SCHEME 1
Rhodium-Catalyzed Diarylation of Oxalates
Using Arylboron Compounds
Sawako Miyamura, Tetsuya Satoh,* and Masahiro Miura*
reagents to give the corresponding R-hydroxydiarylacetates.7
This is a rare example of rhodium-catalyzed intermolecular
arylation on the carbonyl carbon of esters.8 R-Hydroxyesters
are useful materials as the synthetic intermediates of certain
carbo- and heterocyclic compounds, as well as for other
applications including delivery systems of cosmetic and phar-
maceutical agents.9 In addition, related R-dicarbonyl compounds,
benzoylformate and benzil, have also been found to undergo
monophenylation by the rhodium catalysis.
Department of Applied Chemistry, Faculty of Engineering,
Osaka UniVersity, Suita, Osaka 565-0871, Japan
satoh@chem.eng.osaka-u.ac.jp;
ReceiVed December 21, 2006
In an initial attempt, diethyl oxalate (1a) (1 mmol) was treated
with sodium tetrakis(4-methylphenyl)borate (2a) (0.5 mmol)
under conditions similar to those employed for the reaction of
ketones.5 Thus, in the presence of [RhCl(cod)]2 (0.005 mmol)
and NH4Cl (1 mmol) as a catalyst and a proton source,
respectively, in refluxing o-xylene at 120 °C for 13 h, ethyl
2-hydroxy-2,2-bis(4-methylphenyl)acetate (3a) was formed in
75% yield (Table 1, entry 1). The addition of phenol in place
of NH4Cl completely suppressed the reaction (entry 2). The
present arylation was found to proceed effectively without any
additives to afford 3a in 87% yield (entry 3). The hydroxy
complex [Rh(OH)(cod)]2 was as effective as [RhCl(cod)]2 (entry
4), while the activity of Rh(acac)(cod) was very low (entry 5).
It was confirmed that the reaction does not proceed at all without
any rhodium catalyst. At a lower or higher temperature, the yield
of 3a decreased (entries 6 and 7). The reaction proceeded with
somewhat reduced efficiency in refluxing toluene (entry 8),
while a polar solvent, 1,4-dioxane, was found to be unsuitable
(entry 9).
Dimethyl- (1b) and di(n-butyl) oxalate (1c) also underwent
the diarylation upon treatment with 2a under the optimized
conditions to give the corresponding R-hydroxyacetates in good
yields (Scheme 2). In contrast, a sterically hindered ester, di-
(tert-butyl) oxalate (1d), did not react with 2a at all.
Table 2 summarizes the results for the reactions of di(n-butyl)
oxalate (1c) with sodium tetraarylborate 2 or 5,5-dimethyl-2-
aryl[1,3,2]dioxaborinane 4. Tetraphenylborate and tetrakis(4-
fluorophenyl)borate reacted efficiently to give 3d and 3e in 68
and 137% yields, respectively. In the latter case, the yield
exceeding 100% indicates that more than one aryl group in 2
can be utilized. The reactions with arylboronates 4 also
proceeded to give the corresponding diarylated products. The
addition of KF was essential for the reaction with 4 to occur.
A plausible mechanism for the reaction of oxalates 1 with
arylboron reagents 2 or 4 is illustrated in Scheme 3. The reaction
may proceed via nucleophilic addition of an arylrhodium
Dialkyl oxalates undergo selective diarylation on one of their
carbonyl carbons upon treatment with arylboron reagents in
the presence of a rhodium catalyst to give the corresponding
R-hydroxydiarylacetates. Under similar conditions, the ary-
lation of benzoylformate and benzil also proceeds efficiently.
The rhodium-catalyzed nucleophilic addition of organoboron
and -stannane reagents to carbonyl compounds is now recog-
nized to be a highly useful tool for alcohol synthesis (Scheme
1).1 The mild, weakly nucleophilic organometallic reagents are
effectively activated under rhodium catalysis to react readily
with aldehydes (R1 or R2 ) H)2 and structurally or electronically
activated ketones (R1, R2 ) -(CH2)3-;3 R1 or R2 ) COR′;4
etc.).
