Carbopalladation of nitriles: Synthesis of 2,3-diarylindenones and polycyclic aromatic ketones by the Pd-catalyzed annulation of alkynes and bicyclic alkenes by 2-iodoarenenitriles

Article abstract of DOI:10.1021/jo026178g

2-Iodobenzonitrile, its derivatives, and various heterocyclic analogues undergo palladium(O)-catalyzed annulation onto diarylacetylenes or bicyclic alkenes to afford 2,3-diarylindenones and polycyclic aromatic ketones in very good to excellent yields. This reaction represents one of the first examples of the addition of an organopalladium moiety to the carbon-nitrogen triple bond of a nitrile. The reaction is compatible with a number of functional groups. A reaction mechanism, as well as a model accounting for the electronic effects of substituents on the aromatic ring of the nitrile, is proposed.

Full text of DOI:10.1021/jo026178g

Ca r bop a lla d a tion of Nitr iles: Syn th esis of 2,3-Dia r ylin d en on es
a n d P olycyclic Ar om a tic Keton es by th e P d -Ca ta lyzed An n u la tion
of Alk yn es a n d Bicyclic Alk en es by 2-Iod oa r en en itr iles
Alexandre A. Pletnev, Qingping Tian, and Richard C. Larock*
Department of Chemistry, Iowa State University, Ames, Iowa 50011
larock@iastate.edu
Received J uly 10, 2002
2-Iodobenzonitrile, its derivatives, and various heterocyclic analogues undergo palladium(0)-
catalyzed annulation onto diarylacetylenes or bicyclic alkenes to afford 2,3-diarylindenones and
polycyclic aromatic ketones in very good to excellent yields. This reaction represents one of the
first examples of the addition of an organopalladium moiety to the carbon-nitrogen triple bond of
a nitrile. The reaction is compatible with a number of functional groups. A reaction mechanism, as
well as a model accounting for the electronic effects of substituents on the aromatic ring of the
nitrile, is proposed.
In tr od u ction
ance of most important organic functional groups.4
However, as more research in palladium-mediated or-
ganic methodology is being conducted, new reaction
conditions are being discovered that lead to previously
unknown palladium-catalyzed reactions with “unreac-
tive” functional groups.7
The development of new annulation processes is one
of the most challenging and important quests in organic
synthesis. Annulation is one of the most efficient and
economical ways of creating cyclic molecules.1 Combining
two or more independent acyclic moieties to form several
bonds in one process potentially provides an opportunity
to rapidly synthesize complex molecules without having
to spend time and resources on the isolation of interme-
diates and their reintroduction into subsequent steps.
This is especially attractive in this age of high-through-
put and combinatorial chemistry.2 Equally important is
the minimization of waste brought about by a decrease
in the amounts of reagents and solvents required for a
single-step operation as opposed to a multistep endeavor.3
Among many transition metals used in organic syn-
thesis, palladium is particularly useful as it offers the
most versatile possibilities for carbon-carbon bond for-
mation.4 Palladium reagents have been used extensively
to prepare various carbo- and heterocyclic compounds,5
by both cyclic carbopalladation and annulation.6 One of
the most important factors contributing to such wide-
spread application of palladium catalysts is their toler-
The cyano group has long been considered inert toward
organopalladium reagents. Palladium chloride bisaceto-
nitrile and bisbenzonitrile are widely used catalysts, and
acetonitrile is one of the most commonly employed
solvents in palladium-mediated reactions.4a,8 In most
such reactions, the nitriles are not incorporated into the
molecular structure of the products.9 In many cases,
substrates bearing a cyano group can undergo palladium-
mediated processes that lead to products in which the
cyano group remains intact. In fact, the palladium-
catalyzed cyanation of aryl halides is a widely used
synthetic approach to arenenitriles, which, once formed
in the reaction, are not modified in any way despite the
presence of organopalladium intermediates.10 Other ex-
amples of the palladium-catalyzed introduction of a cyano
group into a product include the cyanocarbonylation of
iodobenzene,11 cyanosilylation of alkynes,12 and numerous
(7) (a) Quan, L. G.; Lamrani, M.; Yamamoto, Y. J . Am. Chem. Soc.
2000, 122, 4827. (b) Gai, X.; Grigg, R.; Collard, S.; Muir, J . E. Chem.
Commun. 2000, 1765. (c) Larock, R. C.; Doty, M. J .; Cacchi, S. J . Org.
Chem. 1993, 58, 4579. (d) Larock, R. C.; Yum, E. K.; Doty, M. J .; Sham,
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Yamamoto, Y. Tetrahedron Lett. 1999, 40, 4089.
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Press: New York, 1985.
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product without involving carbopalladation of the cyano group, see:
Hegedus, L. S.; Mulhern, T. A.; Asada, H. J . Am. Chem. Soc. 1986,
108, 6224.
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10.1021/jo026178g CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/26/2002
9276
J . Org. Chem. 2002, 67, 9276-9287

