Cleavage of sp3 C-O bonds via oxidative addition of C-H bonds

Article abstract of DOI:10.1021/ja906930u

(Chemical Equation Presented) (PCP)Ir (PCP = K³-C ₆H₃-2,₆-[CH₂P(t-Bu) ₂]₂) is found to undergo oxidative addition of the methyl-oxygen bond of electron-poor methyl aryl ethers, i

Full text of DOI:10.1021/ja906930u

Published on Web 10/14/2009
Cleavage of sp3 C-O Bonds via Oxidative Addition of C-H Bonds
Jongwook Choi, Yuriy Choliy, Xiawei Zhang, Thomas J. Emge, Karsten Krogh-Jespersen,* and
Alan S. Goldman*
Department of Chemistry and Chemical Biology, Rutgers, The State UniVersity of New Jersey,
New Brunswick, New Jersey 08903
Received August 15, 2009; E-mail: krogh@rutchem.rutgers.edu; alan.goldman@rutgers.edu
The ability of transition-metal complexes to undergo oxidative
addition of strong bonds is one of their most characteristic and
important traits. In organic chemistry, such reactions are obviously
of particular interest in the context of bonds to carbon. The addition
of C-Hal bonds has been studied extensively and is a critical step
in numerous important catalytic reactions. The oxidative addition
of unactivated C-H bonds, first reported in the early 1980s, is now
the subject of widespread study and interest. This interest is largely
based on the potential value of “functionalizing the C-H bond”,
for example, by oxidizing it or adding it across an organic
unsaturated group such as a CdC double bond.1
Figure 1. ORTEP diagrams of 3a (left) and 4b (right).
In contrast to C-Hal and C-H bonds, there is very little
Scheme 1. Reaction of 1 with Anisole
precedent for the oxidative addition of unactivated C-O bonds. A
few noteworthy intramolecular examples have been reported,
involving prior coordination by “directing groups” or ligands.2 To
our knowledge, however, there is only one example of intermo-
lecular addition of an unactivated C(sp3)-O ether bond,3 eq 1
reported by Tolman and Ittel:4
Scheme 2. Reaction of 1 with 3,5-Bis(trifluoromethyl)anisole
Fe(dmpe)2 + CH3OPh f trans-(CH3)(OPh)Fe(dmpe)2
(1)
The microscopic reverse of C-O addition, C-O reductive
elimination, has been studied.5-10 Goldberg and Williams10 have
reported that for Pt(IV) complexes, the mechanism involves
dissociation of hydroxide or aryl oxide and nucleophilic attack on
the alkyl group. In view of the high nucleophilicity of Fe(dmpe)2,
it seems likely that eq 1 proceeds via initial SN2 attack on the anisole
methyl group [i.e., the microscopic reverse of the reaction elucidated
for elimination from Pt(IV)10].
2 is 2.0 kcal/mol more exergonic than is benzene C-H addition,
presumably because of a weak interaction between the methoxy
group and the iridium center (Ir-O distance ) 3.14 Å).12
Heating a solution of 2 for 3 h at 90 °C gave cyclometalated
product 3a (characterized by NMR spectroscopy and X-ray crystal-
lography; Figure 1) in quantitative yield (Scheme 1).12 Thus, not
only (PCP)Ir(I) but also the Ir(III) product of C-H activation, 2,
have the ability to activate C-H bonds.
Pincer-ligated iridium complexes have been investigated exten-
sively in the context of C-H addition, in part because of their ability
to generate three-coordinate d8 species, which often do not undergo
deactivating intramolecular additions or dimerizations. Such species
are reactive toward other bonds as well and indeed have been found
to oxidatively add to O-H, C-Hal, and N-H bonds, for example.
Our preliminary density functional theory (DFT) calculations
indicated that C-O addition would also be thermodynamically quite
favorable.
(PCP)Ir does not add aryl C-H bonds ortho to a methyl group.11
Accordingly, the addition of either 2,6-dimethylanisole or 3,5-
dimethylanisole to a solution of 1, rather than unsubstituted anisole,
did not afford the analogues of products 2 or 3a; heating to 100 °C
gave a complex mixture of products that has not yet been
characterized.
