Palladium-catalyzed ring expansion reaction of (Z)-1-(1,3-butadienyl) cyclobutanols with aryl iodides. Stereospecific synthesis of (Z)-2-(3-aryl-1-propenyl)cyclopentanones

Article abstract of DOI:10.1021/ol049438k

Equation presented. A novel type of cascade ring expansion process has been developed by the palladium-catalyzed reaction of (Z)-1-(1,3-butadienyl) cyclobutanols with aryl iodides. The reaction proceeds in a stereospecific manner to produce (Z)-2-(3-aryl-

Full text of DOI:10.1021/ol049438k

ORGANIC
LETTERS
2004
Vol. 6, No. 12
1979-1982
Palladium-Catalyzed Ring Expansion
Reaction of
(Z)-1-(1,3-Butadienyl)cyclobutanols with
Aryl Iodides. Stereospecific Synthesis of
(Z)-2-(3-Aryl-1-propenyl)cyclopentanones
Masahiro Yoshida,* Kenji Sugimoto, and Masataka Ihara*
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences,
Tohoku UniVersity, Aobayama, Sendai 980-8578, Japan
mihara@mail.pharm.tohoku.ac.jp
Received March 25, 2004
ABSTRACT
A novel type of cascade ring expansion process has been developed by the palladium-catalyzed reaction of (Z)-1-(1,3-butadienyl)cyclobutanols
with aryl iodides. The reaction proceeds in a stereospecific manner to produce (Z)-2-(3-aryl-1-propenyl)cyclopentanones. It has also been
found that regioselective r-arylation of alkenyl cyclopentanones proceeds to afford the r-arylated cyclopentanones.
Palladium-catalyzed reactions of unsaturated compounds with
organic halides are one of the most important carbon-carbon
bond formation reactions in organic synthesis, and a variety
of synthetically useful products are obtained depending on
the substrates.1 It is known that conjugated 1,3-dienes react
with aryl halides and nucleophiles by a cascade process.2
Thus, regioselective insertion of a 1,3-diene into the arylpal-
ladium species gives the π-allylpalladium intermediate,
which regioselectively reacts with a nucleophile to produce
the (E)-1,4-addition product.
Ring rearrangement of vinylcyclobutanol derivatives by
transition metals is a valuable method for the construction
of substituted five-membered ring systems.3 The reaction is
triggered by a release of the strain in four-membered ring
systems, and this transformation has been successfully ap-
plied to the cascade process by introducing various unsatur-
ated groups on the cyclobutane ring. The cascade ring
expansion reaction of cyclobutanols having isopropenyl,4
allenyl,5 acetylenyl,6 and propargyl7 groups has been devel-
oped by us and other groups during the past decade. How-
ever, to the best of our knowledge, there are no examples of
the reaction of 1,3-dienylcyclobutanols, which are expected
to exhibit a different reactivity compared to that of the other
unsaturated groups. Herein, we describe a preliminary result
concerning the palladium-catalyzed insertion-ring expansion
reaction of 1,3-dienylcyclobutanols with aryl iodides.
(2) (a) Patel, B. A.; Dickerson, J. E.; Heck, R. F. J. Org. Chem. 1978,
43, 5018. (b) Patel, B. A.; Kao, L. C.; Cortese, N. A.; Minkiewicz, J. V.;
Heck, R. F. J. Org. Chem. 1979, 44, 918. (c) Stakem, F. G.; Heck, R. F. J.
Org. Chem. 1980, 45, 3584. (d) Fischetti, W.; Mak, K. T.; Rheingold, A.
L.; Heck, R. F. J. Org. Chem. 1983, 48, 948. (e) O’Connor, J. M.; Stallman,
B. J.; Clark, W. G.; Shu, A. Y. L.; Spada, R. E.; Stevenson, T. M.; Dieck,
H. A. J. Org. Chem. 1983, 48, 807. (f) Uno, M.; Takahashi, T.; Takahashi,
S. Chem. Commun. 1987, 785. (g) Grigg, R.; Sridharan, V. Tetrahedron
Lett. 1989, 30, 1139. (h) Larock, R. C.; Fried, C. A. J. Am. Chem. Soc.
1990, 112, 5882. (i) Larock, R. C.; Berrios-Pena, N. G.; Narayanan, K. J.
Org. Chem. 1990, 55, 3447. (j) Larock, R. C.; Berrios-Pena, N. G.; Fried,
C. A.; Yum, E. K.; Tu, C.; Leong, W. J. Org. Chem. 1993, 58, 4509. (k)
Kagechika, K.; Ohshima T.; Shibasaki. M. Tetrahedron 1993, 49, 1773. (l)
Ohshima, T.; Kagechika, K.; Adachi, A.; Sodeoka, M.; Shibasaki. M. J.
Am. Chem. Soc. 1996, 118, 7108. (m) Flubacher, D.; Helmchen, G.
Tetrahedron Lett. 1999, 40, 3867. (n) Deagostino, A.; Prandi, C.; Venturello,
P. Org. Lett. 2003, 5, 3815.
(1) (a) Tsuji, J. Palladium Reagents and Catalysts; John Wiley and
Sons: New York, 1995. (b) Beletskaya, I. P.; Cheprakov, A. V. Chem.
ReV. 2000, 100, 3009. (c) de Meijere, A.; Meyer, F. E. Angew. Chem., Int.
Ed. Engl. 1994, 33, 2379.
10.1021/ol049438k CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/15/2004