Carbopalladation of Nitriles
reactions of nitrile-containing organic substrates, e.g., the
cross-coupling of aryl halides with terminal acetylenes13
or organometallic reagents,14 R-allylation,15 and decar-
boxylation of R-cyanoesters.16
Palladium-mediated reactions that do modify the ni-
trile functionality9,17 usually do not involve carbopalla-
dation of the cyano group. However, there are rare
examples of the carbopalladation of nitriles. Thus, Yang
et al. have described the palladium-catalyzed arylation
of a cyano group in the intramolecular cyclization of
2-bromoarylalkenenitriles,18 and Cheng has reported the
cyano group transfer from solvents to aryl halides medi-
ated by palladium and zinc species.19
of natural products (e.g., steroids and gibberellins),
indanones, indenes, naphthols, and other compounds.7c,23
Traditionally, indenones have been synthesized via
Friedel-Crafts cyclizations or addition of organometallic
reagents to 1,3-indandiones.22a,24 Many transition-metal
reagents and catalysts have been employed in indenone
preparations in recent years.7c,23a Palladium-catalyzed
reactions leading to indenones (including annulation
approaches) have also found a place in synthetic organic
methodology.25 One such procedure developed in this
laboratory involves the annulation of internal alkynes
with 2-halobenzaldehydes.7c Although effective and rea-
sonably general, this procedure could still be improved
if more stable starting materials could be used in place
of easily oxidized aldehydes.
We have recently reported that the intramolecular
carbopalladation of the cyano group in 2-iodobenzonitrile
and 2-iodophenylacetonitrile provides a new synthetic
route to indenones, 2-aminonaphthalenes, and related
compounds.20 At this time, we report the full details of
our investigation of the carboannulation of internal
alkynes and bicyclic alkenes by 2-iodoarenenitriles that
leads to 2,3-diarylindenones and related polycyclic aro-
matic ketones (eq 1).
Resu lts a n d Discu ssion
Ongoing research in our group on palladium-catalyzed
annulation methodology6a,26 prompted us to examine
2-iodobenzonitrile as a possible substrate for annulation
onto diphenylacetylene to produce 2,3-diphenyl-1-inde-
none (1; eq 2). Encouraged by the success of the intramo-
lecular reaction of an aldehyde, a group normally inert
toward organopalladium species,7 we envisioned that a
cyano group might serve as a neighboring functional
group in this reaction and that the vinylpalladium
intermediate might add across the carbon-nitrogen triple
bond (see the later mechanistic discussion).
Under our standard reaction conditions developed for
the synthesis of fluorenes,27 2-iodobenzonitrile reacts with
diphenylacetylene to afford the fluorene product 2 in 63%
yield (eq 3). When PPh3 was omitted from the reaction
Indenones and their derivatives have been employed
as fungicides and fermentation activators.21 Their poten-
tially useful biological activity as binding agents for
estrogen receptors has been used to study the structure
of the receptor’s binding site and the orientation of the
site’s nonsteroidal ligands.22 Indenones also serve as
valuable precursors and intermediates in the synthesis
(12) (a) Chatani, N.; Takeyasu, T.; Horiuchi, N.; Hanafusa, T. J .
Org. Chem. 1988, 53, 3539. (b) Suginome, M.; Kinugasa, H.; Ito, Y.
Tetrahedron Lett. 1994, 35, 8635.
(13) (a) Sakamoto, T.; Shiga, F.; Yasuhara, A.; Uchiyama, D.;
Kondo, Y.; Yamanaka, H. Synthesis 1992, 746. (b) Bumagin, N. A.;
Sukhomlinova, L. I.; Luzikova, E. V.; Tolstaya, T. P.; Beletskaya, I.
P. Tetrahedron Lett. 1996, 37, 897. (c) Sakamoto, T.; Kondo, Y.;
Yamanaka, H. Chem. Pharm. Bull. 1985, 33, 626.
(14) (a) Kosugi, M.; Ishiguro, Y.; Negishi, Y.; Sano, H.; Migita, T.
Chem. Lett. 1984, 1511. (b) Kanai, G.; Miyaura, N.; Suzuki, A. Chem.
Lett. 1993, 845. (c) Miller, J . A.; Farrell, R. P. Tetrahedron Lett. 1998,
39, 7275. (d) Piber, M.; J ensen, A. E.; Rottla¨nder, M.; Knochel, P. Org.
Lett. 1999, 1, 1323.
(15) Sawamura, M.; Sudoh, M.; Ito, Y. J . Am. Chem. Soc. 1996, 118,
3309.
conditions shown in eq 3, the reaction furnished 2 in 56%
yield. When the solvent was changed from DMF to 9:1
DMF-water, to our delight, the major identifiable prod-
uct (28%) was found to be the target indenone 1 (eq 2),
while none of the fluorene 2 was detected.
(16) Minami, I.; Nisar, M.; Yuhara, M.; Shimizu, I.; Tsuji, J .
Synthesis 1987, 992.
(17) (a) Bose, A.; Saha, C. R. J . Mol. Catal. 1989, 49, 271. (b) He´nin,
F.; Le´tinois, S.; Muzart, J . Tetrahedron Lett. 1997, 38, 7187. (c) Wei,
L.-M.; Lin, C.-F.; Wu, M.-J . Tetrahedron Lett. 2000, 41, 1215.
(18) (a) Yang, C.-C.; Tai, H.-M.; Sun, P.-J . J . Chem. Soc., Perkin
Trans. 1 1997, 2843. (b) Deng, J .-H.; Tai, H.-M.; Yang, C.-C. J . Chin.
Chem. Soc. 2000, 47, 327.
(23) (a) Vicente, J .; Abad, J .-A.; Gil-Rubio, J . Organometallics 1996,
15, 3509, and references therein. (b) Buggle, K.; Ghogain, U. N.;
O’Sullivan, D. J . Chem. Soc., Perkin Trans. 1 1983, 2075.
(24) Galatsis, P.; Manwell, J . J .; Blackwell, J . M. Can. J . Chem.
1994, 72, 1656 and references therein.
(19) Luo, F.-H.; Chu, C.-I.; Cheng, C.-H. Organometallics 1998, 17,
1025.
(20) Larock, R. C.; Tian, Q.; Pletnev, A. A. J . Am. Chem. Soc. 1999,
121, 3238.
(25) For the most recent example, see: Hauser, F. M.; Zhou, M.;
Sun, Y. Synth. Commun. 2001, 31, 77.
(21) (a) J ourdan, G. P.; Dreikorn, B. A.; Hackler, R. E.; Hall, H. R.;
Arnold, W. R. In Synthesis and Chemistry of Agrochemicals II; ACS
Symposium Series; American Chemical Society: Washington, DC,
1991; p 566. (b) Frank, R. L.; Eklund, H.; Richter, J . W.; Vanneman,
C. R.; Wennerberg, A. N. J . Am. Chem. Soc. 1944, 66, 1.
(22) (a) Anstead, G. M.; Ensign, J . L.; Peterson, C. S.; Katzenellen-
bogen, J . A. J . Org. Chem. 1989, 54, 1485. (b) Gao, H.; Katzenellen-
bogen, J . A.; Garg, R.; Hansch, C. Chem. Rev. 1999, 99, 723.
(26) (a) Larock, R. C. Pure Appl. Chem. 1999, 71, 1435. (b) Roesch,
K. R.; Zhang, H.; Larock, R. C. J . Org. Chem. 2001, 66, 8042. (c) Zhang,
H.; Larock, R. C. Org. Lett. 2001, 3, 3083. (d) Roesch, K. R.; Larock, R.
C. J . Org. Chem. 2001, 66, 412. (e) Kadnikov, D. V.; Larock, R. C. Org.
Lett. 2000, 2, 3643. (f) Gagnier, S. V.; Larock, R. C. J . Org. Chem. 2000,
65, 1525. (g) Larock, R. C.; Doty, M. J .; Han, X. J . Org. Chem. 1999,
64, 8770.
(27) Larock, R. C.; Tian, Q. J . Org. Chem. 2001, 66, 7372.
J . Org. Chem, Vol. 67, No. 26, 2002 9277