To enhance the reactivity of the C-O bond while blocking the
ortho C-H bond, we investigated the reactivity of 3,5-bis(trifluo-
romethyl)anisole. To our satisfaction, we observed the formation
of (PCP)Ir(CH3)(3,5-bis(trifluoromethyl)phenoxide) (4b) in 65%
yield along with 35% cyclometalated product 3b (Scheme 2).
Diagnostic of the presence of an iridium methyl group in 4b,
We have previously shown that (PCP)Ir(tert-butylvinyl)(H) (1)
(PCP ) κ3-C6H3-2,6-[CH2P(t-Bu)2]2) acts as a precursor of the
active fragment (PCP)Ir.11 The reaction of 1 with 1.05 equiv of
anisole in p-xylene-d10 at room temperature immediately results in
addition of the anisole ortho C-H bond to give 2, which shows a
1
2
resonances appear at 1.75 ppm (t, 3H, JPH ) 4.8 Hz) in the H
sharp hydridic resonance at -45.03 ppm (t, JPH ) 14.4 Hz, 1H,
NMR spectrum12 and -28.67 ppm (t, JPC ) 4.4 Hz) in the 13C
NMR spectrum. The structure of 4b was also confirmed crystal-
lographically (Figure 1). To our knowledge, this is only the second
example, after that of eq 1, of an intermolecular (i.e., without prior
coordination or ligation) oxidative addition of an ether (or alcohol)
Ir-H) in the 1H NMR spectrum.12,13 This complex is spectroscopi-
cally very similar to the previously reported11 complex (PCP)Ir-
(Ph)(H), but in that case, the hydride resonance is too broad to
observe at room temperature as a result of rapid and reversible C-H
elimination. DFT calculations indicate that the formation of complex
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C O M M U N I C A T I O N S
Table 1. Calculated Gibbs Free Energies (kcal/mol) for C-O Bond
Cleavage Reaction Pathways
Scheme 3. Proposed Mechanism for the Oxidative Addition of the
C-O Bond of Methyl Aryl Ethers by (PCP)Ir
Scheme 4. Reaction of 1 with Ethoxybenzene
for metal-to-methylidene H migration reported by Bercaw and co-
workers.18 However, for reasons that are not clear, the calculated
EIE of 3.9 is greater than experimental values reported for C-H/D
addition to metal centers (∼2);19 this could account for the
discrepancy between our calculated (7.0) and experimental [4.3(3)]
KIEs for the overall reaction.
During the course of this work, Grubbs and Whited reported a
rich body of chemistry involving the reactions of pincer-ligated
iridium complexes with ethers.20 This work was focused mostly
on Ozerov’s “PNP” pincer but also explored the anthraphos-based
PCP-type ligand. Remarkably, the use of different ligands and
(perhaps more importantly) different ethers afforded completely
different chemistry than is reported in this paper. As in the present
work, the Grubbs-Whited chemistry is based on addition of a C-H
bond adjacent to oxygen followed by R-elimination, but in marked
contrast to this work, it is R-elimination of H rather than OR of
the CH2OR group that is the key step responsible for their
observations.21 The resulting alkoxycarbene can undergo elimina-
tion of olefin to give a metal carbonyl dihydride. Interestingly, in
that case, the net reaction involves cleavage of four of the five bonds
of the H3C-O-R unit, i.e., all of the bonds except the C-O bond,
which is the only bond that is broken in the net reaction of Scheme
3.
We also investigated the chemistry of ethyl aryl ethers with
(PCP)Ir precursors. The resulting reaction is quite distinct from,
but not unrelated to, that of the methyl aryl ethers. Ethoxybenzene
reacts with 1 at room temperature in p-xylene to give a 1:1 ratio of
(PCP)Ir(H)(OC6H5) (5a; crystallographically characterized)12 and
(PCP)Ir(ethylene) (6)12,22 (Scheme 4).23 Further heating at 125 °C
gives complete conversion to 5a.
Thus, unlike the methylaryloxy C-O oxidative additions, the
presence of substituents on the aryl ring (ortho or otherwise) is not
required in order to permit the C-O cleavage reaction of Scheme
4. However, the initial reaction of 4-ethoxy-2,3,5,6-tetrafluorotolu-
ene (7) with 1 at room temperature is faster (giving the analogous
aryl oxide 5d and 6), and the subsequent reaction to give full
conversion to 5d proceeds at 80 °C instead of 125 °C.
Direct C-O oxidative addition followed by ꢀ-H elimination from
the ethyl group would lead to the products shown in Scheme 4.
