Palladium-catalyzed carbonylative cyclization of 1-iodo-2-alkenylbenzenes

Article abstract of DOI:10.1021/ja9533196

The Pd-catalyzed carbonylation of ω-vinyl-substituted o-iodoalkenylbenzenes 1-4 can provide up to modest yields (50-60%) of 5- and 6-membered Type I cyclic acylpalladation products, i.e., α,β-unsaturated cyclic ketones, in the absence of an external nucleophile and high yields of 5- and 6-membered Type II cyclic acylpalladation products, i.e., α- or β-((alkoxycarbonyl)methyl)substituted cyclic ketones in the presence of an alcohol, e.g., MeOH. In cases where no such processes are available, other side reactions, such as cyclic carbopalladation, polymeric acylpalladation, and trapping of acylpalladiums via esterification and other processes may become predominant. Neither smaller, i.e., 3- or 4-membered, nor 7-membered or larger cyclic ketones appear to be accessible by the reaction. In most cases, the exo-mode cyclic acylpalladation takes place exclusively. However, the cyclic acylpalladation of 3 proceeds exclusively via endo-mode cyclization to give 5-membered ketones. Substitution of one or more hydrogens in the ω-vinyl group with carbon groups has significant effects on the reaction course. Those substrates containing a 1,2-disubstituted alkenyl group in place of a vinyl group, i.e., 19-22 and 24 excluding 25, can give monomeric cyclic acylpalladation products in high yields. These results represent a major deviation from those obtained with 1 and 2. In the absence of an external nucleophile, formation of Type I cyclic acylpalladation products is, in some cases, accompanied by Type III cyclic acylpalladation involving trapping of acylpalladiums by internal enolates. In the presence of MeOH or other alcohols, Type II acylpalladation products have been obtained in respectable yields from 19-20, 23, and 24. In the presence of an alcohol, premature esterification can be a serious side reaction. However, this problem can be alleviated using i-PrOH or t-BuOH in place of MeOH in combination with appropriate solvents, typically those of lower polarity. Heteroatom-containing substituents on the ω-vinyl groups also exert significant effects on cyclic acylpalladation. Electron-donating substituents tend to lead to high yields of cyclic acylpalladation products, while electron-withdrawing alkoxycarbonyl groups conjugated with the ω-alkenyl group tend to give lower yields of cyclic acylpalladation products. With Me₃Si and alkoxycarbonyl groups products of apparent endo-mode cyclic acylpalladation, i.e., naphthols, have been obtained in significant yields (25-50%). Free OH and other nucleophilic heteroatom groups can seriously interfere with cyclic acylpalladation, and they must be appropriately protected in most cases, although there are indications that acylpalladation-lactonization tandem processes similar to Type II cyclic acylpalladation might be developed.

Full text of DOI:10.1021/ja9533196

5904
J. Am. Chem. Soc. 1996, 118, 5904-5918
Palladium-Catalyzed Carbonylative Cyclization of
1-Iodo-2-alkenylbenzenes
Ei-ichi Negishi,* Christophe Cope´ret, Shengming Ma, Takeshi Mita,
Takumichi Sugihara, and James M. Tour
Contribution from the Department of Chemistry, Purdue UniVersity,
West Lafayette, Indiana 47907
ReceiVed September 29, 1995X
Abstract: The Pd-catalyzed carbonylation of ω-vinyl-substituted o-iodoalkenylbenzenes 1-4 can provide up to modest
yields (50-60%) of 5- and 6-membered Type I cyclic acylpalladation products, i.e., R,â-unsaturated cyclic ketones,
in the absence of an external nucleophile and high yields of 5- and 6-membered Type II cyclic acylpalladation
products, i.e., R- or â-((alkoxycarbonyl)methyl)substituted cyclic ketones in the presence of an alcohol, e.g., MeOH.
In cases where no such processes are available, other side reactions, such as cyclic carbopalladation, polymeric
acylpalladation, and trapping of acylpalladiums via esterification and other processes may become predominant.
Neither smaller, i.e., 3- or 4-membered, nor 7-membered or larger cyclic ketones appear to be accessible by the
reaction. In most cases, the exo-mode cyclic acylpalladation takes place exclusively. However, the cyclic
acylpalladation of 3 proceeds exclusively via endo-mode cyclization to give 5-membered ketones. Substitution of
one or more hydrogens in the ω-vinyl group with carbon groups has significant effects on the reaction course.
Those substrates containing a 1,2-disubstituted alkenyl group in place of a vinyl group, i.e., 19-22 and 24 excluding
25, can give monomeric cyclic acylpalladation products in high yields. These results represent a major deviation
from those obtained with 1 and 2. In the absence of an external nucleophile, formation of Type I cyclic acylpalladation
products is, in some cases, accompanied by Type III cyclic acylpalladation involving trapping of acylpalladiums by
internal enolates. In the presence of MeOH or other alcohols, Type II acylpalladation products have been obtained
in respectable yields from 19-20, 23, and 24. In the presence of an alcohol, premature esterification can be a
serious side reaction. However, this problem can be alleviated using i-PrOH or t-BuOH in place of MeOH in
combination with appropriate solvents, typically those of lower polarity. Heteroatom-containing substituents on the
ω-vinyl groups also exert significant effects on cyclic acylpalladation. Electron-donating substituents tend to lead
to high yields of cyclic acylpalladation products, while electron-withdrawing alkoxycarbonyl groups conjugated with
the ω-alkenyl group tend to give lower yields of cyclic acylpalladation products. With Me3Si and alkoxycarbonyl
groups products of apparent endo-mode cyclic acylpalladation, i.e., naphthols, have been obtained in significant
yields (25-50%). Free OH and other nucleophilic heteroatom groups can seriously interfere with cyclic
acylpalladation, and they must be appropriately protected in most cases, although there are indications that
acylpalladation-lactonization tandem processes similar to Type II cyclic acylpalladation might be developed.
Until recently, carbon-carbon bond formation via transition
Scheme 1
metal-catalyzed carbonylation had been dominated by the
transformations shown in Scheme 1. Specifically, formation
of carbon-carbon bonds is achieved predominantly via migra-
tory insertion of CO. Acylmetal derivatives thus formed can
react further with various nucleophiles including carbon nu-
cleophiles, such as organometals, alkynes, and metal cyanides,
for the formation of the second carbon-carbon bond.1
In principle, acylmetal derivatives can add to π-bonds2 via
carbometalation3 (acylpalladation hereafter), but little was known
about synthetic methods and procedures for the preparation of
cyclic ketones based on this process. We have therefore
explored such synthetic methods involving the addition of
acylpalladation derivatives to alkenes and developed a series
of carbonylative cyclization reactions promoted or catalyzed by
Pd complexes, of which Type I-III cyclic acylpalladation (Ac-
Pd hereafter) processes shown in Scheme 2 appear to be of
considerable synthetic significance.4,5 Although the initial
examples of the Type I Ac-Pd reaction were stoichiometric in
Pd,4a we have subsequently demonstrated that this process can
be catalytic.4b The Type I and Type II Ac-Pd processes appear
to be mechanistically related to a carbonylative diene cyclization
reaction6 and a carbonylative polymerization of alkenes produc-
X Abstract published in AdVance ACS Abstracts, June 1, 1996.
(1) (a) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G.
Principles and Applications of Organotransition Metal Chemistry; Univer-
sity Science Books: Mill Valley, CA, 1987. (b) Colquhoun, H. M.;
Thompson, D. J.; Twigg, M. V. Carbonylation; Plenum Press: New York,
1991. (c) For Pd-catalyzed carbonylation reactions, see: Heck, R. F.
Palladium. Reagents in Organic Syntheses; Academic Press: New York,
1985.
(2) For a related reaction involving Ni, see, for example: Chiusoli, G.
P.; Cassar, L. Angew. Chem., Int. Ed. Engl. 1967, 6, 124.
(3) For reviews, see: (a) Negishi, E. Acc. Chem. Res. 1987, 20, 65. (b)
Negishi, E. Pure Appl. Chem. 1992, 74, 323.
(4) (a) Negishi, E.; Miller, J. A. J. Am. Chem. Soc. 1983, 105, 6761.
(b) Zhang, Y.; O’Connor, B.; Negishi, E. J. Org. Chem. 1988, 53, 5588.
(c) Tour, J. M.; Negishi, E. J. Am. Chem. Soc. 1985, 107, 8289. (d) Negishi,
E.; Wu, G.; Tour, J. M. Tetrahedron Lett. 1988, 29, 6745.
(5) (a) Negishi, E.; Tour, J. M. Tetrahedron Lett. 1986, 27, 4869. (b)
Shimoyama, I.; Zhang, Y.; Wu, G.; Negishi, E. Tetrahedron Lett. 1990,
31, 2841. (c) Wu, G.; Shimoyama, I.; Negishi, E. J. Org. Chem. 1991, 56,
6506. (d) For a paper by other workers reporting the Type III process,
see: Roberto, D.; Catellani, M.; Chiusoli, G. P. Tetrahedron Lett. 1988,
29, 2115.
S0002-7863(95)03319-1 CCC: $12.00 © 1996 American Chemical Society

CarbonylatiVe Cyclization of 1-Iodo-2-alkenylbenzenes
J. Am. Chem. Soc., Vol. 118, No. 25, 1996 5905
Scheme 2
ing polyketones.7 However, neither involves the use of organic
halides. Also related are a Pd-catalyzed carbonylative cycliza-
tion reaction of norbornene and allylic halides8 and a Ni-
promoted reaction of alkynes and allylic halides to give
cyclopentanones.9 Noteworthy extensions of cyclic acylpalla-
dation and the corresponding Ni-catalyzed reactions of alkenes
include those cases where organopalladiums generated via Pd
and Ni ene reactions are involved.10 Although different,
alkoxycarbonylpalladation of alkenes and alkynes must also
involve addition of a carbonyl-palladium bond to alkenes11 and
alkynes.12
(10) (a) Oppolzer, W.; Bedaya-Zurita, M.; Switzer, C. Y. Tetrahedron
Lett. 1988, 29, 6433. (b) Oppolzer, W.; Keller, T. H.; Bedoya-Zurita, M.;
Stone, C. Tetrahedron Lett. 1989, 30, 5883. (c) Oppolzer, W. Pure Appl.
Chem. 1990, 62, 1941. (d) Oppolzer, W.; Stone, J. C. HelV. Chim. Acta
1991, 74, 465. (e) Oppolzer, W.; Bienayme´, H.; Genevois-Borella, A. J.
Am. Chem. Soc. 1991, 113, 9660. (f) Keese, R.; Guidetti-Grept, R.; Herzog,
B. Tetrahedron Lett. 1992, 33, 1207. (g) Oppolzer, W.; Ando, A. Chimia
1992, 46, 122. (h) Ihle, N. C.; Heathcock, C. H. J. Org. Chem. 1993, 58,
560. (i) Oppolzer, W.; Robyr, C. Tetrahedron 1994, 50, 415. (j) Oppolzer,
W. In ComprehensiVe Organometallic Chemistry II; Abel, E. W., Stone, F.
G. A., Wilkinson, G., Hegedus, L. S., Eds.; Pergamon: New York, 1995;
Vol. 12, p 905.
(6) Brewis, S.; Hughes, P. R. J. Chem. Soc., Chem. Commun. 1965, 489;
1966, 6.
(7) (a) Tsuji, J.; Hosaka, S. J. Polym. Lett. 1965, 3, 705. (b) Sen, A.;
Lai, T. W. J. Am. Chem. Soc. 1982, 104, 3520.
(8) (a) Amari, E.; Catellani, M.; Chiusoli, G. P. J. Organomet. Chem.
1985, 285, 383. (b) Larock, R. C.; Takagi, K.; Burkhart, J. P.; Hershberger,
S. S. Tetrahedron 1986, 42, 3759.
(9) (a) Camps, F.; Coll, J.; Llebaria, A.; Moreto´, J. M. Tetrahedron Lett.
1988, 29, 5811. (b) Camps, F.; Coll, J.; Moreto´, J. M.; Torras, J. J. Org.
Chem. 1989, 54, 1969. (c) Llebaria, A.; Camps, F.; Moreto´, J. M.
Tetrahedron 1993, 49, 1283.
(11) James, D. E.; Stille, J. K. J. Am. Chem. Soc. 1976, 98, 1810.
(12) Murray, T. F.; Samsel, E. G.; Varma, V.; Norton, J. R. J. Am. Chem.
Soc. 1981, 103, 7520.

5906 J. Am. Chem. Soc., Vol. 118, No. 25, 1996
Negishi et al.
In an attempt to extend the scope of the cyclic acylpalladation
reaction, we unexpectedly found in 198913 that, even in the
presence of CO, cyclic carbopalladation of alkynes to give five-
and six-membered rings proceeded without incorporation of CO
and that the organopalladium cyclization product could then be
trapped by carbonylative esterification. This has been further
developed into a cyclization methodology involving cascade
carbopalladation and termination via carbonylative esterifica-
tion.14 It has also been extended to those cases where alkenes
are used in place of alkynes.15 Despite the failure to incorporate
CO in the cyclization mentioned above we have found that
acylpalladation of alkynes per se is not an intrinsically unfavor-
able process and that both intermolecular16 and intramolecular
versions14 producing five-membered ketones and their deriva-
tives are feasible.
Additionally, we have also found that acylpalladium deriva-
tives can serve as sources of ketenes which can undergo [2 +
2] cycloaddition with alkenes.5c Various possible courses of
the Pd-catalyzed reactions of alkene-containing aryl and alkenyl
halides in the presence of CO and a base, such as Et3N, may be
summarized as shown in Scheme 2. Only the exo-mode cycliza-
tion proceeses are shown in Scheme 2 for the sake of simplicity.
However, the corresponding endo-mode cyclization processes
can proceed and have in fact been observed in some cases (Vide
infra). Despite all of these findings reported mainly since 1983
surprisingly little is known about (a) the scope of cyclic acyl-
palladation and (b) factors governing the selection among the
various paths shown in Scheme 2. The major objective of this
study is to systematically investigate these aspects of Pd-cat-
alyzed cyclic acylmetalation of alkenes17 and related reactions.
o-Iodoallylbenzene (1) was prepared by treatment of iodo-
benzene diacetate with propargyltrimethylsilane (2 equiv) in the
presence of BF3‚OEt2 and MgSO4 in CH2Cl2, which, after
hydrolysis, produced o-iodopropargylbenzene in 60% yield,18
followed by reduction with i-Bu2AlH in hexane at 25 °C.
o-Iodohomoallylbenzene (2) was prepared by the reaction of
o-iodobenzyl bromide with allylmagnesium bromide, while
alkylation of dimethyl allylmalonate with o-iodobenzyl bromide
provided 4. The preparation of 3 was achieved in 73% yield
by the reaction of o-iodobenzaldehyde with H2CdPPh3. In most
of the carbonylation experiments, 5 mol % of Cl2Pd(PPh3)2 was
used as a catalyst, and NEt3 (1.5-4 equiv) was used as a base
to scavenge HI. In most cases, the use of 1.5-2.0 equiv of
NEt3 is satisfactory. Under Conditions I and II, no external
nucleophiles, such as alcohols and amines, were employed with
the expectation that, under such conditions, Type I cyclic Ac-
Pd process might be promoted. It is, however, conceivable to
observe other competitive processes, especially Type III cyclic
Ac-Pd processes. Under Conditions III and IV an alcohol, e.g.,
MeOH, i-PrOH, or t-BuOH, was used to promote the Type II
cyclic Ac-Pd process. In these cases, however, premature
trapping of the initially formed acylpalladium derivatives before
cyclic acylpalladation and other competing processes might also
be observed. The CO pressure under Conditions I and III was
essentially 1 atm, whereas 30-50 atm of CO was employed
under Conditions II and IV. Some other parameters, such as
solvents, times, and temperatures, were varied as deemed
appropriate. The experimental results with 1-4 are summarized
in Table 1.
The Pd-catalyzed carbonylation of o-iodo-ω-alkenylbenzenes
containing a terminal vinyl group (1-4) in the absence of an
external nucleophile can produce up to a modest yield of the
expected Type I cyclic Ac-Pd product, e.g., 5 (58%, entry 1-3)
and 8 (50%, entry 1-7). However, the Heck reaction19,20 can
be a significant side reaction in cases where the Heck reaction
can yield common (5- to 7-membered) rings (entries 1-4, 1-9,
and 1-10). In addition, some apparently polymeric processes
must also competitively take place, as judged by NMR
spectroscopy, GLC analysis, and the viscosity of some isolated
products. Those polymeric acylpalladation processes that are
shown in Scheme 2 appear to be likely candidates for the latter,
although this aspect remains to be further clarified.
Results and Discussion
Scope of Cyclic Acylpalladation with Respect to the Prod-
uct Ring Size. To probe the scope of the cyclic acylpalladation
reaction with respect to the product ring size, 1-4 were prepared
and subjected to four representative reaction conditions (Condi-
tions I-IV): I, CO (1 atm), 5% Cl2Pd(PPh3)2, NEt3 (1.5-4
equiv); II, CO (30-50 atm), 5% Cl2Pd(PPh3)2, NEt3 (1.5-4
equiv); III, CO (1 atm), 5% Cl2Pd(PPh3)2, NEt3 (1.5-4 equiv),
ROH (R ) Me, i-Pr, or t-Bu); and IV, CO (30-50 atm), 5%
Cl2Pd(PPh3)2, NEt3 (1.5-4 equiv), ROH (R ) Me, i-Pr, or t-Bu).
With the hope of suppressing the putative polymerization
processes via intermolecular acylpalladation, we attempted to
trap acylpalladium derivatives with external nucleophiles and
chose MeOH, i-PrOH, and t-BuOH for this purpose. Any
external nucleophile can, a priori, trap acylpalladium derivatives1c
formed before or after cyclic acylpalladation, and both of these
processes may even competitively and simultaneously take place
(Scheme 3). For successful trapping of acylpalladium deriva-
tives after cyclic acylpalladation, it is therefore mandatory that
the relative rates of the pertinent processes be as follows: cyclic
Ac-Pd process > alcoholysis of acylpalladium derivatives >
intermolecular (polymeric) Ac-Pd process.
(18) Ochiai, M.; Ito, T.; Takaoka, Y.; Masaki, Y. J. Am. Chem. Soc.
1991, 113, 1319.
(19) (a) Heck, R. F. Org. React. 1982, 27, 345. (b) de Meijere, A.;
Meyer, F. E. Angew. Chem., Int. Ed. Engl. 1994, 33, 2379. (c) Negishi,
E.; Cope´ret, C.; Ma, S.; Liou, S.-Y.; Liu, F. Chem. ReV. 1996, 96, 365.
(20) For some early examples of the cyclic Heck reaction producing
carbocycles, see: (a) Narula, C. K.; Mak, K. T.; Heck, R. F. J. Org. Chem.
1983, 48, 2792. (b) Grigg, R.; Stevenson, P.; Worakun, T. J. Chem. Soc.,
Chem. Commun. 1984, 1073. (c) Reference 4c. (d) Abelman, M. M.; Oh,
T.; Overman, L. E. J. Org. Chem. 1987, 52, 4133. (e) Negishi, E.; Zhang,
Y.; O’Connor, B. Tetrahedron Lett. 1988, 29, 2915. (f) O’Connor, B.;
Zhang, Y.; Negishi, E. Tetrahedron Lett. 1988, 29, 3903. (g) Zhang, Y.;
O’Connor, B.; Negishi, E. J. Org. Chem. 1988, 53, 5588. (h) Larock, R.
C.; Song, H.; Baker, B. E.; Gong, W. H. Tetrahedron Lett. 1988, 29, 2919.
(13) Zhang, Y.; Negishi, E. J. Am. Chem. Soc. 1989, 111, 3454.
(14) Sugihara, T.; Cope´ret, C.; Owczarczyk, Z.; Harring, L. S.; Negishi,
E. J. Am. Chem. Soc. 1994, 116, 7923.
(15) (a) Grigg, R.; Kennewell, P.; Teasdale, A. Tetrahedron Lett. 1992,
33, 7789. (b) Grigg, R.; Sridharan, V. Tetrahedron Lett. 1993, 34, 7471.
(c) Grigg, R.; Redpath, J.; Sridharan, V.; Wilson, D. Tetrahedron Lett. 1994,
35, 7661.
(16) Cope´ret, C.; Sugihara, T.; Wu, G.; Shimoyama, I.; Negishi, E. J.
Am. Chem. Soc. 1995, 117, 3422.
(17) For our study of acylpalladation of alkynes, see refs 14 and 16.

