Rearrangement of 2-aryloxybenzaldehydes to 2-hydroxybenzophenones by rhodium-catalyzed cleavage of aryloxy C-O bonds

Article abstract of DOI:10.1002/anie.201103599

Lost in the shuffle: An unprecedented rearrangement of the title compounds proceeds by the simultaneous rhodium-catalyzed cleavage of aryloxy C-O and aldehyde C-H bonds (see scheme). The reaction tolerates the presence of various catalytically reactive substituents such as aryl halides, nitrile, and esters.

Full text of DOI:10.1002/anie.201103599

Communications
DOI: 10.1002/anie.201103599
Homogeneous Catalysis
Rearrangement of 2-Aryloxybenzaldehydes to 2-
Hydroxybenzophenones by Rhodium-Catalyzed Cleavage of Aryloxy
À
C O Bonds**
Honghua Rao and Chao-Jun Li*
À
The catalytic cleavage and functionalization of C O bonds
offer great potential for the utilization of biomass (e.g.,
carbohydrates and lignins) as renewable chemical feed-
stocks,[1] and broadening the diversity of functional molecules
in the manufacture of pharmaceuticals and fine chemicals
through the direct functionalization of alkyloxy- and aryloxy-
containing natural products.[2] For transition-metal-catalyzed
bond-cleavage-type chemistry.[6] In particular, anisole deriv-
atives could also serve as a potential substrate for coupling
reactions.[4,7] However, such reactivities still remain challeng-
À
ing because nearly all the reported C O bond-cleavage-type
reactions were performed by using nickel catalysts, and to the
best of our knowledge, there are few examples on the
cleavage of typically unreactive diaryl ether moieties.[8]
Herein, we present an unprecedented rearrangement of 2-
aryloxybenzaldehydes to 2-hydroxybenzophenones through
À
À
C C bond formation by CAr O bond cleavage, Wenkert et al.
reported pioneering studies on the coupling of aryl ethers
with Grignard reagents by employing a nickel catalyst.[3]
Chemistry based on this cleavage-type remained dormant
for nearly several decades until the appearance of improved
catalyst systems involving less aggressive nucleophiles in
recent years.[4] As illustrated in Figure 1, for instance, aryl
triflates, sulfonates, and phosphates were successfully
À
the simultaneous rhodium-catalyzed cleavage of aryloxy C O
À
and aldehyde C H bonds (Scheme 1). Furthermore, the
reaction tolerates the presence of various catalytically reac-
tive substituents such as aryl halides, nitriles, and esters.
employed in the cross-coupling reactions by the direct
[5]
À
activation of the C O bonds. Notably, the recent achieve-
ments indicated that aryl carbamate, carboxylates, and
À
carbonate are also appropriate substrates for the C O
Scheme 1. Rhodium catalyzed rearrangement through the cleavage of
À
À
C O and C H bonds.
As a continuation of our studies into the decarbonylation
reaction,[9] we reacted 2-(phenoxy)benzaldehyde (1a) under
our previous decarbonylative coupling conditions. However,
the expected decarbonylative coupling product was not
observed; instead, the unexpected product 2a, resulting
from the rearrangement of the aryl group and the hydrogen
À
atom by the cleavage of both the aryloxy C O bond and
À
aldehyde C H bond, was detected in approximately 30%
yield. Subsequently, optimization of this unprecedented
rearrangement reaction was carried out with 2-(phenoxy)-
benzaldehyde (1a), under argon in PhCl at 1608C by using
TBP as the oxidant. A series of ruthenium and rhodium
catalysts showed varying efficiencies in catalyzing the rear-
rangement reaction (Table 1, entries 1–10). Whereas all the
ruthenium catalysts tested showed moderate catalytic activ-
ities (entries 1–3), the use of different rhodium catalysts had a
drastic change in catalyzing the reaction (entries 4–10). By
using [{RhCl(CO)2}2] as the catalyst, the desired 2-hy-
droxybenzophenone (2a), was obtained in 53% yield
(entry 4). Other rhodium catalysts having different ligands
À
Figure 1. Transition-metal-catalyzed cleavage of C O bonds.
[*] Dr. H. Rao, Prof. Dr. C.-J. Li
Department of Chemistry, McGill University
Montreal, QC, H3A 2K6 (Canada)
E-mail: cj.li@mcgill.ca
Homepage: http://cjli.mcgill.ca/cj page.htm
À
(such as acac, cod, PPh3), counterions (such as BF4 ), or
[**] We are grateful to the Canada Research Chair Foundation (to C.J.L.),
the CFI, FQRNT Center for Green Chemistry and Catalysis, NSERC,
and McGill University for support of our research.
higher-valent rhodium catalysts such as [Cp*Rh(MeCN)3]-
(SbF6)2 were either much less effective than [{RhCl(CO)2}2]
or exhibited almost no catalytic activity (entries 5–10).
Among the oxidants examined, TBP provided the best yield
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201103599.
8936
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Angew. Chem. Int. Ed. 2011, 50, 8936 –8939

