Direct access to fluorene by successive C-O/C-H bond activations of 2-phenylbenzyl ester

Article abstract of DOI:10.1021/om5001869

Catalytic formation of fluorene has been achieved from 2-phenylbenzyl trifluoroacetate via successive C-O and C-H bond cleavage reactions by Pd(OAc)₂/PPh₃ in 97% yield. This reaction involves the oxidative addition of ester to give (carboxylato)(2-phenylbenzyl)palladium(II) species and deprotonation from the 2-phenylbenzyl group by the cleaved carboxylato group via an internal electrophilic substitution mechanism.

Full text of DOI:10.1021/om5001869

Communication
pubs.acs.org/Organometallics
Direct Access to Fluorene by Successive C−O/C−H Bond Activations
of 2‑Phenylbenzyl Ester
Masafumi Hirano,* Sosuke Kawazu, and Nobuyuki Komine
Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16
Nakacho, Koganei, Tokyo 184-8588, Japan
S
* Supporting Information
ABSTRACT: Catalytic formation of fluorene has been
achieved from 2-phenylbenzyl trifluoroacetate via successive
C−O and C−H bond cleavage reactions by Pd(OAc)2/PPh3
in 97% yield. This reaction involves the oxidative addition of
ester to give (carboxylato)(2-phenylbenzyl)palladium(II)
species and deprotonation from the 2-phenylbenzyl group by
the cleaved carboxylato group via an internal electrophilic substitution mechanism.
Scheme 2
irect C−H functionalization is one of the major current
1
Dtopics in organometallic chemistry.
In many cases,
hydrogen is believed to be abstracted as a proton by an
associated basic ligand such as carboxylato at a transition-metal
center. This process is now widely accepted as the internal
electrophilic substitution (IES)2 mechanism, although other
names such as concerted metalation−deprotonation (CMD)3
and ambiphilic metal−ligand activation (AMLA)4 have been
also used. This process normally involves (i) an oxidative
addition of carbon−halogen bond, (ii) anion exchange from
halido to carboxylato in a polar solvent, and then (iii)
abstraction of hydrogen in a substrate as a proton by the
coordinating carboxylato group (Scheme 1).
co-workers have documented extensive Tsuji−Trost type
transformations,8 no direct C−H functionalization using benzyl
carboxylates has been reported.9 We describe here the first
catalytic formation of fluorene by successive C−O/C−H bond
activation of 2-phenylbenzyl esters.
Scheme 1
Because electron-deficient carboxylates would lead to facile
C−O bond oxidative addition10 and 1,8-diazabicyclo[5.4.0]-
undec-7-ene (DBU) is a potentially effective base for trapping
of evolved carboxylic acid,11 we started the screening using 2-
phenylbenzyl trifluoroacetate in the presence of DBU and
Pd(OAc)2 as the catalyst precursor (Table 1).
Upon screening of a broad range of ligands (entries 1−6),
the PPh3 system showed a promising performance to give
fluorene, which is currently attractive for OLEDs and solar
cells.12 Note that there was almost no catalytic activity (0−2%)
in the presence of non-phosphorus ligands such as NHC/Ag2O
and 2,2′-bipyridine or in the absence of ligand. Nonpolar
solvents such as benzene gave the best result (entries, 1 and 7−
9). This reaction requires addition of base (entry 12), and
Proton Sponge was not effective for this reaction (entry 13).
The optimized amount of DBU is 1 equiv with respect to
substrate (entries 1, 10, and 11). Because DBU having an
If we can directly access the key intermediate A from esters, a
straightforward transformation would be achieved without
using organic halides, carboxylato anion, and a polar solvent
that is generally difficult to remove. One of the major
difficulties may arise from the C−O bond oxidative addition
of esters that generally gives the undesired (acyl)(alkoxo)metal
species B rather than A (Scheme 2).5
However, when benzyl, allyl, and alkenyl esters are employed,
the (carboxylato)(organo)metal species A is formed.5,6 In
addition, naphthyl and some aryl esters are recently found to
give A by Ni(0) as an intermediate in the C−H
functionalization.7 For benzyl esters, although Kuwano and
Received: February 21, 2014
Published: April 15, 2014
© 2014 American Chemical Society
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Organometallics
Communication
similar C−O bond oxidative addition of a simple benzyl ester to
Table 1. Effect of Solvent, Base, and Ligand on the C−O/C−
a
Pd(0) was also reported by Yamamoto and co-workers.14
H Bond Activation
entry
solvent
base
L
yield (%)
1
2
3
4
5
6
7
8
9
benzene
benzene
benzene
benzene
benzene
benzene
THF
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
PPh3
56
52
2
P(m-tol)3
PCy3
The molecular structure of 2 clearly shows the oxidative
addition of the C−O bond to give (carboxylato)(2-
phenylbenzyl)palladium(II), as shown in Figure 1.15 The C−
P(OPh)3
DPPP
BINAP
PPh3
1
1
2
47
18
46
4
acetone
DME
PPh3
PPh3
b
10
benzene
benzene
benzene
benzene
benzene
toluene
PPh3
c
11
PPh3
31
9
d
12
13
14
n.a.
PPh3
Proton Sponge
MTBD
PPh3
21
85
97
PPh3
e
15
MTBD
PPh3
a
Conditions: Pd(OAc)2, 10 mol %; L, 20 mol % (10 mol % for DPPP
b
c
d
and BINAP). DBU, 2 equiv. DBU, 0.5 equiv. No addition of base.
e
Temperature 100 °C.
amidine framework was a promising base, we thought that the
similar superbase 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene
(MTBD) was worth trying. In fact, MTBD gave the best result
among these trials and the yield of fluorene improved to 97%.