Recently, we succeeded in conducting the intermolecular
arylation of relatively less reactive electrophiles such as unac-
tivated ketones as well as imines and nitriles under suitable
conditions.5 In the course of our study of rhodium-catalyzed
arylation reactions,6 it has been found that dialkyl oxalates
undergo diarylation selectively upon treatment with arylboron
(1) Reviews: (a) Fagnou, K.; Lautens, M. Chem. ReV. 2003, 103, 169.
(b) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103, 2829.
(2) For early examples, see: (a) Oi, S.; Moro, M.; Inoue, Y. Chem.
Commun. 1997, 1621. (b) Sakai, M.; Ueda, M.; Miyaura, N. Angew. Chem.,
Int. Ed. 1998, 37, 3279. (c) Fu¨rstner, A.; Krause, H. AdV. Synth. Catal.
2001, 343, 343.
(3) (a) Matsuda, T.; Makino, M.; Murakami, M. Org. Lett. 2004, 6, 1257.
(b) Matsuda, T.; Makino, M.; Murakami, M. Bull. Chem. Soc. Jpn. 2005,
78, 1528.
(4) (a) Oi, S.; Moro, M.; Fukuhara, H.; Kawanishi, T.; Inoue, Y.
Tetrahedron 2003, 59, 4351. (b) Shintani, R.; Inoue, M.; Hayashi, T. Angew.
Chem., Int. Ed. 2006, 45, 3353. For Rh-catalyzed vinylation of R-ketoesters,
see: (c) Kong, J.-R.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc. 2006,
128, 718. (d) Kong, J. R.; Krische, M. J. J. Am. Chem. Soc. 2006, 128,
16040.
(7) The stepwise diarylation of diethyl oxalate using Grignard reagents
has been reported: Levy, A.; Rakowitz, A.; Mills, N. S. J. Org. Chem.
2003, 68, 3990.
(5) Ueura, K.; Miyamura, S.; Satoh, T.; Miura, M. J. Organomet. Chem.
2006, 691, 2821.
(8) For an intramolecular version, see: Miura, T.; Sasaki, T.; Nakazawa,
H.; Murakami, M. J. Am. Chem. Soc. 2005, 127, 1390.
(6) (a) Oguma, K.; Miura, M.; Satoh, T.; Nomura, M. J. Am. Chem.
Soc. 2000, 122, 10464. (b) Oguma, K.; Miura, M.; Satoh, T.; Nomura, M.
J. Organomet. Chem. 2002, 648, 297. (c) Sugihara, T.; Satoh, T.; Miura,
M.; Nomura, M. Angew. Chem., Int. Ed. 2003, 42, 4672. (d) Sugihara, T.;
Satoh, T.; Miura, M.; Nomura, M. AdV. Synth. Catal. 2004, 346, 1765. (e)
Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2005, 7, 2229.
(9) (a) Flavin, M. T.; Lu, M. C.; Thompson, E. B.; Bhargava, H. N. J.
Med. Chem. 1987, 30, 278. (b) Ohwada, T.; Shudo, K. J. Am. Chem. Soc.
1988, 110, 1862. (c) Sydorenko, N.; Hsung, R. P.; Saleh Darwish, O.; Hahn,
J. M.; Liu, J. Org. Chem. 2004, 69, 6732. (d) Ikemoto, K.; Yamada, K.
Jpn. Kokai Tokkyo Koho JP2004239986, 2004. (e) Gupta, S. K. U.S. Patent
Appl. 20060110415, 2006.
10.1021/jo062628j CCC: $37.00 © 2007 American Chemical Society
Published on Web 02/20/2007
J. Org. Chem. 2007, 72, 2255-2257
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