Table 1: Optimization of the rearrangement of 2-(aryloxy)benzaldehydes
Table 2: Scope of the rhodium-catalyzed rearrangement of 2-(aryloxy)-
to 2-hydroxybenzophenones.[a]
benzaldehydes to 2-hydroxybenzophenones.[a]
Entry
1
2
Yield
[%][b]
Entry
Catalyst
Solvent
[O]
Yield [%][b]
1
2
3
4
5
6
7
8
[RuCl2(PPh3)3]
[{Cp*RuCl2}2]
[RuCl2(CO)3]
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
benzene
toluene
DCE
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
TBP
TBP
TBP
TBP
TBP
TBP
TBP
TBP
TBP
TBP
TBHP
DCP
mCPBA
TBP
TBP
TBP
TBP
TBP
TBP
TBP
TBP
TBP
–
22
37
37
53
<10
12
40
12
24
trace
<10
<10
trace
35
17
11
46
46
1
2
3
4
2a
2b
2c
2d
51
83
71
81
[{RhCl(CO)2}2]
[Rh(CO)2acac]
[{RhCl(cod)}2]
[RhCl(PPh3)3]
[RhCl(CO)(PPh3)2]
[Rh(cod)2BF4]
[Cp*Rh(MeCN)3](SbF6)2
[{RhCl(CO)2}2]
[{RhCl(CO)2}2]
[{RhCl(CO)2}2]
[{RhCl(CO)2}2]
[{RhCl(CO)2}2]
[{RhCl(CO)2}2]
[{RhCl(CO)2}2]
[{RhCl(CO)2}2]
[{RhCl(CO)2}2]
[{RhCl(CO)2}2]
[RhCl(CO)2]2
9
10
11
12
13
14
15
16
17[c]
18[d]
19[e]
20[f]
21[g]
22[h]
23
24
5
2e
86
42
21
39
<10
trace
trace
6
7
8
9
2 f
2g
2h
2i
66
60
55
60
[{RhCl(CO)2}2]
[{RhCl(CO)2}2]
–
TBP
[a] Reaction conditions: 1a (0.1 mmol), cat. (5 mol%), [O] (2.5 equiv),
and solvent (0.25 mL) at 1608C for 24 h under argon. [b] Yield
determined by H NMR spectroscopy using mesitylene as an internal
1
standard. [c] tBuOH (1.0 equiv) as an additive. [d] H2O (1.0 equiv) as an
additive. [e] PivOH (1.0 equiv) as an additive. [f] DPPE (10 mol%) as the
ligand. [g] [{RhCl(CO)2}2] (2.5 mol%). [h] TBP (0.5 equiv). [O]=oxidant,
acac=acetylacetonate, cod=1,5-cyclooctadiene, Cp*=pentamethylcy-
clopentadienyl, DCE=1,2-dichloroethane, DCP=dicumyl peroxide,
DPPE=1,2-bis(diphenylphosphino)ethane, mCPBA=3-chlorobenzo-
peroxoic acid, PivOH=pivalic acid, TBP=tert-butyl peroxide,
TBHP=tert-butyl hydroperoxide.
10
2j
61
11
12
2k
2l
40
71
of the corresponding rearrangement product (entries 11–13).
The use of different solvents also strongly influenced the
reaction: When the reaction was carried out in benzene,
toluene, or DCE the yield of the desired product decreased
dramatically (entries 14–16). The introduction of some proton
donors such as tBuOH, H2O, or PivOH as additives slightly
reduced the product yields (entries 17–19). Other endeavors
to increase the yield of 2-hydroxybenzophenone were
attempted. For instance, the addition of 10 mol% DPPE as
the ligand did not improve this transformation (entry 20).
When the reaction was conducted with a reduced amount of
the catalyst (2.5 mol%) or TBP, the product yield was
reduced (entries 21 and 22). Interestingly, a trace amount of
the product was obtained when using either no catalyst or no
TBP (entries 23–24).
[a] Reaction conditions: 1 (0.20 mmol), [{RhCl(CO)2}2] (5 mol%), TBP
(2.5 equiv), PhCl (0.50 mL), at 1608C for 24 h under argon. [b] Yield of
isolated product.
and PhCl as the solvent. As summarized in Table 2, this
rearrangement was successfully performed with different
substituents at the para, meta, or ortho position of the aryloxy
unit, and the desired 2-hydroxybenzophenones were obtained
in moderate to good yields (Table 2, entries 2–11). The
reaction could tolerate a range of functional groups with
rearrangement occurring in the presence of electron-with-
drawing groups such as ester (entry 2), cyano (entry 3),
halogen (entries 4–8), and trifluoromethyl groups (entry 9),
as well as electron-donating groups such as phenyl (entry 10)
and methoxy groups (entry 11), all of which promise addi-
tional functionalization of the products. Notably, the aryloxy
With the optimized reaction conditions in hand, the
substrate scope was explored at 1608C under argon using
5 mol% [{RhCl(CO)2}2] as the catalyst, TBP as the oxidant,
Angew. Chem. Int. Ed. 2011, 50, 8936 –8939
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8937

