Ruthenium-Catalyzed Functionalization of Aryl Carbon-Oxygen Bonds in Aromatic Ethers with Organoboron Compounds

Article abstract of DOI:10.1021/ja0393170

The ruthenium-catalyzed reaction of aryl ethers having a carbonyl group at the ortho position to the ether group with organoboronates (R?B(OCH₂CMe₂CH₂O), R = aryl, alkenyl, and alkyl) resulted in site-selective C?C bond formation. Among the transition metal complexes screened, the RuH₂(CO)(PPh₃)₃ complex showed the highest activity. Several aromatic ketones having methoxy or phenoxy groups at the ortho position can also be used in this coupling reaction. A variety of arylboronates containing electron-donating (NMe₂, OMe, methyl, and vinyl) and -withdrawing (F and CF₃) groups reacted with methoxy ketones to give the corresponding coupling products in high yields. Copyright

Full text of DOI:10.1021/ja0393170

Published on Web 02/12/2004
Ruthenium-Catalyzed Functionalization of Aryl Carbon-Oxygen Bonds in
Aromatic Ethers with Organoboron Compounds
Fumitoshi Kakiuchi,*,†,‡ Mayumi Usui,† Satoshi Ueno,† Naoto Chatani,† and Shinji Murai†
Department of Applied Chemistry, Faculty of Engineering, Osaka UniVersity, Suita, Osaka 565-0871, Japan, and
PRESTO, JST, 4-1-8 Honcho Kawaguchi, Saitama, Japan
Received October 30, 2003; E-mail: kakiuchi@chem.eng.osaka-u.ac.jp
Table 1. Ruthenium-Catalyzed Phenylation of Aromatic Ketones
with Phenylboronate 2 via a Carbon-Oxygen Bond Cleavagea
The development of catalytic methods involving the cleavage
of unreactive bonds such as carbon-hydrogen,1 carbon-carbon,2
and carbon-fluorine3 bonds has been a highly attractive research
area in organic and organometallic chemistry. In addition to the
above bonds, the aryl carbon-oxygen bond in aryl ethers (Ar-
OR) is also unreactive because of its large bond dissociation energy
(ca. 100 kcal/mol).4 For the cleavage of aryl C-O bonds by low-
valent transition metal complexes, the presence of a strong electron-
withdrawing group, such as CF3SO2, near a phenolic oxygen is
typically required. Thus, the cleavage of aryl C-O bonds is
generally difficult without assistance from a strong electron-
withdrawing group.
In 1979, Wenkert reported that the nickel-catalyzed reaction of
aryl methyl ethers with Grignard reagents resulted in the production
of alkylated arenes.5 To the best of our knowledge, this is the only
example of a transition metal-catalyzed reaction involving an aryl
C-O (Ar-OR) bond cleavage.6 However, only a limited number
of examples have been examined for this reaction. In this Com-
munication, we describe a ruthenium-catalyzed reaction of aromatic
ethers with organoboronic acid esters (organoboronates) via aryl
C-O bond cleavage by means of chelation assistance.
As part of an ongoing program in chelation-assisted reactions
of aromatic ketones with arylboronates,7 we discovered a unique
protocol for the conversion of aryl C-O bonds to C-C bonds with
the aid of RuH2(CO)(PPh3)3. The reaction of 2′-methoxy-6′-
methylacetophenone (1) with 5,5-dimethyl-2-phenyl-[1,3,2]dioxa-
borinane (2) was carried out in the presence of RuH2(CO)(PPh3)3
(3) as a catalyst. The ortho phenylated product 4 was obtained in
quantitative yield in 20 h (eq 1). To the best of our knowledge,
this reaction is the first example of the efficient catalytic conversion
of Ar-OR bonds in aryl ethers to C-C bonds via an oxidative
addition to the ruthenium complex. This result motivated us to
examine this coupling reaction more extensively.
a Reaction conditions: ketone (0.5 mmol), phenylboronate 2 (0.6 mmol),
RuH2(CO)(PPh3)3 (3) (0.02 mmol), and toluene 1 mL, reflux. b Isolated
yield. c 1.2 mmol of 2 was used.
CH(CH3)O (57%), OC(CH3)2C(CH3)2O (42%), O(CH2)3O (62%),
OCH(CH3)CH2CH(CH3)O (76%), or OCH2C(CH3)2CH2O (2) (83%)],
2 was chosen for the coupling reactions described here.
Several aromatic ketones having alkoxy groups at the ortho
position can be used in this coupling reaction. Some selected results
are shown in Table 1. The reaction of 2′,6′-dimethoxyacetophenone
with 2 gave the corresponding 1:2 coupling product 5 in 96% yield
(run 1). The use of 2′-methoxypivalophenone (6) resulted in the
formation of the monophenylated product as the major end product
(run 2). In this case, two reaction sites are possible. One is a C-O
bond and the other a C-H bond.7 The coupling reaction proceeded
only at the C-O bond. In the case of the reaction of 2′,4′-
dimethoxypivalophenone, phenylation occurred exclusively at the
position ortho to the pivaloyl group, and the para MeO group
remained intact (run 3). Fused aromatic ketones can also be used.
In the case of 6-methoxy-R-tetralone, the phenylation product was
obtained in 55% yield (run 4). The reaction of 3,6-dimethoxy-R-
