 mmol) of 2-phenyl-
ethynylbenzaldehyde in 50 mL of ether at 0 °C. The solution
was stirred at 25 °C for 2 h and then poured into a saturated
NH4Cl solution. The ether layer was separated, and the
aqueous portion was extracted with ether. The combined ether
extracts were dried over Na2SO4, filtered, and concentrated
under reduced pressure. Flash silica gel chromatography
afforded 2.26 g (80%) of 1-(2-phenylethynylphenyl)-5-hexen-
6-Tr im et h ylsilyl-1-(2-p h en ylet h yn ylp h en yl)-1-h ex-5-
yn -on e. To a 250 mL flask containing 0.8 g (34 mmol) of
magnesium metal was added a solution of 6.0 g (22 mmol) of
5-iodo-1-trimethylsilyl-1-pentyne in 50 mL of ether at such a
rate so as to produce a mild exotherm. After the addition was
complete, the reaction was allowed to stir for 1 h and was then
added to a solution of 4.7 g (23 mmol) of 2-phenylethynylbenz-
aldehyde in 50 mL ether at 25 °C. The solution was poured
into an ice-cold saturated NH4Cl solution, the ether layer was

Rhodium(II)-Catalyzed Carbocyclization Reactions
J . Org. Chem., Vol. 65, No. 12, 2000 3731
separated, and the aqueous layer was extracted with ether.
Removal of the solvent gave 4.9 g (63%) of 6-trimethylsilyl-1-
(2-phenylethynylphenyl)-1-hex-5-yn-ol, which was used di-
rectly in the next step. A solution of this alcohol in 50 mL of
CH2Cl2 was added to a stirring suspension of 3.4 g (16 mmol)
of PCC and 6.0 g of Celite in 75 mL of CH2Cl2. After the
solution was stirred for 4 h, 100 mL of ether was added, and
the mixture was filtered through a pad of Florisil. The filter
cake was washed with ether, and the combined ether extracts
were concentrated under reduced pressure. Removal of the
solvent followed by silica gel chromatography afforded 5.6 g
(72%) of the titled compound as a pale yellow oil: IR (neat)
nitrogen inlet was added a solution of 0.7 g (2.8 mmol) of the
above ester and 1.9 g (6.0 mmol) of azido-tris(diethylamino)-
phosphonium bromide (11) in 10 mL of dry THF. The reaction
mixture was stirred at -78 °C for 20 min, and then 0.12 g (3
mmol) of NaH (60% in mineral oil) was added in one portion.
After being stirred for 1 h at 0 °C, the reaction mixture was
washed with a 10% NH4Cl solution and the aqueous layer was
extracted with ether. The combined ether extracts were dried
over Na2SO4, concentrated under reduced pressure, and puri-
fied by flash silica gel chromatography to give 0.7 g (84%) of
diazophenylacetic acid 3-phenylprop-2-ynyl ester (31) as a pale
yellow oil that was immediately used in the next step: IR
(neat) 2931, 2115, 2086, 1702 cm-1; 1H NMR (300 MHz, CDCl3)
δ 5.09 (s, 2H), 7.17-7.52 (m, 10H); 13C NMR (75 MHz, CDCl3)
δ 53.1, 82.9, 86.7, 122.1, 124.0, 125.6, 126, 128.3, 128.8, 129.0,
131.9, 164.4.
1
1685, 1250, 840 cm-1; H NMR (300 MHz, CDCl3) δ 0.10 (s,
9H), 2.05 (q, 2H, J ) 7.0 Hz), 2.36 (t, 2H, J ) 7.0 Hz), 3.28 (t,
2H, J ) 7.0 Hz), 7.34 (m, 5H), 7.48-7.71 (m, 4H); 13C NMR
(75 MHz, CDCl3) δ 0.1, 19.4, 25.1, 40.7, 85.4, 88.3, 94.7, 106.4,
121.4, 122.9, 128.3, 128.5, 128.6, 128.7, 131.0, 131.6, 133.9,
140.9, 202.3. Anal. Calcd for C23H24OSi: C, 80.20; H, 7.03.
Found: C, 80.34; H, 6.97.