Communications
units with electron-withdrawing groups displayed higher
by the CHO and 2-aryloxy groups is essential for the
rearrangement. Meanwhile, when o-anisaldehyde was sub-
jected to the standard reaction conditions, no 2’-hydroxyace-
tophenone was observed, thus indicating the important role of
reactivities than those with electron-donating groups
(entries 2–11), as it is much easier to undergo the cross-
dehydrogenative coupling reactions to 9H-xanthen-9-one
derivatives with electron-donating substituents.[10] To expand
the substrate scope, the benzaldehyde unit bearing a 4-CF3
group underwent rearrangement smoothly to afford the
desired ethyl 4-(2-hydroxy-5-(trifluoromethyl)benzoyl)ben-
zoate in 71% yield (entry 12).
To explore the reaction mechanism for this rearrange-
ment, control experiments were conducted under the stan-
dard reaction conditions (Scheme 2). The reaction of benzal-
dehyde with bromo biphenyl either gave no phenol or
bromophenol (Scheme 2a). When 3-(phenoxy)benzaldehyde
was subjected to the optimized reaction conditions, it also did
À
the 2-aryloxy group for this C O bond-cleavage chemistry
(Scheme 2c). Additionally, when [Rh2(OAc)4] (usually
employed in radical reactions involving nitroene or carbene
radical species)[11] was used instead of [{RhCl(CO)2}2], the
desired product was not obtained, thus suggesting that this
reaction may not involve a radical mechanistic pathway
(although
a radical mechanism cannot be excluded;
Scheme 2d). Finally, a cross-experiment showed no cross-
rearrangement product, thus indicating that this rearrange-
ment most probably proceeded through an intramolecular
process (Scheme 2e).
À
not generate the C O bond-cleavage product (Scheme 2b),
thus demonstrating that the chelation to the rhodium catalyst
On the basis of the above investigations, a tentative
À
mechanism for this aryloxy C O bond-cleavage chemistry is
À
depicted in Scheme 3. Initially, the chelating aldehyde C H
insertion of 2-(aryloxy)benzaldehydes 1 by RhI generates
the RhIII hydride species 3.[12] Upon reaction with TBP, the
Scheme 3. Tentative mechanism for the rhodium-catalyzed rearrange-
ment of 2-(aryloxy)benzaldehydes to 2-hydroxybenzophenones.
RhIII complex 4 is formed, thus liberating one molecule of
tBuOH. Then complex 4 may undergo an intramolecular
SNAr process to afford the complex 5 upon heating to
1608C,[13] thereby generating the RhIII complex 6 (an
alternative process through 1,4-elimination of Ar–Rh–
tOBu from 4 with subsequent conjugate addition of Ar–
Rh–tOBu to the resulting enone species may be excluded
based on the result of the cross-experiment), which could
release one molecule of acetone (detected by GC-MS) to
afford the RhIII/Me complex 7.[14] Finally, reaction of the
previously formed tBuOH with complex 7 can release one
molecule of the desired product 2 and form [RhIII(Me)-
(tOBu)] (8),[14e,f,15] which could regenerate the RhI catalyst
through a reductive elimination process by releasing
tBuOMe (detected by GC-MS).
Scheme 2. Investigation of the mechanistic pathway for the rearrange-
ment.
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Angew. Chem. Int. Ed. 2011, 50, 8936 –8939

c) H. N. Nguyen, X. Huang, S. L. Buchwald, J. Am. Chem. Soc.
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In summary, we have developed a rhodium-catalyzed
rearrangement of 2-(aryloxy)benzaldehydes to 2-hydroxy-
À
benzophenones, which serves as a novel aryloxy C O bond-
cleavage protocol that proceeds through a chelating strategy.
This reaction can tolerate a variety of functional groups,
thereby indicating the wide potential of applications for this
reaction. Additional investigations into the mechanism and
applications of the reaction are now ongoing in our labo-
ratory.
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Experimental Section
An oven-dried reaction vessel was charged with [{RhCl(CO)2}2]
(3.9 mg, 0.01 mmol, 5 mol%) and 2-(aryloxy)benzaldehydes
(0.2 mmol). After the vessel was filled with argon, dry PhCl
(0.5 mL) and TBP (100 uL, 2.5 equiv) were added by syringe
sequentially under argon, and the reaction mixture was stirred at
room temperature for 5 min. Then the vessel was sealed, placed into
an oil bath, and heated at 1608C for 24 h. The resulting mixture was
cooled to room temperature, filtered through a short silica gel pad
and washed with ethyl acetate. The above solution was evaporated
under vacuum, and the residue was purified by column chromatog-
raphy on silica gel with n-hexane/ethyl acetate (30:1 to 20:1) as the
eluent to give the analytically pure 2-hydroxybenzophenones.
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Received: May 26, 2011
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Published online: August 10, 2011
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Keywords: arenes · homogeneous catalysis · rearrangement ·
rhodium · synthetic methods
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