Our initial studies focused on reactions of 1,3-dienylcy-
clobutanol 1a with iodobenzene (2a) (Table 1). When (Z)-
reactions using PCy3 and P(o-Tol)3 with Pd2(dba)3‚CHCl3
also successfully proceed to give 3aa and 4aa in 55% and
85% yield, respectively (entries 2 and 3). The reactivity has
been decreased when bidentate ligands such as dppe and dppf
are used (entries 4 ad 5). It is clear from the studies of the
reaction temperature in the presence of P(o-Tol)3 that the
yield has been improved to 98% by carrying out the reaction
at 45 °C, and 3aa is produced with high selectivity at room
temperature (entries 6 and 7). On the other hand, the reaction
does not proceed when the (E)-isomer 1a is used as a
substrate (entry 8).
Table 1. Palladium-Catalyzed Reaction of Dienylcyclobutanols
(Z)- and (E)-1a with Iodobenzene (2a)a
Some results of palladium-catalyzed reactions of (Z)-1a
with various aryl iodides 2b-i are summarized in Table 2.
temp
(°C)
yield
(%)a
entry
substrate
ligand
3a a :4a a b,c
d
Table 2. Palladium-Catalyzed Reaction of Dienylcyclobutanols
(Z)-1a with Aryl Iodides 2b-ia
1
2
3
4
5
6
7
8
(Z)-1a
(Z)-1a
(Z)-1a
(Z)-1a
(Z)-1a
(Z)-1a
(Z)-1a
(E)-1a
PPh3
PCy3
60
60
60
60
60
45
25
60
77
55
85
2 (66)
8 (25)
98
87 (94)
nr
1.7:1
1.7:1
1.8:1
3a a only
3a a only
5.5:1
P(o-Tol)3
dppe
dppf
P(o-Tol)3
P(o-Tol)3
P(o-Tol)3
14:1
a The yields in parentheses are based on recovered starting material. b The
1
configurations of 3aa and 4aa were determined by NOESY and H NMR
yield
(%)a
coupling constants of olefinic protons. c The ratios were determined by the
isolation of each products. d 10 mol % Pd(PPh3)4 was used as a palladium
catalyst.
entry
Ar
product
3:4a
1
2
3
4
5
6
7
8
2-methoxyphenyl (2b)
4-methoxyphenyl (2c)
2-tolyl (2d )
4-tolyl (2e)
1-naphthyl (2f)
4-nitrophenyl (2g)
4-acetylphenyl (2h )
2-bromophenyl (2i)
3a b
80
77
91
88
62
86
57
73
3a b only
8.6:1
6.0:1
4.2:1
9.3:1
3a g only
3a h only
3a i only
3a c/4a c
3a d /4a d
3a e/4a e
3a f/4a f
3a g
1a is reacted with 2a in the presence of 10 mol % Pd(PPh3)4
and Ag2CO3 in toluene at 60 °C, the reaction is complete
within 2 h to afford a aryl-substituted cyclopentanone 3aa
along with further R-arylated product 4aa in 77% yield with
a ratio of 1.7:1 (entry 1). Interestingly, the geometries of
the obtained products 3aa and 4aa are determined as Z, and
the corresponding (E)-products are not observed. The
products 3aa and 4aa are not produced at all when K2CO3
and Cs2CO3 are used instead of Ag2CO3 as a base. The
3a h
3a i
a Products ratios were determined by isolation of the each products.
Substitution with methoxy and methyl groups in the ortho
and para positions exhibits similar reactivity to give the
corresponding products 3ab-ae in good yields with a small
amount of R-arylated products 4ac-ae (entries 1-4). The
reaction using 1-iodonaphthalene (2f) also proceeds to afford
3af and 4af in 63% yield with a ratio of 9.3:1 (entry 5). In
the reactions with nitro- and acetyl-substituted aryl iodides
2g and 2h, the corresponding products 3ag and 3ah are
obtained as the sole products, respectively (entries 6 and 7).
When 2-bromoiodobenzene (2i) is used, the 2-bromophenyl-
substituted cyclopentanone 3ai is chemoselectively produced
without the influence of a bromo atom (entry 8).
We next examined the reactions of various 1,3-dienylcy-
clobutanols 1b-d with 2a (Table 3). A substrate (Z)-1b
having a dipentyl group on the cyclobutane ring is success-
fully transformed to 3ba in 89% yield (entry 1). A trans-
3ca is obtained as the sole product by the reaction of trans-
(Z)-1c (entry 2). On the other hand, the reaction of the
diastereomer cis-(Z)-1c exclusively provides cis-3ca (entry
3). It is ascertained from these results that the ring expansion
process proceeds in a stereospecific manner.8 Substrate (Z)-
1d, substituted with a methyl group at the 3-position on the
(3) (a) Boontanonda, P.; Grigg, R. J. Chem. Soc., Chem. Commun. 1977,
583. (b) Clark, G. R.; Thiensathit, S. Tetrahedron Lett. 1985, 26, 2503. (c)
Demuth, M.; Pandey, B.; Wietfeld, B.; Said, H.; Viader, J. HelV. Chim.
Acta 1988, 71, 1392. (d) de Almeida Barbosa, L.-C.; Mann, J. J. Chem.
Soc., Perkin Trans. 1 1990, 177. (e) Kim, S.; Uh, K. H.; Lee, S.; Park, J.
H. Tetrahedron Lett. 1991, 32, 3395. (f) Nemoto, H.; Miyata, J.; Fukumoto,
K. Tetrahedron 1996, 52, 10363. (g) Nemoto, H.; Nagamochi, M.;
Fukumoto, K. J. Chem. Soc. Perkin Trans. 1 1993, 2329. (h) Nemoto, H.;
Nagamochi, M.; Ishibashi, H.; Fukumoto, K. J. Org. Chem. 1994, 59, 74.
(i) Nemoto, H.; Miyata, J.; Ihara, M. Tetrahedron Lett. 1999, 40, 1933. (j)
Nemoto, H.; Takahashi, E.; Ihara, M. Org. Lett. 1999, 1, 517. (k) Nishimura,
T.; Ohe, K.; Uemura, S. J. Am. Chem. Soc. 1999, 121, 2645.
(4) (a) Nemoto, H.; Shiraki, M.; Fukumoto, K. Synlett 1994, 599. (b)
Nemoto, H.; Miyata, J.; Yoshida, M.; Raku, N.; Fukumoto, K. J. Org. Chem.
1997, 62, 7850. (c) Nemoto, H.; Yoshida, M.; Fukumoto, K.; Ihara, M.
Tetrahedron Lett. 1999, 40, 907. (d) Yoshida, M.; Ismail, M. A.-H.; Nemoto,
H.; Ihara, M. J. Chem. Soc., Perkin Trans. 1 2000, 2629.
(5) (a) Nemoto, H.; Yoshida, M.; Fukumoto, K. J. Org. Chem. 1997,
62, 6450. (b) Yoshida, M.; Sugimoto, K.; Ihara, M. Tetrahedron Lett. 2000,
41, 5089. (c) Yoshida, M.; Sugimoto, K.; Ihara, M. Tetrahedron 2002, 58,
7839. (d) Yoshida, M.; Sugimoto, K.; Ihara, M. Tetrahedron Lett. 2001,
42, 3877.
(6) (a) Liebeskind, L. S.; Mitchell, D.; Foster, B. S. J. Am. Chem. Soc.
1987, 109, 7908. (b) Mitchell, D.; Liebeskind L. S. J. Am. Chem. Soc. 1990,
112, 291. (c) Larock, R. C.; Reddy, Ch. K. Org. Lett. 2000, 2, 3325. (d)
Larock, R. C.; Reddy, Ch. K. J. Org. Chem. 2002, 67, 2027. (e) Yoshida,
M.; Sugimoto, K.; Ihara, M. ARKIVOC 2003, xiii, 35.
(7) Yoshida, M.; Nemoto, H.; Ihara, M. Tetrahedron Lett. 1999, 40, 8583.
1980
Org. Lett., Vol. 6, No. 12, 2004

