Cleavage of carbonyl carbon and α-carbon bond of acetophenones by iridium(III) porphyrin complexes

Article abstract of DOI:10.1021/om1000887

Selective carbonyl carbon (C( - O)) and α-carbon (C(methyl)) bond activation of acetophenones was discovered by the high-valent, iridium(III) 5,10,15,20-tetrakis-4-tolylporphyrinato carbonyl chloride (Ir(ttp)Cl(CO)), which also acted as a Lewis acid in catalyzing the aldol condensation of acetophenones together with release of the coproduct water. Preliminary mechanistic studies suggest that both aliphatic and aromatic carbon-hydrogen bond activation products are kinetic products, which can be converted by reaction with water to iridium porphyrin hydride (Ir(ttp)H) via iridium porphyrin hydroxide (Ir(ttp)OH). Both Ir(ttp)OH and Ir(ttp)H were the possible intermediates to cleave the C( - O)-C(methyl) bond of acetophenones and to generate iridium porphyrin acyl complexes as the thermodynamic products.

Full text of DOI:10.1021/om1000887

Organometallics 2010, 29, 2001–2003 2001
DOI: 10.1021/om1000887
Cleavage of Carbonyl Carbon and r-Carbon Bond of Acetophenones by
Iridium(III) Porphyrin Complexes
Bao Zhu Li, Xu Song, Hong Sang Fung, and Kin Shing Chan*
Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories,
Hong Kong, People’s Republic of China
Received February 4, 2010
Summary: Selective carbonyl carbon (C(dO)) and R-carbon
are mechanistically intriguing due to the difficulty of
forming high-valent transition metal(V) intermediates,
which are particularly sterically demanding, with three
substitutents located in a cis-manner to the same face of a
porphyrin plane. Herein, we report that iridium(III)
5,10,15,20-tetrakis-4-tolylporphyrinato carbonyl chlor-
ide (Ir(ttp)Cl(CO)) 1a7 cleaves the C(dO)-C(R) bonds
of acetophenones to selectively give iridium porphyrin
acyl complexes.6b
Ir(ttp)Cl(CO) 1a was found to undergo successful selec-
tive CCA with a variety of p-substituted acetophenones
in solvent-free conditions at the less sterically hindered
C(dO)-C(methyl) bonds rather than the C(dO)-C(aryl)
bonds to yield Ir(ttp)COAr (Table 1, eq 1). For example,
Ir(ttp)Cl(CO) reacted with acetophenone at 200 °C in
20 days to give Ir(ttp)COPh 3b in 71% yield together with
the aromatic CHA products Ir(ttp)(p-COMe-Ph) 4b in
4% yield and Ir(ttp)(m-COMe-Ph) 4c in 8% yield, respec-
tively (Table 1, entry 2). Both electron-rich and electron-
poor p-substituted acetophenones required shorter reac-
tion times of 12 to 15 days to give 3a and 3c,d in similar
product yields (Table 1, entries 1, 3, and 4), while these
p-substituted acetophenones did not yield any aromatic
CHA product.
(C(methyl)) bond activation of acetophenones was discovered
by the high-valent, iridium(III) 5,10,15,20-tetrakis-4-tolylpor-
phyrinato carbonyl chloride (Ir(ttp)Cl(CO)), which also acted
as a Lewis acid in catalyzing the aldol condensation of
acetophenones together with release of the coproduct water.
Preliminary mechanistic studies suggest that both aliphatic
and aromatic carbon-hydrogen bond activation products are
kinetic products, which can be converted by reaction with water
to iridium porphyrin hydride (Ir(ttp)H) via iridium porphyrin
hydroxide (Ir(ttp)OH). Both Ir(ttp)OH and Ir(ttp)H were the
possible intermediates to cleave the C(dO)-C(methyl) bond
of acetophenones and to generate iridium porphyrin acyl
complexes as the thermodynamic products.