However, on the basis of the above conclusion that direct C-O
addition does not occur with methyl aryl ethers, this would seem
unlikely. Accordingly, we calculated that the barriers to C(sp3)-O
a Ar ) p-C6F4Me
C-O bond involving a simple alkyl group (probably the most
important examples with “activated” carbon centers are allylic14).
To fully block the formation of ortho C-H activation products,
pentafluoroanisole was investigated. Treatment of 1 with 1.05 equiv
of pentafluoroanisole at room temperature resulted in an immediate
color change from dark-red to red. NMR spectroscopy revealed
quantitative formation of (PCP)Ir(CH3)(OC6F5) (4c), whose structure
was confirmed crystallographically.12
In contrast with the Ittel-Tolman system, a simple SN2 mech-
anism seems unlikely in the present case. Evidence against such a
mechanism, and against a direct C-O oxidative addition pathway,
was obtained from isotope effect experiments wherein addition of
mixtures containing an excess of 4-methoxy-2,3,5,6-tetrafluoro-
toluene and its deuteromethoxy analogue were added to a p-xylene
solution of 1; the observed kinetic isotope effect (KIE) was kOCH
/
3
kOCD ) 4.3(3) at room temperature.12,15,16
3
DFT calculations (Table 1) predict that direct oxidative addition
(three-centered transition state) of (PCP)Ir to the Me-O bond of
MeO(p-C6F4Me) has a barrier of ∆Gq ) 39.6 kcal/mol [relative to
(PCP)Ir and the free aryl ether]. A pathway calculated to be
significantly more favorable (∆Gq ) 29.0 kcal/mol) is that shown
in Scheme 3. Methoxy C-H addition is followed by R-aryloxy
elimination17 to give a methylidene complex. A subsequent 1,2-
migration of H from Ir to the carbene gives the observed product.
Importantly, the mechanism in Scheme 3 accounts for the large
isotope effect. The calculated overall KIE is 7.0, which can be
expressed as the product of the equilibrium isotope effect (EIE)
calculated for formation of the methylidene complex (3.9) and
KIEM-CH for the metal-to-carbene H migration (1.8). The calculated
2
KIEM-CH is in good agreement with the experimental KIE of 2.0(6)
2
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C O M M U N I C A T I O N S
Scheme 5. Proposed Mechanism for Cleavage of the C-O Bond
(Dehydroaryloxation) of Ethyl Aryl Ethers by (PCP)Ir
Peterson, T. H. Acc. Chem. Res. 1995, 28, 154. (b) Shilov, A. E.; Shul’pin,
G. B. Chem. ReV. 1997, 97, 2879. (c) Sen, A. Acc. Chem. Res. 1998, 31,
550. (d) Guari, Y.; Sabo-Etiennne, S.; Chaudret, B. Eur. J. Inorg. Chem.
1999, 1047. (e) Jones, W. D. Science 2000, 287, 1942. (f) Crabtree, R. H.
J. Chem. Soc., Dalton Trans. 2001, 17, 2437. (g) Labinger, J. A.; Bercaw,
J. E. Nature 2002, 417, 507. (h) Goldman, A. S.; Goldberg, K. I. ACS
Symp. Ser. 2004, 885, 1.
(2) (a) van der Boom, M. E.; Liou, S.-Y.; Ben-David, Y.; Vigalok, A.; Milstein,
D. Angew. Chem., Int. Ed. Engl. 1997, 36, 625. (b) van der Boom, M. E.;
Liou, S.-Y.; Ben-David, Y.; Shimon, L. J. W.; Milstein, D. J. Am. Chem.
Soc. 1998, 120, 6531. (c) Ueno, S.; Mizushima, E.; Chatani, N.; Kakiuchi,
F. J. Am. Chem. Soc. 2006, 128, 16516.
Scheme 6. Competition Experiment To Determine the Relative
Rates of Reaction of (PCP)Ir with Methyl versus Ethyl Aryl Ether
(3) Wolczanski has reported the oxidative addition to tantalum of the C-O
bond of strained and vinylic cyclic ethers. See: Bonanno, J. B.; Henry,
T. P.; Neithamer, D. R.; Wolczanski, P. T.; Lobkovsky, E. B. J. Am. Chem.
Soc. 1996, 118, 5132.