To a 25 mL flask containing 0.13 g (0.5 mmol) of R-diazo
ketone 31 in 10 mL of dry CH2Cl2 was added 2 mg of rhodium-
(II) acetate. The solution was stirred at 25 °C for 10 min and
was then concentrated under reduced pressure. Silica gel
chromatography of the residue afforded 0.11 g (92%) of 34 as
a yellow solid: mp 138-139 °C; IR (neat) 2926, 1757, 1452
3-P h en yl-2-t r im et h ylsila n ylet h yn yl-2,3-d ih yd r o-1H -
cyclop en ta [a ]in d en -8-on e (30). To a 50 mL flask of 0.21 g
of NaH (60% in mineral oil) was added 5 mL of ether
containing two drops of absolute ethanol. The flask was cooled
to 0 °C, and a solution of 0.6 g (1.7 mmol) of the above ketone,
0.4 mL of ethyl formate, and 5 mL of ether was added
dropwise. The mixture was stirred at 0 °C for 3 h and at 25
°C for 12 h. A solution of 0.6 g (5.2 mmol) of mesyl azide in 10
mL ether was added, and the reaction mixture was stirred for
an additional 2 h. The solution was quenched with 2 mL of
water, the ether layer was washed with 10% NaOH, and the
aqueous layer was extracted with ether. The combined ether
extracts were dried over Na2SO4 and were concentrated under
reduced pressure. The crude oil that was obtained was purified
by flash silica gel chromatography to give 0.2 g (33%) of
2-diazo-6-trimethylsilyl-1-(2-phenylethynylphenyl)-1-hex-5-
ynone (28) as a pale yellow oil that was immediately used in
1
cm-1; H NMR (300 MHz, CDCl3) δ 4.89 (s, 1H), 4.92 (d, 1H,
J ) 18.8 Hz), 5.10 (d, 1H, J ) 18.8 Hz), 7.06 (d, 2H, J ) 6.3
Hz), 7.24-7.37 (m, 6H), 7.72 (d, 1H, J ) 7.1 Hz); 13C NMR (75
MHz, CDCl3) δ 53.0, 69.1, 121.1, 125.1, 127.1, 127.7, 127.8,
127.9, 129.3, 133.9, 136.1, 136.8, 151.5, 167.5, 175.7. Anal.
Calcd for C17H12O2: C, 82.23; H, 4.87. Found: C, 82.31; H,
4.77.
2-Eth oxy-1-p h en ylcyclop r op a n eca r boxylic Acid 3-
P h en ylp r op -2-yn yl Ester (37). A solution contaning 0.1 g
(0.4 mmol) of R-diazo ester 31 and 0.14 g (2.0 mmol) of ethyl
vinyl ether in 30 mL of CH2Cl2 was treated with 2 mg of
rhodium(II) acetate. The mixture was allowed to stir at 25 °C
for 30 min and was then concentrated under reduced pressure.
Chromatography of the resulting oil on silica gel gave 0.12 g
(93%) of 37 as a clear oil as the only product formed: IR (neat)
the next step: IR (neat) 2959, 2174, 2080, 1614, 1350 cm-1
;
1H NMR (300 MHz, CDCl3) δ 0.15 (s, 9H), 2.58 (m, 2H), 2.74
(m, 2H), 7.29 (m, 5H), 7.51 (m, 4H); 13C NMR (75 MHz, CDCl3)
δ 0.1, 25.1, 37.5, 69.5, 71.8, 86.2, 94.3, 107.3, 120.5, 122.7,
125.4, 128.4, 128.5, 130.0, 131.5, 132.6, 146.6, 189.2.
2974, 2231, 1716, 1251 cm-1 1H NMR (300 MHz, CDCl3) δ
;
0.99 (t, 1H, J ) 6.7 Hz), 1.71 (dd, 1H, J ) 5.5, 4.9 Hz), 1.88
(dd, 1H, J ) 6.7, 5.5 Hz), 3.56 (q, 2H, J ) 6.7 Hz), 4.00 (dd,
1H, J ) 6.7, 4.9 Hz), 4.85-4.94 (m, 2H), 7.28-7.51 (m, 10H);
13C NMR (75 MHz, CDCl3) δ 14.9, 21.1, 35.2, 53.3, 65, 65.6,
80.8, 83.2, 86.2, 122.3, 127.3, 127.9, 128.3, 128.7, 131.5, 131.9,
To a 25 mL flask containing 0.05 g (0.13 mmol) of R-diazo
ketone 28 in 10 mL of CH2Cl2 was added 2 mg of rhodium(II)
acetate, and the solution was stirred for 12 h at 25 °C. Removal
of the solvent followed by silica gel chromatography of the
reaction mixture afforded 0.04 g (83%) of 30: IR (neat) 3025,
133.9, 172.3; HRMS calcd for
320.1410.
