Rhodium-catalyzed addition/ring-opening reaction of arylboronic acids with cyclobutanones

Article abstract of DOI:10.1021/ol049833a

Cyclobutanones react with arylboronic acids in the presence of a catalytic amount of Rh(I) complex to afford butyrophenone derivatives through the addition of an arylrhodium(I) species to the carbonyl group, followed by ring-opening of the resulting rhodium(I) cyclobutanolate.

Full text of DOI:10.1021/ol049833a

ORGANIC
LETTERS
2004
Vol. 6, No. 8
1257-1259
Rhodium-Catalyzed Addition/
Ring-Opening Reaction of Arylboronic
Acids with Cyclobutanones
Takanori Matsuda, Masaomi Makino, and Masahiro Murakami*
Department of Synthetic Chemistry and Biological Chemistry, Kyoto UniVersity,
Katsura, Kyoto 615-8510, Japan
murakami@sbchem.kyoto-u.ac.jp
Received January 28, 2004
ABSTRACT
Cyclobutanones react with arylboronic acids in the presence of a catalytic amount of Rh(I) complex to afford butyrophenone derivatives
through the addition of an arylrhodium(I) species to the carbonyl group, followed by ring-opening of the resulting rhodium(I) cyclobutanolate.
Carbon-carbon bond cleavage by means of transition metals
has attracted much attention because it may achieve a new
transformation that is otherwise difficult.1 We have been
studying the catalytic C-C bond-cleaving reactions of
cyclobutanones, wherein a rhodium(I) complex undergoes
insertion between the carbonyl carbon and the R-carbon.2
On the other hand, rhodium-catalyzed addition reactions of
arylboronic acid derivatives to unsaturated organic function-
alities have been recently developed.3,4 An arylrhodium(I)
species formed by transmetalation is assumed as the inter-
mediate in these reactions. We expected that an arylrhodium-
(I) species is more electron-rich than a rhodium(I) halide or
a cationic rhodium(I) complex and, hence, is more easily
oxidized to a rhodium(III) species during insertion between
the carbonyl and R carbons. Thus, we examined the rhodium-
(I)-catalyzed reaction of cyclobutanones with arylboronic
acids.
of a rhodium(I) catalyst bearing tri-tert-butylphosphine (5
mol % Rh, Rh:P ) 1:2) and Cs2CO3 (1 equiv).5,6 After
heating at 100 °C for 3 h, 1a was completely consumed and
butyrophenone derivative 3aa and tertiary cyclobutanol 4aa
were formed (3aa:4aa ) 90:10). The structure of the major
product 3a could arise from the cleavage of the C(acyl)-
C(R) bond of 1a and bonding of the o-tolyl group of 2a to
the acyl carbon. The minor product 4aa resulted from the
addition of the aryl group of 2a to the carbonyl group of 1a.
(3) For reactions with R,â-unsaturated carbonyl compounds, see: (a)
Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics 1997, 16, 4229. (b)
Cauble, D. F.; Gipson, J. D.; Krische, M. J. J. Am. Chem. Soc. 2003, 125,
1110. (c) Itooka, R.; Iguchi, Y.; Miyaura, N. J. Org. Chem. 2003, 68, 6000.
For reactions with aldehydes and ketones, see: (d) Sakai, M.; Ueda, M.;
Miyaura, N. Angew. Chem., Int. Ed. 1998, 37, 3279. (e) Ueda, M.; Miyaura,
N. J. Org. Chem. 2000, 65, 4450. (f) Takezawa, A.; Yamaguchi, K.;
Ohmura, T.; Yamamoto, Y.; Miyaura, N. Synlett 2002, 1733. For reactions
with alkenes, see: (g) Oguma, K.; Miura, M.; Satoh, T.; Nomura, M. J.
Am. Chem. Soc. 2000, 122, 10464. (h) Lautens, M.; Roy, A.; Fukuoka, K.;
Fagnou, K.; Mart´ın-Matute, B. J. Am. Chem. Soc. 2001, 123, 5358. (i)
Murakami, M.; Igawa, H. Chem. Commun. 2002, 390. For reaction with
alkynes, see: (j) Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara, M. J.
Am. Chem. Soc. 2001, 123, 9918. (k) Murakami, M.; Igawa, H. HelV. Chim.
Acta 2002, 85, 4182. (l) Lautens, M.; Yoshida, M. J. Org. Chem. 2003, 68,
762.
In an initial attempt, 3-phenylcyclobutanone (1a) was
reacted with o-tolylboronic acid (2a, 3 equiv) in the presence
(1) (a) Murakami, M.; Ito, Y. In ActiVation of UnreactiVe Bond and
Organic Synthesis; Murai, S., Ed.; Springer: Berlin, 1999; p 97. (b)
Rybtchinski, B.; Milstein, D. Angew. Chem., Int. Ed. 1999, 38, 870. (c)
Jun, C.-H.; Moon, C. W.; Lee, D.-Y. Chem. Eur J. 2002, 8, 2422.
(2) (a) Murakami, M.; Amii, H.; Ito, Y. Nature 1994, 370, 540. (b)
Murakami, M.; Amii, H.; Shigeto, K.; Ito, Y. J. Am. Chem. Soc. 1996,
118, 8285. (c) Murakami, M.; Takahashi, K.; Amii, H.; Ito, Y. J. Am. Chem.
Soc. 1997, 119, 9307. (d) Murakami, M.; Itahashi, T.; Amii, H.; Takahashi,
K.; Ito, Y. J. Am. Chem. Soc. 1998, 120, 9949. (e) Murakami, M.; Tsuruta,
T.; Ito, Y. Angew. Chem., Int. Ed. 2000, 39, 2484. (f) Murakami, M.;
Itahashi, T.; Ito, Y. J. Am. Chem. Soc. 2002, 124, 13976.
(4) For reviews: (a) Fagnou, K.; Lautens, M. Chem. ReV. 2003, 103,
169. (b) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103, 2829.
(5) Use of [RhCl(cod)]2 or [Rh(OH)(cod)]2 resulted in low conversion
(<40%), while [Rh(cod)2]BF4 was totally ineffective. The orders of the
influence of several phosphines and bases on the reactivity are as follows:
P(t-Bu)3 > P(c-Hex)3 . PPh3 > DPPP, DPPB; Cs2CO3 g KOH > KF >
NaHCO3 ≈ none.
(6) Reaction with o-tolylboronic acid was slower in the absence of Cs2-
CO3, whereas Cs2CO3 showed little accelerating effect for the reaction with
less sterically hindered phenylboronic acid.
10.1021/ol049833a CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/20/2004