Acetate, benzoate, and 4-nitrobenzoate did not give fluorene
under these conditions (Table 2). On the basis of the
Figure 1. Molecular structure of Pd(OCOCF3)(2-phenylbenzyl)-
(dppe) (2). All hydrogen atoms, incorporated Et2O, and disordered
CF3 groups are omitted for clarity. Ellipsoids represent 50%
probability.
Table 2. Effect of Carboxylate on the C−O/C−H Bond
Activation
O bond oxidative addition of a benzyl ester proceeds despite
the existence of a bulky substituent at the ortho position. The
31P{1H} NMR spectrum of 2 shows two doublets at δ 57.35 (d,
1P) and 39.96 (d, 1P), suggesting a cis configuration. In the 1H
NMR, the most characteristic benzylic methylene protons
appear at δ 2.90 (dd, 2H). The trifluoromethyl group resonates
at δ −73.77 (s). The IR spectrum of 2 shows intense ν(CO)
and ν(C−O) bands at 1688 and 1435 cm−1, respectively,
suggesting κ1O monodentate coordination to the Pd
center.16,17
entry
R1
yield (%)
1
2
3
4
CF3
Me
Ph
97
0
1
C6H4NO2-4
2
Conditions: Pd(OAc)2, 10 mol %; L, 20 mol%.
In contrast to the case for trifluoroacetate, the C−O bond
oxidative addition of 2-phenylbenzyl acetate did not proceed at
all under the same conditions, and at 70 °C 1 resulted in
decomposition and no C−O oxidative addition occurred. Thus,
the C−O bond oxidative addition must be the key for the
present reaction.
Treatment of 2 with MTBD at 70 °C for 8 h gave fluorene in
74% yield (Table 3, entry 1). When DBU was employed in this
reaction, fluorene was also produced in 68% yield (entry 2).
NEt3 and Cs2CO3 were not suitable bases for this reaction
(entries 3 and 4). The best result was obtained by the reaction
in toluene with MTBD at 100 °C to give fluorene in
quantitative yield (entry 5).
pioneering report by Chang and co-workers, fluorene was
also formed from 2-phenylbenzyl chloride by Pd(OAc)2/
BINAP or P(m-tol)3 in the presence of Cs2CO3, and they noted
that 2-phenylbenzyl acetate did not give fluorene at all.13
In order to understand the mechanism, we also tried
stoichiometric reactions. When Pd(styrene)(dppe) (1) was
treated with 2-phenylbenzyl trifluoroacetate in benzene, C−O
bond oxidative addition to Pd(0) took place smoothly within 1
h at room temperature to give Pd(OCOCF3)(2-phenylbenzyl)-
(dppe) (2) quantitatively in 42% isolated yield as analytically
pure brown crystals from cold THF/Et2O (eq 1). Note that a
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Organometallics
Communication
Table 3. Effect of Base on Stoichiometric Formation of
Fluorene from Pd(OCOCF3)(2-phenylbenzyl)(dppe)
entry
base
yield (%)
1
2
3
4
MTBD
DBU
74
68
NEt3
43
Cs2CO3
MTBD
33
a
5
100
Figure 2. Computed reaction profile for key steps in the catalysis. All
hydrogen atoms are omitted for clarity.
a
In toluene at 100 °C.
These results, taken together, are consistent with the catalytic
cycle shown in Scheme 3 for the catalytic successive C−O/C−
TS1. A significant polarization in the calculated natural atomic
charges for the species at TS1 occurs at the activating C−H
bond, the negative charge at C increasing by −0.526, while the
H becomes more positive by +0.399, suggesting the IES
mechanism. The overall mechanism is similar to aromatic C−H
bond activation through the IES mechanism by Pd(II),19,20 but
this is closer to the Wheland type species.21 The rate-
determining step is the reductive elimination step involving
TS2 that gives a η2-coordinating fluorene complex of Pd(0),
INT4.
Scheme 3. Proposed Catalytic Cycle
In summary, we have a new example for successive C−O/
C−H bond cleavage reaction of a benzyl ester by Pd(0)
catalyst. The key for the present reaction seems to be facile
oxidative addition of the C−O bond, and trifluoroacetate is one
of the best candidates. This fundamental finding should open
up direct C−H functionalization using benzyl esters on the
basis of the IES mechanism.
ASSOCIATED CONTENT
* Supporting Information
■
S
Text, figures, tables, and a CIF file giving synthetic details and
full characterization data for all compounds prepared in this
paper, crystallographic data for 2, and computational details.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*M.H.: e-mail, hrc@cc.tuat.ac.jp; tel and fax, +81 423 887 044.
Notes
H bond activation. A key Pd(0) species, PdLn, is generated by
the facile reduction of Pd(OAc)2 with PPh3.17 The C−O bond
oxidative addition of the ester to Pd(0) gives C, which has been
isolated in the case of the dppe analogue 2. Because the 2-
phenyl group is forced in proximity to the Pd(II) center, the
internal C−H bond activation proceeds to give E. A similar
cyclometalation has also been reported.18 Finally, reductive
elimination from E releases fluorene.
DFT calculations were performed on the model reaction
using cis-Pd(OCOCF3-κ1O)(2-phenylbenzyl)(PH3)2 (2-PH3).
Because the monophosphine compound Pd(OCOCF3-
κ2O,O′)(2-phenylbenzyl)(PH3) (INT1) is 8.1 kcal mol−1
more stable than the bis-phosphine species cis-Pd(OCOCF3-
κ1O)(2-phenylbenzyl)(PH3)2, the reaction initiates from INT1
(Figure 2). Then haptotropic change of the carboxylato group
occurs to give INT2 and the C−H bond is cleaved by the
carboxylato group to form the six-membered transition state
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank Ms. S. Kiyota for elemental analysis.
■
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