CarbonylatiVe Cyclization of 1-Iodo-2-alkenylbenzenes
J. Am. Chem. Soc., Vol. 118, No. 25, 1996 5907
Table 1. Pd-Catalyzed Carbonylation of o-Iodo-ω-alkenylbenzenes in the Absence of an Alcohol or an External Nucleophile
products (yield,a %)
entry
substrate
cond.
solvent
DMF
DMF
MeCN-THF
DMF
DMF
temp, °C
time, h
Type Ib Ac-Pd
Type IIIc Ac-Pd
Heckd
others
1-1
1-2
1-3
1-4
1-5
1-6
1-7
1-8
1-9
1-10
1
1
1
2
2
3
3
3
4
4
Ie
IIh
II
I
II
I
I
II
I
60
100
80
100
100
80
24
15
18
24
24
1
5 (25)
5 (20)
5 (58)
6 (trace)
6 (trace)
8 (9)
8 (50)
8 (20)
10 (f)
f
f
f
f
f
f
f
f
f
f
f
f
f
g
g
g
g
g
j
7 (16)
7 (trace)
DMF
f
f
f
MeCN-PhH
MeCN-THF
MeCN-THF
MeCN-THF
80
6
9 (11)
j
100
100
100
12
12
12
11 (92)k
11 (54)k
II
10 (f)
a By NMR spectroscopy or GLC. b Type I cyclic acylpalladation product. See text for its definition. c Type III cyclic acylpalladation product.
See text for its defintion. d Type I cyclic carbopalladation product or cyclic Heck reaction product. e I: 1 atm of CO, 5 mol % of Cl2Pd(PPh3)2, NEt3
(1.5-4 equiv) unless otherwise mentioned. f Not detected. g Apparently polymeric. h II: 30-50 atm of CO, 5 mol % of Cl2Pd(PPh3)2, NEt3 (1.5-4
equiv) unless otherwise mentioned. i Exo/endo ) 63/37. j At least several other products are present. k Exo/endo ) 45/55.
Table 2. Pd-Catalyzed Carbonylation of o-Iodo-ω-alkenylbenzenes in the Presence of an Alcohol
O
COOR
O
O
O
COOMe
COOMe
COMe
COMe
O
MeOOC COOMe
COOMe
15
17a (R = Me)
13
12
14
16
COOR
18a (R = Me)
18b (R = t-Bu)
COOMe
COOMe
18
products (yield,a %)
cond
(alcohol, equiv)
temp,
°C
time,
h
Type Ib
Ac-Pd
Type IIc
Ac-Pd
premature
alcoholysis
entry
substrate
solvent
others
2-1
2-2
2-3
2-4
2-5
2-6
2-7
2-8
2-9
2-10
1
1
2
2
2
3
3
4
4
4
III (MeOH, 4)
IV (MeOH, 4)
III (MeOH, 100)
III (MeOH, 100)
IV (MeOH, 4)
III (MeOH, 4)
IV (MeOH, 4)
IV (MeOH, 4)
IVg (t-BuOH, 4)
IVi (t-BuOH, 4)
MeCN-THF
DMF
MeOH
80
100
65
reflux
100
80
100
100
100
100
20
20
24
6
11
6
5 (18)
e
e
e
d
8 (26)
8 (e2)
10 (e)
10 (e)
10 (e)
12 (16)
12 (90)
e
e
14 (85)
15 (e3)
15 (74)
e
e
e
d
d
d
d
13 (37)
13 (5)
d
16 (14)
16f (e2)
17a (26)
e
7 (48)
MeOH
7 (72)f
MeCN-PhH
MeCN-PhH
PhH
MeCN-PhH
PhH
d
9 (28)
e
6
12
24
24
11f (33)h and 18a (21)
11 (68)h and 18b (5)
11 (30)h and 18b (26)
PhH
e
a By NMR spectroscopy or GLC. b Type I cyclic acylpalladation product. See text for its definition. c Type II cyclic acylpalladation product.
See text for its definition. d Not analyzed. e Not detected. f Exo/endo ) 50/50. g 15 atm of CO used. h Exo/endo ) 45/55. i 80 atm of CO used.
Scheme 3
I Ac-Pd reaction, the cyclic Heck reaction, and premature esteri-
fication can be serious side reactions (entries 2-1, 2-3, 2-4, and
2-6). In the reaction of 3 at 1 atm of CO in the presence of
MeOH (Conditions III, entry 2-6), an amino derivative 9 was
obtained as a byproduct, which must have arisen via conjugate
addition of Et2NH to 8, which indeed occurs readily on mixing
the two reagents. Oxidation of Et3N catalyzed by Pd complexes
to give Et2NH and acetaldehyde upon hydrolysis is a known
process.21
In contrast with the reactions of 1-3, that of 4 does not
undergo cyclic acylpalladation to give 7-membered-ring ketones
(entry 2-8). Throughout this study no 7-membered-ring or larger
cyclic ketones have been obtained via cyclic acylpalladation.
Instead, 4 cyclizes via carbopalladation to give 6-membered
rings (entries 2-8 through 2-10). At low pressures of CO (15
atm), the cyclic Heck reaction, i.e., the Type I cyclic carbopalla-
dation (C-Pd hereafter) process, which does not incorporate CO
into the product at all, is dominant (entry 2-9), while the Type
II cyclic C-Pd process involving a cyclic carbopalladation-
The experimental results obtained with 1-4 under Conditions
III and IV are summarized in Table 2, which reveal the follow-
ing. Under Conditions IV using 30-50 atm of CO and MeOH
(4 equiv) as an alcohol 1-3 are converted in high yields (70-
90%) into the Type II Ac-Pd products, i.e., 12 (entry 2-2), 14
(entry 2-5), and 15 (entry 2-7), respectively, even though 4 has
failed to produce the desired product 10 in a detectable yield
(entries 2-8 through 2-10). At lower pressures of CO, e.g., 1
atm, the yields of Type II Ac-Pd products are low, and the Type
(21) Murahashi, S.; Hirao, T.; Yano, T. J. Am. Chem. Soc. 1978, 100,
348.

5908 J. Am. Chem. Soc., Vol. 118, No. 25, 1996
Negishi et al.
carbonylative esterification tandem competes with the Heck
reaction at higher pressures of CO, e.g., 80 atm (entry 2-10).
In summary, the Pd-catalyzed carbonylation of o-iodoalk-
enylbenzenes containing a terminal vinyl group can provide up
to modest yields of 5-membered Type I cyclic Ac-Pd products
at 1 atm of CO in the absence of a nucleophile (Conditions I)
and high yields of 5- and 6-membered Type II cyclic Ac-Pd
products at 30-50 atm of CO in the presence of an alcohol,
e.g., MeOH (Conditions IV). In cases where no such processes
are available, other processes, such as cyclic carbopalladation,
polymeric acylpalladation, and trapping of acylpalladiums via
esterification, may become dominant. Neither smaller, i.e., 3-
or 4-membered, nor 7-membered or larger cyclic ketones appear
to be accessible by the reaction. In most cases, the exo-mode
cyclic acylpalladation takes place exclusively. However, the
cyclic acylpalladation of 3 proceeds exclusively via endo-mode
cyclization to give 5-membered rings (entries 1-7, 2-6, and 2-7).
Endo-mode cyclization via either carbopalladation or acylpal-
ladation is relatively rare. We earlier reported examples of
endo-mode acylpalladation to produce quinones5a (eq 1). We
also demonstrated a few years ago that some “apparent” endo-
mode carbopalladation reactions producing 6- and 7-membered
compounds actually proceed via exo-mode carbopalladation-
cyclopropanation-cyclopropylcarbinyl-to-homoallyl rearrange-
ment with concomitant ring expansion22 (eq 2). The endo-mode
acylpalladation reaction of 3 to give 5-membered ketones
appears to be unprecedented. Although no further mechanistic
insights are available at this time, it appears likely that the
reaction proceeds via a direct endo-mode cyclization process.
Although cyclopropanation via carbopalladation has been shown
to be very favorable,22 the corresponding cyclopropenation
appears to be much less favorable and has never been
observed.13,14,22 There have also been ample indications13,14,22
that formation of 4-membered rings via either carbopalladation
or acylpalladation must be generally unfavorable.23
provided 21a, while replacement of the methylation in the above
sequence with Pd-catalyzed phenylation gave 21b. The reac-
tions of o-iodobenzyl bromide with the lithio derivative of
methyl 1-cyclohexenecarboxylate and methallylmagnesium
chloride provided 22 and 23, respectively. The Wittig reaction
of o-iodobenzaldehyde with CH3CHdPPh3 gave 24 as a 60:40
mixture of the cis and trans isomers, while that of o-
iodoacetophenone with CH2dPPh3 afforded 25.
The experimental results obtained under Conditions I-IV are
summarized in Table 3. Those substrates containing a 1,2-
disubstituted alkene, i.e., 19 and 21a-22, all underwent the Pd-
catalyzed carbonylation in the absence of an alcohol to give
monomeric cyclic Ac-Pd products in high yields (entries 3-1 to
3-3, 3-9, 3-11, and 3-12). Specifically, conversion of 19, 21b,
and 22 into the corresponding Type I Ac-Pd products 26, 35,
and 36, respectively, proceeded cleanly in high yields (entries
3-1 to 3-3, 3-11, and 3-12), even though these products consisted
of both E and Z isomers. These results indeed represent a major
deviation from those obtained with 1 and 2 at 30-40 atm of
CO under Conditions II (cf. Table 1). The reaction of 21a under
the same conditions yielded a mixture of 29-31 in 84%
combined yield (entry 3-9). The use of a chelating ligand dppe,
i.e., (Ph2PCH2)2, in place of PPh3 led to a nearly exclusive
formation of 30 albeit only in 52% yield (Scheme 4). It should
be recalled that the parent o-iodohomoallylbenzene (2) failed
to produce 7 or any monomeric cyclization products in
detectable yields at 30-50 atm of CO in the absence of a
nucleophile (Condition II, entry 1-5). On the other hand,
conversion of 24 into 39 at 1 atm of CO under Conditions I
(entry 3-14) was lower-yielding than that of 3 into 8 (entry 1-7).
Both E and Z isomers of 19 gave a roughly 93:7 mixture of the
E and Z isomers of 26 (entries 3-1 to 3-3), indicating that the
products are thermodynamically equilibrated. In view of the
widely observed, strict requirement for â-cis hydrogens in the
â-elimination step,1c,22 the initial Ac-Pd product from 22 must
be a â,γ-unsaturated enone which then isomerizes to give 36
(entry 3-12).
Effects of Carbon Substituents in the ω-Vinyl Group. The
substrates 1-4 all contain the parent vinyl group. Substitution
of one or more of the three vinylic hydrogens was anticipated
to exert some profound effects on the reaction courses. To probe
this matter we chose 19-25 as simple and representative o-iodo-
ω-alkenylbenzenes containing variously di- and tricarbosubsti-
tuted alkenyl groups. The reaction of o-iodobenzyl bromide
with (E)-n-HexCHdCH(n-Bu)(i-Bu)2AlLi and lithium 1-cyclo-
hexenyltrimethylaluminate24 provided 19a and 20, respectively
(eq 3), while the Z isomer of 19a, i.e., 19b, was prepared by a
sequence shown in eq 4. Successive treatment of o-iodobenzyl
bromide with HCtCCH2MgBr, LDA and MeI, and DIBAH
(22) Owczarczyk, Z.; Lamaty, F.; Vawter, E. J.; Negishi, E. J. Am. Chem.
Soc. 1992, 114, 10091. See also: Terakado, M.; Miyazawa, M.; Yamamoto,
K. Synlett 1994, 134.
(23) For the formation of 4-membered rings, see: (a) Carpenter, N. E.;
Kucera, D. J.; Overman, L. E. J. Org. Chem. 1989, 54, 5846. (b) Grigg,
R.; Sridharan, V.; Sukirthalingam, S. Tetrahedron Lett. 1991, 32, 3855.
(24) Baba, S.; Van Horn, D. E.; Negishi, E. Tetrahedron Lett. 1976,
1927.
The reactions of these substrates in the presence of an alcohol
yielded similarly favorable results. Thus, 19b, 20, 23, and 24
afforded Type II Ac-Pd products in good yields at 30-50 atm

