Palladium-catalyzed sequential carbon-carbon bond cleavage/formation producing arylated benzolactones

Article abstract of DOI:10.1021/ol802218a

(Chemical Equation Presented) 3-(2-Hydroxyphenyl)cyclobutanones react with aryl bromides in the presence of palladium catalysts to afford 4-arylmethyl-3,4-dihydrocoumarins in high yields through a sequence involving carbon-carbon bond cleavage and formation. In the case of the reaction with 2-(2-hydroxyphenyl)cyclobutanones, five- or seven-membered lactones were produced depending on the presence of an additional substituent at the 2-position.

Full text of DOI:10.1021/ol802218a

ORGANIC
LETTERS
2008
Vol. 10, No. 22
5219-5221
Palladium-Catalyzed Sequential
Carbon-Carbon Bond Cleavage/
Formation Producing Arylated
Benzolactones
Takanori Matsuda,† Masanori Shigeno, and Masahiro Murakami*
Department of Synthetic Chemistry and Biological Chemistry, Kyoto UniVersity,
Katsura, Kyoto 615-8510, Japan
murakami@sbchem.kyoto-u.ac.jp
Received September 23, 2008
ABSTRACT
3-(2-Hydroxyphenyl)cyclobutanones react with aryl bromides in the presence of palladium catalysts to afford 4-arylmethyl-3,4-dihydrocoumarins
in high yields through a sequence involving carbon-carbon bond cleavage and formation. In the case of the reaction with 2-(2-
hydroxyphenyl)cyclobutanones, five- or seven-membered lactones were produced depending on the presence of an additional substituent at
the 2-position.
We recently developed a rhodium-catalyzed reaction of 3-(2-
hydroxyphenyl)cyclobutanones forming 3,4-dihydroxycou-
Scheme 1
marins. 1 The intermediate rhodium cyclobutanolate under-
went ring opening by ꢀ-carbon elimination.2 With the
resulting organorhodium species,3 a rhodium shift im-
mediately followed to place a methyl substituent at the
4-position (Scheme 1, path a). Nishimura and Uemura
reported a palladium-catalyzed reaction of cyclobutanols with
aryl halides producing arylated ring-opened ketones.4 The
† Present address: Department of Applied Chemistry, Tokyo University
of Science, Shinjuku, Tokyo 162-8601, Japan.
(1) (a) Matsuda, T.; Shigeno, M.; Murakami, M. J. Am. Chem. Soc.
2007, 129, 12086. See also: (b) Matsuda, T.; Makino, M.; Murakami, M.
Org. Lett. 2004, 6, 1257. (c) Matsuda, T.; Shigeno, M.; Makino, M.;
Murakami, M. Org. Lett. 2006, 8, 3379, and references therein.
(2) (a) Nishimura, T.; Uemura, S. Synlett 2004, 201. (b) Satoh, T.; Miura,
M. Top. Organomet. Chem. 2005, 14, 1. (c) Murakami, M.; Makino, M.;
Ashida, S.; Matsuda, T. Bull. Chem. Soc. Jpn. 2006, 79, 1315.
(3) (a) Fagnou, K.; Lautens, M. Chem. ReV. 2003, 103, 169. (b) Hayashi,
T.; Yamasaki, K. Chem. ReV. 2003, 103, 2829. (c) Miura, T.; Murakami,
M. Chem. Commun. 2007, 217.
facile ꢀ-carbon elimination occurring with a palladium
cyclobutanolate led us to examine a similar reaction system
with 3-(2-hydroxyphenyl)cyclobutanone substrates (Scheme
1, path b). Herein, we report the palladium-catalyzed reaction
10.1021/ol802218a CCC: $40.75
Published on Web 10/28/2008
2008 American Chemical Society