C21H20O3 320.1412, found
6-P h en yl-2-oxa bicyclo[3.1.0]h exa n e-6-ca r boxylic Acid
3-P h en ylp r op -2-yn yl Ester (38). A solution contaning 0.1 g
(0.4 mmol) of R-diazo ester 31 and 0.14 g (2.0 mmol) of
dihydrofuran in 32 mL of CH2Cl2 was treated with 2 mg of
rhodium(II) acetate. The mixture was allowed to stir at 25 °C
for 30 min and was concentrated under reduced pressure.
Chromatography of the resulting oil on silica gel gave 0.02 g
(26%) of butenolide 34 and 0.08 g (65%) of 38. Cyclopropane
38 exhibited the following spectral properties: IR (neat) 3054,
2897, 1709 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.85 (ddd, 1H,
J ) 11.4, 8.7, 3.7 Hz), 2.18-2.30 (m, 1H), 2.38 (q, 1H, J ) 8.7
Hz), 2.70 (t, 1H, J ) 5.8 Hz), 3.77 (ddd, 1H, J ) 11.4, 8.7, 3.7
Hz), 4.56 (d, 1H, J ) 5.8 Hz), 4.79 (s, 2H), 7.24-7.46 (m, 10H);
13C NMR (75 MHz, CDCl3) δ 26.2, 32.6, 38.1, 53.2, 70.1, 83.2,
86.1, 122.3, 127.6, 128.3, 128.5, 128.7, 131.6, 131.8, 131.9,
170.6. Anal. Calcd for C21H18O3: C, 79.21; H, 5.70. Found: C,
79.05; H, 5.66.
1
1712, 1421, 1135 cm-1; H NMR (300 MHz, CDCl3) δ 0.10 (s,
9H), 2.70 (ddd, 1H, J ) 16.8, 7.1, 2.1 Hz), 2.93 (dd, 1H, J )
16.8, 8.6 Hz), 3.94 (ddd, 1H, J ) 8.6, 7.9, 7.1 Hz), 4.42 (dt, 1H,
J ) 7.9, 2.1 Hz), 6.57-6.59 (m, 1H), 7.08-7.38 (m, 7H); 13C
NMR (75 MHz, CDCl3) δ 0.3, 32.8, 40.9, 51.6, 89.8, 105.6,
120.0, 122.5, 127.4, 128.2, 128.7, 129.0, 133.0, 136.1, 136.8,
139.5,142.2, 170.4, 192.4; HRMS calcd for C23H22OSi 342.1440,
found 342.1455.
P h en yla cetic Acid 3-P h en ylp r op -2-yn yl Ester . To a
solution containing 3.3 g (25 mmol) of 3-phenyl-prop-2-yn-1-
ol and 3.0 g (22 mmol) of phenylacetic acid in 50 mL of CH2-
Cl2 was added 5.2 g (25 mmol) of dicyclohexylcarbodiimide and
1.2 g (10 mmol) of 4-(dimethylamino)pyridine at 0 °C under
N2. After being stirred for 2 h, the reaction mixture was
warmed to 25 °C over a 12 h period. The mixture was filtered
through Celite and concentrated under reduced pressure. The
residue was taken up in 100 mL of ethyl acetate and was
washed with a saturated Na2CO3 solution followed by brine.