CarbonylatiVe Cyclization of 1-Iodo-2-alkenylbenzenes
J. Am. Chem. Soc., Vol. 118, No. 25, 1996 5909
Table 3. Pd-Catalyzed Carbonylation of o-Iodo-ω-alkenylbenzenes Containing Di- and Tricarbosubstituted Alkenes
O
O
O
O
O
COOMe
O
O
O
Bu-n
Me
Me
Bu-n
COOMe
26
Me
28
31
30
27
29
O
O
O
O
O
COOMe
Me
Me
OMe
COOMe
COOMe
Ph
O
COOMe
34
35
36
37
32
33
O
O
O
COOMe
Me
Me
Me
COOMe
Me
COOMe
40a
COOPr-i
40b
Me
38
39
41
products (yield,a %)
temp, time,
Type Ib
Ac-Pd
Type IIc
Ac-Pd
premature
esterification
entry substrate
conditions (solv, equiv)
solvent
°C
h
others
3-1
3-2
3-3
3-4
19a
19b
19b
19b
II
I
II
DMF
DMF
DMF
DMF
MeOH
100
60
100
60
18
26 (82)d
26 (87)d
26 (91)d
26 (50)d
e
e
e
e
e
e
f
f
f
f
f
15
17
18
III (CO, 1 atm MeOH, 37)
27 (37)g
27 (63)g
27 (80)g
27 (90)g
28 (84)
e
3-5
3-6
3-7
3-8
3-9
19b
19b
19b
20
III (CO, 14 atm MeOH, 37) DMF
100
100
100
100
100
16
22
16
24
22
26 (31)d
26 (15)d
26 (8)d
f
f
f
f
f
f
MeOH
IV (CO, 42 atm MeOH, 37) DMF
MeOH
IV (CO, 84 atm MeOH, 37) DMF
MeOH
f
f
IV (MeOH, 4)
MeCN
PhH
MeCN
THF
DMF
DMF
MeCN
THF
f
21a
II
29 (43)h
e
30 (15) and 31 (26)
3-10
3-11
3-12
21a
21b
22
IV (MeOH, 4)
II
II
100
100
100
20
28
18
29 (24)
35 (96)j
36 (67)
32 (45)i
e
e
34 (31)
e
e
f
f
f
3-13
3-14
3-15
23
24
24
IV (MeOH, 4)
I
CH3CN
PhH
MeCN
PhH
MeCN
PhH
PhH
100
80
16
12
6
e
37 (53)
e
38 (17)
e
f
f
f
39 (22)
39 (e3)
IV (MeOH, 4)
100
40a (9)
41 (77)
3-16
3-17
3-18
24
24
25
IV (MeOH, 4)
IV (i-PrOH-4)
IV (MeOH or i-PrOH, 4)
100
100
100
6
24
16-24
f
40a (34)k
40b (63)m
41a (57)l
41b (15)n
f
f
PhH
PhH
39 (13)
messy reaction with no products formed in significant yields
a By NMR spectroscopy or GLC. b Type I cyclic acylpalladation product. See text for its definition. c Type II cyclic acylpalladation product.
See text for its definition. d E/Z = 93/7. e Not applicable. f Not detected or analyzed. g 1:1 Diastereomeric mixture. h E/Z ) 82/18. i Contains a 10%
yield of 33. j E/Z ) 58/42. k Trans/cis ) 85/15. l Cis/trans ) 72/28. m Trans/cis ) 90/10. n Cis/trans ) 88/12.
of CO in the presence of MeOH or i-PrOH (Conditions IV)
(entries 3-4 to 3-8, 3-13, and 3-17), although 25 failed to give
significant yields of monocyclic products (entry 3-18). Since
the numbers of CO molecules incorporated in the Type I and II
Ac-Pd products are 1 and 2, respectively, the Type II/Type I
ratio was expected to increase by elevating the CO pressure. A
series of experiments with 19b where the CO pressure was
varied from 1 to 84 atm under otherwise the same conditions
showed that the Type II/Type I ratio indeed changed from 37/
50 to 90/8 (entries 3-4 to 3-7). Here again, premature
esterification can be a serious side reaction in cases where the
desired Ac-Pd step is slow. Thus, the extents of premature
esterification observed with 21a, 23, and 24 (entries 3-10, 3-13,
3-15, and 3-16) were 31, 17, and 57-77%, respectively, even
though it was negligible in the reaction of 19 and 20 producing
5-membered ketones (entries 3-4 to 3-18). As indicated in
Scheme 3, one simple solution to this problem was to slow down
alcoholysis relative to cyclic acylpalladation. Indeed the use
of i-PrOH in place of MeOH in the reaction of 24 provided the
desired Type II Ac-Pd product 40b (trans/cis ) 90/10) in 63%
yield along with a 13% yield of 39 and only a 15% yield of the
premature esterification product 41 (entry 3-17). In cases where
more than one diastereomer can be formed, the products were
generally diastereomeric mixtures. We believe, however, that
the formation of diastereomeric mixtures is due to epimerization
after cyclization. Thus, 28 lacking hydrogens R to the ketonic
carbonyl group was diastereomerically >95% pure as judged
by NMR spectroscopy (entry 3-8). It must be the isomer in
which the two carbonyl groups are cis to each other, but this
point remains to be established.

5910 J. Am. Chem. Soc., Vol. 118, No. 25, 1996
Negishi et al.
Scheme 4
Scheme 5
Effects of Heteroatom Substituents. Heteroatom substit-
uents can exert influences on the chemoselectivity, rate, and
other aspects of the cyclic acylpalladation reaction. Since
acylpalladium derivatives are known to react readily with a
variety of nucleophiles,1 such as alcohols, amines, and eno-
lates,5,25 such groups present in the substrates can compete with
alkenes for the acylpalladium bonds. To probe the chemose-
lectivity aspect, we chose to compare the relative reactivity of
alkenes and alcohols toward acylpalladium derivatives and
prepared 42 and 43. The reaction of o-iodobenzaldehyde with
vinylmagnesium bromide provided 42, while the LDA-mediated
alkylation of ethyl crotonate with o-iodobenzyl bromide fol-
lowed by DIBAH reduction gave 43. The Pd-catalyzed car-
bonylation reaction of 42 at 40 atm of CO either in the absence
of MeOH (Conditions II) or in its presence (Conditions IV) gave
the premature lactonization product 44 in 90 and 65% yields,
respectively, as a roughly 90:10 mixture of the Z and E isomers.
In the latter reaction, 45 was also obtained in 24% yield. It is
likely that methanolysis of 44 partially converted it into 45. In
addition to these premature esterification products, however,
the above obtained reaction mixtures also contained 46 albeit
only in 3 and 8% yields, respectively (Scheme 5). In the
reaction of 43 in benzene at 40 atm of CO in the absence of an
alcohol (Conditions II), the Type II Ac-Pd product 47 (trans/
cis ) 82/18) and the premature lactonization product 48 were
obtained in 36 and 31% yields, respectively (Scheme 5). It
should be possible to observe cases where the Type II Ac-Pd
process is even more strongly favored over premature lacton-
ization. In general, however, hydroxyl groups must be protected
to avoid premature lactonization. Indeed, the TBDMS (t-
BuMe2Si) derivative (49) of 42 under Conditions IV (MeOH,
4 equiv) produced 50 as a 3:1 trans and cis stereoisomeric
mixture in 75% yield, even though the yield of the Type I Ac-
Pd product 51 obtained under Conditions II was only 25%
(Scheme 5). Treatment of 50 (trans/cis ) 3/1) with pyridinium
p-toluenesulfonate (PPTS) in benzene at 50-60 °C provided a
4/1 mixture of the trans isomer of the hydroxy ester and 46 in
73% overall yield.
The effects of ester, protected hydroxymethyl, e.g., CH2-
OSiMe2Bu-t, and silyl groups directly bonded to the ω-alkenyl
CdC group were also probed and summarized in Scheme 6.
Alkylation of the lithio derivative of 52 with o-iodobenzyl
bromide gave a 1:1 mixture of 53a and 53b. Successive
treatment of o-iodopropargylbenzene and o-iodohomopropar-
gylbenzene with DIBAH in hexanes and ClCOOMe or ClCOO-
Et provided 54 and 55, respectively, while hydroalumination
(25) Negishi, E.; Zhang, Y.; Shimoyama, I.; Wu, G. J. Am. Chem. Soc.
1989, 111, 8018.

CarbonylatiVe Cyclization of 1-Iodo-2-alkenylbenzenes
J. Am. Chem. Soc., Vol. 118, No. 25, 1996 5911
Scheme 6
of the Me3Si derivative of o-iodopropargylbenzene with DIBAH
in Et2O yielded 56 upon hydrolysis. Reduction of 55 with
DIBAH (2.3 equiv) followed by OH protection with t-BuMe2-
SiCl gave 57.
17% yield without incorporation of CO even at 40 atm along
with some unidentified products which appeared to be dimeric.
The use of t-BuOH in place of MeOH as a trapping agent
boosted the yield of the Type II Ac-Pd product, i.e., 62b, to
40%. The corresponding reaction of 54 using MeOH as a
trapping agent provided three cyclic Ac-Pd products (12, 59,
and 60) in 58% combined yield, but none was dominant. The
naphthalene derivative 60 must represent yet another example
of the endo-mode Ac-Pd reaction. A related endo-mode Ac-
Pd reaction must take place in the conversion of 56 into 66.
Since the combined yields of the cyclic Ac-Pd products derived
from 56 are 68-75%, the presence of a Me3Si group on the
alkenyl carbon distal to the iodobenzene moiety does not appear
to hinder cyclic acylpalladation. In the reaction of 57 at 40
As indicated earlier by the results with 22 (entry 3-12),
unconjugated ester groups appear to exert only minor effects
on cyclic acylpalladation. On the other hand, those ester groups
that are in conjugation with the ω-alkenyl group tend to retard
or hinder cyclic acylpalladation. Thus, for example, 55 gives
under Conditions IV using MeOH (5 equiv) as a trapping agent
gave only a 13% yield of the Type II Ac-Pd product 62a along
with an 84% yield of the premature esterification product 63a.
Surprisingly, omission of MeOH from the conditions used above
led to the formation of the cyclic Heck reaction product 64 in

5912 J. Am. Chem. Soc., Vol. 118, No. 25, 1996
Negishi et al.
atm of CO in the absence of an alcohol (Conditions II), the
combined yield of the cyclic Ac-Pd products 67 and 68 was
97%. Furthermore, when the crude product was treated with
10% HCl, 68 was obtained in 83% overall yield without
contamination with 67.
Experimental Section
General Procedures. All reactions were conducted under a dry
Ar atmosphere. Gas chromatographic measurements were performed
on SE-30 (Chromosorb W) columns with appropriate saturated
hydrocarbon standards. 1H and 13C NMR spectra were recorded in
CDCl3 on Varian Gemini-200, VXR-500, and GE QE-300 NMR
spectrometers using Me4Si as an internal standard unless otherwise
noted. All commercially available reagents were used without further
purification unless otherwise noted. THF was distilled from sodium
benzophenone ketyl. Benzene, CH3CN, DMF, and NEt3 were dried
over molecular sieves 4A. The preparation of PdCl2(PPh3)2 was
performed as reported in the literature.26 Pd-catalyzed high-pressure
carbonylation experiments were carried out in a 22-mL autoclave (Parr
Instrument Co.).
Preparation of ω-Alkene-Containing Aryl Iodides 1-4. (a)
2-Allyl-1-iodobenzene (1). A solution of 1-(2′-iodophenyl)-2-propyne18
(2.0 g, 8.25 mmol) in n-hexane (8.0 mL) was successively treated with
i-Bu2AlH (1.75 mL, 1.41 g, 9.9 mmol, 25 °C then 50 °C, 20 h) and
H2O (2.0 mL, -78 °C). The reaction mixture was warmed to 25 °C,
filtered through Celite, washed with brine, dried over MgSO4, and
evaporated. Chromatography on silica gel (n-hexane) afforded 1.37 g
(68%) of 1: 1H NMR δ 3.47 (d, J ) 6.4 Hz, 2 H), 4.95-5.2 (m, 2 H),
5.8-6.1 (m, 1 H), 6.86 (dt, J ) 7.5, 2.0 Hz, 1 H), 7.1-7.3 (m, 2 H),
7.80 (d, J ) 7.8 Hz, 1 H); 13C NMR δ 45.53, 101.47, 117.32, 128.55,
128.95, 130.20, 136.28, 140.01, 143.22.
(b) 2-(3′-Butenyl)-1-iodobenzene (2). A solution of 2-iodobenzyl
bromide (3.05 g, 10 mmol) in THF (20 mL) was treated with a 1.0 M
solution of allylmagnesium bromide in Et2O (20 mL, 20 mmol, 25 °C).
After being heated at reflux for 12 h, the reaction mixture was quenched
with H2O, extracted with Et2O, dried over MgSO4, and evaporated.
Chromatography on silica gel (n-pentane) afforded 1.82 g (69%) of 2:
1H NMR δ 2.25-2.45 (m, 2 H), 2.80 (t, J ) 8.0 Hz, 2 H), 4.95-5.15
(m, 2 H), 5.75-6.0 (m, 1 H), 6.80-6.95 (m, 1 H), 7.15-7.35 (m, 2
H), 7.80 (d, J ) 7.5 Hz, 1 H); 13C NMR δ 34.13, 40.20, 100.55, 115.23,
127.71, 128.21, 129.41, 137.47, 139.42, 144.24; IR (neat) 3076 (s),
1640 (s) cm-1; high-resolution MS calcd for C10H11I 257.9906, found
257.9909.
Conclusions
1. The Pd-catalyzed carbonylation reaction of o-iodo-ω-
alkenylbenzenes containing a terminal vinyl group (1-3) in the
absence of an external nucleophile (Conditions I and II) can
produce up to modest yields of five- and six-membered ring
Type I cyclic Ac-Pd products, e.g., 5 and 8. However, the Heck
reaction can be a significant side reaction in cases where it can
yield common rings. In addition, some apparently polymeric
processes must also competitively take place. Seven-membered-
ring ketones do not appear to be formed by this reaction.
2. In the presence of an external nucleophile, e.g., MeOH,
i-PrOH, and t-BuOH, 1-3 containing a terminal vinyl group
can be converted to five- and six-membered-ring Type II Ac-
Pd products in high yields, typically 70-90%, using 30-50
atm of CO (Conditions IV). Here again, seven-membered-ring
ketones are not obtainable in significant yields. In general, the
scope of the cyclic Ac-Pd reaction appears to be limited to the
formation of five- and six-membered-ring ketones. The use of
1 atm of CO (Conditions III) leads to significantly lower yields
of the Type II Ac-Pd products. The Type I Ac-Pd reaction,
the Heck reaction, and premature esterification tend to be
significant side reactions in cases where the yields of the desired
Type II Ac-Pd products are low.
3. The effects of carbon substituents in the ω-vinyl group
are profound. First, the Type I Ac-Pd products, e.g., 26, 35,
and 36, can be obtained in high yields from those substrates
containing a 1,2-disubstituted alkene even in the absence of an
external nucleophile (Conditions I or II). This reaction is
Z-stereoselective but not stereospecific, indicating that the
products are of thermodynamic control. In some cases,
however, the Type III Ac-Pd process involving trapping of
putative acylpalladium intermediates with internal enolates can
be a significant side reaction under Conditions II. Third, the
Type II Ac-Pd products can also be obtainable in high yields at
30-50 atm of CO in the presence of an alcohol, e.g., MeOH
(Conditions IV). It should be noted that this process can proceed
well even in cases where the substrates cannot undergo the Type
I Ac-Pd process due to the absence of an appropriately
positioned hydrogen. Here again, the Type I Ac-Pd reaction
and premature esterification can be significant side reactions,
although the Heck reaction does not appear to be significant
with these substrates.
(c) 2-Vinyl-1-iodobenzene (3). This compound was prepared
according to the literature procedure.27
(d) 4,4-Bis(dimethoxycarbonyl)-5-(2′-iodophenyl)-1-pentene (4).
To a suspension of NaH (240 mg, 6.0 mmol, 60% dispersion of NaH
in mineral oil, 0 °C, 1 h) were successively added methyl 2-(meth-
oxycarbonyl)-4-pentenoate (860 mg, 5 mmol, 0 °C then 25 °C, 30 min)
dissolved in THF (25 mL) and 2-iodobenzyl bromide (1.51 g, 5.1 mmol,
25 °C, 3 h) dissolved in THF (5.0 mL). The reaction mixture was
diluted, washed with H2O, dried over MgSO4, and evaporated.
Chromatography on silica gel (97/3 n-pentane/Et2O) afforded 1.70 g
(88%) of 4: 1H NMR δ 2.68 (d, J ) 7.2 Hz, 2 H), 3.50 (s, 2 H), 3.69
(s, 6 H), 5.0-5.2 (m, 2 H), 5.7-5.95 (m, 1 H), 6.8-6.95 (m, 1 H),
7.15-7.3 (m, 2 H), 7.83 (d, J ) 7.9 Hz, 1 H); 13C NMR δ 38.17,
42.66, 52.43, 59.24, 102.76, 118.99, 128.11, 128.57, 130.07, 132.92,
139.62, 139.92, 171.01; IR (neat) 1736 cm-1; high-resolution MS calcd
for C15H17IO4 (M + 1) 389.0250, found 389.0242.
Pd-Catalyzed Carbonylation of o-Iodo-ω-alkenylbenzenes in the
Absence of an External Nucleophile (Table 1). (a) Carbonylation
of 1 at 1 atm of CO. Representative Procedure under Conditions
I. Compound 1 (244 mg, 1.0 mmol), Et3N (0.28 mL, 0.20 g, 2.0 mmol),
Cl2Pd(PPh3)2 (35 mg, 0.05 mmol), and DMF (2 mL) were placed at 25
°C in a flask equipped with a reflux condenser previously flushed with
CO and connected to a balloon containing CO (1 atm). The reaction
mixture was stirred for 24 h at 65 °C (bath temperature), treated with
4. The effects of heteroatom substituents are diverse, and
the overall picture is not yet clear. Even so, the following
observations are noteworthy. First, those OH groups that can
participate in the formation of common ring (5- through
7-membered) lactones must be protected to avoid competitive
lactonization. The use of a suitable protecting group, e.g.,
TBDMS, can avoid lactonization. Second, ester groups con-
jugated with the ω-alkenyl groups can lead to the formation of
a variety of products, limiting the yields of the desired Type I
and II products. In such cases, the Heck reaction and premature
esterification can be significant side reactions depending on the
reaction conditions. In addition, formation of phenols presum-
ably via “endo-mode” Ac-Pd processes has also been observed.
However, the exact course of the reaction remains to be further
clarified. Unconjugated ester groups appear to exert relatively
minor influences.
(26) Jenkins, J. M.; Verkade, J. G. Inorg. Synth. 1968, 11, 108.
(27) Acheson, R. M.; Lee, G. C. M. J. Chem. Soc., Perkin Trans. 1 1987,
2321.
(28) Olah, G. A.; Wang, Q.; Prakash, S. G. K. Synlett 1992, 647.
(29) Braude, E. R.; Coles, J. A. J. Chem. Soc. 1950, 2014.
(30) Hermann, J. L.; Kieczykowsky, G. R.; Schlessinger, R. H. Tetra-
hedron Lett. 1973, 2433.
(31) Llebaria, A.; Delgado, A.; Camps, F.; Moreto´, J. M. Organometallics
1993, 12, 2825.
(32) Ree, K.; Kim, D. Y.; Oh, D. Y. Tetrahedron Lett. 1988, 29, 667.
(33) Echavarren, A. M.; Stille, J. K. J. Am. Chem. Soc. 1988, 110, 1557.

