Base-promoted selective activation of benzylic carbon-hydrogen bonds of toluenes by rhodium(III) porphyrins

Article abstract of DOI:10.1021/om060848h

Toluenes underwent selective benzylic carbon-hydrogen bond activation with rhodium porphyrin chlorides. Both the rates and functional group compatibility were enhanced in the presence of K₂CO₃.

Full text of DOI:10.1021/om060848h

© Copyright 2007
Volume 26, Number 5, February 26, 2007
American Chemical Society
Communications
Base-Promoted Selective Activation of Benzylic Carbon-Hydrogen
Bonds of Toluenes by Rhodium(III) Porphyrins
Kin Shing Chan,* Peng Fai Chiu, and Kwong Shing Choi
Department of Chemistry, The Chinese UniVersity of Hong Kong, Shatin, New Territories, Hong Kong,
People’s Republic of China
ReceiVed September 15, 2006
Summary: Toluenes underwent selectiVe benzylic carbon-
hydrogen bond actiVation with rhodium porphyrin chlorides.
Both the rates and functional group compatibility were enhanced
in the presence of K2CO3.
and has been previously interpreted to be favored on both
thermodynamic and kinetic grounds.3 Sterically hindered ligands
of metal complexes can direct the benzylic CHA to be more
selective, presumably due to kinetically less hindered approach
at the metal center.4 However, the benzylic CHA has also been
recently observed to be the thermodynamic pathway by Bercaw
and others in Pt complexes in which reversible aromatic CHA
allows shifting the equilibrium to the formation of benzyl
complex via additional stabilization by arene coordination.3 The
interplay of steric and electronic factors is of interest in the
control and understanding of the selective activation of toluenes.
Selective intermolecular carbon-hydrogen bond activation
(CHA) by transition-metal complexes is an important area of
research in organometallic chemistry for the controlled activation
and functionalization of hydrocarbons.1 Toluene is a unique
hydrocarbon substrate, as three types of aromatic CHA and
benzylic CHA are possible. The preferences for selective
activation in toluene are not very well understood and are often
case-2,3 and mechanism-dependent.4-6 Aromatic CHA (ArCHA)
generally shows preference over the benzylic CHA (BnCHA)
Rhodium(III) porphyrins (por) have been reported to undergo
CHA. Rh(oep)Cl (oep ) octaethylporphyrinate) in the presence
of AgClO4 reacts with arenes via aromatic CHA to give para-
substituted arylrhodium porphyrins.8 On the basis of the para-
substituted pattern of products and Hammett studies, an
electrophilic aromatic mechanism was proposed. We have
reported earlier the selective meta-aromatic CHA of benzoni-
* To whom correspondence should be addressed. E-mail: ksc@
cuhk.edu.hk.
(1) (a) Shilov, A. E.; Shul’pin, G. B. Chem. ReV. 1997, 97, 2879-2932.
(b) Crabtree, R. H. Dalton Trans. 2001, 17, 2437-2450. (c) Labinger, J.
A.; Bercaw, J. E. Nature 2002, 417, 507-514. (d) Lersch, M.; Tilset, M.
Chem. ReV. 2005, 105, 2471-2526.
(2) For reports where the product ratio of transition-metal-mediated C-H
bond activation changed as a function of time or temperature, see: (a) Yung,
C. M.; Skaddan, M. B.; Bergman, R. G. J. Am. Chem. Soc. 2004, 126,
13033-13043. (b) Jones, W. D.; Feher, F. J. J. Am. Chem. Soc. 1984, 106,
1650-1663.
(3) For recent reports of the time-dependent selectivity of CHA of
toluene: (a) Heyduk, A. F.; Driver, T. G.; Labinger, J. A.; Bercaw, J. E. J.