Pletnev et al.
TABLE 1. Op tim iza tion of th e P d -Ca ta lyzed An n u la tion of Dip h en yla cetylen e by 2-Iod oben zon itr ile (Eq 2)a
additive
(amt, equiv)
amt of Et3N
(equiv)
isolated yield
entry
catalyst
solvent
DMF
DMF
DMF
time (h)
of 1b (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
5% Pd(OAc)2
5% Pd(OAc)2
5% Pd(OAc)2
5% Pd(OAc)2
5% Pd(OAc)2
5% Pd(OAc)2
10% Pd(dba)2
10% Pd(dba)2
10% Pd(dba)2
10% Pd(dba)2
10% Pd(dba)2
10% Pd(dba)2
10% Pd(dba)2
10% Pd(dba)2
10% Pd(dba)2
10% Pd(dba)2
10% Pd(dba)2
10% Pd(dba)2
10% Pd(dba)2
10% Pd(dba)2
10% Pd(dba)2
n-Bu4NCl (1)
n-Bu4NCl (1)
n-Bu4NCl (1)
n-Bu4NCl (1)
n-Bu4NCl (1)
n-Bu4NCl (1), PPh3 (0.2)
n-Bu4NCl (1)
3
3
2
2
2
2
2
2
48
48
48
24
24
24
24
24
48
24
24
72
24
13
17
48
24
24
24
24
24
30
25c
30
45
42
42
4:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
9:1 DMF-H2O
62
60
11d
10
0.5
1
2
3
1
1
1
1
1
74
59
48
61 (71)d
66 (70)d
38e
Ag3PO4 (0.4)
AgNO3 (1.2)
TlPF6 (1.2)
PPh3 (0.2)
trace
trace
25 (40)d
62
1
1
1
TPPTS (0.2)f
66
a
b
All reactions were run with 3 equiv of diphenylacetylene at 100 °C unless specified otherwise. All yields in parentheses are corrected
for unreacted starting material. c A 2 equiv sample of water was added to the reaction mixture. Incomplete conversion of 2-iodobenzonitrile.
d
e This reaction was run at 80 °C. f TPPTS ) tris(3-sulfonatophenyl)phosphine, sodium salt.
lation of 2-iodophenylacetonitrile,20 the details of which
SCHEME 1
will be reported in due course, we ran the reaction using
catalytic Pd(OAc)2 under conditions described in Table
1, entry 1. This procedure led to a 30% yield of 1. The
yield did not improve upon addition of 2 equiv of water,
nor upon reducing the amount of the base (entries 2 and
3, respectively). Using aqueous DMF as a solvent resulted
in higher yields of 1 (entries 4 and 5). The addition of
triphenylphosphine, intended to facilitate the initial
reduction of Pd(II) to Pd(0), as well as to serve as a ligand
for palladium, had no effect on the reaction (entry 6). We
then decided to use a Pd(0) catalyst. Employing 10%
Pd(dba)2 raised the yield of 1 to 62% (entry 7). An almost
identical yield was obtained when n-Bu4NCl was omitted,
proving that a chloride source was unnecessary for the
annulation (entry 8). Since 1 equiv of ammonia was
supposedly formed in the reaction (Scheme 1), we ques-
tioned whether using 2 equiv of triethylamine was
required, and studied the effect of the amount of base on
the reaction yield (entries 9-13). The best results were
obtained when we employed only 1 equiv of triethylamine
(entry 11), whereas using both lesser and greater amounts
was detrimental to the success of the annulation. It was
also established that the reaction required a full 24 h,
since using shorter reaction times resulted in incomplete
consumption of the 2-iodobenzonitrile (entries 14 and 15).
Lowering the reaction temperature slowed the annulation
considerably and led to only a 38% yield of 1 after 48 h
(entry 16). Finally, we studied the effect of some additives
on the reaction (entries 17-21). Hoping that a cationic
palladium intermediate similar to I (Scheme 1) might
coordinate to the carbon-nitrogen bond more strongly
and thus affect the carbopalladation step favorably, we
employed silver and thallium salts known to sequester
halide anions from palladium complexes (entries 17-
19),29 only to find that their use decreased the yield of
the indenone 1. Using phosphine ligands resulted in
On the basis of our previous research on alkyne
annulation chemistry,6a,26a we propose the following
mechanism for the formation of 1 from 2-iodobenzonitrile
and diphenylacetylene (Scheme 1). Oxidative addition of
2-iodobenzonitrile to Pd(0), formed in situ from Pd(II), is
followed by diphenylacetylene insertion that leads to the
vinylpalladium intermediate I. The latter then adds
across the carbon-nitrogen triple bond of the neighboring
cyano group to produce the iminopalladium intermediate
II,28 which hydrolyzes to the indenone 1. Reduction of
the Pd(II) species produced is required to afford a
catalytic process and occurs at some point in the reaction.
Since the yield of the reaction was low, substantial
optimization efforts were undertaken to improve the yield
of this annulation (Table 1). Drawing on the findings of
concurrent work on the optimization of a similar annu-
(28) The exact opposite process, â-carbon elimination from a strained
cyclobutaniminopalladium complex to produce a γ-cyanoalkylpalladium
species, has been reported: Nishimura, T.; Uemura, S. J . Am. Chem.
Soc. 2000, 122, 12049.
9278 J . Org. Chem., Vol. 67, No. 26, 2002

