General and greener route to ketones by palladium-catalyzed direct conversion of carboxylic acids with organoboronic acids

Article abstract of DOI:10.1246/cl.2001.1242

Cross-coupling reaction of carboxylic acids with organoboron compounds catalyzed by palladium complexes in the presence of an activator such as dimethyl dicarbonate under mild conditions gives ketones in excellent yields except for certain substrates.

Full text of DOI:10.1246/cl.2001.1242

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242
Chemistry Letters 2001
General and Greener Route to Ketones by Palladium-Catalyzed Direct Conversion of
Carboxylic Acids with Organoboronic Acids
Ryuki Kakino, Hirohisa Narahashi, Isao Shimizu, and Akio Yamamoto*
Department of Applied Chemistry, Graduate School of Science and Engineering, Waseda University,
3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555
Advanced Research Institute for Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555
(Received September 25, 2001; CL-010949)
Cross-coupling reaction of carboxylic acids with organo-
We have previously observed that treatment of carboxylic
acids with less reactive carboxylic anhydride such as pivalic
anhydride (2,2-dimethylpropanoic anhydride) leads to the anhy-
dride mixture, which can be subjected to the C–O bond cleav-
boron compounds catalyzed by palladium complexes in the pres-
ence of an activator such as dimethyl dicarbonate under mild
conditions gives ketones in excellent yields except for certain
substrates.
7
age process and further hydrogenolysis to yield aldehydes. By
application of the similar concept we now developed the new
catalytic method of directly converting carboxylic acids into
8
Ketones occupy pivotal positions as intermediates in organic
synthesis as well as end products for various commercial uses.
Although quite a variety of synthetic methods are available,
most methods entail some shortcomings in efficiency and envi-
ronmental problems.1
mixed ketones using organoboronic acids.
We first examined the effects of various activators in pro-
motion of direct conversion of heptanoic acid into heptanophe-
none with phenylboronic acid in the presence of [Pd(PPh ) ].
Strong effects of the nature and molar amounts of the activators
added to the catalyst system on the yields of ketone were noted.
Pivalic anhydride that was most suitable for aldehyde syn-
3
4
The C–O bond in various oxygen-containing compounds
2
can be cleaved by transition metal complexes. We have previ-
7
ously found that the C–O bonds in carboxylic esters and anhy-
drides are readily cleaved on interaction with Pd(0) complexes
to give acylpalladium aryloxides or carboxylates (eq 1).3
thesis proved to be not the best activator, giving 83% yield of
the ketone. Among the activators examined, dimethyl dicar-
bonate was most effective giving 95% yield of the ketone with
usage of 1.2 equiv of dimethyl dicarbonate per heptanoic acid.
With further decrease in the amount of the activator down to
,4
1.0 equiv a slight decrease in the yield was noted. Other addi-
tives such as acetic anhydride and di-tert-butyl dicarbonate
showed poor to moderate activities.
The catalyst system composed of [Pd(PPh ) ] and 1.2 equiv
3
4
The acylpalladium complexes react with organoboronic
acids to yield ketones. On further application of the findings
we could develop catalytic synthesis of ketones from carboxylic
of (MeOCO) O was effective affording a variety of ketones as
2
summarized in Table 1 by treating carboxylic acids and
organoboronic acids in the presence of the activator in dioxane
at 80 °C for 6 h.
5
,6
anhydrides and activated esters.
The catalytic synthesis of ketones is based on the reaction of
the acylpalladium complex 1 to undergo exchange of the aryl-
oxido or carboxylato ligand with phenylboronic acids to yield
acyl(phenyl)palladium species 2 that readily releases the phenyl
ketone on reductive elimination (eq 2).
The present process is applicable to various aromatic, hete-
rocyclic, and aliphatic carboxylic acids with organoboron com-
pounds and is tolerant to a variety of functional groups. Benzoic
acid derivatives having functional groups such as methoxy,
chloro, formyl, cyano, and nitro groups at the para positions can
be catalytically converted into the corresponding ketones in