Scheme 1
Table 1. Rh-Catalyzed Addition/Ring-Opening Reaction of
Arylboronic Acids 2 with Cyclobutanones 1a
When the reaction mixture was heated for 24 h, only the
product 3aa remained, indicating that 4aa isomerized to 3aa.
In fact, heating of 4aa7 in the presence of the rhodium(I)
catalyst gave the ring-opening product 3aa. On the other
hand, no reaction occurred on heating 4aa in the absence of
the rhodium(I) catalyst, suggesting that the ring-opening
reaction was also catalyzed by the rhodium(I) (Scheme 2).
These results indicated that the reaction proceeded via the
addition of arylrhodium to the carbonyl group of 1a followed
by the ring-opening of the resulting rhodium alcoholate
through â-carbon elimination, rather than via the direct
insertion of rhodium(I) between the carbonyl carbon and the
R-carbon.
Scheme 2
When the boronic ester 2′b was used instead of boronic
acid, no reaction occurred in dioxane. In contrast, the addition
of water to the solvent effectuated the reaction. It is likely
that protic hydrogens are requisite for the regeneration of
the rhodium(I) catalyst from the product by protonolysis.
Much to our surprise, when the reaction was carried out in
dioxane/D2O (1:1), deuterium was incorporated not at the
γ-position of the produced ketone but at the R-position
exclusively (Scheme 3).8
a Unless otherwise noted, cyclobutanone 1 (0.50 mmol) and 2a (1.5
mmol) were heated in the presence of Rh(acac)(C2H4)2 (0.025 mmol),
P(t-Bu)3 (0.050 mmol), and Cs2CO3 (0.50 mmol) in dioxane (1.0 mL) at
100 °C for 24 h. b Isolated yield. c Reaction was carried out on 0.21 mmol
scale.
Scheme 3
lustrated in Scheme 4 seems to be plausible. The catalytic
cycle involves (i) addition of arylrhodium species 5 to
cyclobutanone 1, (ii) ring-opening of rhodium cyclobutano-
(7) Tertiary cyclobutanol 4aa was synthesized independently by the
reaction of 1a with the Grignard reagent as a diastereomeric mixture (cis:
trans ) 74:26).
On the basis of the experimental results mentioned above
and the previous reports on the rhodium(I)-catalyzed addition
of arylboronic acids to aldehydes,3d,e the mechanism il-
(8) Diastereomeric ratio of 3ab-d was determined to be 64:36 by 1H
NMR; however, the relative stereochemistries were not determined.
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Org. Lett., Vol. 6, No. 8, 2004