Carbopalladation of Nitriles
TABLE 2. Effect of th e Solven t a n d Ba se on th e
An n u la tion (Eq 2)a
SCHEME 2
entry
base
Et3N
Et3N
collidine
i-Pr2NEt
solvent
time (h)
yield of 1 (%)
1
2
3
4
DMF
DMA
DMF
DMF
24
24
48
24
74
69
11
57
a
Reactions were run with 3 equiv of diphenylacetylene, 10 mol
% Pd(dba)2, and 1 equiv of the base in a 9:1 solvent-water mixture
at 100 °C.
lower yields compared to phosphine-free annulation
(entries 20 and 21).
We also conducted several experiments designed to
elucidate the identity of the reagent responsible for the
reduction of Pd(II) back to Pd(0) (Table 2). After analysis
of the reaction conditions, we focused on two possibilities.
Under our reaction conditions, it seemed plausible that
DMF could react with water to produce formic acid, which
is known to reduce Pd(II) species.30 However, when we
employed DMA instead of DMF (Table 2, entry 2), the
yield of 1 remained virtually unaffected, which strongly
discounts the possible role of DMF in the reduction.
Alternatively, the reduction could be effected by triethyl-
amine since alkylamines containing R-carbon-hydrogen
bonds are also capable of reducing Pd(II) complexes.31
Substitution of triethylamine by collidine, a nonreducing
amine, using our best reaction conditions resulted in a
sharply lower yield of the annulation product (entry 3).
This suggests that Et3N may be the reducing agent.
Obtaining 1 in a 57% yield in the experiment using
i-Pr2NEt, instead of Et3N (entry 4), seems to support our
hypothesis that the alkylamine base may be the reagent
actually reducing Pd(II) to Pd(0) in the catalytic cycle in
Scheme 1. The lower yield in entry 4 is presumably
caused by fewer R-C-H bonds available for the reduction
in i-Pr2NEt compared to Et3N or simply the greater
difficulty Pd(II) is going to have in coordinating to this
more hindered amine.
We propose the following two tentative mechanisms
for the reduction of Pd(II) by triethylamine (Scheme 2).
A palladium(II) species, such as A, may undergo insertion
into the R-C-H bond activated by the nitrogen in Et3N
(pathway a). Examples of such insertion have been
reported.32 Following reductive elimination of the organic
product, the (R-aminoalkyl)palladium complex B is formed.
Fragmentation of B leads to a Pd(0) species, which
returns to the catalytic cycle, and an iminium salt, C,
generation of which has also been proposed as the key
step in Pd-catalyzed transformations of trialkylamines.32
Alternatively, A could coordinate to the nitrogen in Et3N
and then undergo pseudo â-hydride elimination to afford
C and an organopalladium species, D, which produces
Pd(0) upon reductive elimination (pathway b).33
Using our best reaction conditions (Table 1, entry 11),
we proceeded to test the applicability of our procedure
to the annulation of other alkynes (eq 4). The annulation
of 2-iodobenzonitrile onto 1-phenyl-1-propyne resulted in
the formation of an inseparable 1:1 mixture of regioiso-
meric indenones 3 and 4 in a combined 32% yield after a
48 h reaction period (Table 3, entry 1). Only a trace
amount of 2,3-di-n-propyl-1-indenone (5) was detected in
the reaction of 4-octyne (entry 2), with about 40% of the
starting 2-iodobenzonitrile still present after 48 h. Inde-
none 6 was formed in low yield when 2-iodobenzonitrile
was annulated onto 4,4-dimethyl-2-pentyne (entry 3). The
annulation of 2-methyl-4-phenyl-3-butyn-2-ol afforded
the expected indenone 7 in an 8% yield along with
3-phenyl-2-(2-propenyl)-1-indenone (8), which was ap-
parently derived from 7 (entry 4). This reaction also
suffered from low conversion of the starting nitrile.
Finally, we were able to obtain 2-tert-butyl-3-(tert-butyl-
ethynyl)-1-indenone (9) in a 16% yield from the reaction
between 2-iodobenzonitrile and 2,2,7,7-tetramethyl-3,5-
octadiyne (entry 5). The reasons behind the poor
yields in the annulation of alkynes other than diphenyl-
acetylene are unclear considering that these alkynes have
readily participated in many other palladium-mediated
annulation reactions.6a,7c,26a
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1978, 100, 348. (b) Murahashi, S.-I.; Watanabe, T. J . Am. Chem. Soc.
1979, 101, 7429. (c) Murahashi, S.-I.; Yano, T. J . Chem. Soc., Chem.
Commun. 1979, 270.
We have also screened a large number of different
olefins in an attempt to extend the nitrile annulation
(33) A different mechanism involving insertion of a Pd(II) complex
into the â- rather than R-C-H bond of the trialkylamine (see ref 31b)
seems unlikely, since the former process should be much less favorable
than the latter. Reaction between D2O and our intermediate C can
explain the formation of deuterium-containing products in ref 31b
without involving â-C-H bond activation.
J . Org. Chem, Vol. 67, No. 26, 2002 9279

Pletnev et al.
TABLE 3. An n u la tion of 2-Iod oben zon itr ile on to Va r iou s Alk yn es (Eq 4)a
a
All reactions were run with 3 equiv of the alkyne, 10 mol % Pd(dba)2, and 1 equiv of Et3N in a 9:1 DMF-water mixture at 100 °C.
Isolated as a 1:1 inseparable mixture of isomers 3 and 4. c Incomplete conversion of 2-iodobenzonitrile.
b
methodology to include alkenes and dienes. No annula-
alkenes by the inability of palladium to align in a cis
fashion with the bridgehead hydrogen. Such elimination
would also produce a very strained bridgehead olefin.
We have also observed the beneficial effect of increas-
ing the temperature on the yields of this reaction (Table
4). Thus, polycyclic ketone 11 was obtained in 85%
yield when the annulation was run at 100 °C. The yield
improved to 93% when the temperature was raised to
130 °C (entry 1). The expected exo stereochemistry of 11
was confirmed by comparing its 1H NMR spectrum to
literature data.34 A high reaction temperature proved
even more beneficial for the annulation of 2-iodobenzo-
nitrile onto bicyclo[2.2.2]octene (entry 2). Not only did it
increase the yield of the product ketone 12, it also
enhanced the reaction rate, which was sluggish at 100
°C, presumably because of steric hindrance around the
double bond of the olefin. Functionalized polycyclic ketone
13 was obtained from the corresponding norbornene
derivative in 89% yield (entry 3), demonstrating the
nitrile annulation’s tolerance of the ester functionality.
The reaction of benzonorbornadiene (prepared from ben-
zyne and cyclopentadiene by a Diels-Alder cycloaddi-
tion)35 at 100 °C was slow, but this problem was rectified
by raising the temperature (entry 4). Repeated attempts
to carry out a double annulation of 2-iodobenzonitrile onto
norbornadiene failed as the nitrile was recovered even
at a high temperature and after a prolonged reaction
tion products were observed in the reactions of 2-iodo-
benzonitrile with cis-stilbene, indene, 3,4-dihydronaph-
thalene, 2,3-dioxene, N-phenylmaleimide, undeca-1,2-
diene, 1-phenylpropa-1,2-diene, 1,3-cyclohexadiene, and
1,4-cyclohexadiene. However, the reaction of 2-iodoben-
zonitrile with acenaphthylene afforded a Heck type
product, 10, in 57% yield (eq 5). We believe that the latter
reaction follows our proposed annulation mechanism, but
the benzylic palladium intermediate formed undergoes
solvolysis faster than it can add to the cyano group. The
driving force behind this solvolysis is probably the
formation of a stable, highly delocalized benzylic cation,
which, upon losing a proton, leads to 10.
During the course of our study of the scope of the
nitrile annulation chemistry, we have found that bicyclic
alkenes undergo facile annulation by 2-iodobenzonitrile
(eq 6). Palladium hydride elimination during annulation,
(34) (a) Amrein, W.; Larsson, I.-M.; Schaffer, K. Helv. Chim. Acta
1974, 57, 2519. (b) Brown, D.; Grigg, R.; Sridharan, V.; Tambyraiah,
V.; Thornton-Pett, M. Tetrahedron 1998, 54, 2595. (c) For 1H NMR
spectroscopic methods of assigning the stereochemistry of bicyclic
systems, see: Mayo, P.; Tam, W. Tetrahedron 2001, 57, 5943 and
references therein.
which is likely the major factor in the failure of other
olefins and alkylacetylenes, is prevented in bicyclic
(35) Friedman, L.; Logullo, F. M. J . Org. Chem. 1969, 34, 3089.
9280 J . Org. Chem., Vol. 67, No. 26, 2002