excellent yields on treatment with arylboronic acids in the pres-
ence of dimethyl dicarbonate and [Pd(PPh ) ]. Heterocyclic car-
3
4
boxylic acids such as 2-thiophenecarboxylic acid, 3-furoic acid
and nicotinic acid readily coupled with phenylboronic acid
under standardized conditions to give the corresponding ketones
in good yields. trans-Cinnamic acid having the double bond
that may interact with the palladium center could be also used,
although the yield was moderate. Various aliphatic carboxylic
acids such as heptanoic acid are converted smoothly into hep-
tanophenone in combination with phenylboronic acid, whereas a
bulky aliphatic carboxylic acid such as 2,2-dimethylpropanoic
acid resulted in a low yield probably due to the less reactivity of
its mixed anhydride in oxidative addition to a Pd(0) species.
We propose the catalytic cycle consisted of several elemen-
tary processes as shown in Scheme 1 to account for the catalytic
formation of ketones from carboxylic acids and organoboron
We have constructed catalytic processes on the basis of
these elementary processes to convert various carboxylic anhy-
drides and aryl esters into ketones using palladium complexes
,6
(
eq 3).5
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
1243
compounds in the presence of dimethyl dicarbonate.
The carboxylic acid employed is considered to undergo the
exchange reaction with dimethyl dicarbonate to form a mixed
anhydride, whose acyl–O bond is cleaved on interaction with
Pd(0) complex A to give B. The acylpalladium complex B may
undergo decarboxylation (ii), transmetallation (iii) and reduc-
tive elimination (iv) producing the product and the catalyst.
The similar concept can be applied to α,β-alkynyl ketone
synthesis, suggesting wide applicability of the process (eq 4).
The process is not limited to homogeneous systems. The
combination of Pd/BaSO used in the presence of 4 equiv of
4
PPh gave 88% yield of benzophenone from benzoic acid with
3
phenylboronic acid and dimethyl dicarbonate in dioxane at 90
°C for 6 h.
The present process does not require the prior synthesis of
carboxylic acid derivatives such as acyl halides, anhydrides, nor
needs any extra base. The versatility of the process, mild
experimental conditions, a wide scope of applications, and
environmentally benign nature makes the process promising as
one of the useful synthetic methods of ketones.
References and Notes
1
a) B. T. O’Neill, “Comprehensive Organic Synthesis,” ed. by
B. M. Trost and I. Fleming, Pergamon, Oxford (1991), Vol. 1,
pp 397–458. b) T. V. Lee, “Comprehensive Organic
Synthesis,” ed. by B. M. Trost and I. Fleming, Pergamon,
Oxford (1991), Vol. 7, pp 296–298. c) S. V. Ley and A.
Madin, “Comprehensive Organic Synthesis,” ed. by B. M.
Trost, and I. Fleming, Pergamon, Oxford (1991), Vol. 7, pp.
2
60–267. d) G. A. Olah, “Friedel–Crafts and Related
Reactions,” Wiley-Interscience, New York (1964), Vol. 1.
a) A. Yamamoto, Adv. Organometal. Chem., 34, 111 (1992).
b) Y. -S. Lin and A. Yamamoto, “Topics in Organometallic
Chemistry,” ed. by S. Murai, Springer, Berlin (1999), Vol. 3,
pp 161–192. c) A. Yamamoto, R. Kakino, and I. Shimizu,
Helv. Chim. Acta, in press.
2
3
4
C–O bond cleavage in aryl trifluoroacetates: K. Nagayama, I.
Shimizu, and A. Yamamoto, Bull. Chem. Soc. Jpn., 72, 799
(1999).
C–O bond cleavage in carboxylic anhydrides: a) K.
Nagayama, F. Kawataka, M. Sakamoto, I. Shimizu, and A.
Yamamoto, Bull. Chem. Soc. Jpn., 72, 573 (1999). b) K.
Nagayama, F. Kawataka, M. Sakamoto, I. Shimizu, and A.
Yamamoto, Chem. Lett., 1995, 367.
5
6
7
From carboxylic anhydrides: R. Kakino, S. Yasumi, I.
Shimizu, and A. Yamamoto, Bull. Chem. Soc. Jpn., in press.
From phenyl trifluoroacetates: R. Kakino, I. Shimizu, and A.
Yamamoto, Bull. Chem. Soc. Jpn., 74, 371 (2001).
a) K. Nagayama, I. Shimizu, and A. Yamamoto, Chem. Lett.,
1998, 1143. b) K. Nagayama, I. Shimizu, and A. Yamamoto,
Bull. Chem. Soc. Jpn., 74, 1803 (2001).
8
While preparing the paper, we found that Gooβen et al. inde-
pendently succeeded in catalytic preparation of ketones direct-
ly from carboxylic acids and organoboronic acids using pivalic
anhydride as the activator on the basis of similar concept as
described here. L. J. Gooβen and K. Ghosh, Angew. Chem. Int.
Ed., 40, 3458 (2001).