CarbonylatiVe Cyclization of 1-Iodo-2-alkenylbenzenes
J. Am. Chem. Soc., Vol. 118, No. 25, 1996 5913
H2O, extracted with Et2O, dried over MgSO4, filtered, and evaporated.
Analysis of the crude mixture by H NMR spectroscopy showed the
(17%) of 5 and 26 mg (13%) of 12:35 1H NMR δ 2.62 (dd, J ) 17.1,
9.4 Hz, 1 H), 2.8-3.1 (m, 3 H), 3.43 (dd, J ) 17.1, 7.4 Hz, 1 H), 3.68
(s, 3 H), 7.37 (t, J ) 7.4 Hz, 1 H), 7.46 (d, J ) 7.8 Hz, 1 H), 7.59 (dt,
J ) 7.4, 1.2 Hz, 1 H), 7.75 (d, J ) 7.6 Hz, 1 H); 13C NMR δ 33.44,
35.37, 44.02, 52.30, 124.40, 127.00, 127.96, 135.36, 136.74, 153.72,
1
formation of 2-methylene-2,3-dihydro-1H-inden-1-one (5) in 25% yield.
Chromatography on silica gel (80/20 pentane/Et2O) afforded 25 mg
(18%) of 5:33 1H NMR δ 3.76 (bs, 2 H), 5.63 (dt, J ) 1.8, 1.0 Hz, 1
H), 6.36 (dt, J ) 2.2, 1.0 Hz, 1 H), 7.41 (dt, J ) 7.8, 1.0 Hz, 1 H),
7.50 (dd, J ) 7.8, 1.0 Hz, 1 H), 7.60 (dt, J ) 7.8, 1.2 Hz, 1 H), 7.86
(d, J ) 7.8 Hz, 1 H); 13C NMR δ 32.28, 119.76, 125.08, 126.87, 128.09,
172.91, 207.10; IR (neat) 1735, 1718 cm-1
.
(2) Representative Procedure under Conditions IV. A mixture
of 1 (244 mg, 1.0 mmol), Et3N (0.28 mL, 0.20 g, 2.0 mmol), MeOH
(0.16 mL, 0.13 g, 4.0 mmol), Cl2Pd(PPh3)2 (35 mg, 0.05 mmol), and
DMF was stirred at 100 °C under 40 atm of CO. Analysis of the crude
135.37, 138.71, 143.79, 150.37, 193.92; IR (neat) 1700 cm-1
.
Representative Procedure under Conditions II. The above
reaction was performed at 100 °C at 40 atm of CO for 15 h in a 22 mL
1
reaction mixture by H NMR spectroscopy showed the formation of
1
autoclave. Analysis of the crude mixture by H NMR spectroscopy
12 in 90% yield. Chromatography on silica gel (67/33 n-hexane/Et2O)
afforded 168 mg (82%) of 12.
showed the formation of 5 in 20% yield. Chromatography on silica
gel (80/20 n-pentane/Et2O) afforded 26 mg (18%) of 5. Using a 1:1
mixture of THF/benzene in place of DMF at 80 °C for 18 h under
otherwise the same conditions as above, 5 was obtained in 58% NMR
yield. Chromatography on silica gel (80/20 n-pentane/Et2O) afforded
66 mg (46%) of 5.
(b) Carbonylation of 2. Under Conditions I (1 atm of CO, 100
°C, 24 h, DMF), 2 (258 mg, 1.0 mmol) gave a 1:1 mixture of
1-methyleneindane and 3-methyl-1H-indene (7) in 16% NMR yield
along with traces of 2-methylene-3,4-dihydronaphthalen-1-one (6). 7:20e
(b) Carbonylation of 2. Under Conditions III (1 atm of CO, 65
°C, 24 h, MeOH as a solvent), 2 (258 mg, 1.0 mmol) was converted to
7 in 48% NMR yield along with a 37% yield of methyl 2-(3′-butenyl)-
benzoate (13): 1H NMR δ 2.2-2.4 (m, 2 H), 2.9-3.05 (m, 2 H), 3.82
(s, 3 H), 4.85-5.05 (m, 2 H), 5.81 (ddt, J ) 17.0, 10.3, 6.6 Hz, 1 H),
7.1-7.25 (m, 2 H), 7.3-7.4 (m, 1 H), 7.75-7.85 (m, 1 H); IR (neat)
1750 cm-1. Under the conditions described above (MeOH reflux, 6
h), 2 gave 7 in 72% NMR yield along with a 5% yield of 13. The
product 14 was not detected. Under Conditions IV (100 °C, 11 h, 1:1
mixture of acetonitrile/benzene), 2 (258 mg, 1.0 mmol) gave 2-((meth-
oxycarbonyl)methyl)-1-tetralone (14) in 85% NMR yield. Kugelrohr
distillation afforded 130 mg (58%) of 14: 1H NMR δ 1.6-3.2 (m, 7
H), 3.70 (s, 3 H), 7.2-7.6 (m, 6 H), 8.0-8.1 (m, 1 H); 13C NMR δ
29.24, 34.85, 44.78, 51.60, 126.52, 127.38, 128.78, 132.19, 133.37,
144.03, 172.85, 198.11; IR (neat) 1740 cm-1; high-resolution MS calcd
for C13H14O3 218.0943, found 218.0943.
1H NMR δ 2.1-2.2 (m, 2 H), 2.7-2.85 (m, 2 H), 2.9-3.05 (m, 2 H),
3.29 (bs), 5.0-5.1 (m, 1 H), 5.4-5.5 (m, 1H), 6.15-6.25 (bs, 1 H),
7.0-7.6 (m, 4 H); 13C NMR δ 12.93, 30.12, 31.26, 37.25, 102.34,
118.84, 120.65, 123.58, 124.50, 125.33, 126.07, 126.43, 128.27, 128.61,
139.98, 141.16, 144.33, 146.14, 145.67, 150.88. Under Conditions II
(40 atm of CO, 100 °C, 24 h, DMF) 2 gave 6 and 7 only in trace
amounts, if any.
(c) Carbonylation of 3. Under Conditions I (1 atm of CO, 80 °C,
6 h, a 1:1 mixture of CH3CN/benzene), 3 (230 mg, 1.0 mmol) gave
1H-indenone (8) in 46% NMR yield along with an 11% yield of
3-(diethylamino)-2,3-dihydro-1H-inden-1-one (9). Chromatography on
silica gel (95/5 n-pentane/Et2O) afforded 65 mg (50%) of 8:34 1H NMR
δ 5.89 (d, J ) 7.1 Hz, 1 H), 7.2-7.3 (m, 1 H), 7.3-7.4 (m, 1 H), 7.43
(d, J ) 7.2 Hz, 1 H), 7.57 (dd, J ) 6.0, 0.7 Hz, 1 H); 13C NMR δ
122.24, 122.64, 127.18, 129.25, 130.36, 133.67, 144.61, 149.81, 198.44.
9: 1H NMR δ 1.07 (d, J ) 7.1 Hz, 6 H), 2.25-2.55 (m, 4 H), 2.6-
2.75 (m, 2 H), 4.71 (t, J ) 5.4 Hz, 1 H), 7.3-7.8 (m, 4 H); 13C NMR
δ 13.98, 37.11, 44.15, 58.98, 122.95, 126.37, 128.32, 134.68, 137.42,
156.35, 205.02; high-resolution MS calcd for C11H17NO 203.1310,
found 203.1312. Under Conditions I (1 atm of CO, 80 °C, 1 h, DMF),
3 gave 8 in 9% NMR yield along with unidentified polymeric products.
Under Conditions II (40 atm of CO, 100 °C, 12 h, DMF), 3 gave 8 in
20% NMR yield.
(d) Carbonylation of 4. Under Conditions I (1 atm of CO, 100
°C, 12 h, DMF), 4 (388 mg, 1.0 mmol) gave a 1:1 mixture of 2,2-bis-
(methoxycarbonyl)-4-methyl-1,2-dihydronaphthalene and 2,2-bis-
(methoxycarbonyl)-4-methylene-1,2,3-trihydronaphthalene (11) in 94%
NMR yield with no sign of the formation of the carbonylated product
10. 11: 1H NMR δ 2.12 (s, 3 H), 3.04 (s, 2 H, exo), 3.32 (s, 2 H,
exo), 3.36 (s, 2 H, endo), 3.67 (s, 6 H), 3.68 (s, 6 H), 5.06 (s, 1 H,
exo), 5.55 (s, 1 H, exo), 5.96 (s, 1 H, endo), 7.0-7.6 (m, 4 H); 13C
NMR δ 19.35, 34.53, 35.46, 37.86, 52.71, 52.83, 54.36, 54.68, 111.01,
121.01, 123.37, 123.84, 126.40, 126.88, 127.65, 127.86, 128.17, 128.49,
128.87, 132.54, 133.24, 134.90, 138.82, 170.84, 171.02; high-resolution
MS calcd for C15H16O4 260.1049, found 260.1052. Under Conditions
II (100 °C, 12 h, DMF), 4 gave 11 in 54% NMR yield with no sign of
the formation of the other monomeric products (<3%).
(c) Carbonylation of 3. Under Conditions III (1 atm of CO, 70
°C, 24 h, MeOH), 3 (230 mg, 1.0 mmol) gave methyl 2-vinylbenzoate
(16) in 14% NMR yield along with 8 and 9 obtained in 26 and 28%
yields, respectively. The compound 15 was not detected (<3%). 16:
1H NMR δ 3.90 (s, 3 H), 5.36 (dd, J ) 11.0, 1.3 Hz, 1 H), 5.65 (dd,
J ) 17.5, 1.3 Hz, 1 H), 7.25-7.4 (m, 1 H), 7.4-7.6 (m, 3 H), 7.88 (d,
J ) 7.9, 1.3 Hz, 1 H); 13C NMR δ 52.08, 116.46, 127.19, 127.37,
128.55, 130.29, 132.09, 135.84, 139.54, 167.83; IR (neat) 1722 cm-1
;
high-resolution MS calcd for C10H10O2 162.0681, found 162.0678.
Under Conditions IV (40 atm of CO, 100 °C, 11 h, benzene), 3 gave
3-(methoxycarbonyl)-2,3-dihydro-1H-indenone (15) in 74% yield as
the sole product. Chromatography on silica gel (90/10 n-pentane/Et2O)
afforded 139 mg (73%) of 15:36 1H NMR δ 2.88 (dd, J ) 19.1, 8.1 Hz,
1 H), 3.15 (dd, J ) 19.1, 3.6 Hz, 1 H), 3.78 (s, 3 H), 4.31 (dd, J ) 8.1,
3.6 Hz, 1 H), 7.4-7.5 (m, 1 H), 7.6-7.7 (m, 2 H), 7.76 (d, J ) 7.7
Hz, 1 H); 13C NMR δ 39.48, 43.59, 52.68, 123.88, 126.52, 128.79,
134.99, 136.32, 151.06, 172.21, 204.03.
(d) Carbonylation of 4. Under Conditions IV (40 atm of CO, 100
°C, 10 h, MeOH (4 equiv), 1/1 acetonitrile-benzene), 4 (306 mg, 0.78
mmol) gave 11 in 33% NMR yield along with a 26% yield of methyl
2-(2′,2′-bis(methoxycarbonyl)-4′-pentyl)benzoate (17a) and a 21% yield
1
of 18a: H NMR δ 1.99 (dd, J ) 13.6, 10.0 Hz, 1 H), 2.52 (dd, J )
15.9, 10.9 Hz, 1 H), 2.68 (ddd, J ) 13.6, 6.3, 1.9 Hz, 1 H), 2.89 (dd,
J ) 15.9, 4.8 Hz, 1 H), 3.1-3.5 (m, 5 H), 3.66 (s, 3 H), 3.71 (s, 3 H),
3.74 (s, 3 H), 7.05-7.2 (m, 4 H); 13C NMR δ 32.37, 34.51, 35.21,
40.69, 51.69, 52.69, 52.81, 53.63, 126.34, 126.44, 126.68, 128.99,
133.78, 136.99, 171.07, 172.03, 172.55; IR (neat) 1734 (bs) cm-1. 17a:
1H NMR δ 2.59 (dd, J ) 7.2, 0.8 Hz, 2 H), 3.62 (s, 6 H), 3.75 (s, 2 H),
3.88 (s, 3 H), 5.0-5.2 (m, 2 H), 5.65-5.8 (m, 1 H), 7.2-7.55 (m, 3
H), 7.75-7.85 (m, 1 H); 13C NMR δ 35.29, 38.43, 52.03, 52.21, 59.44,
118.91, 126.81, 130.44, 131.29, 131.55, 131.99, 132.79, 137.42, 171.15;
IR (neat) 1736 (s) cm-1. Under Conditions IV (15 atm of CO, 100
°C, 24 h, t-BuOH (4 equiv), benzene), 4 (388 mg, 1.0 mmol) gave 11
in 68% NMR yield along with a 5% yield of 18b. Under Conditions
IV (100 °C, 24 h, 80 atm, t-BuOH (4 equiv), benzene), 4 (388 mg, 1.0
mmol) gave 11 in 30% NMR yield along with a 26% yield of 18b: 1H
NMR δ 1.43 (s, 9 H), 2.02 (dd, J ) 13.5, 10.5 Hz, 1 H), 2.43 (dd, J
Pd-Catalyzed Carbonylation of o-Iodo-ω-alkenylbenzenes in the
Presence of an Alcohol (Table 2). (a) Carbonylation of 1. (1)
Representative Procedure under Conditions III. A mixture of 1
(244 mg, 1.0 mmol), Et3N (0.28 mL, 0.20 g, 2.0 mmol), MeOH (0.16
mL, 0.13 g, 4.0 mmol), Cl2Pd(PPh3)2 (35 mg, 0.05 mmol), and a 1:1
mixture of acetonitrile/benzene (4.0 mL) was stirred at 80 °C under 1
atm of CO (Vide supra, see Conditions I for more details) for 20 h,
treated with H2O, extracted with Et2O, dried over MgSO4, filtered, and
evaporated. Analysis of the crude reaction mixture by 1H NMR
spectroscopy showed the formation of 5 in 18% yield along with
2-(methoxycarbonyl)methyl-1-indanone (12) produced in 16% yield.
Chromatography on silica gel (80/20 n-hexane/Et2O) afforded 25 mg
(35) Boger, D. L.; Mathvink, R. J. J. Org. Chem. 1992, 57, 1429.
(36) Greenewald, G. L.; Sall, D. J.; Monn, J. A. J. Med. Chem. 1988,
31, 453.
(37) Masui, M.; Ando, A.; Shioiri, T. Tetrahedron Lett. 1988, 29, 2835.
(38) Chatterjee, A.; Banerjee, S.; Hazra, B. G. Indian J. Chem. 1974,
12, 41.
(34) Bellamy, F. D.; Chazan, J. B.; Ou, K. Tetrahedron 1983, 39, 2803.