(4) (a) Ittel, S. D.; Tolman, C. A.; English, A. D.; Jesson, J. P. J. Am. Chem.
Soc. 1978, 100, 7577. (b) Tolman, C. A.; Ittel, S. D.; English, A. D.; Jesson,
J. P. J. Am. Chem. Soc. 1979, 101, 1742.
(5) (a) Matsunaga, P. T.; Hillhouse, G. L.; Rheingold, A. L. J. Am. Chem.
Soc. 1993, 115, 2075. (b) Koo, K.; Hillhouse, G. L. Organometallics 1998,
17, 2924, and references therein.
(6) (a) Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2046. (b) Stambuli,
J. P.; Weng, Z.; Incarvito, C. D.; Hartwig, J. F. Angew. Chem., Int. Ed.
2007, 46, 7674, and references therein.
(7) (a) Widenhoefer, R. A.; Zhong, H. A.; Buchwald, S. L. J. Am. Chem. Soc.
1997, 119, 6787. (b) Widenhoefer, R. A.; Buchwald, S. L. J. Am. Chem.
Soc. 1998, 120, 6504, and references therein.
(8) (a) Khusnutdinova, J. R.; Zavalij, P. Y.; Vedernikov, A. N. Organometallics
2007, 26, 3466. (b) Khusnutdinova, J. R.; Newman, L. L.; Zavalij, P. Y.;
Lam, Y.-F.; Vedernikov, A. N. J. Am. Chem. Soc. 2008, 130, 2174.
(9) (a) Dick, A. R.; Kampf, J. W.; Sanford, M. S. J. Am. Chem. Soc. 2005,
127, 12790. (b) Racowski, J. M.; Dick, A. R.; Sanford, M. S. J. Am. Chem.
Soc. 2009, 131, 10974, and references therein.
(10) (a) Smythe, N. A.; Grice, K. A.; Williams, B. S.; Goldberg, K. I.
Organometallics 2009, 28, 277. (b) Williams, B. S.; Goldberg, K. I. J. Am.
Chem. Soc. 2001, 123, 2576. (c) Williams, B. S.; Holland, A. W.; Goldberg,
K. I. J. Am. Chem. Soc. 1999, 121, 252.
addition are ∆Gq ) 44.4 kcal/mol for 4-ethoxy-2,3,5,6-tetrafluo-
rotoluene and 46.3 kcal/mol for ethoxybenzene (Table 1). In
contrast, we calculated barriers that are far lower for a pathway
involving addition of the terminal C-H bond followed by ꢀ-aryloxy
elimination and loss of ethylene (Scheme 5): ∆Gq ) 20.5 and 22.6
kcal/mol for 4-ethoxy-2,3,5,6-tetrafluorotoluene and ethoxybenzene,
respectively.
In accord with the much lower calculated barriers for the
ꢀ-aryloxy eliminations (Scheme 5; Table 1) than for the R-aryloxy
elimination pathway (Scheme 3), when a mixture of 4-methoxy-
2,3,5,6-tetrafluorotoluene and 7 was reacted with 1, complexes 5d
and 6 (the same products that are obtained from pure 7) were formed
exclusively (Scheme 6); i.e., there was no evidence of any reaction
with 4-methoxy-2,3,5,6-tetrafluorotoluene.12
In conclusion, we have presented two classes of reactions in
which the C-O bond of alkyl aryl ethers is cleaved. In the first
case, the net reaction is an unusual oxidative addition of the alkyl
(methyl) C-O bond. The second is a dehydroaryloxation reaction.
In both cases, the initial step is C(sp3)-H activation at the CH3 of
the methoxy and ethyl groups, respectively. It is noteworthy that
whereas the C-H bond has historically been characterized by its
inertness in contrast to “functional” groups, the results herein
suggest that C-H oxidative addition may provide an entry point
toward breaking bonds in a molecule that are significantly weaker24
than the C-H bond itself but kinetically less reactive toward
transition metals. In particular, this seems surprising in the case of
the C-O oxidative addition, wherein the C-H bond is re-formed
following the C-O bond cleavage step. Perhaps even less intuitive
is the conclusion, based on microscopic reversibility, that C-O
reductive elimination from complexes 4 would proceed via an initial
R-H migration. We are currently exploring ways to exploit both of
these reactions catalytically in either the direction observed in this
study or the reverse.