tetralone took place only at the 6-position (run 5). There are two
different aryl C-O bonds in 2′-phenoxypivalophenone (run 6). The
phenylation took place only at the benzene ring containing the
pivaloyl group, giving 7 in 60% yield. In the case of runs 3, 5, and
Among complexes such as RuH2(CO)(PPh3)3 (3), Ru3(CO)12, Ru-
(CO)2(PPh3)3, RuHCl(CO)(PPh3)3, and Cp*Rh(C2H3SiMe3)2, 3
showed the highest catalytic activity, but the activity of the others
was poor (less than 10% yield). A substituent on the boron atom
affects the reactivity of the phenylboronates. Because boronate 2
exhibited the highest reactivity among the phenylboronates screened
[e.g., Ph-B(OR)2, where (OR)2 ) OCH2CH2O (72%), OCH(CH3)-
† Osaka University.
‡ PRESTO, JST.
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10.1021/ja0393170 CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. A Possible Reaction Pathway
Table 2. Ruthenium-Catalyzed Coupling Reaction of 6 with
Several Organoboronatesa,b
A naphthalene derivative is also applicable. Alkenylation using
alkenylboronates provided styrene derivatives in high yields. The
reactions with 2-propenyl- and 2-methyl-1-propenylboronates gave
the alkenylation products in 61% and 81% yields, respectively.
Reactions using alkylboronates such as methyl-, benzyl-, and
phenethylboronates afford the alkylation product. In the cases of
alkenylation and alkylation, a higher loading of the catalyst and a
higher reaction temperature were required to attain a high yield.
Although the mechanism for this reaction has not been elucidated,
we speculate that this coupling reaction proceeds via the pathway
shown in Scheme 1. The ortho C-O bond can be cleaved by the
ruthenium complex to give (aryl)(methoxy)ruthenium intermediate
A. A transmetalation between the organoboronates and intermediate
A would result in the formation of (diorgano)ruthenium complex
B. Reductive elimination from B provides the coupling product
with the active catalyst species being regenerated.
In summary, this paper has presented our results concerning the
cleavage of unreactive aryl C-O (Ar-OR) bonds in aromatic ethers
by means of chelation assistance and catalytic conversion of these
C-O bonds to C-C bonds using organoboron compounds. These
results lead to the conclusion that otherwise unreactive aryl C-O
bonds can be used in organic synthesis without transformation to
Ar-OSO2CF3 bonds. We are currently broadening the scope of
this reaction in an attempt to elucidate the pathway of this reaction.
a Reaction conditions: ketone 6 (0.5 mmol), organoboronate (0.6 mmol),
RuH2(CO)(PPh3)3 (3) (0.02 mmol), and toluene 1 mL, reflux. b Isolated
yield. c Ketone 6 (0.5 mmol), organoboronate (1 mmol), 3 (0.05 mmol),
and xylene 1 mL, reflux.
6, phenylation took place predominantly at the position ortho to
the carbonyl group. In addition, no reaction occurred in the case
of the reaction of anisole with the phenylboronate. These results
strongly suggest that the coordination of the carbonyl group to the
ruthenium is essential for the C-O bond cleavage to occur. The
reaction with 1-naphthylboronate afforded the corresponding cou-
pling product in 84% yield (run 7).
The reaction of 2′,6′-dimethoxyacetophenone gave 5 as a major
product. From this product selectivity, we proposed that the second
C-O bond cleavage took place without dissociation of the 1:1
coupling product from the ruthenium center.8 To confirm this
possibility, a competitive reaction of 2′,6′-dimethoxyacetophenone
and 2′-methoxy-6′-phenylacetophenone with p-tolylboronate was
performed (eq 2). This reaction gave 2′,6′-di(tolyl)acetophenone
as a major product (62% yield based on the boronate). This result
suggests that a major portion of 5 is formed without dissociation
of the 1:1 coupling product.
Acknowledgment. This work was supported, in part, by
PRESTO, JST.
Supporting Information Available: Experimental procedures and
spectral analyses of all reaction products (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
References
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A variety of organoboronates involving aryl, alkenyl, and
alkylboronates can be used in this reaction. Some selected results
are listed in Table 2. This coupling reaction is tolerant of both
electron-donating and -withdrawing substituents such as NMe2,
OMe, vinyl, F, CF3, and Me. In the case of the p-styrylboronate,
two reaction sites are available. One is the Ar-B moiety and the
other the vinyl moiey.1c,8 Interestingly, aryl C-O/ArB(OR)2
coupling occurred exclusively. It appears that the aryl C-O/ArB-
(OR)2 coupling proceeds readily compared to C-H/olefin coupling.
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