complex 6 reacts with base to form a zwitterionic π-allylpal-
ladium intermediate 7,9 which subsequently causes a ring
rearrangement to produce a ring-expanded product 3 and
regenerated palladium(0).
Table 3. Reactions Using Various 1-(1,3-Dienyl)cyclobutanols
1b-d with Iodobenzene (2a)a
Mechanistic rationalizations of the observed (Z)-specificity
and diastereospecificity are described in Scheme 2. In case
Scheme 2
a All reactions were carried out in the presence of 1.5 equiv of
iodobenzene, 5 mol % Pd2(dba)3, 20 mol % P(o-Tol)3, and 2.0 equiv of
Ag2CO3 in toluene at 45 °C for 3-6 h. b Pen ) pentyl.
dienyl group, gives the (Z)- and (E)-3da as a 5.3:1 mixture
in 82% yield (entry 4).
A plausible mechanism for the reaction is shown in
Scheme 1. Regioselective insertion of the 1,3-dienyl moiety
in 1 to an arylpalladium complex 5, resulting from aryl iodide
2 with palladium(0), affords an allylpalladium species 6. The
of the (Z)-substrate, coordination of both the olefin and
hydroxyl groups in (Z)-1 to arylpalladium 5 initially forms
the intermediate (Z)-1‚5, in which the dienyl group is located
at the less hindered site to avoid a steric repulsion with
substituents R1 and R2.10 Regio- and diastereoselective
insertion to palladium gives allylpalladium 6′, which is
successively transformed to π-allylpalladium syn-7′. It is
expected that there is an equilibrium between syn- and anti-
7′. The complex syn-7′ interconverts by π-σ-π isomerization
to the isomer anti-7′, which successively causes the concerted
rearrangement of the cyclobutane ring on the opposite face
of the palladium to produce (Z)-3 in a stereospecific manner.
A reason for the low reactivity of the (E)-substrate could be
that the chelation-controlled insertion of the intermediate (E)-
1‚5 is difficult because the distance between the hydroxy
Scheme 1
(8) For studies about the diastereoselectivity in the ring expansion reaction
of cyclobutanols, see refs 4b-d, 5b,c, and 7.
(9) As another possibility, the intermediate that palladium cation forms
a bond to the alkoxide anion is also expected.
(10) The conformation of (Z)-1‚5 was predicted from the result of
MOPAC 97/PM3 calculation of (Z)-1a.
Org. Lett., Vol. 6, No. 12, 2004
1981