(11) Kanzelberger, M.; Singh, B.; Czerw, M.; Krogh-Jespersen, K.; Goldman,
A. S. J. Am. Chem. Soc. 2000, 122, 11017.
(12) See the Supporting Information.
(13) Ben-Ari, E.; Cohen, R.; Gandelman, M.; Shimon, L. J. W.; Martin, J. M. L.;
Milstein, D. Organometallics 2006, 25, 3190.
(14) (a) Trovitch, R. J.; Lobkovsky, E.; Bouwkamp, M. W.; Chirik, P. J.
Organometallics 2008, 27, 6264. (b) Eisch, J. J.; Im, K. R. J. Organomet.
Chem. 1977, 139, C45. (c) Yamamoto, T.; Akimoto, M.; Yamamoto, A.
Chem. Lett. 1983, 12, 1725. (d) Yamamoto, T.; Akimoto, M.; Saito, O.;
Yamamoto, A. Organometallics 1986, 5, 1559.
(15) Davico, G. E. Org. Lett. 1999, 1, 1675.
(16) Secondary KIEs for SN2 reactions are generally small and typically even
inverse (<1). See: Kato, S.; Hacaloglu, J.; Davico, G. E.; DePuy, C. H.;
Bierbaum, V. M. J. Phys. Chem. A 2004, 108, 9887, and references therein.
(17) Lara, P.; Paneque, M.; Poveda, M. L.; Salazar, V.; Santos, L. L.; Carmona,
E. J. Am. Chem. Soc. 2006, 128, 3512.
(18) Parkin, G.; Bunel, E.; Burger, B. J.; Trimmer, M. S.; Van Asselt, A.;
Bercaw, J. E. J. Mol. Catal. 1987, 41, 21.
(19) See: (a) Parkin, G. Acc. Chem. Res. 2009, 42, 315. (b) Janak, K. E.; Parkin,
G. J. Am. Chem. Soc. 2003, 125, 6889, and references therein.
(20) (a) Whited, M. T.; Grubbs, R. H. Organometallics 2008, 27, 5737. (b)
Whited, M. T.; Grubbs, R. H. J. Am. Chem. Soc. 2008, 130, 5874. (c)
Whited, M. T.; Grubbs, R. H. J. Am. Chem. Soc. 2008, 130, 16476. (d)
Whited, M. T.; Grubbs, R. H. Organometallics 2009, 28, 161. (e) Whited,
M. T.; Zhu, Y.; Timpa, S. D.; Chen, C.-H.; Foxman, B. M.; Ozerov, O. V.;
Grubbs, R. H. Organometallics 2009, 28, 4560.
(21) For other chemistry involving C-O cleavage and R-substituent elimination,
see: Ferrando, G.; Coalter, J. N., III; Gerard, H.; Huang, D.; Eisenstein,
O.; Caulton, K. G. New J. Chem. 2003, 27, 1451.
Acknowledgment. We thank the National Science Foundation
(Grant CHE-0719307) for support of this work.
(22) Gomez-Benitez, V.; Redon, R.; Morales-Morales, D. ReV. Soc. Quim. Mex.
2003, 47, 124.
Supporting Information Available: Experimental details and
procedures, details of DFT calculations, spectral data, and crystal-
lographic data for complexes 3a, 4b-d, 5a, and 5d (CIF). This material
is available free of charge via the Internet at http://pubs.acs.org.
(23) Analogous reactions of ethers with zirconocenes have been reported. See:
(a) Bradley, C. A.; Veiros, L. F.; Chirik, P. J. Organometallics 2007, 26,
3191. (b) Bradley, C. A.; Veiros, L. F.; Pun, D.; Lobkovsky, E.; Keresztes,
I.; Chirik, P. J. J. Am. Chem. Soc. 2006, 128, 16600.
(24) The H3C-OPh bond dissociation energy (BDE) is 63.8 ( 1 kcal/mol. The
H-CH2OPh BDE has not been reported but is probably not very different
from the H-CH2OCH3 BDE, which is 93 ( 1 kcal/mol. See: McMillen,
D. F.; Golden, D. M. Annu. ReV. Phys. Chem. 1982, 33, 493.
References
(1) For some reviews of alkane C-H bond activation by organometallic
complexes, see: (a) Arndtsen, B. A.; Bergman, R. G.; Mobley, T. A.;
JA906930U
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