Scheme 2
Scheme 3
.
Palladium-Catalyzed Arylation of Cyclobutanones 1
Forming Six-Membered Lactones 3a
of cyclobutanones having a pendant phenol moiety with aryl
halides, which produces arylated five- to seven-membered
benzolactones.
Initially, the reaction of 3-ethyl-3-(2-hydroxyphenyl)cy-
clobutanone (1a) and 4-bromoanisole (2a) was examined in
the presence of various palladium catalysts. As shown in
Scheme 2, when tri-tert-butylphosphine was used as a ligand
in combination with K2CO3 as a base, 4-ethyl-4-(4-meth-
oxybenzyl)-3,4-dihydrocoumarin (3aa) was obtained in 98%
yield. We assume the reaction proceeds via (i) oxidative
addition of 2a to palladium(0), (ii) replacement of a bromide
ion with a phenoxide forming arylpalladium(II) aryloxide
A, (iii) addition of the Pd-O bond to the CdO bond
generating arylpalladium(II) cyclobutanolate B, (iii) ring
opening by ꢀ-carbon elimination from B, giving (aryl)-
(alkyl)palladium(II) intermediate C, and (iv) reductive
elimination affording the product and palladium(0).5 On the
basis of reports that show alkene insertion into a Pd-O bond
of arylpalladium(II) alkoxide6 and aldehyde insertion into a
Rh-O bond of rhodium(I) alkoxide,7 we suppose that
analogous carbonyl insertion to the Pd-O bond might occur
in the present catalytic cycle. Although the asymmetric
variant of the reaction was examined with various chiral
phosphines, barely 15% ee was achieved with BINAP.8
Results with other 3-(2-hydroxyphenyl)cyclobutanones are
shown in Scheme 3. The reaction of cyclobutanone 1a and
aryl bromides 2b-d occurred in 1,4-dioxane at 100 °C to
give 4,4-disubstituted 3,4-dihydrocoumarins 3ab-3ad in
good yields. 2-Bromothiophene (2e) underwent the reaction
with 1a to give the corresponding product 3ae in 70% yield,
while 2-bromopyridine failed to couple with 1a under
identical reaction conditions. Alkenylation could also be
carried out with isobutenyl bromide 2f. The reaction of
cyclobutanones 1b-e bearing several substituents at the
a
Conditions: 1 mol % Pd2(dba)3·CHCl3, 2.5 mol % [HP(t-Bu)3]BF4
(1.25 equiv to Pd), 1.1 equiv K2CO3, 1,4-dioxane, 100 °C, 4 h. b 17 h. c
equiv 2f, 3 mol % Pd2(dba)3·CHCl3, 7.5 mol % [HP(t-Bu)3]BF4, 90 °C,
14 h. d 1.5 equiv 2a, 5 mol % Pd2(dba)3·CHCl3, 12.5 mol % [HP(t-Bu)3]BF4,
1.3 equiv Cs2CO3, toluene, 50 °C, 24 h.
3
3-positions afforded the corresponding arylated lactones
3ba-3ea.9 Arylation of 3-monosubstituted cyclobutanone,
3-(2-hydroxyphenyl)cyclobutanone (1f), with 2a proceeded
in a similar manner to afford 4-monosubstituted 3,4-
dihydrocoumarin 3fa in 83% yield.
An analogous reaction of the regioisomers of 1, i.e., 2-(2-
hydroxyphenyl)cyclobutanones 4, was then examined. Use
of iodoarenes 2′ were found to be effective for the reaction
with cyclobutanones 4a and 4b lacking an additional
substituent at the 2-position (Table 1). In the presence of
the Pd(0)-P(t-Bu)3 catalyst, the reaction of 4a and 2′d gave
seven-membered benzolactone 5ad in 79% yield via ring
expansion by selective cleavage of the more sterically
congested carbon-carbon (C1-C2) bond (entry 1).10
A
proper choice of the base is crucial for attaining good yield
of 5. Whereas methyl-substituted 4b yielded slightly better
results than 4a, use of the corresponding bromide 2d led to
poor results (entry 2). The reaction with iodobenzene (2′b)
that lacks electron-withdrawing substituents led to a complex
mixture of products (entry 4). The reaction of sterically
demanding 2′h was inefficient (entry 5).
(4) (a) Nishimura, T.; Uemura, S. J. Am. Chem. Soc. 1999, 121, 11010.
(b) Matsumura, S.; Maeda, Y.; Nishimura, T.; Uemura, S. J. Am. Chem.
Soc. 2003, 125, 8862.
In contrast, cleavage of the less substituted carbon-carbon
(C1-C4) bond took place selectively to give five-membered
1
(5) Because H NMR spectrum of cyclobutanone 1a suggested that it
equilibrated with the corresponding hemiketal (cyclobutanone:hemiketal )
89:11), B might also be formed from the hemiketal.
(6) Hay, M. B.; Wolfe, J. P. J. Am. Chem. Soc. 2005, 127, 16468.
(7) Krug, C.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 1674.
(8) Result with 4-bromotoluene (3 equiv) and Cs2CO3 (1 equiv) in the
presence of the Pd catalyst (10 mol % Pd).
(9) The lower yield of the product 3ba was due to the formation of
protonation product (ca. 30%).
(10) Matsuda, T.; Makino, M.; Murakami, M. Angew. Chem., Int. Ed.
2005, 44, 4608.
5220
Org. Lett., Vol. 10, No. 22, 2008

Table 1. Palladium-Catalyzed Arylation of Cyclobutanones 4
Forming Seven-Membered Lactones 5a
Table 2. Palladium-Catalyzed Arylation of Cyclobutanone 4c
Forming Five-Membered Lactones 6a
entry
2
Ar
6
yield (%)
1
2
3
4
2a
2b
2d
2g
4-MeOC6H4
Ph
4-EtO2CC6H4
4-NCC6H4
6a
6b
6d
6g
86
93 (35b)
86
83
a 5 mol % Pd2(dba)3·CHCl3, 12.5 mol % [HP(t-Bu)3]BF4, 1.3 equiv
K2CO3, p-xylene, 130 °C, 10-16 h. b The reaction was carried out with
Cs2CO3.
a 5 mol % Pd2(dba)3·CHCl3, 12.5 mol % [HP(t-Bu)3]BF4, 1.3 equiv
Cs2CO3, toluene, 40 °C, 15-25 h. b The reaction was carried out with K2CO3
in 1,4-dioxane. c The reaction was carried out with the corresponding
bromide 2d. d A complex mixture of products was obtained.
In summary, we have developed a palladium-catalyzed
arylation reaction producing five- to seven-membered ben-
zolactones via a sequential carbon-carbon bond cleavage/
formation process. This reaction provides an access to 2,4-,
3,4-, and 4,4-diarylbutyric acid derivatives, which are
intermediates in the synthesis of natural products and
pharmaceuticals.11
benzolactones 6 when 2,2-disubstituted cyclobutanone 4c was
used as the substrate (Table 2). Migration of the palladium
to the tertiary carbon atom would be difficult due to steric
reasons, thereby resulting in the cleavage of another
carbon-carbon bond. Good yields were attained irrespec-
tively to the electronic nature of the aryl bromides.
Acknowledgment. This work was supported by The Asahi
Glass Foundation and Grant-in-Aid for Scientific Research
(A) (no. 19205013) from the Ministry of Education, Culture,
Sports, Science and Technology, Japan. M.S. thanks the
Japan Society for the Promotion of Science for a fellowship
support.
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Supporting Information Available: Experimental pro-
cedures and NMR spectral data for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL802218A
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