5914 J. Am. Chem. Soc., Vol. 118, No. 25, 1996
Negishi et al.
) 15.4, 8.7 Hz, 1 H), 2.6-2.75 (m, 1 H), 2.79 (dd, J ) 15.4, 4.6 Hz,
1 H), 3.20 (d, J ) 16.0 Hz, 1 H), 3.25-3.45 (m, 2 H), 3.67 (s, 3 H),
3.75 (s, 3 H), 7.05-7.20 (m, 4 H); 13C NMR δ 28.02, 29.69, 32.55,
34.42, 35.27, 41.99, 52.68, 52.82, 53.69, 80.64, 126.31, 126.45, 126.55,
9.76 mmol, -65 °C, 25 min) in THF (4 mL), and CH3I (4.3 mL, 68.75
mmol, -70 °C) in HMPA (2.5 mL). The reaction mixture was warmed
to 25 °C, quenched with aqueous NH4Cl, extracted with Et2O, dried
over MgSO4, and evaporated. Chromatography on silica gel (n-pentane)
afforded 2.26 g (86%) of 2-(3′-pentynyl)-1-iodobenzene: 1H NMR δ
1.78 (t, J ) 2.0 Hz, 3 H), 2.35-2.5 (m, 2 H), 2.90 (t, J ) 6.8 Hz, 2
H), 6.8-7.0 (m, 1 H), 7.2-7.35 (m, 2 H), 7.80 (d, J ) 6.9 Hz, 1 H).
Reduction of 2-(3′-pentynyl)-1-iodobenzene (2.0 g, 7.4 mmol) with
i-Bu2AlH (1.5 equiv, 50 °C, 20 h) as described in the preparation of 1
gave 1.69 g (84%) of 21a after chromatography on silica gel
(n-pentane): 1H NMR δ 1.55 (d, J ) 4.6 Hz, 3 H), 2.25-2.45 (m, 2
H), 2.75 (t, J ) 8.0 Hz, 2 H), 5.3-5.6 (m, 2 H), 6.8-6.95 (m, 1 H),
7.1-7.35 (m, 2 H), 7.80 (d, J ) 7.7 Hz, 1 H); 13C NMR δ 12.80,
27.52, 40.64, 100.55, 125.02, 127.64, 128.17, 128.91, 129.52, 139.40,
144.50; high-resolution MS calcd for C11H13I 272.5063, found 272.5060.
128.90, 133.77, 137.23, 171.13, 171.41, 172.13; IR (neat) 1736 (s) cm-1
;
high-resolution MS calcd for C20H26O6 362.1729, found 362.1725.
Preparation of ω-Alkene-Containing Aryl Iodides 19-25. (a)
(E)-2-(2′-Heptenyl)-1-iodobenzene (19a). A solution of 1-hexyne (4.1
g, 50 mmol) in hexane (50 mL) was successively treated with i-Bu2-
AlH (8.5 g, 11.1 mL, 60 mmol, 50 °C, 4 h), a 1.6 M solution of n-BuLi
in hexane (38 mL, 60 mmol, 25 °C, 30 min), 2-iodobenzyl bromide
(11.9 g, 40 mmol, 18 h, 50 °C) in hexane, and HMPA (10 mL, 10.7 g,
60 mmol) in THF (30 mL). The reaction mixture was quenched with
aqueous NH4Cl, extracted with Et2O, dried over MgSO4, and evapo-
rated. Chromatography on silica gel (n-hexane) afforded 4.8 g (37%)
of 19a: 1H NMR δ 0.8-1.0 (m, 3 H), 1.15-1.5 (m, 4 H), 1.9-2.1
(m, 2 H), 3.3-3.5 (m, 2 H), 5.45-5.6 (m, 2 H), 6.9-7.1 (m, 1 H),
7.3-7.5 (m, 2 H), 7.7-7.9 (m, 1 H); 13C NMR δ 14.52, 22.79, 32.09,
32.84, 44.47, 100.37, 126.93, 127.56, 128.10, 129.35, 133.01, 139.27,
143.52; high-resolution MS calcd for C13H17I 300.0375, found 300.0372.
(b) (Z)-2-(2′-Heptenyl)-1-iodobenzene (19b). A solution of 1-hex-
yne (2.51 g, 30.6 mmol) in THF (30 mL) was treated with a 2.5 M
solution of n-BuLi (11.2 mL, 28 mmol, 0 °C, 1 h). The resultant
mixture was added to a solution of 2-iodobenzaldehyde (5.0 g, 21.5
mmol) in THF (20 mL) at -78 °C. After 3 h, the reaction mixture
was treated with NH4Cl, extracted with Et2O, washed with brine, dried
over MgSO4, and evaporated to give 6.68 g (99%) of crude 1-(2′-
iodophenyl)-2-heptyn-1-ol. A mixture of the crude alcohol (5.93 g,
18.9 mmol), triethylsilane (3.9 mL, 2.84 g, 24.4 mmol), NH4F (0.91 g,
24.6 mmol), and CH2Cl2 (30 mL) was treated with a solution of CF3-
COOH (7.3 mL, 10.80 g, 94.7 mmol, 0 °C, addition over 30 min)28 in
CH2Cl2 (10 mL) and stirred for 2 h at 0 °C. The reaction mixture was
poured into ice-water, extracted with Et2O, washed with aqueous
NaHCO3, dried over MgSO4, and evaporated to yield 5.57 g (99%) of
crude 1-(2′-iodophenyl)-2-heptyne. Reduction of 1-(2′-iodophenyl)-
2-heptyne (1.40 g, 4.7 mmol) by i-Bu2AlH (1.2 equiv, 50 °C, 20 h) as
described in the preparation of 1 gave 1.12 g (79%) of 19b after
chromatography on silica gel (n-hexane): 1H NMR δ 0.8-1.0 (m, 3
H), 1.2-1.5 (m, 4 H), 2.15 (q, J ) 6.8 Hz, 2 H), 3.46 (d, J ) 6.2 Hz,
2 H), 5.4-5.65 (m, 2 H), 6.86 (dt, J ) 7.3, 2.2 Hz, 1 H), 7.15-7.35
(m, 2 H), 7.81 (dd, J ) 7.8, 1.0 Hz, 1 H); 13C NMR δ 14.46, 22.76,
31.66, 32.50, 78.32, 98.85, 128.03, 129.09, 129.67, 130.77, 134.33,
(e) (Z)-2-(4′-Phenyl-3′-butenyl)-1-iodobenzene (21b). A mixture
of 2-(3′-butynyl)-1-iodobenzene (1.0 g, 3.9 mmol), iodobenzene (15.9
g, 77.9 mmol), CuI (7.4 mg, 0.039 mmol), and Cl2Pd(PPh3)2 (13.7 mg,
0.031 mmol) in Et2NH (24 mL) was stirred at 25 °C for 24 h. The
reaction mixture was quenched with H2O, extracted with Et2O, dried
over MgSO4, and evaporated. Chromatography on silica gel (n-hexane)
afforded 388 mg (30%) of 2-(4′-phenyl-3′-butynyl)-1-iodobenzene: 1H
NMR δ 2.72 (t, J ) 6.3 Hz, 2 H), 3.05 (t, J ) 6.3 Hz, 2 H), 6.85-7.0
(m, 1 H), 7.2-7.45 (m, 7 H), 7.85 (d, J ) 8.2 Hz, 1 H). This compound
was reduced with i-Bu2A1H (1.5 equiv, 50 °C, 20 h) as described in
the preparation of 1. The compound 21b was isolated in 50% yield
after chromatography on silica gel (n-pentane): 1H NMR δ 2.5-3.0
(m, 4 H), 5.72 (dt, J ) 7.1 Hz, 10.8 Hz, 1 H), 6.48 (d, J ) 10.8 Hz,
1 H), 6.75-6.9 (m, 1 H), 7.05-7.4 (m, 7 H), 7.80 (d, J ) 8.3 Hz, 1
H).
(f) 3-Carbomethoxy-3-(2′-iodobenzyl)cyclohexene (22). To i-Pr2-
NH (0.36 mL, 2.6 mmol) in THF (4.0 mL) were successively added a
2.5 M solution of n-BuLi in n-hexane (1.05 mL, 2.6 mmol, 0 °C, 15
min), HMPA (0.61 mL, 3.50 mmol, -78 °C, 5 min), 1-carbomethoxy-
cyclohexene (322 mg, 2.3 mmol, -78 °C, 30 min), and 2-iodobenzyl
bromide (820 mg, 2.8 mmol, -78 °C, 2 h) dissolved in THF.30 The
reaction mixture was diluted with Et2O, washed with 2.5 N HCl solution
and aqueous NaHCO3, dried over MgSO4, and evaporated. Chroma-
tography on silica gel (95/5 n-hexane-Et2O) afforded 663 mg (81%)
1
of 22: H NMR δ 1.5-2.2 (m, 6 H), 3.18 (d, J ) 5.0 Hz, 2 H), 3.67
(s, 3 H), 5.7-5.8 (m, 2 H), 6.8-7.8 (m, 4 H); 13C NMR δ 19.49, 24.62,
30.96, 48.34, 51.76, 102.86, 127.68, 128.05, 128.61, 129.05, 129.95,
139.89, 145.52; IR (neat) 1462 (s), 1432 (s), 1010 (s), 746 (s) cm-1
.
139.57, 140.22, 175.66; IR (neat) 1740 cm-1
.
(c) 2-((1′-Cyclohexenyl)methyl)-1-iodobenzene (20). A solution
of Me3Al (2.3 g, 3.2 mL, 32 mmol) in THF (15 mL) was successively
treated with a 1.5 M solution of 1-cyclohexenyllithium in Et2O (20
mL, 29 mmol, 0 °C then 25 °C, 15 min) prepared according to the
literature procedure,29 HMPA (7.0 mL, 7.2 g, 40 mol), and 2-iodobenzyl
bromide (7.40 g, 33 mmol, 25 °C, 2 h) dissolved in THF (5 mL).30
The reaction mixture was slowly poured into water, extracted with
n-hexane, acidified with HCl, washed with aqueous NaHCO3, dried
over MgSO4, and evaporated. Purification of the crude oil by Kugelrohr
distillation afforded 3.30 g (55%) of 20: 1H NMR δ 1.5-2.2 (m, 8
H), 3.37 (s, 2 H), 5.31 (bs, 1 H), 6.8-7.0 (m, 1 H), 7.2-7.4 (m, 2 H),
7.8-7.9 (m, 1 H); 13C NMR δ 22.43, 23.00, 25.39, 28.62, 48.76, 101.74,
123.94, 127.66, 128.01, 129.94, 135.73, 139.41, 143.00.
(d) (Z)-2-(3′-Pentenyl)-1-iodobenzene (21a). To a mixture of I2
(5 mg), HgCl2 (64 mg, 0.235 mmol), Mg turnings (6.0 g, 250 mmol),
and THF (35 mL) was added a solution of propargyl bromide (80% in
toluene, 14 mL, 125 mmol) in THF (90 mL) at a rate that kept the
reaction mixture refluxing. After refluxing for an additional 15 min,
it was transferred to a solution of 2-iodobenzyl bromide (7.38 g, 24.8
mmol) in THF (25 mL). After refluxing for 12 h, the reaction mixture
was quenched with aqueous NH4Cl at 0 °C, extracted with Et2O, dried
over MgSO4, and evaporated. Chromatography on silica gel (n-pentane)
afforded 5.80 g (91%) of 2-(3′-heptynyl)-1-iodobenzene: 1H NMR δ
2.00 (bs, 1H), 1.4-1.6 (m, 2 H), 2.85-3.05 (m, 2 H), 6.8-7.0 (m, 1
H), 7.2-7.4 (m, 2 H), 7.80 (d, J ) 6.4 Hz, 1 H); 13C NMR δ 19.08,
39.59, 69.30, 83.13, 100.32, 128.25, 129.77, 139.45, 142.61. To (i-
Pr)2NH (1.80 mL, 12.96 mmol) in THF (18 mL) were successively
added a 2.1 M solution of n-BuLi in n-hexane (5.9 mL, 2.39 mmol,
-50 °C, 20 min), a solution of 2-(3′-butynyl)-1-iodobenzene (2.50 g,
(g) 2-(3′-Methyl-3′-butenyl)-1-iodobenzene (23). Compound 23
was prepared in 63% yield following the procedure described for 2
using 2-methyl-2-propenylmagnesium chloride in THF in place of
allylmagnesium bromide: 1H NMR δ 1.8 (s, 3 H), 2.25 (t, J ) 7.0 Hz,
2 H), 2.85 (t, J ) 7.0 Hz, 2 H), 4.75 (s, 2 H), 6.8-6.95 (m, 1 H),
7.15-7.35 (m, 2 H), 7.83 (d, J ) 6.4 Hz, 1 H); 13C NMR δ 22.59,
38.25, 39.41, 100.60, 110.46, 127.69, 128.30, 129.27, 139.44, 149.50,
145.00.
(h) (E)- and (Z)-2-(1′-Propenyl)-1-iodobenzene (24). This com-
pound was prepared in 84% yield according the reported procedure
described for the preparation of 3,27 except that ethyltriphenylphos-
phonium bromide was used in place of methyltriphenylphosphonium
bromide. Compound 24 thus obtained was a 60/40 mixture of the Z/E
isomers: Z-24: 1H NMR δ 1.74 (dd, J ) 7.0, 0.65 Hz, 3 H), 5.7-5.9
(m, 1 H), 6.36 (d, J ) 11.4 Hz, 1 H), 6.8-7.0 (m, 1 H), 7.2-7.35 (m,
2 H), 7.85 (d, J ) 7.9 Hz, 1 H); 13C NMR δ 14.19, 100.19, 127.56,
127.66, 128.15, 128.24, 129.77, 133.67, 140.78. The following signals
were discernible for E-24: 1H NMR δ 1.91 (dd, J ) 6.5, 0.5 Hz, 1 H),
6.0-6.2 (m, 1 H), 6.57 (d, J ) 15.5 Hz, 1 H), 6.8-7.0 (m, 1 H), 7.2-
7.35 (m, 1 H), 7.41 (d, J ) 7.7 Hz, 1 H), 7.79 (d, J ) 7.9 Hz, 1 H);
13C NMR δ 18.54, 99.21, 126.26, 128.91, 134.68, 138.91, 139.25,
140.84; IR (neat) 1462 (m), 1432 (m), 1266 (c), 1012 (s) cm-1; high-
resolution MS calcd for 243.9749, found 243.9752.
(i) 2-(1′-Methylethenyl)-1-iodobenzene (25). A solution of 2-io-
dobenzaldehyde (1.16 g, 5.0 mmol, 0 °C, 10 min) in THF (10 mL)
was treated with a 2.7 M solution of MeMgBr in THF (1.8 mL, 5.0
mmol). The reaction mixture was quenched with H2O, extracted with
Et2O, dried over MgSO4, and evaporated. A mixture of the crude