The organic layer was dried over Na2SO4 and was concentrated
under reduced pressure. The crude ester was purified by flash
silica gel chromatography to give 5.1 g (92%) of the titled
7-P h en yl-2-oxa bicyclo[4.1.0]h ep ta n e-7-ca r boxylic Acid
3-P h en ylp r op -2-yn yl Ester (39). A solution contaning 0.1 g
(0.4 mmol) of R-diazo ester 31 and 0.15 g (2.0 mmol) of
dihydropyran in 30 mL of CH2Cl2 was treated with 2 mg of
rhodium(II) acetate. The mixture was allowed to stir at 25 °C
for 30 min and was concentrated under reduced pressure and
analyzed by HPLC. Chromatography of the resulting oil on
silica gel gave 0.06 g (69%) of butenolide 34 and 0.03 g (22%)
of 39. Cyclopropane 39 exhibited the following spectral proper-
compound as a clear oil: IR (neat) 2931, 2856, 1744, 1142 cm-1
;
1H NMR (300 MHz, CDCl3) δ 3.71 (s, 2H), 4.94 (s, 2H), 7.31-
7.35 (m, 8H), 7.44-7.46 (m, 2H); 13C NMR (75 MHz, CDCl3) δ
41.1, 53.2, 82.9, 86.6, 122.2, 127.2, 128.3, 128.7, 128.8, 129.3,
131.9, 133.6, 170.9. Anal. Calcd for C17H14O2: C, 81.57; H, 5.64.
Found: C, 81.32; H, 5.61.
ties: IR (neat) 3025, 2229, 1709 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 0.22-0.38 (m, 1H), 0.98-1.06 (m, 1H), 1.85-2.07 (m,
2H), 2.21 (t, 1H, J ) 7.1 Hz), 3.29 (dt, 1H, J ) 11.2, 1.0 Hz),
3.40 (dt, 1H, J ) 11.2, 3.3 Hz), 4.26 (d, 1H, J ) 7.1 Hz), 4.78
8-P h en yl-1,8-d ih yd r o-2-oxa cyclop en ta [a ]in d en -3-on e
(34). To a 50 mL flask equipped with a stirring bar and

3732 J . Org. Chem., Vol. 65, No. 12, 2000
Padwa and Weingarten
(m, 2H), 7.31-7.46 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 17.5,
21.1, 25.6, 34.6, 53.2, 62.2, 64.5, 83.3, 86.0, 122.3, 127.2, 128.1,
128.2, 128.6, 131.9, 132.6, 132.9, 148.6, 172.4. Anal. Calcd for
3-oxobutyric acid 3-phenylprop-2-ynyl ester. After the mixture
was stirred for 30 min at 25 °C, 0.7 g (4.7 mmol) of 80%
propargyl bromide in toluene was added. The reaction mixture
was stirred for 4 h at 60 °C and then cooled to 25 °C. The
solution was poured into an ice-cold saturated NH4Cl solution,
the ether layer was separated, and the aqueous layer was
extracted with ether. Removal of the solvent under reduced
pressure afforded 0.7 g (60%) of 2-acetylpent-4-ynoic acid
3-phenylprop-2-ynyl ester: IR (neat) 3289, 2225, 1745, 1716
C
22H20O3: C, 79.48; H, 6.07. Found: C, 79.32; H, 6.05.
3-Oxobu tyr ic Acid 3-P h en ylp r op -2-yn yl Ester . To a
solution containing 3.0 g (23 mmol) of 3-phenylprop-2-yn-1-ol
in 10 mL of xylene was added 3.0 mL (23 mmol) of 2,2,6-
trimethyl-4H-1,3-dioxin-4-one under a nitrogen atmosphere.
After being heated for 2 h at 140 °C, the reaction was cooled
to 25 °C, filtered through Celite, and concentrated under
reduced pressure. The crude â-keto ester was purified by flash
silica gel chromatography to give 4.5 g (92%) of the titled
1
cm-1; H NMR (300 MHz, CDCl3) δ 2.01 (t, 1H, J ) 2.7 Hz),
2.35 (s, 3H), 2.76 (dd, 2H, J ) 7.5 and 2.7 Hz), 3.79 (t, 1H, J
) 7.5 Hz), 5.00 (s, 2H), 7.28-7.45 (m, 5H); 13C NMR (75 MHz,
CDCl3) δ 17.4, 29.6, 54.0, 58.0, 70.5, 80.1, 82.1, 87.1, 121.8,
128.4, 128.9, 131.9, 167.5, 200.4. Anal. Calcd for C16H14O3: C,
75.56; H, 5.55. Found: C, 75.38; H, 5.44.
compound as a clear oil: IR (neat) 3061, 2229, 1745, 1716 cm-1
;
1H NMR (300 MHz, CDCl3) δ 2.26 (s, 3H), 3.50 (s, 2H), 4.94
(s, 2H), 7.28-7.31 (m, 3H), 7.41-7.44 (m, 2H); 13C NMR (75
MHz, CDCl3) δ 30.1, 49.8, 53.6, 82.3, 87.0, 121.9, 128.3, 128.9,
131.9, 166.4, 199.9. Anal. Calcd for C13H12O3: C, 72.20; H, 5.60.