either at C(1)-C(4) or C(1)-C(2) bond to yield two products
3dc and 3′dc, with the former predominating (entry 4).
o-Tolyl- and p-tolylboronic acids (2a and 2b) also gave the
corresponding butyrophenones (3aa and 3ab) in good yield
(entries 5 and 6). However, phenylboronic acids having
trifluoromethyl and methoxy groups at the p-position (2d
and 2e) resulted in unsatisfactory yields (entries 7 and 8).
Whereas an arylboronic acid adds to a ketone intramolecu-
larly,3f there has been no report on the intermolecular
addition to a ketone. In fact, no reaction occurred with
4-phenylcyclohexanone under the present reaction conditions.
Therefore, it is of note that an arylboronic acid adds to the
ketonic carbonyl group of cyclobutanone intermolecularly.
The increased reactivity is ascribed to the strain of the four-
membered ring;11 the carbonyl sp2 carbon changes to an sp3
carbon on addition of the arylrhodium, thereby diminishing
the ring strain. The â-carbon elimination step would be also
promoted by the release of the ring strain.
Scheme 4
In summary, we have developed a new catalytic ring-
opening of cyclobutanones with arylboronic acids. Contrary
to our initial expectation, the reaction involved the addition
of the Rh-C bond to the ketonic carbonyl group followed
by â-carbon elimination from the resulting rhodium alco-
holate.
late 6 by â-carbon elimination to alkylrhodium intermediate
7,9 (iii) successive â-hydride elimination/re-addition sequence
leading to rhodium enolate 8,10 and (iv) protonolysis and/or
transmetalation with the boronic acid 2 giving butyrophenone
3 and arylrhodium species 5.
Acknowledgment. This research was supported by a
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 Tech-
nology, Japan.
Other examples of the addition/ring-opening of cyclobu-
tanones are listed in Table 1. The reaction of 3-phenylcy-
clobutanone (1a) and phenylboronic acid (2c) afforded the
product 3ac in high yield (entry 1). In the reaction of
2-phenylcyclobutanone (1d), â-carbon elimination took place
(9) For â-carbon elimination from Pd(II) cyclobutanolate, see: (a)
Nishimura, T.; Uemura, S. J. Am. Chem. Soc. 1999, 121, 11010. (b)
Nishimura, T.; Ohe, K.; Uemura, S. J. Org. Chem. 2001, 66, 1455. (c)
Matsumura, S.; Maeda, Y.; Nishimura, T.; Uemura, S. J. Am. Chem. Soc.
2003, 125, 8862.
(10) For transition metal-hydride elimination followed by re-addition
with opposite regiochemistry, see: (a) Yoshida, K.; Hayashi, T. J. Am.
Chem. Soc. 2003, 125, 2872. (b) Gagnier, S. V.; Larock, R. C. J. Am. Chem.
Soc. 2003, 125, 4804. (c) Suginome, M.; Matsuda, T.; Ito, Y. J. Am. Chem.
Soc. 2000, 122, 11015. (d) Ittel, S. D.; Johnson, L. K. Chem. ReV. 2000,
100, 1169.
Supporting Information Available: Experimental pro-
cedures and characterization data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL049833A
(11) For synthetic applications of cyclobutane derivatives, see: Namyslo,
J. C.; Kaufmann, D. E. Chem. ReV. 2003, 103, 1485.
Org. Lett., Vol. 6, No. 8, 2004
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