Activation of carbon-carbon bonds (CCA) adjacent to a
carbonyl group by transition metal complexes has been
widely investigated due to not only its mechanistic under-
standings but also its potential utility in organic synthesis.1
Most examples of CCA reactions of carbonyl compounds
involve strained systems.2 Among these, cyclobutanones are
the most widely used substrates, which have been proposed
to undergo oxidative addition with low-valent transition
metal complexes in the carbon-carbon bond activation.2
Another approach for CCA reactions of carbonyl com-
pounds is driven by chelation assistance of an adjacent
coordinating atom.1,3
High-valent transition metal complexes are much less
known to cleave carbon-carbon bonds since oxidative
addition is uncommon with high-valent transition metal
complexes.4 However, Cp*(PMe3)Ir(CH3)OTf has been
shown recently to react with alkoxy- and siloxy-substituted
cyclopropanes to undergo CCA reaction, and an Ir(V) alkyl
intermediate was proposed.5
During the reaction, water-like droplets were observed
to form and likely come from the Ir(ttp)Cl(CO)-catalyzed
aldol condensation of acetophenone. Indeed, we found
that acetophenone did undergo an Ir(ttp)Cl(CO)-cata-
lyzed aldol condensation reaction to give 5a and 5b in
a shorter reaction time of 1 day. Therefore, the coforma-
tion of water in reactions of 1a and 2a-d was confirmed
(eq 2).8,9
We have reported that high-valent metalloporphyrins
of rhodium(III) and iridium(III) can activate aldehydic
carbon-hydrogen bonds (CHA).6 These bond activations
*Corresponding author. E-mail: ksc@cuhk.edu.hk.
(1) Park, Y, J.; Park, J.-W.; Jun, C.-H. Acc. Chem. Res. 2008, 41, 222–
234.
(2) (a) Murakami, M.; Ashida, S. Chem. Commun. 2006, 4599–4601.
(b) Matsuo, J.-i.; Sasaki, S.; Tanaka, H.; Ishibashi, H. J. Am. Chem. Soc.
2008, 130, 11600–11601.
Upon more careful examination of the reaction mixture of
acetophenone with 1a at a lower temperature of 120 °C in 5
days, only the R-CHA product 4a was isolated in 11% yield10
(3) Ahn, J.-A.; Chang, D.-H.; Park, Y. J.; Yon, Y. R.; Loupy, A.; Jun,
C.-H. Adv. Synth. Catal. 2006, 348, 55–58.
(4) For oxidative addition (OA) of the C-H bond, see: (a) Gomez,
M.; Robinson, D. J.; Maitlis, P. M. J. Chem. Soc., Chem. Commun.
1983, 825-826. For OA of the Si-H bond, see: (b) Klei, S. R.; Tilley, T. D.;
Bergman, R. G. J. Am. Chem. Soc. 2000, 122, 1816–1817.
(5) Anstey, M. R.; Yung, C. M.; Du, J.; Bergman, R. G. J. Am. Chem.
Soc. 2007, 129, 776–777.
(7) Yeung, S. K.; Chan, K. S. Organometallics 2005, 24, 6426–6430.
(8) Lyle, R. E.; DeWitt, E. J.; Nichols, N. M.; Cleland, W. J. Am.
Chem. Soc. 1953, 75, 5959–5961.
(9) For the Lewis acid-catalyzed aldol condensation of acetophenone
via the Rh(oep)CH2COR (oep = octaethylporphyrinato) intermediate
from a more reactive Rh(oep)ClO4: Aoyama, Y.; Tanaka, Y.; Yoshida,
T.; Toi, H.; Ogoshi, H. J. Organomet. Chem. 1987, 329, 251–266.
(10) According to TLC analysis, most Ir(ttp)Cl(CO) still remained,
while it decomposed upon chromatography on alumina.
ꢀ
(6) (a) Chan, K. S.; Lau, C. M. Organometallics 2006, 25, 260–265.
(b) Song, X.; Chan, K. S. Organometallics 2007, 26, 965–970.
r
2010 American Chemical Society
Published on Web 04/14/2010
pubs.acs.org/Organometallics

2002 Organometallics, Vol. 29, No. 9, 2010
Table 1. CCA of Acetophenones by Ir(ttp)Cl(CO)
Li et al.