Am. Chem. Soc. 2004, 126, 15034-15035. (b) Driver, T. G.; Day, M. W.;
Labinger, J. A.; Bercaw, J. E. Organometallics 2005, 24, 3644-3654. (c)
Zhao, S. B.; Song, D.; Jia, W. L.; Wang, S. Organometallics 2005, 24,
3290-3296.
(4) For a recent report of ligand chelation ring size on selectivities of
CHA of toluene, see: Johansson, L.; Ryan, O. B.; Rømming, C.; Tilset,
M. J. Am. Chem. Soc. 2001, 123, 6579-6590.
(5) For recent mechanistic reports of transition-metal-mediated C-H
bond activation, see: (a) Johansson, L.; Ryan, O. B.; Rmming, C.; Tilset,
M. J. Am. Chem. Soc. 2001, 123, 6579-6590. (b) Northcutt, T. O.; Wick,
D. D.; Vetter, A. J.; Jones, W. D. J. Am. Chem. Soc. 2001, 123, 7257-
7270. (c) Tan, K. L.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc.
2002, 124, 3202-3203. (d) Tellers, D. M.; Yung, C. M.; Arndtsen, B. A.;
Adamson, D. R. Bergman, R. G. J. Am. Chem. Soc. 2002, 124, 1400-
1410. (e) Zhang, F.; Jennings, M. C.; Puddephatt, R. J. Organometallics
2004, 23, 1396-1404.
(6) Cui, W.; Wayland, B. B. J. Am. Chem. Soc. 2004, 126, 8266-8274.
(7) Collman, J. P.; Boulatov, R. Inorg. Chem. 2001, 40, 2461-2464.
(8) Aoyama, Y.; Yashida, T.; Saikurai, K. I.; Ogoshi, H. Organometallics
1986, 5, 168-173.
10.1021/om060848h CCC: $37.00 © 2007 American Chemical Society
Publication on Web 01/30/2007

1118 Organometallics, Vol. 26, No. 5, 2007
Communications
Scheme 1. Mechanism of CHA
Table 1. Temperature Effect on CHA Reaction
Table 2. Base Effect in CHA
yield/%a
entry
base
time/min
yield/%
entry
temp/°C
time/days
2
3
4
1
2
3
4
NaOH
KOH
K2CO3
KHCO3
45
60
30
94
94
97
94
1
2
3
120
120
200
3
7
1
26
28
65
26
14
13
14
600
a Estimated from the integration of the mixture after chromatography
by H NMR.
(ttp)(4-tolyl) were obtained in 46 and 18% yields, respectively,
after 3 days at 120 °C.
1
Further improvements in selectivity, rate enhancement, and
yields were discovered with other inorganic bases (Table 2, eq
2). When 10 equiv of K2CO3 was added, Rh(ttp)Bn was
trile.9 Selective aldehydic CHA of benzaldehydes10 without any
aromatic CHA with rhodium(III) porphyrin complexes also
occurs. In exploring the CHA with rhodium(III) porphyrins, we
have successfully identified the base-promoted, selective ben-
zylic CHA of functionalized toluenes by rhodium(III) tetrakis-
(4-tolylporphyrin) chloride (Rh(ttp)Cl).
Initially, toluene reacted with Rh(ttp)Cl at 120 °C in 3 days
to give a mixture of 3-tolyl and 4-tolyl as well as benzylic
rhodium porphyrin complexes (Table 1, eq 1). The absence of
selectively formed and isolated in 97% yield after 30 min (Table
2, entry 3). A lower loading of K2CO3 gave a slower reaction
with a lower yield, and a higher loading (up to 100 equiv)
resulted in little improved reaction efficiency. Other bases such
as NaOH, KOH, and KHCO3 were also effective but required
longer reaction times.
When the optimized base-promoted reaction conditions were
applied to various 4-substituted toluenes, high yields of rhodium
porphyrin benzyls were obtained (Table 3, eq 3). With added
Rh(ttp)(2-tolyl) is likely due to steric hindrance. Nonselective
CHA had occurred. Prolonged heating of the reaction mixture
for 7 days resulted in similar yields of products. However, at
200 °C after 1 day, only Rh(ttp)Bn was formed in 65% yield.