Found: C, 72.15; H, 5.65.
4-P h en yl-3H-isoben zofu r a n -1-on e (45). To a dry 25 mL
flask containing 0.2 g (0.8 mmol) of the above â-keto ester was
added 10 mL of CH2Cl2 and 0.2 g (0.9 mmol) of p-nitrobenz-
enesulfonyl azide. The flask was placed in an ice bath, and
0.25 mL (1.8 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene was
added. The mixture was stirred at 0 °C for 10 min and then
filtered through a pad of silica. The filter cake was washed
with ethyl acetate, and the combined extracts were concen-
trated under reduced pressure. The crude diazo ester was
purified by flash silica gel chromatography to give 0.14 g (75%)
of 2-diazopent-4-ynoic acid 3-phenylprop-2-ynyl ester (43) as
a clear oil that was used in the next step without further
purification: IR (neat) 3289, 2228, 2093, 1688 cm-1; 1H NMR
(300 MHz, CDCl3) δ 2.18 (t, 1H, J ) 2.7 Hz), 3.33 (d, 2H, J )
2.7 Hz), 5.01 (s, 2H), 7.30-7.33 (m, 3H) and 7.44-7.47 (m,
2H); 13C NMR (75 MHz, CDCl3) δ 13.8, 53.2, 71.6, 77.3, 82.6,
86.6, 122.1, 128.3, 128.8, 131.9, 165.3.
2-Ben zyl-3-oxobu tyr ic Acid 3-P h en ylp r op -2-yn yl Es-
ter . To a suspension containing 0.1 g (2.4 mmol) of NaH (60%
in mineral oil) in 10 mL of THF was added 0.44 g (2.0 mmol)
of the above â-keto ester. After being stirred for 30 min at 25
°C, 0.3 mL (2.4 mmol) of benzyl bromide was added. The
mixture was stirred for 4 h at 60 °C and then cooled to 25 °C.
The solution was poured into an ice-cold saturated NH4Cl
solution, the ether layer was separated, and the aqueous layer
was extracted with ether. Removal of the solvent under
reduced pressure gave 3.5 g (91%) of the titled compound as a
clear oil (5:1 keto/enol): IR (neat) 3431, 3025, 2228, 1745, 1716
1
cm-1; H NMR (300 MHz, CDCl3) δ 2.04 (s, 3H), 2.20 (s, 3H),
3.19 (d, 2H, J ) 7.6 Hz), 3.62 (s, 2H), 3.84 (t, 1H, J ) 7.6 Hz),
4.84-4.90 (m, 2H), 4.94-4.96 (m, 2H), 7.31-7.48 (m, 20H),
12.73 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 19.2, 29.7, 31.5,
34.0, 52.8, 53.7, 61.1, 82.3, 83.1, 86.5, 87, 99.1, 122.0, 126.0,
126.8, 127.9, 128.3, 128.4, 128.7, 128.8, 128.9, 131.9, 137.9,
140.7, 168.5, 172.4, 174.8, 201.8. Anal. Calcd for C20H18O3: C,
78.40; H, 5.93. Found: C, 78.33; H, 5.81.
To a 25 mL flask containing 0.13 g (0.55 mmol) of R-diazo
ester 43 in 10 mL of benzene at 80 °C was added 2 mg of
rhodium(II) acetate. The solution was heated at reflux for 12
h, cooled to 25 °C, and concentrated under reduced pressure.
Silica gel chromatography of the crude residue afforded 0.02
g (16%) of Z-pent-2-en-4-ynoic acid 3-phenylprop-2-ynyl ester
(44) and 0.08 g (76%) of 4-phenyl-3H-isobenzofuran-1-one63
(45). Compound 44 exhibited the following spectral proper-
Z-3-P h en ylacr ylic Acid 3-P h en ylpr op-2-yn yl Ester (41).