Scheme 1. Transformation from Ir(ttp)OH to Ir(ttp)H
entry
FG
F 2a
H 2b
Me 2c
OMe 2d
time/d
product (yield/%)
1
2
3
4
13
20
12
15
Ir(ttp)CO(4-F-Ph) 3a (74)
Ir(ttp)COPh 3b (71)a
Ir(ttp)CO(4-Me-Ph) 3c (78)
Ir(ttp)CO(4-OMe-Ph) 3d (79)
4a was hydrolyzed by water (100 equiv) in benzene-d6 at
200 °C for 3 days (eq 6).13 Likely, water attacks at the iridium
center to give Ir(ttp)OH14 and acetophenone. Ir(ttp)OH can
undergo reduction at high temperature to yield IrII(ttp);15
IrII(ttp) further rapidly disproportionates into IrIII(ttp)-
aAromatic CHA products of Ir(ttp)(p-COMe-Ph) 4b and Ir(ttp)(m-COMe-Ph)
4c were also isolated in 4% and 8% yield, respectively. For the typical experimental
details see ref 20.
þ
(OH2)n (n = 1 or 2) and IrI(ttp)-,16 which upon proton-
ation with H2O gives Ir(ttp)H (Scheme 1). We propose that
Ir(ttp)CH2COPh 4a, as the kinetic product, likely converts to
Ir(ttp)OH and Ir(ttp)H in the presence of water, or Ir(ttp)Cl
in the presence of HCl at high temperature. As Ir(ttp)H did
not react with benzene to give the aromatic CHA product of
Ir(ttp)Ph, more likely Ir(ttp)OH cleaves the aromatic C-H
bond to form 4b-c.14d,17
without any 3b formed (eq 3). The R-CHA reaction is a facile,
kinetic process.
The possible intermediacy of 4a for CCA was further
examined by independent reactions between 4a and 2b at
200 °C. After 15 days, 4b and 4c were produced in 21% and
42% yield, respectively, together with 3b in 21% yield (eq 4).
After 26 days, 3b was formed in 75% yield, while 4b,c still
remained in 8% and 16% yield, respectively (eq 4). Further-
more, when the more accessible Ir(ttp)Ph11 1b was used as an
analogue of Ir(ttp)(p- and m-COMe-Ph) (4b and 4c) to react
with acetophenone, the CCA product 3b was isolated in trace
amount (<5%) only with the recovery of 1b in 88% yield
after heating for 28 days at 200 °C (eq 5). These results
suggest that 4b,c are less likely the direct intermediates for
CCA, as they reacted very slowly. Furthermore, a direct
σ-bond metathesis of metal-C and C-C bonds is sterically
difficult and unprecedented.12 We therefore considered other
more plausible mechanistic fates for 4a-c.
Similar to 4a, 4b,c can be hydrolyzed to convert to Ir(ttp)OH
and Ir(ttp)H or Ir(ttp)Cl in the presence of water or HCl.
Indeed, with the addition of 100 equiv of water in the reaction
of Ir(ttp)Ph and acetophenone, a higher yield of Ir(ttp)COPh
3b was obtained in 12% yield (eq 7 vs eq 5). The slower rate of
hydrolysis of 1b compared with 4a is likely due to the stronger
and more hindered metal aryl bond than the metal alkyl
bond.18
As both Ir(ttp)OH and Ir(ttp)H are proposed inter-
mediates for CCA, the more accessible and observed
Ir(ttp)H was reacted with acetophenone independently.
(14) For Rh(oep)OH, see: (a) Del Rossi, K. J.; Wayland, B. B. J. Am.
Chem. Soc. 1985, 107, 7941-7944. For Rh(tspp)OH (tspp = tetra-p-
sulfonatophenylporphyrinato), see: (b) Fu, X.; Wayland, B. B. J. Am.
Chem. Soc. 2004, 126, 2623–2631. (c) Fu, X.; Li, S.; Wayland, B. B.