High temperature favored the selective formation of the appar-
ently less stable Rh(ttp)Bn, as RhAr has a stronger Rh-alkyl
bond.11 Both Rh(ttp)(4-tolyl) and Rh(ttp)Bn were stable toward
toluene at an elevated temperature of 200 °C for 2 days without
any interconversion; therefore, the benzylic CHA occurred in a
parallel pathway with the aromatic CHA.
In view of the reported base-promoted aromatic CHA by
transition-metal complexes,12,13 we had examined the effect of
added ligands and bases. Coordinating ligands such as Ph3P and
pyridine were not effective, as they likely formed only
coordination complexes with Rh(ttp)Cl without any CHA
occurring. The noncoordinating base 2,6-di-tert-butylpyridine
(30 equiv) proved to be encouraging, as Rh(ttp)Bn and Rh-
K2CO3, most reaction times were shortened to 30 min from 2-3
days and product yields were in general higher. The basic
reaction conditions were more functional group compatible. No
Me-O activation occurred in anisole (Table 2, entry 1).10 Even
CN- and NO2-substituted toluenes (Table 3, entries 7 and 8)
reacted successfully, in contrast to no reaction or decomposition
observed in the absence of base. The reactions were also
successful with 10 equiv of toluene used in benzene solvent,
though with slightly lower efficiency. Rh(ttp)Bn was obtained
in a lower yield, 75%, after 1.5 h at 120 °C.
The observed isotope effects (kH/kD)obs for the reactions of
toluene with Rh(ttp)Cl at 120 °C were measured by competition
experiments with an equimolar mixture of toluene and toluene-
d8. Without any base, (kH/kD)obs values were measured to be
6.6 for aromatic CHA (indistinguishable of para and meta) and
4.0 for benzylic CHA. With K2CO3 added, (kH/kD)obs was found
to be 3.95. No benzyl exchange occurred under the same basic
conditions, as Rh(ttp)Bn did not react with toluene-d8 to give
any Rh(ttp)Bn-d7. These values suggested that the CHA steps
were involved in or prior to the rate-determining step in the
reactions.
(9) (a) Zhou, X.; Wang, R-J.; Mak, T. C. W.; Chan, K. S. Inorg. Chim.
Acta 1998, 270, 551-554. (b) Zhou, X.; Wang, R-J.; Xue, F.; Mak, T. C.
W.; Chan, K. S. J. Organomet. Chem. 1999, 580, 22-25. (c) Zhou, X.;
Tse, M. K.; Wu, D.-D.; Mak, T. C. W.; Chan, K. S. J. Organomet. Chem.
2000, 598, 80-86.
(10) Chan, K. S.; Lau, C. M. Organometallics 2006, 25, 260-265.
(11) Martinho Simoes, J. A.; Beauchamp, J. L. Chem. ReV. 1990, 90,
629-688.
(12) Harkins, S. B.; Peters, J. C. Organometallics 2002, 1753-1755.
(13) Liang, L.-C.; Lin, J.-M.; Lee, W.-Y. Chem. Commun. 2005, 2462-
2465.
Scheme 1 illustrates the proposed mechanism. Initially, Rh-
(ttp)Cl dissociates into a Rh(ttp) cation.8,10 In the absence of

Communications
Table 3. Benzylic CHA of Toluenes
Organometallics, Vol. 26, No. 5, 2007 1119
benzene solvent. The ratios of Rh(ttp)(4-FG-benzyl) to Rh(ttp)-
Bn were measured to be 3.95 (MeO), 0.28 (tBu), 2.48 (F), 4.59
(CHO), 6.45 (CN), and 7.45 (NO2). The ratios were kinetic ones,
as no 2e formed when Rh(ttp)Bn (2) was reacted with 4-fluo-
rotoluene in benzene with 10 equiv of K2CO3 at 120 °C for 1
h. We rationalize the rates of forming the benzylic C-H
complex or its stability and cleaving the C-H bonds are
dependent on the electronic effects of substituents in an opposing
manner.17 An electron-donating MeO substituent likely favors
the formation of a C-H complex but disfavors the cleavage,
due to its less acidic proton in comparison with a more electron
withdrawing group.