Carbopalladation of Nitriles
TABLE 4. Effect of th e Tem p er a tu r e on th e An n u la tion of Bicyclic Alk en es a n d Alk yn es (Eqs 4 a n d 6)a
a
b
See the Experimental Section for the reaction conditions. The reaction time was 72 h. c The yield was not determined due to the low
d
conversion of the 2-iodobenzonitrile after 48 h. Isolated as a 1:1 inseparable mixture of isomers 3 and 4.
time. We believe that norbornadiene may have formed a
strong complex with the palladium catalyst, thus remov-
ing the latter from the reaction.36 This could also explain
the low reactivity of benzonorbornadiene (entry 4), which
is capable of forming a similar complex with Pd.
Similarly, elevating the reaction temperature improved
the yield of 2,3-diphenylindenone (1), which was previ-
ously obtained in 74% yield using our original reaction
conditions (Table 1, entry 11), to almost a quantitative
yield (Table 4, entry 5). However, no improvement was
observed when 2-iodobenzonitrile was allowed to react
with 1-phenyl-1-propyne. The annulation at 130 °C
afforded an inseparable 1:1 mixture of the two possible
regioisomers 3 and 4 (entry 5) in a yield almost identical
to that obtained at a lower temperature (Table 3, entry 1).
On the basis of the aforementioned results, our optimal
annulation conditions are as follows: 0.25 mmol of
2-iodobenzonitrile, 3 equiv of diphenylacetylene or bicy-
clic alkene, 10 mol % Pd(dba)2, 1 equiv of Et3N, and 5
mL of 9:1 DMF-water as the solvent at 130 °C for 24 h.
This procedure is expected to be a useful method for the
synthesis of various 2,3-diarylindenones other than 1, as
illustrated by the 79% yield of indenone 15 we have
obtained (eq 7).
We have also found that the analogous annulation of
2-(2-iodophenyl)-2-methylpropanenitrile onto diphenyl-
acetylene affords a high yield of the expected six-
membered ring aromatic ketone 16 (eq 8). Mirroring our
observations in the indenone synthesis, regioisomeric
naphthenones 17 and 18 are formed in 18% and 11%
yields, respectively, when the unsymmetrical alkyne
1-phenyl-1-propyne is used in the annulation.
Having established the alkyne and olefin limitations
of the nitrile annulation methodology, we set out to
explore the range of nitrile-containing components
(36) (a) Wertz, D. W.; Moseley, M. A. Spectrochim. Acta, Part A
1980, 36A, 467. (b) Borsub, N.; Kutal, C. J . Am. Chem. Soc. 1984, 106,
4826.
J . Org. Chem, Vol. 67, No. 26, 2002 9281

Pletnev et al.
SCHEME 3a
TABLE 5. P r ep a r a tion of o-Iod oa r en en itr iles by
Nitr ile-Dir ected Or th o-Lith ia tion (Eq 9)a
a
Reagents and conditions: (a) SOCl2, ether, rt; (b) NH3, ether,
rt; (c) POCl3, reflux; (d) LAH, ether, rt; (e) MnO2, ether, rt; (f)
H2NNMe2, benzene, reflux; then MeI; (g) MeONa, MeOH, reflux;
(h) KOH, I2, DMF, rt; (i) NaH, DMF, 0 °C; then MeI or PhSO2Cl,
rt.
SCHEME 4a
a
Reagents and conditions: (a) ClSO2NCO, MeCN, 0 °C, then
Et3N, rt; (b) NaH, DMF, 0 °C; then MeI or PhSO2Cl, rt; (c) LiTMP,
THF, -78 °C; then I2, -78 °C to rt.
pyridine produced a hard-to-separate mixture of regio-
isomeric 24 and 25 that were partially isolated by column
chromatography.
a
b
See the Experimental Section for the reaction conditions.
A
two-step reaction sequence was employed here. c Isolated as a 1:1
We also prepared two series of regioisomeric hetero-
cyclic substrates designed to probe the effect of steric
hindrance and electron density in an indole ring on the
nitrile annulation. Substituted iodoindolecarbonitriles 27
and 28 were synthesized as shown in Schemes 3 and 4,
respectively. Depending on the immediate availability of
the starting materials, 2-cyanoindole was obtained in
good yield from either indole-2-carboxylic acid or ethyl
indole-2-carboxylate and then iodinated to afford 27a ,
which was derivatized at the nitrogen atom to give 27b
and 27c (Scheme 3). 2-Iodoindole-3-carbonitrile (28a ) was
prepared from 2-iodoindole and was then functionalized
to produce indoles 28b and 28c (Scheme 4). An alterna-
tive method starting with indole-3-carbonitrile worked
well for the N-methyl compound, but ortho-lithiation-
iodination of the N-sulfonylated precursor to hopefully
produce 28c afforded a mixture of products that had to
be separated.
hard-to-separate mixture of isomers 24 and 25.
we might employ. Several strategies were used to syn-
thesize a series of aromatic o-iodoarenenitrile starting
materials.
Using the synthetically underutilized ability of the
cyano group to direct ortho-lithiation,37 we successfully
adopted the procedure of Fraser and Savard for the
synthesis of o-iodoarenenitriles (eq 9).38 Nitrile-containing
substrates 19-23 were prepared in good yields by ortho-
lithiation of the corresponding arenenitriles with lithium
tetramethylpiperidide (LiTMP), followed by quenching
with iodine (Table 5, entries 1-5). 2,3-Dicyano-1,4-
diiodobenzene (23) was obtained from sequential intro-
duction of each iodine substituent into the molecule
(entry 5). The procedure was also applicable to the
synthesis of heterocyclic o-iodoarenenitriles 24-26 (en-
tries 6 and 7). Ortho-lithiation-iodination of 3-cyano-
Finally, we synthesized substituted 2-iodobenzonitriles
29 and 30 for a study of the electronic effect of substit-
uents on the benzene ring. 2-Iodo-5-nitrobenzonitrile (29)
was obtained in 65% yield by iodination of the diazonium
salt prepared from 5-nitroanthranilonitrile (eq 10). A
(37) Gawley, R. E.; Rein, K. In Comprehensive Organic Synthesis;
Trost, B. M., Ed.; Pergamon Press: New York, 1991; Vol. 1, Chapter
2.1, pp 461 and 468.
(38) Fraser, R. R.; Savard, S. Can. J . Chem. 1986, 64, 621.
9282 J . Org. Chem., Vol. 67, No. 26, 2002