To a dry 25 mL flask containing 0.3 g (0.9 mmol) of the above
â-keto ester was added 10 mL of CH2Cl2 and 0.3 g (1.3 mmol)
of p-nitrobenzenesulfonyl azide. The flask was cooled to 0 °C,
and 0.25 mL (1.7 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene
was added dropwise. The mixture was stirred at 0 °C for 10
min and filtered through a pad of silica. The filter cake was
washed with ethyl acetate, and the combined extracts were
concentrated under reduced pressure. The crude diazoester
was purified by flash silica gel chromatography to give 0.2 g
(72%) of 2-diazo-3-phenylpropionic acid 3-phenylprop-2-ynyl
ester (40) as a clear oil that was used in the next step without
ties: IR (neat) 3282, 2229, 1730, 1161 cm-1 1H NMR (300
;
MHz, CDCl3) δ 3.67 (d, 1H, J ) 2.3 Hz), 5.01 (s, 2H), 6.20 (dd,
1H, J ) 11.5, 2.5 Hz), 6.29 (d, 1H, J ) 11.5 Hz), 7.47-7.26
(m, 5H); 13C NMR (75 MHz, CDCl3) δ 52.9, 79.4, 82.6, 86.7,
90.0, 122.1, 123.2, 128.3, 128.8, 129.7, 131.8, 163.5; HRMS
calcd for C14H10O2 210.0681, found 210.0679.
4-Phenyl-3H-isobenzofuran-1-one (45) exhibited the follow-
ing spectral properties: mp 118-119 °C; IR (neat) 3061, 2923,
1
1763 cm-1; H NMR (300 MHz, CDCl3) δ 5.41 (s, 2H), 7.43-
further purification: IR (neat) 3025, 2229, 2086, 1688 cm-1
;
7.53 (m, 5H), 7.63 (t, 1H, J ) 7.5 Hz), 7.73 (d, 1H, J ) 7.3 Hz)
and 7.92 (d, 1H, J ) 7.2 Hz); 13C NMR (75 MHz, CDCl3) δ
69.7, 124.6, 126.4, 127.7, 128.5, 129.2, 129.8, 133.8, 137.0,
137.6, 144.1, 171.1. Anal. Calcd for C14H10O2: C, 79.97; H, 4.80.
Found: C, 79.83; H, 4.78.
1H NMR (300 MHz, CDCl3) δ 3.66 (s, 2H), 5.02 (s, 2H), 7.24-
7.32 (m, 8H), 7.44-7.47 (m, 2H); 13C NMR (75 MHz, CDCl3) δ
29.4, 53.1, 83.1, 86.5, 122.1, 127.2, 128.3, 128.4, 128.8, 128.8,
131.9, 137.0.
To a 25 mL flask containing 0.18 g (0.6 mmol) of R-diazo
ester 40 in 10 mL of CH2Cl2 was added 2 mg of rhodium(II)
acetate. The solution was stirred for 1 h at 25 °C and
concentrated under reduced pressure. Silica gel chromatog-
raphy of the crude residue afforded 0.15 g (92%) of 41 as a
clear oil: IR (neat) 3054, 2236, 1723, 1147 cm-1; 1H NMR (300
MHz, CDCl3) δ 4.95 (s, 2H), 6.00 (d, 1H, J ) 12.6 Hz), 6.99 (d,
1H, J ) 12.6 Hz), 7.29-7.35 (m, 6H), 7.43-7.46 (m, 2H), 7.60-
7.63 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 52.6, 83.0, 86.5,
118.6, 122.2, 128.1, 128.3, 128.8, 129.3, 129.9, 131.9, 134.5,
144.5, 165.3. Anal. Calcd for C18H14O2: C, 82.41; H, 5.38.
Found: C, 82.57; H, 5.35.
Ack n ow led gm en t. We gratefully acknowledge the
National Science Foundation (CHE-9806331) for gener-
ous support of this work. We also wish to thank Dr. Paul
H. Mueller for some experimental assistance.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for new compounds lacking elemental analyses. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O991938H
2-Acetylp en t-4-yn oic Acid 3-P h en ylp r op -2-yn yl Ester .
To a suspension containing 0.2 g (4.8 mmol) of NaH (60% in
mineral oil) in 20 mL of THF was added 1.0 g (4.6 mmol) of
(63) Noguchi, M.; Kakimoto, S.; Kawakami, H. Kajigaeshi, S.
Heterocycles 1985, 23, 1085.