CarbonylatiVe Cyclization of 1-Iodo-2-alkenylbenzenes
J. Am. Chem. Soc., Vol. 118, No. 25, 1996 5915
compound, Celite (2.1 g), and pyridinium chlorochromate (2.15 g, 10
mmol) in CH2Cl2 was stirred for 2 h, diluted with pentane, and filtered
through a short column of silica gel (9/1 n-pentane-Et2O) to give 1.10
g (94%) of 2-iodoacetophenone. This compound was converted to 25
in 42% yield according to the reported procedure described for the
preparation of 327 using 2-iodoacetophenone in place of 2-iodobenzal-
dehyde. The starting material was recovered to the extent of 50%. 25:
1H NMR δ 2.06 (s, 3 H), 4.8-4.95 (m, 1 H), 5.15-5.25 (m, 1 H),
7.1-7.2 (m, 1 H), 7.2-7.35 (m, 2 H), 7.82 (d, J ) 7.9 Hz, 1 H); 13C
NMR δ 23.86, 96.91, 115.99, 127.94, 128.29, 128.40, 139.08, 148.25,
gave a 43% NMR yield of 1,2,3,4-tetrahydro-2-ethylidene-1-oxonaph-
thalene (29) as an 81/19 mixture of two diastereomers along with a
15% yield of 30 and a 26% yield of 31. Chromatography on silica gel
(10/1 n-hexane/ethyl acetate) afforded 24 mg (37%) of 29 and 28 mg
(37%) of a mixture of 30 and 31. 29:37 1H NMR δ 1.88 (d, J ) 7.9
Hz, 3 H, E), 2.15 (d, J ) 7.9 Hz, 3 H, Z), 2.7-2.85 (m, 2 H), 2.9-
3.05 (m, 2 H), 7.02 (q, J ) 7.9 Hz, 1 H), 7.2-7.55 (m, 3 H), 8.10 (d,
J ) 7.8 Hz, 1 H); 13C NMR δ 14.00, 25.00, 28.50, 112.30, 126.50,
128.00, 133.00, 133.50, 134.50, 136.00, 144.00, 187.70; IR (neat) 1736,
1684 cm-1. 30:38 1H NMR δ 1.85 (s, 3 H), 2.7-2.9 (m, 2 H), 2.95-
148.69; IR (neat) 1642 (m), 1584 (w), 1563 (w), 1012 (s), 904 (s) cm-1
high-resolution MS calcd for C9H9I 243.9749, found 243.9752.
;
3.1 (m, 2 H), 5.70 (s, 1 H), 7.15-7.4 (m, 3 H), 7.45-7.6 (m, 1 H); 13
NMR δ 8.50, 22.20, 28.10, 78.80, 121.00, 124.80, 137.20, 128.00,
128.40, 134.00, 135.80, 161.00, 175.00; IR (neat) 1712 cm-1
The
C
.
Pd-Catalyzed Carbonylation of o-Iodo-ω-alkenylbenzenes Con-
taining Di- and Trisubstituted Alkenes (Table 3). (a) Carbonylation
of 19a or 19b. Under Conditions II (40 atm of CO, 100 °C, 15 h,
DMF), 19a (300 mg, 1.0 mmol) gave 2-pentylidene-2,3-dihydro-1H-
inden-1-one (26) in 82% NMR yield as a 93/7 mixture of the E and Z
isomers. Chromatography on silica gel (83/17 n-hexane/Et2O) afforded
166 mg (83%) of (E)-26 and 12 mg (6%) of (Z)-26, which slowly
isomerized to an equilibrium mixture of the E and Z isomers (E/Z )
94/6). (E)-26: 1H NMR δ 0.93 (t, J ) 7.2 Hz, 3 H), 1.3-1.6 (m, 4
H), 2.30 (q, J ) 7.3 Hz, 2 H), 3.63 (bs, 2 H), 6.88 (tt, J ) 7.7, 2.1 Hz,
1 H), 7.37 (dt, J ) 7.4, 1.0 Hz, 1 H), 7.48 (d, J ) 7.4 Hz, 1 H), 7.56
(dt, J ) 7.3, 1.2 Hz, 1 H), 7.84 (d, J ) 7.8 Hz, 1 H); 13C NMR δ
14.37, 22.98, 30.06, 30.41, 31.05, 124.72, 126.79, 127.87, 134.84,
136.84, 138.78, 139.37, 149.85, 193.82; IR (neat) 1702 cm-1; high-
resolution MS calcd for C14H16O 200.1201, found 200.1199. The
following signals were discernible for (Z)-26: 1H NMR δ 0.94 (t, J )
7.1 Hz, 3 H), 1.3-1.6 (m, 4 H), 2.94 (q, J ) 7.3 Hz, 2 H), 3.68 (bs,
2 H), 6.30 (tt, J ) 7.7, 1.6 Hz, 1 H), 7.38 (t, J ) 7.6 Hz, 1 H), 7.46
(d, J ) 7.6 Hz, 1 H), 7.56 (dt, J ) 7.3, 1.2 Hz, 1 H), 7.81 (d, J ) 7.4
Hz, 1 H); 13C NMR δ 14.40, 22.98, 28.16, 31.97, 33.52, 124.36, 126.57,
127.70, 134.51, 134.68, 140.08, 144.29, 149.72, 195.09. Under
Conditions I (1 atm of CO, 60 °C, 15 h, DMF), 19b (300 mg, 1.0
mmol) gave 26 in 87% NMR yield as an 84/16 mixture of the E and
Z isomers. Under Conditions II (40 atm of CO, 100 °C, 15 h, DMF),
19b (300 mg, 1.0 mmol) gave 26 in 91% NMR yield as a 94/6 mixture
of the E and Z isomers. Chromatography on silica gel (83/17 n-hexane/
Et2O) afforded 166 mg (83%) of (E)-26 and 12 mg (6%) of (Z)-26.
Under Conditions III (1 atm of CO, 60 °C, 18 h, a 1:1 mixture of
MeOH (37 equiv)/DMF), 19b (300 mg, 1.0 mmol) gave 26 in 50%
NMR yield along with a 37% yield of 2-(1′-(methoxycarbonyl)pentyl)-
1-indanone (27) as a 1:1 mixture of its two diastereomers. At 14 atm
of CO in a 1:1 mixture of MeOH (37 equiv)/DMF), 19b (300 mg, 1.0
mmol) gave, after 16 h at 100 °C, 26 in 31% NMR yield along with a
63% yield of 27 as a 1:1 mixture of two diastereomers. Chromatog-
raphy on silica gel (83/17 pentane/Et2O) afforded 45 mg (23%) of 26
following signals were assignable to 31: 1H NMR δ 2.42 (t, J ) 8.6
Hz, 2 H), 2.50 (t, J ) 8.6 Hz, 2 H), 2.76 (t, J ) 8.6 Hz, 2 H), 2.88 (t,
J ) 8.6 Hz, 2 H), 7.1-7.6 (m, 4 H); 13C NMR δ 24.00, 26.40, 27.40,
29.00, 111.90, 121.00, 126.40, 126.60, 126.70, 129.00, 135.00, 168.60.
Under Conditions II (40 atm of CO, 100 °C, 48 atm, 22 h, Pd(OAc)2
(5 mol %), dppe (5 mol %), 1:1 mixture of acetonitrile/THF), 21a (272
mg, 1.0 mmol) gave 30 in 51% NMR yield as the only monomeric
product. Chromatography on silica gel (10/1 n-hexane/ethyl acetate)
afforded 40 mg (52%) of 30. Under Conditions IV (40 atm of CO,
100 °C, 20 h, a 1:1 mixture of benzene/acetonitrile), 21a (272 mg, 1.0
mmol) gave 100 mg (44%) of a mixture of 1,2,3,4-tetrahydro-2-
((methoxycarbonyl)methyl)-1-oxonaphthalene (32) (77/23 mixture of
diastereomers) and 33, 40 mg (24%) of 1,2,3,4-tetrahedro-2-ethylidene-
1-oxonaphthalene (29), and 60 mg (31%) of methyl (Z)-2-(3′-pentenyl)-
benzoate (34) after chromatography on silica gel (10/1 n-hexne/ethyl
acetate). Data for 32:39 1H NMR δ 1.18 (d, J ) 6.8 Hz, 3 H), 1.30 (d,
J ) 6.8 Hz, 3 H), 2.0-2.3 (m, 2 H), 2.8-3.3 (m, 4 H), 3.70 (s, 3 H),
3.75 (s, 3 H), 7.2-8.15 (m, 4 H); 13C NMR δ 13.50, 26.00, 29.00,
39.00, 50.20, 51.60, 126.60, 127.60, 128.40, 132.40, 133.60, 143.80,
175.00, 198.00; IR (neat) 1736, 1684, 1600 cm-1. The following signals
were discernible for 33:40 1H NMR δ 1.75-2.05 (m, 2 H), 2.1-2.4
(m, 2 H), 2.45-2.65 (m, 3 H), 2.95-3.15 (m, 2 H), 3.70 (s, 3 H),
7.2-7.4 (m, 2 H), 7.4-7.6 (m, 1 H), 8.05 (d, J ) 7.8 Hz, 1 H); 13C
NMR δ 25.20, 28.40, 28.80, 31.60, 46.40, 51.60, 126.20, 127.00,
128.40, 132.20, 133.60, 144.00, 174.00, 199.40; IR (neat) 1736, 1684,
1600 cm-1. 34: 1H NMR δ 1.55 (d, J ) 4.7 Hz, 3 H), 2.3-2.45 (m,
2 H), 3.00 (d, J ) 7.0 Hz, 2 H), 3.90 (s, 3 H), 5.4-5.55 (m, 2 H),
7.2-7.9 (m, 4 H).
(d) Carbonylation of 21b. Under Conditions II (40 atm of CO,
100 °C, 28 h, DMF), 21b (334 mg, 1.0 mmol) gave 226 mg (96%) of
35 as a 1:1 mixture of the E and Z isomers after chromatography on
silica gel (10:1 n-hexane/ethyl acetate):39 1H NMR δ 2.85-3.0 (m, 2
H), 3.05-3.2 (m, 2H), 6.84 (s, 1 H, Z), 6.89 (s, 1 H, E), 7.2-7.55 (m,
8 H), 8.12 (t, J ) 6.9 Hz, 1 H); 13C NMR δ 27.20, 28.80, 31.00, 36.00,
126.80, 127.00, 127.80, 127.90, 128.10, 128.20, 128.40, 128.50, 129.40,
129.80, 133.20, 133.30, 133.40, 134.20, 135.40, 135.70, 135.80, 136.40,
1
and 170 mg (65%) of 27: 1:1 mixture of diastereomers, H NMR δ
0.8-1.0 (m, 6 H), 1.2-2.05 (m, 12 H), 2.8-3.4 (m, 8 H), 3.50 (s, 3
H), 3.74 (s, 3 H), 7.35 (t, J ) 7.8 Hz, 2 H), 7.4-7.5 (m, 2 H), 7.45-
7.55 (m, 2 H), 7.7-7.8 (m, 2 H); 13C NMR δ 14.10, 14.33, 22.96,
23.02, 28.85, 30.22, 30.31, 30.38, 45.60, 46.20, 48.68, 49.57, 51.92,
52.17, 124.21, 124.30, 126.92, 127.76, 127.93, 135.02, 135.32, 137.15,
137.26, 153.66, 153.86, 174.66, 175.82, 206.55, 207.22; IR (neat) 1738,
1718 cm-1; high-resolution MS calcd for C16H20O3 260.1412, found
260.1410. Under Conditions IV (40 atm of CO, 100 °C, 22 h, 1:1
mixture of MeOH (37 equiv)/DMF), 19b gave 26 in 15% NMR yield
along with an 80% yield of 27 as a 1:1 mixture of its diastereomers.
Under Conditions IV (80 atm of CO, 100 °C, 16 h, DMF), 19b gave
26 in 8% NMR yield along with a 90% yield of 27 as a 1:1 mixture of
two diastereomers.
(b) Carbonylation of 20. Under Conditions IV (40 atm of CO,
100 °C, 24 h, 1:1 mixture acetonitrile/benzene), 20 (298 mg, 1.0 mmol)
gave 173 mg (67% yield) of 2-methoxycarbonylspiro(cyclohexane-1′,2′-
indan-1-one) (28) after Kugelrohr distillation. 28: bp 105-110 °C
(0.15 mm Hg); 1H NMR δ 1.2-3.3 (m, 11 H), 3.48 (s, 3 H), 7.2-7.8
(m, 4 H); 13C NMR δ 20.73, 25.18, 25.69, 35.58, 43.15, 48.77, 50.97,
51.50, 123.91, 126.08, 134.10, 136.90, 151.16, 174.26, 208.02; IR (neat)
1725, 1700 cm-1; high-resolution MS calcd for C16H18O3 258.1256,
found 258.1259.
136.60, 143.20, 143.50, 188.00, 189.00; IR (neat) 1664, 1602 cm-1
.
(e) Carbonylation of 22. Under Conditions II (40 atm of CO, 100
°C, 16 h, Pd(PPh3)4 (0.05 equiv), a 1:1 mixture of acetonitrile/benzene),
22 (356 mg, 1.0 mmol) gave 170 mg (67%) of 36 after purification by
chromatography on silica gel (63/27 hexane/Et2O): 1H NMR δ 1.6-
1.8 (m, 3 H), 2.3-2.4 (m, 3 H), 2.96 (d, J ) 15.0 Hz, 1 H), 3.37 (d,
J ) 15.0 Hz, 1 H), 3.45 (s, 3 H), 7.2-8.1 (m, 5 H); 13C NMR δ 18.78,
26.04, 34.26, 40.38, 48.39, 52.26, 127.30, 127.78, 128.15, 132.66,
133.24, 135.87, 139.15, 139.77, 175.62, 185.80; high-resolution MS
calcd for C16H16O3 256.1100, found 256.1097.
(f) Carbonylation of 23. Under Conditions IV (40 atm of CO, 100
°C, 15.5 h), a 1/1 mixture of acetonitrile/benzene), 23 (272 mg, 1.0
mmol) gave 122 mg (53%) of 1,2,3,4-tetrahydro-2-((methoxycarbonyl)-
methyl)-2-methyl-1-oxonaphthalene (37) along with 35 mg (17%) of
methyl 2-(3′-butenyl)benzoate (38) after chromatography on silica gel
(10/1 n-hexane/ethyl acetate). 37:41 1H NMR δ 1.12 (s, 3 H), 1.98 (dt,
J ) 2.3, 6.8 Hz, 1 H), 2.15-2.25 (m, 1 H), 2.25 (d, J ) 7.5 Hz, 1 H),
(39) El-Rayyes, N. R.; Al-Jawhary, A. J. Heterocycl. Chem. 1986, 23,
135.
(40) Mizuno, K.; Okamoto, H.; Pac, C.; Sakurai, H.; Murai, S.; Sonoda,
N. Chem. Lett. 1975, 237.
(41) Barlocco, D.; Pinna, G. A.; Carboni, L.; Ciplooa, P. Farmaco 1989,
44, 967.
(c) Carbonylation of 21a. Under Conditions II (40 atm of CO,
100 °C, 22 h, a 1:1 mixture of THF/CH3CN), 21a (272 mg, 1.0 mmol)