J. Am. Chem. Soc. 2006, 128, 8947-8954. For hydrolysis of Rh-
(tspp)CH2COR with water to form Rh(tspp)OH, see: (d) Zhang, J.; Li, S.;
Fu, X.; Wayland, B. B. Dalton Trans. 2009, 3661–3663. (e) Zhang, J.;
Wayland, B. B.; Yun, L.; Li, S.; Fu, X. Dalton Trans. 2010, 39, 477-483.
For Ir(acac)2OH, see: (f) Tenn, W. J., III; Young, K. J. H.; Oxgaard, J.;
Nielsen, R. J.; Goddard, W. A., III; Periana, R. A. Organometallics 2006, 25,
5173–5175. (g) Attempted synthesis of Ir(ttp)OH from the reaction of
Ir(ttp)Cl(CO) with KOH remains unsuccessful.
(15) Hydroxide ion is an effective one-electron reducing agent; see:
Sawyer, D. T.; Roberts, J. L., Jr. Acc. Chem. Res. 1988, 21, 469–476.
(16) Analogous disproportionation reactions of Rh(por)II, see: (a) In
excess MeOH: Li, S.; Cui, W.; Wayland, B. B. Chem. Commun. 2007,
4024-4025. (b) By strong ligand: Wayland, B. B.; Balkus, K. J., Jr.; Farnos,
M. D. Organometallics 1989, 8, 950-955. (c) Wayland, B. B.; Sherry, A. E.;
Bunn, A. G. J. Am. Chem. Soc. 1993, 115, 7675–7684.
Indeed, Ir(ttp)H7 1c was observed in 20% yield together
with acetophenone 2b in 20% yield when Ir(ttp)CH2COPh
(11) Ogoshi, H.; Setsune, J.-i.; Omura, T.; Yoshida, Z.-i. J. Am.
Chem. Soc. 1975, 97, 6461–6466.
(12) Direct σ-bond metathesis of the C-C bond is unprecedented,
ꢀ
and it was proposed but later amended. See: Soulivong, D.; Coperet, C.;
Thivolle-Cazat, J.; Basset, J.-M.; Maunders, B. M.; Pardy, R. B. A.;
Sunley, G. J. Angew. Chem., Int. Ed. 2004, 43, 5366–5369.
(13) (a) The lower yield obtained is likely due to the competitive
decomposition of Ir(ttp)H. (b) 4a was consumed completely, and no
Ir(ttp)COPh and Ir(ttp)(p- and m-COMe-Ph) were observed. (c) The
alternate nucleophilic attack on the R-carbon of 4a would have produced
PhCOCH2OH, which was not detected. This mode of reaction has been
reported in strongly alkaline media for analogous rhodium porphyrin
complexes in intramolecular cases. See: Sanford, M. S.; Groves, J. T.
Angew. Chem., Int. Ed. 2004, 43, 588–590.
(17) For reported examples of the aromatic C-H bond cleavages by
M
IIIOH, see: (a) Kloek, S. M.; Heinekey, D. M.; Goldberg, K. I. Angew.
Chem., Int. Ed. 2007, 46, 4736–4738. (b) Hanson, S. K.; Heinekey, D. M.;
Goldberg, K. I. Organometallics 2008, 27, 1454–1463. (c) Bercaw, J. E.;
Hazari, N.; Labinger, J. A. Organometallics 2009, 28, 5489–5492.
ꢀ
(18) Clot, E.; Megret, C.; Eisenstein, O.; Perutz, R. N. J. Am. Chem.
Soc. 2006, 128, 8350–8357.

Communication
Organometallics, Vol. 29, No. 9, 2010 2003
Scheme 2. Proposed Mechanism for CCA of Acetophenone by
Ir(ttp)Cl(CO)
undergoing σ-bond metathesis to give CCA product 3b as the
thermodynamic product, since oxidative addition of the
C(dO)-C(R) bond to high-valent Ir(III) porphyrin com-
plexes to form Ir(V) is sterically demanding.19 The cleavage
of the carbonyl carbon and R-carbon bond is not more
kinetically favorable than the carbon(R)-hydrogen bonds
due to the steric hindrance. This proposed mechanism can
also explain the faster reaction rates and higher yields for
p-substituted acetophenones, as the p-substituents prevent
the formation of nonproductive aromatic CHA intermedi-
ates and products.