entry A (K2CO3)
entry B (no K2CO3)
product
product
(yield/%)
entry
FG
time/min
(yield/%)
time/days
1
2
3
4
5
6
7
8
OMe
tBu
Me
3,5-Me2
H
F
30
45
45
45
30
240
60
30
2a (92)
2b (98)
2c (90)
2d (45)
2 (97)
2e (64)
2f (83)
2g (98)
2
2
2a (78)
2b (84)
3
3
3
3
1
2d (35)
2 (26)
2e (72)
no reacn
no pdt
CN
NO2
base, toluene can coordinate to the Rh(ttp) cation to form the
(arene)Rh complex B, which then gives (aryl)Rh(ttp) in the
ArCHA pathway. Alternatively, the benzylic C-H bond can
coordinate to the Rh(ttp) cation to yield the benzylic C-H/Rh
complex A, which then gives Rh(ttp)Bn in the BnCHA pathway.
In the presence of base, the benzylic C-H/Rh(ttp) complex
likely undergoes more facile deprotonation, due to the more
acidic benzylic proton and sterically more favored coordination.
An alternate mechanism involving Rh(ttp)OH formed by ligand
substitution of Rh(ttp)Cl with hydroxide remains plausible. Rh-
(ttp)OH reacts with the benzylic CH bond to give Rh(ttp)Bn
and water. A rhodium porphyrin hydroxide is known.14 IrOMe15
and RuOH16 complexes are known to undergo CHA. We
currently favor the former mechanism involving a CH complex,
in view of the similar observed kinetic isotope effects for
benzylic CHA with and without base of 3.95 and 4.0, respec-
tively. It remains hard to reconcile the lack of an anion effect
on the magnitude of the kinetic isotope effect for the reactions
with Rh(ttp)Cl and Rh(ttp)OH.
In summary, we have discovered a base-promoted, selective,
and functional group compatible benzylic CHA of toluenes with
Rh(ttp)Cl. Further studies are ongoing.
Acknowledgment. We thank the Research Grants Council
of the HKSAR, People’s Republic of China (No. CUHK
400105), for financial support.
Supporting Information Available: Text giving experimental
details and spectroscopic data for products. This material is available
free of charge via the Internet at http://pubs.acs.org.
OM060848H
(14) Fu, X.; Li, S.; Wayland, B. B. J. Am. Chem. Soc. 2006, 128, 8947-
8954.
(15) Tenn, W. J., III; Young, J. J. H.; Bhalla, G.; Oxgaard, J.; Goddard,
W. A., III; Periana, R. A. J. Am. Chem. Soc. 2005, 127, 14172-14173.
(16) Feng, Y.; Lail, M.; Barakat, K. A.; Cundari, T. R.; Gunnoe, T. B.;
Petersen, J. L. J. Am. Chem. Soc. 2005, 127, 14174-14175.
(17) (a) Burger, B. J.; Santarsiero, B. D.; Trimmer, M. S.; Bercaw, J. E.
J. Am. Chem. Soc. 1988, 110, 3134. (b) Nelson, D. J.; Li, R.; Brammer, C.
J. Org. Chem. 2005, 70, 761-767. (c) Halpern, J.; Okamato, J. Inorg. Chem.
Acta. 1984, 89, L53-54.
The base-promoted BnCHA did not follow a simple electronic
effect. Competitive experiments were carried out with an equi-
molar mixture of 4-substituted (FG) toluene and toluene in reac-
ting with Rh(ttp)Cl using K2CO3 (10 equiv) at 120 °C in 1 h in