5916 J. Am. Chem. Soc., Vol. 118, No. 25, 1996
Negishi et al.
2.47 (d, J ) 7.5 Hz, 1 H), 2.4-2.6 (m, 2 H), 3.82 (s, 3 H), 7.2-7.4
(m, 2 H), 7.44 (t, J ) 3.8 Hz, 1 H), 8.04 (d, J ) 3.8 Hz, 1 H); 13C
NMR δ 21.90, 25.30, 33.13, 42.15, 43.63, 51.45, 126.70, 128.08,
(d) 5-(2′-Iodophenyl)-4-(methoxycarbonyl)-2-pentenoate (53a)
and 5-(2′-Iodophenyl)-4-(methoxycarbonyl)-3-pentenoate (53b). To
i-Pr2NH (2.6 mL, 1.87 g, 18.5 mmol, -78 °C, 0.5 h) in THF (20 mL)
were successively added a 2.0 M solution of n-BuLi in hexane (10.1
mL, 20.2 mmol), dimethyl pentenedioate (2.8 g, 17.7 mmol, -78 °C,
1 h) in THF (10 mL), and 2-iodobenzyl bromide (5.0 g, 16.8 mmol,
-78 °C) in THF (20 mL). The reaction mixture was warmed and
stirred at 25 °C for 2 h, quenched with aqueous NH4Cl, extracted with
Et2O, washed with aqueous NaHCO3, dried over MgSO4, and evapo-
rated. Chromatography on silica gel (3/1 n-hexane/pentane) afforded
5.24 g (83%) of a 1:1 mixture of 53a and 53b: 1H NMR δ 2.8-3.8
(m, 19 H), 6.6-7.4 (m, 9 H), 7.7-7.9 (m, 2 H).
128.63, 131.19, 133.23, 142.89, 171.88, 200.68; IR (neat) 1734 cm-1
.
38: 1H NMR δ 1.80 (s, 3 H), 2.30 (t, J ) 8.8 Hz, 2 H), 3.10 (t, J )
8.8 Hz, 2 H), 3.90 (s, 3 H), 4.72 (bs, 2 H), 7.2-7.35 (m, 2 H), 7.35-
7.5 (m, 1 H), 7.85-7.95 (m, 1 H); 13C NMR δ 22.52, 33.06, 39.82,
51.90, 110.14, 125.85, 129.43, 130.63, 130.90, 131.89, 143.99, 145.53,
168.08; IR (neat) 1724 cm-1; high-resolution MS calcd for C13H16O2
204.1150, found 204.1149.
(g) Carbonylation of 24. Under Conditions I (1 atm of CO, 80
°C, 12 h, a 1:1 mixture of acetonitrile/benzene), 24 (244 mg, 1.0 mmol)
gave 39 in 22% NMR yield:42 1H NMR δ 1.87 (d, J ) 1.7 Hz, 3 H),
6.93 (d, J ) 7.1 Hz, 1 H), 7.0-7.2 (m, 2 H), 7.2-7.35 (m, 1 H), 7.36
(d, J ) 7.0 Hz, 1 H). Under Conditions IV (40 atm of CO, 100 °C, 6
h, a 1:1 mixture of acetonitrile/benzene), 24 (244 mg, 1.0 mmol) gave
3-(methoxycarbonyl)-2-methyl-2,3-dihydro-1-H-indenone (40a) in 9%
yield along with methyl 2-(1′-propenyl)benzoate (41a) (70%). Chro-
matography on silica gel (90/10 n-pentane/Et2O) afforded 120 mg (67%)
of 41a as a 3/2 mixture of the (E) and (Z) isomers. trans-40a: 1H
NMR δ 1.39 (d, J ) 7.4 Hz, 3 H), 3.12 (dq, J ) 7.4, 4.6 Hz, 1 H),
3.82 (s, 3 H), 3.87 (d, J ) 4.6 Hz, 1 H), 7.4-7.5 (m, 1 H), 7.6-7.7
(m, 2 H), 7.78 (d, J ) 7.6 Hz, 1 H); 13C NMR δ 15.17, 45.92, 52.13,
52.56, 124.08, 126.28, 128.76, 134.99, 135.64, 149.42, 172.23, 206.16;
IR (neat) 1722 cm-1; high-resolution MS calcd for C12H12O3 204.0786,
found 204.0790. The following signals were discernible for cis-40a:
1H NMR δ 1.28 (d, J ) 7.4 Hz, 3 H), 3.01 (p, J ) 7.7 Hz, 1 H), 3.71
(s, 3 H), 4.41 (d, J ) 4.6 Hz, 1 H), 7.81 (d, J ) 7.7 Hz, 1 H). (Z)-
41a: 1H NMR δ 1.73 (dd, J ) 7.05, 1.8 Hz, 3 H), 3.87 (s, 3 H), 5.84
(dq, J ) 11.6, 7.05 Hz, 1 H), 6.8-7.0 (m, 1 H), 7.2-7.6 (m, 3 H),
7.9-8.0 (m, 1 H); 13C NMR δ 14.27, 51.92, 126.22, 126.54, 129.26,
(e) Methyl (E)-4-(2′-Iodophenyl)-2-butenoate (54). Reduction of
1-(2′-iodophenyl)-2-propyne (1.96 g, 8.1 mmol) with i-Bu2AlH (1.05
equiv, 25 °C, 16 h) followed by treatment with methyl chloroformate
(2.30 g, 24.3 mmol, 0 to 25 °C, 3 h) afforded, upon quenching with
H2O (2 mL), 1.50 g (61%) of 54 after chromatography on silica gel
(83/17 hexane/Et2O): 1H NMR δ 3.63 (dd, J ) 6.5, 1.5 Hz, 2 H), 3.70
(s, 3 H), 5.79 (dt, J ) 15.6, 1.6 Hz, 1 H), 6.92 (dt, J ) 7.6, 1.8 Hz, 1
H), 7.05 (dt, J ) 15.6, 6.5 Hz, 1 H), 7.17 (dd, J ) 7.6, 1.8 Hz, 1 H),
7.29 (dt, J ) 7.4, 1.2 Hz, 1 H), 7.82 (d, J ) 8.0 Hz, 1 H); 13C NMR
δ 43.75, 52.04, 101.20, 123.11, 129.11, 130.43, 140.17, 141.14, 146.37,
167.22; IR (neat) 1718 cm-1
.
(f) Ethyl (E)-5-(2′-Iodophenyl)-2-pentenoate (55). This compound
was prepared in 69% yield as described in the preparation of 54 using
4-(2′-iodophenyl)-1-butyne (Vide supra, preparation of 21a) in place
of 3-(2′-iodophenyl)-1-propyne: 1H NMR δ 1.28 (t, J ) 7.3 Hz, 3 H),
2.4-2.6 (m, 2 H), 2.8-2.95 (m, 2 H), 4.19 (q, J ) 7.3 Hz, 2 H), 5.8-
5.95 (m, 1 H), 6.8-6.95 (m, 1 H), 6.95-7.1 (m, 1 H), 7.1-7.35 (m,
2 H), 7.75-7.85 (m, 1 H); 13C NMR δ 14.42, 32.70, 39.41, 60.34,
122.19, 128.21, 128.57, 129.48, 139.71, 143.40, 147.49, 166.57.
(g) (Z)-2-(3′-(Trimethylsilyl)-2′-propenyl)-1-iodobenzene (56).
Reduction of 1-(2′-iodophenyl)-3-(trimethylsilyl)-2-propyne32 (0.90 g,
2.90 mmol) with i-Bu2AlH (1.5 equiv, 40 °C, 18 h) gave 56 after
chromatography on silica gel (n-hexane): 1H NMR δ 0.18 (s, 9 H),
3.57 (d, J ) 7.0 Hz, 2 H), 5.73 (dt, J ) 14.0, 1.4 Hz, 1 H), 6.38 (dt,
J ) 14.0, 7.0 Hz, 1 H), 6.89 (dt, J ) 7.2, 1.6 Hz, 1 H), 7.15-7.35 (m,
2 H), 7.82 (d, J ) 7.8 Hz, 1 H); 13C NMR δ 0.78, 44.82, 101.52,
128.49, 128.90, 129.69, 132.00, 139.92, 143.59, 145.63; IR (neat) 1606
(s), 1464 (s), 1436 (s), 1248 (s), 1012 (s), 838 (s), 746 (s) cm-1; high-
resolution MS calcd for C12H17ISi 316.0144, found 316.0141.
(h) (E)-1-(tert-Butyldimethylsilyl)oxy)-5-(2′-iodophenyl)-2-pentene
(57). A solution of 2-iodobenzyl bromide (5.94 g, 20 mmol) in THF
(20 mL) was treated with a solution of allenylmagnesium bromide (Vide
supra, preparation of 21a) and heated at reflux for 10 h. The reaction
mixture was quenched with aqueous NH4Cl, extracted with Et2O,
washed with aqueous NaHCO3, dried over MgSO4, and evaporated.
Chromatography on silica gel (99/1 n-pentane/Et2O) afforded 5.10 g
(99%) of 4-(2′-iodophenyl)-1-butyne: 1H NMR δ 1.97 (t, J ) 2.6 Hz,
1 H), 2.46 (dt, J ) 7.5, 2.6 Hz, 2 H), 2.92 (t, J ) 7.5 Hz, 2 H), 6.8-
6.95 (m, 1 H), 7.2-7.3 (m, 2 H), 7.78 (d, J ) 8.3 Hz, 1 H); 13C NMR
δ 19.01, 39.51, 69.27, 83.04, 100.25, 129.16, 129.67, 139.35, 142.49.
Reduction of 4-(2′-iodophenyl)-1-butyne (5.10 g, 19.9 mmol) with
i-Bu2AlH (1.05 equiv, 25 °C, 10 h) followed by treatment with ethyl
chloroformate (5.71 mL, 59.7 mmol, 0 °C then 25 °C, 2 h) gave 5.65
g (86%) of ethyl (E)-4-(2′-iodophenyl)-2-butenoate. A portion of this
crude product (651 mg, 1.97 mmol) in CH2Cl2 was treated with i-Bu2-
AlH (0.81 mL, 4.55 mmol, 0 °C, 1 h). The reaction mixture was
quenched with NH4Cl, extracted with Et2O, washed with NaHCO3, dried
over MgSO4, and evaporated to give 567 mg (100%) of (E)-4-(2′-
iodophenyl)-2-buten-1-ol. A mixture of (E)-4-(2′-iodophenyl)-2-buten-
1-ol (394 mg, 1.37 mmol), tert-butylchlorodimethylsilane (248 mg, 1.65
mmol), and imidazole (100 mg, 2.06 mmol) in DMF (2 mL) was stirred
at 25 °C for 1 h. The reaction mixture was diluted with n-pentane,
extracted with H2O, dried over MgSO4, and evaporated. Chromatog-
raphy on silica gel (8/1 n-pentane/Et2O) afforded 535 mg (97%) of 57:
1H NMR δ 0.52 (s, 6 H), 0.90 (s, 9 H), 2.25-2.4 (m, 2 H), 2.7-2.85
(m, 2 H), 4.05-4.2 (m, 2 H), 5.5-5.8 (m, 2 H), 6.8-6.9 (m, 1 H),
7.1-7.3 (m, 2 H), 7.76 (d, J ) 7.7 Hz, 1 H); 13C NMR δ -5.11, 18.39,
25.98, 32.60, 40.44, 63.82, 100.54, 127.65, 128.18, 129.30, 129.53,
130.08, 139.38, 144.26; IR (neat) 1462 (s), 1262 (s) cm-1; high-
resolution MS calcd for C12H17ISi 316.0114, found 316.0141.
129.61, 130.41, 130.85, 131.46, 138.79, 167.73; IR (neat) 1722 cm-1
;
high-resolution MS calcd for C11H12O2 176.0837, found 176.0839. The
following signals were discernible for (E)-41a: 1H NMR δ 1.92 (dd,
J ) 6.6, 1.7 Hz, 3 H), 3.89 (s, 3 H), 6.15 (dq, J ) 15.6, 6.6 Hz, 1 H),
7.1-7.2 (m, 1 H), 7.2-7.6 (m, 3 H), 7.83 (dd, J ) 7.8, 1.3, 1 H).
Under Conditions IV (40 atm of CO, 100 °C, 6 h, benzene), 24 (244
mg, 1.0 mmol) gave 40a in 34% yield along with a 57% yield of 41a.
Under Conditions IV (40 atm of CO, 100 °C, 24 h, i-PrOH (4 equiv),
benzene), 24 (244 mg, 1.0 mmol) gave 3-(isopropoxycarbonyl)-2-
methyl-2,3-dihydro-1H-indenone (40b) in 63% NMR yield along with
a 15% yield of isopropyl 2-(1′-propenyl)benzoate (41b) and a 13%
yield of 39. Chromatography on silica gel (90/10 n-pentane/Et2O)
afforded 128 mg (55%) of 40b as a single isomer. trans-40b: 1H NMR
δ 1.31 (d, J ) 6.3 Hz, 6 H), 1.39 (d, J ) 7.3 Hz, 3 H), 3.12 (dq, J )
7.3, 4.5 Hz, 1 H), 3.81 (d, J ) 4.5 Hz, 1 H), 5.12 (sept, J ) 6.25 Hz,
1 H), 7.4-7.5 (m, 1 H), 7.6-7.75 (m, 2 H), 7.78 (d, J ) 7.7, 1 H); 13
C
NMR δ 15.08, 21.76, 21.80, 45.79, 52.41, 69.06, 124.04, 126.06,
128.63, 134.89, 135.65, 149.75, 171.18, 206.41; IR (neat) 1722 cm-1
high-resolution MS calcd for C14H16O3 232.1099, found 232.1104.
;
(h) Carbonylation of 25. Under Conditions IV (40 atm of CO,
100 °C, 24 h, i-PrOH (4 equiv), benzene), 25 (244 mg, 1.0 mmol) did
not yield monomeric cyclization products.
Preparation of ω-Alkene-Containing Aryl Iodides 42, 43, 49, and
53-57. (a) 2-(1′-Hydroxy-2′-propenyl)-1-iodobenzene (42). Com-
pound 42 was prepared according to a reported procedure.31
(b) 2-(2′-(Hydroxymethyl)-3′-butenyl)-1-iodobenzene (43). Using
the procedure described for the preparation of 22,30 except that ethyl
crotonate was used in place of 1-carbomethoxycyclohexene, ethyl R-(o-
iodobenyl)vinylacetate was obtained. Its reduction with i-Bu2AlH (3
equiv, -78 °C, 10 min) gave 43 in 46% yield after chromatography
on silica gel (90/10 pentane/Et2O): 1H NMR δ 1.64 (bs, 1 H), 2.55-
2.8 (m, 2 H), 2.89 (dd, J ) 13.3, 6.55 Hz, 1 H), 3.4-3.8 (m, 2 H),
5.0-5.2 (m, 2 H), 5.65-5.85 (m, 1 H), 6.8-6.95 (m, 1 H), 7.1-7.3
(m, 2 H), 7.81 (d, J ) 7.8 Hz, 1 H); 13C NMR δ 41.64, 46.69, 64.60,
101.00, 117.71, 127.94, 127.98, 130.60, 138.51, 139.51, 142.33; IR
(neat) 3346 (bs), 1030 (s) cm-1; high-resolution MS calcd for C11H13-
IO 289.0089, found 289.0080.
(c) 2-(1′-(tert-Butyldimethylsilyloxy)-2′-propenyl)-1-iodobenzene
(49). Compound 49 was prepared according to a reported procedure.31
(42) Floyd, M. B.; Allen, G. R. J. Org. Chem. 1970, 35, 2847.