In summary, we have discovered the selective carbonyl
carbon and R-carbon bond activation of acetophenones
by high-valent iridium porphyrin carbonyl chloride. The
iridium porphyrin carbonyl chloride functions as a Lewis
acid to catalyze the aldol condensation of acetophenones
with water formed. Both aliphatic and aromatic carbon-
hydrogen bond activation products are kinetic products,
which can convert to intermediates Ir(ttp)OH and/or Ir(ttp)H
in the presence of acid or water. Both Ir(ttp)OH and Ir(ttp)H
are the possible intermediates to cleave the C(dO)-C(methyl)
bond and give Ir(ttp)COAr as the thermodynamic products.
Further works to synthesize Ir(ttp)OH and its chemistry are
ongoing.
However, Ir(ttp)H 1c reacted with acetophenone to give the
R-CHA product Ir(ttp)CH2COPh 4a in 68% yield in just
1 day at 200 °C (eq 8). The direct cleavage of the C-C bond
by Ir(ttp)H most likely is inhibited by the competitive R-CHA.
The hydrolysis pathway must be responsible for the reconver-
sion of 4a back to Ir(ttp)OH and Ir(ttp)H.
Acknowledgment. We are grateful for the Research
Grants Council of Hong Kong of the SAR of China for
financial support (No. 400308).
On the basis of the above findings, we propose a mechan-
ism for the C(dO)-C(R) bond activation of acetophenones
by Ir(ttp)Cl(CO) (Scheme 2). First, 1a can react as a Lewis
acid to catalyze the aldol condensation of acetophenone to
give 5a,b and water.9 On the other hand, 1a can also react
with acetophenone 2b to give the R-CHA product 4a as a
result of the nucleophilic attack of the enol form of 2b.9 4a
undergoes interconversion with Ir(ttp)Cl 1a0 and Ir(ttp)H 1c
via Ir(ttp)OH in acetophenone in the presence of HCl
(coproduct of R-CHA) or H2O (coproduct from the aldol
condensation). Ir(ttp)OH then reacts with 2b to give the
ArCHA products 4b,c, which are more kinetically and
thermodynamically stable than 4a. However, in the presence
of HCl, 4b,c can convert back to Ir(ttp)Cl or Ir(ttp)OH and
Ir(ttp)H in the presence of H2O. Besides the R-CHA14d,e
and aromatic CHA, Ir(ttp)OH or Ir(ttp)H, once formed
again, cleaves the C(dO)-C(R) bond directly, most likely
Supporting Information Available: Experimental details and
characterizations of compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
(19) We were not able to detect the coproduct of MeOH or MeH by
GC-MS analysis; therefore, the possible intermediacy of Ir(ttp)OH and
Ir(ttp)H can not be distinguished.
(20) Details for a typical experiment of the C(dO)-C(R) bond
activation of acetophenone with Ir(ttp)Cl(CO): Acetophenone (0.8
mL, 500 equiv) was added to Ir(ttp)Cl(CO) (12.4 mg, 0.013 mmol) in a
Teflon screw-head stoppered tube, and the mixture was degassed by the
freeze-pump-thaw method (3 cycles). Then the mixture was heated at
200 °C for 20 days under N2. The solvent was then removed under vacuum,
and the crude product was purified by column chromatography on
alumina. The purple solid of Ir(ttp)COPh6b 3b (8.9 mg, 0.0092 mmol,
71%) and Ir(ttp)(p-COMe-Ph) 4b (0.5 mg, 0.0005 mmol, 4%) together with
Ir(ttp)(m-COMe-Ph) 4c (1.0 mg, 0.0010 mmol, 8%) were isolated as the
second fraction.