Carbopalladation of Nitriles
TABLE 6. An n u la tion of 2-Iod oa r en en itr iles (Sch em e 6)a
a
d
See the Experimental Section for the reaction conditions. b Isolated yield. c A complex product mixture is formed. Isolated as a mixture
of diastereomers.
SCHEME 5a
SCHEME 6
a
Reagents and conditions: (a) NaNO2, H2SO4, 0 °C; then CuCN,
NaCN, H2O; (b) SnCl2, AcOH, DME, 60 °C; (c) NaNO2, H2SO4, 0
°C; then KI, H2O, rt.
derivative 34, which apparently is formed from 33 so as
to relieve the former compound’s anti-aromaticity (Table
6, entry 2). This phenomenon has been previously
observed in an unrelated synthesis of 33.39 The reaction
of 20 with norbornene proceeded smoothly and led to
polycyclic ketone 35 in high yield (entry 2). An attempted
double annulation of 2,3-dicyano-1,4-diiodobenzene (23)
onto diphenylacetylene afforded a complex reaction
mixture, in which we were unable to identify any
individual annulation products (entry 3). However, the
three-step synthesis based on variations of the Sand-
meyer reaction afforded the electron-rich 2-iodo-4-meth-
oxybenzonitrile (30) in 30% overall yield (Scheme 5).
With various o-iodoarenenitriles in hand, we proceeded
to explore their annulation onto diphenylacetylene and
norbornene (Scheme 6). 1-Cyano-2-iodonaphthalene (19)
readily participated in both reactions, affording polycyclic
ketones 31 and 32 in excellent yields identical to those
obtained with 2-iodobenzonitrile (Table 6, entry 1). To
our surprise, the annulation of 9-cyano-10-iodophenan-
threne (20) onto diphenylacetylene produced not only the
expected fully conjugated ketone 33, but also its dihydro
(39) Moritani, I.; Toshima, N.; Nakagawa, S.; Yakushiji, M. Bull.
Chem. Soc. J pn. 1967, 40, 2129.
J . Org. Chem, Vol. 67, No. 26, 2002 9283

Pletnev et al.
TABLE 7. An n u la tion of Nor bor n en e w ith In d oleca r bon itr ilesa
a
b
See the Experimental Section for the reaction conditions. The yield in parentheses is corrected for the diverted starting material.
double annulation succeeded in the case of norbornene,
and polycyclic dione 36 was obtained as a mixture of
several diastereomers (entry 3).
An obstacle of a different kind was encountered in the
attempted annulation of 2-iodothiophene-3-carbonitrile
(26). Instead of incorporating diphenylacetylene into
the product structure, this reaction afforded the homo-
coupling product 39 in 85% yield (eq 11). Presumably,
the palladium catalyst is ligated by the sulfur atom in
26, making coordination to the alkyne less favorable.
Somewhat surprisingly, no annulation products were
observed when o-iodonicotinonitriles 24 and 25 were
allowed to react with diphenylacetylene (entries 4 and
5). The failure may possibly be caused by competing
coordination of the pyridines and alkynes with palladium.
Yet, no problems were encountered in the annulation of
24 onto norbornene, which produced the heterocyclic
ketone 37 in a good yield (entry 4). We found, however,
that the reaction between 25 and norbornene did not lead
to the expected annulation product, but rather to 2-(2-
norbornyl)pyridine-3-carbonitrile (38) in 40% yield (entry
5). It seems quite likely that the nitrogen atom of the
pyridine ring chelates to the palladium center in the
intermediate corresponding to I in Scheme 1, thus
preventing the norbornylpalladium species from adding
to the cyano group and eventually leading to reduction
of the C-Pd bond in this intermediate.
Although no annulation products were observed in the
reaction between several indolecarbonitriles (27a , 27c,
28b) and diphenylacetylene, compounds 27 and 28 were
subjected to annulation onto norbornene (Table 7). The
more electron-rich N-methyl-2-iodo-3-indolecarbonitrile
(28b ) and the parent cyanoindole 28a furnished no
9284 J . Org. Chem., Vol. 67, No. 26, 2002