CarbonylatiVe Cyclization of 1-Iodo-2-alkenylbenzenes
J. Am. Chem. Soc., Vol. 118, No. 25, 1996 5917
Pd-Catalyzed Carbonylation of o-Iodo-ω-alkenylbenzenes Con-
taining Heteroatom Substituents (Schemes 5 and 6). (a) Carbon-
ylation of 42. Under Conditions II (40 atm of CO, 100 °C, 20 h),
where a 1:1 mixture of acetonitrile/benzene was used in place of DMF,
42 (260 mg, 1.0 mmol) gave 3-ethylidene-1-isobenzofuranone (44) in
90% yield along with a 3% yield of 3,3a,8b-trihydro-2,4-2H-indeno-
[1,2-b]furandione (46). 44-(E):31 1H NMR δ 2.01 (d, J ) 7.2 Hz, 3
H), 5.67 (q, J ) 7.2 Hz, 1 H), 7.4-7.55 (m, 1 H), 7.55-7.75 (m, 2 H),
7.86 (d, J ) 7.7 Hz, 1 H); 13C NMR δ 11.29, 104.23, 119.58, 124.33,
125.14, 129.32, 134.29, 139.48, 146.36, 167.13. The following signals
were discernible for 44-(Z): 1H NMR δ 2.15 (d, J ) 7.9 Hz, 3 H),
5.92 (q, J ) 7.2 Hz, 1 H), 7.56 (t, J ) 7.5 Hz, 3 H), 7.7-7.8 (m, 2 H),
7.86 (m, 1 H), 7.86 (d, J ) 7.9 Hz, 1 H), 7.94 (d, J ) 7.7 Hz, 1 H).
An authentic sample of 46 was prepared by heating at 50 °C a mixture
of 50 (50 mg, 0.15 mmol, Vide infra for preparation) and pyridinium
p-toluenesulfonate (0.3 equiv) in CH3OH for 24 h. The reaction mixture
was evaporated, diluted with Et2O, washed with H2O, dried over
MgSO4, and evaporated. Chromatography on silica gel (90/10 pentane/
Et2O) gave 23 mg (71%) of a 1/4 mixture of 46 and 2-trans-((methoxy-
carbonyl)methyl)-3-hydroxy-1-indanone: 1H NMR δ 2.67 (dd, J )
18.0, 10 Hz, 1 H), 2.75-2.9 (m, 1 H), 3.20 (dd, J ) 18.0, 4.0 Hz, 1
H), 3.73 (s, 3 H), 4.15 (bs, 1 H), 5.11 (d, J ) 6.0 Hz, 1 H), 7.47 (t, J
) 7.5 Hz, 1 H), 7.6-7.8 (m, 3 H); 13C NMR δ 32.70, 52.17, 54.24,
74.39, 123.09, 125.44, 129.07, 135.22, 135.29, 153.17, 173.96, 201.81.
The following signals were discernible for 46: 1H NMR δ 3.06 (dd, J
) 19.0, 12.5 Hz, 1 H), 3.55-3.65 (m, 2 H), 6.00 (d, J ) 6.7 Hz, 1 H);
13C NMR δ 31.03, 45.69, 79.06, 124.34, 127.48, 131.06, 135.98, 136.07,
149.57, 174.78, 202.42. Under Conditions IV (40 atm of CO, 100 °C,
20 h, a 1:1 mixture of acetonitrile/benzene), 42 (260 mg, 1.0 mmol)
gave 44 in 65% NMR yield along with a 24% yield of 45 and a 3%
yield of 46. 45:39 1H NMR δ 1.23 (t, J ) 7.2 Hz, 3 H), 2.81 (q, J )
7.2 Hz, 2 H), 3.89 (s, 3 H), 7.3-7.4 (m, 1 H), 7.4-7.6 (m, 2 H), 7.85-
7.95 (m, 1 H).
25.67, 30.11, 49.79, 54.49, 73.87, 122.94, 125.14, 128.78, 134.86,
135.50, 153.97, 154.14, 171.98, 202.09; IR (neat) 1718 cm-1
. The
following signals were discernible for the cis isomer: 1H NMR δ 0.14
(s, 3 H), 0.17 (s, 3 H), 0.84 (s, 9 H), 3.1-3.3 (m, 1 H), 3.60 (s, 3 H),
5.51 (d, J ) 6.0 Hz, 1 H); 13C NMR (17.88, 25.61, 29.71, 49.52, 49.64,
70.27, 123.44, 126.24, 129.26, 134.78, 135.44, 153.97, 172.91, 204.72.
(d) Carbonylation of 53a and 53b. Under Conditions IV (40 atm
of CO, 100 °C, 15 h, 4 equiv of t-BuOH DMF), a 1:1 mixture of 53a
and 53b (374 mg, 1.0 mmol) gave 125 mg (46%) of 2-((methoxycar-
bonyl)methyl)-2-(2′-methoxycarbonylvinyl)-1-indanone (58) after chro-
matography on silica gel (1/1 n-pentane/Et2O): 1H NMR δ 3.37 (d, J
) 17.3 Hz, 1 H), 3.72 (s, 3 H), 3.76 (s, 3 H), 3.91 (d, J ) 17.3 Hz, 1
H), 5.97 (d, J ) 16 Hz, 1 H), 7.3-7.85 (m, 5 H); 13C NMR δ 37.93,
52.28, 53.89, 63.12, 122.72, 125.91, 126.88, 128.76, 134.26, 136.44,
144.49, 152.61, 166.59, 169.89, 198.66.
(e) Carbonylation of 54. Under Conditions IV (40 atm of CO,
100 °C, 10 h, DMF), 54 (302 mg, 1.0 mmol) gave methyl 2-(2-(2,3-
dihydro-1-oxo-1H-indenyl))malonate (59) in 23% NMR yield along
with methyl 1-hydroxy-2-naphthoate (60) (25%), 12 (10%), 4-(2′-
(methoxycarbonyl)phenyl)-3-butenoate (61a) (12%), and 4-(2′-(meth-
oxycarbonyl)phenyl)-2-butenoate (61b) (3%) obtained in the yields
indicated in parentheses. Chromatography on silica gel (83/17 n-hex-
ane/Et2O) afforded 57 mg (22%) of 59, 50 mg (25%) of 60,43 11 mg
(5%) of 12, and 37 mg of a mixture of 61a (12%) and 61b (3%). 59:
1H NMR δ 3.1-3.5 (m, 3 H), 3.66 (s, 3 H), 3.82 (s, 3 H), 4.16 (d, J
) 5.0 Hz, 1 H), 7.38 (dt, J ) 7.4, 1.0 Hz, 1 H), 7.47 (d, J ) 7.8 Hz,
1 H), 7.61 (dt, J ) 7.4, 1.2 Hz, 1 H), 7.77 (d, J ) 7.6, 1.0 Hz, 1 H);
13C NMR δ 31.14, 46.91, 51.86, 53.13, 53.30, 124.52, 126.94, 128.01,
135.44, 136.59, 153.64, 168.63, 169.57, 205.02; high-resolution MS
calcd for C14H14O5 203.0708, found 203.0697. 60:43 1H NMR δ 3.96
(s, 3 H), 6.55-6.7 (m, 2 H), 6.7-6.85 (m, 2 H), 6.85-6.9 (m, 2 H),
8.15-8.25 (m, 1 H), 11.98 (s, 1 H); 13C NMR δ 52.23, 105.53, 118.55,
123.82, 124.17, 124.70, 125.70, 127.41, 129.44, 137.14, 160.87, 171.38.
61a: 1H NMR δ 3.32 (dd, J ) 7.0, 1.6 Hz, 1 H), 3.73 (s, 3 H), 3.90
(s, 3 H), 6.22 (dt, J ) 15.8, 7.1 Hz, 1 H), 7.25-7.4 (m, 2 H), 7.47 (dt,
J ) 7.4, 1.6 Hz, 1 H), 7.57 (dd, J ) 7.8, 1.4 Hz, 1 H), 7.87 (d, J )
7.8, 1.4 Hz, 1 H); 13C NMR δ 38.76, 52.42, 52.57, 124.95, 127.70,
127.99, 130.87, 132.61, 139.17, 148.34, 168.27, 172.49. The following
signals were discernible for 61b: 1H NMR δ 3.7 (s, 3 H), 3.88 (s, 3
H), 5.74 (dt, J ) 15.6, 1.7 Hz, 1 H), 7.15 (dt, J ) 15.8, 6.6 Hz, 1 H),
7.47 (d, J ) 7.8 Hz, 1 H), 7.61 (dt, J ) 7.4, 1.2 Hz, 1 H), 7.77 (dd, J
) 7.96, 1.5 Hz, 1 H).
(f) Carbonylation of 55. Under Conditions II (40 atm of CO, 100
°C, 10 h, DMF), 55 (402 mg, 1.0 mmol) gave a 17% NMR yield of
1-(ethoxycarbonyl)methyleneindane (64):43 a 1/1 mixture of the E and
Z isomers: 1H NMR δ 1.25 (t, J ) 7.2 Hz, 3 H), 1.32 (t, J ) 7.2 Hz,
3 H), 2.9-3.15 (m, 2 H), 3.2-3.35 (m, 2 H), 3.36 (s, 2 H), 3.57 (s, 2
H), 4.1-4.3 (m, 4 H), 6.30 (t, J ) 2.5 Hz, 1 H), 6.42 (s, 1 H), 7.1-7.6
(m, 8 H); 13C NMR δ 14.33, 14.58, 30.73, 31.28, 34.28, 38.06, 59.82,
60.99, 107.80, 119.27, 121.74, 123.89, 124.96, 125.76, 126.25, 126.89,
130.96, 131.77, 140.09, 144.17, 144.59, 149.59, 163.09, 167.68, 171.11.
Under Conditions IV (40 atm of CO, 100 °C, 10 h, DMF), 55 (402
mg, 1.0 mmol) gave an 84% NMR yield of ethyl (E)-5-(2′-(methoxy-
carbonyl)phenyl)-2-pentanoate (63) along with a 13% yield of ethyl
methyl 2-(1-tetralone)malonate (62), obtained as a 1:1 mixture of two
diastereomers. Chromatography on silica gel (6/1 pentane/Et2O)
afforded 194 mg (78%) of 63 and 27.6 mg (13%) of 62a: 1H NMR δ
1.27 (t, J ) 7.2 Hz, 3 H), 1.31 (t, J ) 7.2 Hz, 3 H), 2.1-2.3 (m, 4 H),
2.9-3.2 (m, 4 H), 3.3-3.45 (m, 2 H), 3.76 (s, 3 H), 3.81 (s, 3 H),
3.95-4.1 (m, 2 H), 4.23 (q, J ) 7.2 Hz, 2 H), 4.26 (q, J ) 7.2 Hz, 2
H), 7.2-7.4 (m, 2 H), 7.4-7.55 (m, 1 H), 7.65-7.75 (m, 2 H), 8.10
(d, J ) 7.9 Hz, 1 H); IR (neat) 1734, 1684 cm-1; high-resolution MS
calcd for C16H18O5 290.1154, found 290.1150. 63a: 1H NMR δ 1.28
(t, J ) 7.0 Hz, 3 H), 2.4-2.6 (m, 2 H), 3.05-3.2 (m, 2 H), 3.88 (s, 3
H), 4.18 (q, J ) 7.0 Hz, 2 H), 5.84 (d, J ) 16.4 Hz, 1 H), 6.95-7.1
(m, 1 H), 7.15-7.35 (m, 2 H), 7.35-7.5 (m, 1 H), 7.90 (d, J ) 8.1
Hz, 1 H); 13C NMR δ 14.13, 32.97, 33.93, 51.82, 59.98, 121.56, 126.16,
129.13, 130.78, 130.86, 132.02, 142.69, 148.09, 166.42, 167.55; IR
(neat) 1718 cm-1; high-resolution MS calcd for C15H18O4 262.1205,
(b) Carbonylation of 43. Under Conditions II (40 atm of CO, 100
°C, 20 h, benzene), 43 (288 mg, 1.0 mmol) gave 3-vinyl-3,4,5-trihydro-
2-benzoxepin-1-one (48) in 31% NMR yield along with a 36% yield
of 4,4a,10,10a-tetrahydro-3,4-1H-naphtho[2,3-c]pyrandione (48). Chro-
matography on silica gel (90/10 n-pentane/Et2O) afforded 58 mg (31%)
of 47, and further elution (80/20 CH2Cl2/Et2O) afforded 75 mg (35%)
of 48. trans-47: 1H NMR δ 2.4-2.6 (m, 1 H), 2.7-3.3 (m, 5 H),
4.19 (t, J ) 11.15 Hz, 1 H), 4.52 (dd, J ) 11.15, 4.5 Hz, 1 H), 7.2-
7.45 (m, 2 H), 7.5-7.6 (m, 1 H), 7.95-8.05 (m, 1 H); 13C NMR δ
29.69, 30.62, 35.33, 45.06, 72.60, 127.44, 127.56, 128.99, 131.30,
134.25, 140.88, 169.49, 195.63; IR (neat) 1743, 1690 cm-1; high-
resolution MS calcd for C13H12O3 216.0786, found 216.0781. The
following signals were discernible for the cis isomer: 13C NMR δ 28.72,
28.88, 32.33, 35.33, 45.06, 72.60, 127.44, 127.56, 128.99, 131.30,
134.47, 140.89, 195.85. 48: 1H NMR δ 2.77 (dd, J ) 13.15, 5.15 Hz,
1 H), 2.9-3.15 (m, 2 H), 3.91 (dd, J ) 12.2, 6.65 Hz, 1 H), 4.18 (dd,
J ) 12.2, 5.55 Hz, 1 H), 5.05-5.15 (m, 2 H), 5.7-5.85 (m, 1 H), 7.22
(d, J ) 7.4 Hz, 1 H), 7.38 (t, J ) 7.5 Hz, 1 H), 7.45-7.55 (m, 1 H),
7.74 (d, J ) 7.5, 1 H); 13C NMR δ 35.75, 43.08, 70.02, 116.75, 127.53,
129.25, 130.30, 131.39, 132.57, 136.27, 136.75, 171.99; IR (neat) 1726
cm-1; high-resolution MS calcd for C12H12O2 188.0837, found 188.0841.
(c) Carbonylation of 49. Under Conditions II (40 atm of CO, 100
°C, 18 h, DMF), 49 (374 mg, 1.0 mmol) gave 3-((tert-butyldimethyl-
silyl)oxy)-2-methylene-2,3-dihydro-1H-inden-one (51) in 25% NMR
yield. Chromatography on silica gel (86/14 n-hexane/Et2O) afforded
57 mg (20%) of 51:31 1H NMR δ 0.19 (s, 3 H), 0.25 (s, 3 H), 0.96 (s,
9 H), 5.67 (bs, 1 H), 6.43 (d, J ) 2.2 Hz, 1 H), 7.48 (dt, J ) 7.2, 1.0
Hz, 1 H), 7.63 (d, J ) 6.8 Hz, 1 H), 7.69 (dt, J ) 7.2, 1.2 Hz, 1 H),
7.85 (d, J ) 7.6 Hz, 1 H); 13C NMR δ -3.36, 18.58, 26.26, 70.58,
121.14, 124.32, 126.32, 129.80, 135.87, 137.84, 149.07, 152.45, 191.83;
IR (neat) 1718 cm-1. Under Conditions IV (40 atm of CO, 100 °C,
18 h, a 1:1 mixture of acetonitrile/benzene), 49 (374 mg, 1.0 mmol)
gave 2-((methoxycarbonyl)methyl)-3-((dimethyl-tert-butylsilyl)oxy)-1-
indanone (50) in 75% NMR yield as a 3/1 mixture of the trans and cis
isomers. Chromatography on silica gel (83/17 n-hexane/Et2O) afforded
231 mg (69%) of 5031 as a 74/26 mixture of the trans and cis isomers.
Data for the trans isomer: 1H NMR δ 0.18 (s, 3 H), 0.26 (s, 3 H),
0.46 (s, 9 H), 2.7-3.2 (m, 3 H), 3.65 (s, 3 H), 5.23 (d, J ) 4 Hz, 1 H),
7.4-7.7 (m, 3 H), 7.7-7.9 (m, 1 H); 13C NMR δ -4.24, -4.08, 17.89,
(43) Broom, N. J. P.; Sammes, P. J. J. Chem. Soc., Perkin Trans. 1 1981,
465.

5918 J. Am. Chem. Soc., Vol. 118, No. 25, 1996
Negishi et al.
found 262.1208. Using t-BuOH (4 equiv) in place of MeOH in the
procedure described above, 62b was obtained in 40% NMR yield.
(g) Carbonylation of 56. Under Conditions II (40 atm of CO, 100
°C, 17 h, DMF), 56 (316 mg, 1.0 mmol) gave 2-((trimethylsilyl)-
methylene)-2,3-dihydro-1H-inden-1-one (65) in 15% NMR yield along
with a 52% yield of 1-naphthol (66). Chromatography on silica gel
(80/20 n-hexane/Et2O) afforded 36 mg (17%) of 65 and 75 mg (52%)
of 66. 65: E/Z ) 97/3, 1H NMR δ 0.26 (s, 9 H), 3.76 (bs, 2 H), 7.09
(t, J ) 1.8 Hz, 1 H), 7.35-7.65 (m, 3 H), 7.89 (d, J ) 7.6 Hz, 1 H);
13C NMR δ -0.44, 32.77, 125.39, 126.83, 128.07, 135.28, 136.71,
138.29, 149.97, 150.47, 192.80; high-resolution MS calcd for C13H16-
OSi 217.1049, found 217.1042. Under Conditions IV (40 atm of CO,
100 °C, 18 h, DMF), 56 (316 mg, 1.0 mmol) gave 12 in 35% NMR
yield along with a 40% yield of 1-naphthol (66). Chromatography on
silica gel (75/25 n-hexane/Et2O) afforded 70 mg (34%) of 12 and 54
mg (38%) of 66.
(h) Carbonylation of 57. Under Conditions II (40 atm of CO, 100
°C, 10 h, DMF), 57 (402 mg, 1.0 mmol) gave a 73% NMR yield of 67
as a 1:1 mixture of two diastereomers along with a 24% yield of
2-(formylmethyl)-1-tetralone (68). The following signals were assign-
able to E-67: 1H NMR δ 0.14 (s, 6 H), 0.91 (s, 9H), 1.9-2.3 (m, 2
H), 2.9-3.2 (m, 3 H), 5.21 (dd, J ) 12.0, 8.1 Hz, 1 H), 6.37 (d, J )
12.0 Hz, 1 H), 7.1-7.6 (m, 3 H), 7.95-8.2 (m, 1 H); 13C NMR δ
-5.2, 25.64, 27.95, 30.48, 46.84, 108.50, 126.58, 127.60, 128.63,
133.18, 142.75. The following signals are discernible for Z-67: 1H
NMR δ 3.6-3.9 (m, 2 H), 3.95-4.05 (m, 1 H), 4.45 (d, J ) 5.8 Hz,
1 H), 4.78 (dd, J ) 8.0, 5.8 Hz, 1 H). A mixture of the crude products,
1 M HCl (0.6 mL), and THF (1.2 mL) was stirred at 25 °C for 1 h,
diluted with Et2O, washed with NaHCO3, dried over MgSO4, and
evaporated. Analysis of the crude reaction mixture by 1H NMR
spectroscopy indicated the formation of 68 in 83% yield. Chroma-
tography on silica gel (6:1 n-pentane/Et2O) afforded 150 mg (80%) of
68: 1H NMR δ 1.9-2.1 (m, 1 H), 2.15-2.35 (m, 1 H), 2.45-2.65 (m,
1 H), 2.9-3.1 (m, 1 H), 3.1-3.3 (m, 3 H), 7.2-7.4 (m, 2 H), 7.4-
7.55 (m, 1 H), 8.02 (d, J ) 8.2 Hz, 1 H), 9.92 (d, J ) 1.1 Hz, 1 H);
13C NMR δ 29.29, 29.41, 43.24, 126.68, 127.45, 128.74, 131.91, 133.52,
143.98, 198.36, 200.61; high-resolution MS calcd for C12H12O2
188.0837, found 188.0835.
Acknowledgment. We thank the National Institutes of
Health (GM 36792) and Nissan Chemical Co., Ltd., Japan, for
support of this research. Johnson Matthey kindly provided
PdCl2. C.C. was a Purdue Research Foundation Graduate
Research Fellow (1993-94), and T.S. was a Uehara Memorial
Foundation Postdoctoral Fellow (1992-93). T.M. was on leave
from Nissan Chemical Co. (1993-95). B. O’Connor and Y.
Zhang provided some experimental results described herein. J.
A. Miller, G. Wu, I. Shimoyama, and J. Amanfu participated
in aspects of this project which are to be published separately.
This paper is dedicated to the memory of Professor Wolfgang
Oppolzer.
JA9533196