group and the olefin becomes longer than that of (Z)-1‚5. In
the case of the methyl-substituted substrate (Z)-1d, it is
expected that there is an equilibrium between the two
intermediates s-trans- and s-cis-(Z)-1d‚5 by the allylic strain
of the methyl group. As a result, (E)-3da has been provided
as a minor product via syn-8 along with the major production
of (Z)-3da.
Scheme 4
The formation of the R-arylated cyclopentanone 4 is
explained by the palladium-catalyzed R-arylation of the
resulting 3 (Scheme 3).11 Thus, regioselective enolization of
Scheme 3
3 with base affords the thermodynamically stable conjugated
enolate 9, followed by transmetalation with arylpalladium
complex to produce 4 via the palladium enolate 10.
To confirm the observed R-arylation process, several
further experiments were carried out (Scheme 4). When 3aa
is reacted with 1a in the presence of 10 mol % Pd(PPh3)4
and Cs2CO3, 4aa is produced in 81% yield as a sole product.
The result indicates that the R-arylated product 4 is formed
from 3, not directly from the substrate 1. On the other hand,
the reaction of 11 containing a saturated alkyl side chain
does not proceed at all. Improvement of the direct production
of 4aa from 1a has been performed by further addition of
the reagents after the completion of the initial ring expansion
reaction.
also been found that regioselective R-arylation proceeds to
afford the R-arylated cyclopentanones. The present results
would provide a new method for the synthesis of highly
functionalized cyclopentanones, and synthetic applications
of the reaction are now in progress.
Acknowledgment. This work was supported in part by
Grant-in-Aid for Scientific Research on Priority Areas (A)
“Exploitation of Multi Element Cyclic Molecules” from the
Ministry of Education, Culture, Sports, Science and Technol-
ogy, Japan.
Supporting Information Available: Synthetic procedures
and characterization data of the substrates 1a-d and 11;
general experimental procedures and characterization data
for products 3aa-ai, 3ba-da, 4aa, and 4ac-af; and
procedure for determining the stereochemistry of trans-(Z)-
1c, cis-(Z)-1c, trans-3ca, and cis-3ca by NOESY correlations.
This material is available free of charge via the Internet at
http://pubs.acs.org.
In conclusion, we have developed a novel type of pal-
ladium-catalyzed cascade insertion-ring expansion reaction
of 1,3-dienylcyclobutanols with aryl iodides. Various sub-
stituted cyclopentanones having a (Z)-3-aryl-1-propenyl
group can be synthesized in a stereospecific manner. It has
(11) (a) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 1999, 121,
1473. (b) Fox, J. M.; Huang, X.; Chieffi, A.; Buchwald, S. L. J. Am. Chem.
Soc. 2000, 122, 1360.
OL049438K
1982
Org. Lett., Vol. 6, No. 12, 2004