Carbopalladation of Nitriles
TABLE 8. An n u la tion of Su bstitu ted 2-Iod oben zon itr iles (Sch em e 6)a
a
b
See the Experimental Section for the reaction conditions. The reaction time was 48 h. c A byproduct, 4-methoxybenzonitrile, was
isolated in 16% yield.
annulation products (entries 1 and 2). Considering the
possibility that sluggish oxidative addition of the electron-
rich 28a and 28b to the palladium catalyst may be
responsible for these disappointing results, we examined
the reaction of norbornene with the more electron-poor
28c. This reaction afforded mostly N-(benzenesulfonyl)-
indole-3-carbonitrile. However, the annulation product
40 was also obtained, albeit only in a modest 16% yield
(entry 3). Steric hindrance around the reaction site
probably accounts for the large amount of the reduced
starting material in this reaction.
To separate sterics from electronic effects, a series of
indolecarbonitriles with a different substitution pattern
was studied. The electron-rich 27b furnished a 77% yield
of the heterocyclic annulation product 41 (entry 4), whose
skeleton is related to that of a key intermediate in the
synthesis of a natural product, yuehchukene, and its
analogues.40 The unprotected indolecarbonitrile 27a af-
forded 2-cyanoindole in a high yield and no annulation
product (entry 5). This result is likely caused by the ease
of nitrogen deprotonation in 27a , which leads to the
formation of a negatively charged arylpalladium inter-
mediate and impedes its coordination and subsequent
addition to norbornene. The annulation of N-(benzene-
sulfonyl)-3-iodoindole-2-carbonitrile (27c) was far more
successful, the target product 42 being formed in a 69%
isolated yield (entry 6). Desulfonylation and subsequent
reduction of the C-I bond in 27c accounted for 20% of
the starting material, which brings the corrected yield
of 42 to 86%. Interestingly, no desulfonylated annulation
products were detected in the reactions of either 27c or
28c (entries 3 and 6).
The steric hindrance around the reaction site appears
to have a pronounced effect on the annulation of indole-
carbonitriles (compare entries 3 and 6, and 1 and 4),
although other factors cannot be excluded. However, the
success of the annulation of both the electron-rich 27b
and the electron-poor 27c suggests that the electronic
density of the indole ring does not play a significant role
in this reaction.
In contrast, the electronic effects of the substituents
in the benzene ring appear to have a major influence
on the alkyne annulation with substituted 2-iodobenzo-
nitriles (Table 8). Thus, annulation of electron-deficient
benzonitrile derivatives 29 and 22 onto diphenylacetylene
afforded only moderate yields of indenones 43 and 44
(entries 1 and 2) compared to the reaction with the parent
system (entry 3). The electron-rich 2-iodo-3-methoxy-
benzonitrile (21) also produced indenone 45 in a modest
yield (entry 4). On the other hand, the annulation of
diphenylacetylene by the less sterically hindered 30
resulted in the formation of indenone 46 in a much higher
yield (entry 5).
Both electron-deficient and electron-rich benzonitriles
gave equally good results when used in the annulation
of norbornene (Table 8). The yields of the polycyclic
ketones 47-50 were as good as, or better than, the yields
of the corresponding indenones. Electron-withdrawing
(40) Cheng, K. F.; Chan, T. T.; Lai, T. F.; Kong, Y. C. J . Chem. Soc.,
Perkin Trans. 1 1988, 3317.
J . Org. Chem, Vol. 67, No. 26, 2002 9285

Pletnev et al.
iodoarenenitriles has been developed. The reaction is
compatible with a variety of functional groups and affords
products in good to excellent yields. We have also gained
some insights into the mechanism of nitrile carbopalla-
dation through variation of the base and a study of
electronic and steric effects in substituted 2-iodobenzoni-
triles and indolecarbonitriles. This chemistry illustrates
that there may be other organopalladium reactions which
will occur intramolecularly that normally do not occur
by intermolecular processes.
F IGURE 1. Electronic effects of substituent Z on annulations
involving 2-iodobenzonitriles.
substituents did not have nearly as big an effect on the
annulation of norbornene with 29 and 22 (entries 1 and
2), although the yields of 47 and 48 were still lower than
those obtained with 2-iodobenzonitrile itself (entry 3).
Annulation of the relatively hindered 21 onto norbornene
gave a higher yield compared to the corresponding
reaction with diphenylacetylene (entry 4) for reasons that
are not obvious. A reduction product, 4-methoxybenzo-
nitrile, was formed in 16% yield from 30, diverting some
starting material from the annulation and lowering the
otherwise excellent yield of 50 (entry 5).
Exp er im en ta l Section
Gen er a l P r oced u r es. 1H and 13C NMR spectra were
recorded at 300 and 75 MHz or 400 and 100 MHz, respectively.
Thin-layer chromatography was performed using commercially
prepared 60-mesh silica gel plates, and visualization was
effected with short-wavelength UV light (254 nm) and basic
KMnO4 solution [3 g of KMnO4 + 20 g of K2CO3 + 5 mL of
NaOH (5%) + 300 mL of H2O]. All melting points are
uncorrected. All reagents were used directly as obtained
commercially unless otherwise noted. Pd(OAc)2 and PPh3 were
donated by commercial sources. Pd(dba)2 was prepared ac-
cording to a published procedure.42 The preparation and
characterization of all starting materials can be found in the
Supporting Information.
Gen er a l P r oced u r e for th e P a lla d iu m -Ca ta lyzed An -
n u la tion of Alk yn es a n d Bicyclic Alk en es w ith 2-Iod o-
a r en en itr iles. Palladium bis(dibenzylideneacetone) (14.4 mg,
0.025 mmol), Et3N (25.3 mg, 0.25 mmol), 2-iodoarenenitrile
(0.25 mmol), the alkyne or bicyclic alkene (0.75 mmol), and 5
mL of a 9:1 DMF-water mixture were placed in a 4 dram vial,
which was heated in an oil bath at 130 °C for the appropriate
period of time. The reaction mixture was cooled, diluted with
ether, washed with saturated aq NH4Cl, dried over anhydrous
Na2SO4, and filtered. The solvent was evaporated under
reduced pressure, and the product was isolated by chroma-
tography on a silica gel column.
We propose the following model to account for the
electronic effects of the substituent on the aromatic ring
in the annulations onto alkynes and alkenes (Figure 1).
For the organopalladium intermediate III to successfully
add to the cyano group, there has to be a sufficient partial
negative charge (δ-) on the carbon atom of the Pd-C
bond, as well as reasonable electron density in the
carbon-nitrogen triple bond for the nitrile to effectively
coordinate to palladium. When the annulation involves
an alkyne, intermediate IIIa is formed, in which an
electron-withdrawing substituent, Z, directly reduces, via
conjugation, both the electron density of the cyano group
and the partial negative charge on the carbon bearing
the palladium moiety, thus inhibiting vinylpalladium
attack on the CN and lowering the yield of the annula-
tion.41 In the case of norbornene, Z has no direct effect
on the partial negative charge δ- of the Pd-C bond
(intermediate IIIb) and only affects the coordinating
ability of the cyano group. It is also possible that nitrile
carbopalladation in IIIb is promoted by steric interac-
tions between the Pd and the bridging methylene unit
of the norbornyl system as it relieves the steric conges-
tion. As a result, norbornene annulation by electron-poor
substrates furnishes higher yields than the corresponding
diphenylacetylene reactions. An electron-donating Z group
should not interfere with the annulation, except perhaps
by slowing the initial oxidative addition, as observed in
the case of 30 (entry 5, Table 8).
The following compounds, prepared by the above procedure,
have been previously reported: indenones 1, 3, 4, 5, 6, 7, and
9, polycyclic aromatic ketones 11 and 12, and naphthenone
16.7c,20
7-Aza -1,2,3,4,4a ,9a -h exa h yd r o-1,4-m et h a n oflu or en -9-
on e (37). Compound 37 was obtained in a 52% yield from the
reaction of 3-cyano-4-iodopyridine (24) and norbornene under
the indicated conditions after purification by column chroma-
tography using 1:2 hexanes/EtOAc: light yellow solid, mp 53-
54 °C (hexanes/EtOAc); 1H NMR (CDCl3) δ 0.75-0.82 (m, 1H),
0.98-1.05 (m, 1H), 1.33-1.54 (m, 2H), 1.62-1.84 (m, 2H), 2.46
(d, J ) 3.9 Hz, 1H), 2.54 (d, J ) 6.3 Hz, 1H), 2.65 (d, J ) 3.6
Hz, 1H), 3.19 (d, J ) 6.3 Hz, 1H), 7.48 (dt, J ) 5.1, 0.9 Hz,
1H), 8.74 (d, J ) 5.1 Hz, 1H), 8.87 (d, J ) 0.9 Hz, 1H); 13C
NMR (CDCl3) δ 28.7, 29.1, 32.7, 40.8, 41.3, 48.2, 55.9, 121.7,
134.8, 146.3, 154.3, 164.9, 207.8; IR (neat) 1714, 2954 cm-1
;
Con clu sion s
HRMS m/z 199.09995 (calcd for C13H13NO, 199.099714).
N-Meth yl-6-oxo-6a,7,8,9,10,10a-h exah ydr o-7,10-m eth an o-
6H-in d en o[2,1-b]in d ole (41). Compound 41 was obtained in
a 77% yield from the reaction of N-methyl-3-iodoindole-2-
carbonitrile (27b) and norbornene under the indicated condi-
tions after purification by column chromatography using 4:1
hexanes/EtOAc: light yellow oil; 1H NMR (CDCl3) δ 0.94-1.03
(m, 2H), 1.33-1.37 (m, 1H), 1.41-1.45 (m, 1H), 1.62-1.77 (m,
2H), 2.46 (d, J ) 2.7 Hz, 1H), 2.54 (d, J ) 2.7 Hz, 1H), 2.76 (d,
J ) 3.6 Hz, 1H), 3.11 (d, J ) 3.6 Hz, 1H), 3.90 (s, 3H), 7.16-
7.20 (m, 1H), 7.34-7.43 (m, 2H), 7.73-7.75 (m, 1H); 13C NMR
(CDCl3) δ 28.7, 28.9, 30.0, 32.0, 38.6, 38.8, 42.3, 62.0, 110.9,
120.1, 121.8, 122.5, 126.6, 140.9, 145.2, 146.2, 196.3; IR (neat)
The carbon-nitrogen triple bond of aryl and heteroaryl
nitriles has been observed to readily participate in
organopalladium annulation reactions. An efficient pro-
cedure for the synthesis of 2,3-diarylindenones and
polycyclic aromatic ketones from readily prepared o-
(41) This model can also account for the results we have obtained
in the attempted annulation of diphenylacetylene by 2-bromobenzoni-
trile (30% yield of 1 with 80% conversion of the starting material after
72 h) and 2-cyanophenyl triflate (no annulation product). The annu-
lation is probably impeded since the Pd-Br bond in IIIa (X ) Br) would
reduce the partial negative charge on the vinylic carbon due to
bromine’s relatively high electronegativity, and palladium triflates
(IIIa , X ) OTf) are known to easily dissociate and form cationic
palladium complexes, obviously incapable of nucleophilic reactions.
(42) Ukai, T.; Kawazura, H.; Ishii, Y.; Bonnet, J . J .; Ibers, J . A. J .
Organomet. Chem. 1974, 65, 253.
9286 J . Org. Chem., Vol. 67, No. 26, 2002

Carbopalladation of Nitriles
1682, 2952, 3054 cm-1; HRMS m/z 251.131315 (calcd for
Ack n ow led gm en t. We thank the donors of the
Petroleum Research Fund, administered by the Ameri-
can Chemical Society, for partial support of this re-
search, and J ohnson Matthey, Inc. and Kawaken Fine
Chemicals Co., Ltd. for donating the palladium acetate
and triphenylphosphine.
C
17H17NO, 251.131014).
5-Cya n o-2,3-d ip h en yl-1-in d en on e (44). Compoud 44 was
obtained in a 47% yield from the reaction of 1,4-dicyano-2-
iodobenzene (22) and diphenylacetylene under the indicated
conditions after purification by column chromatography using
1
1:2 hexanes/EtOAc: red solid, mp 179-181 °C (hexanes); H
NMR (CDCl3) δ 7.25-7.31 (m, 5H), 7.35-7.41 (m, 3H), 7.45-
7.47 (m, 3H), 7.63-7.67 (m, 2H); 13C NMR (CDCl3) δ 116.6,
118.2, 122.9, 123.6, 128.3, 128.4, 128.5, 128.9, 129.2, 129.7,
129.9, 130.0, 131.6, 133.8, 133.9, 146.0, 154.4, 194.6; IR (neat)
1716, 2229, 3053 cm-1; HRMS m/z 307.100183 (calcd for
Su p p or tin g In for m a tion Ava ila ble: Preparation and
characterization of the starting materials, references to the
preparation methods and characterization data for all known
products, and characterization data for all new compounds
1
(including copies of H and 13C NMR spectra). This material
C
22H13NO, 307.099714).
is available free of charge via the Internet at http://pubs.acs.org.
Characterization of all other annulation products prepared
in this study can be found in the Supporting Information.
J O026178G
J . Org. Chem, Vol. 67, No. 26, 2002 9287