Chelating N-heterocyclic carbene alkoxide as a supporting ligand for PdII/IV C-H bond functionalization catalysis

Article abstract of DOI:10.1021/ja905713t

(Chemical Equation Presented) A Pd^IV complex that represents a viable catalytic intermediate in Pd-catalyzed C-H bond halogenation reactions has been isolated and structurally characterized. It contains the first examples of both a Pd^IV NHC bond and a Pd^IV alkoxide bond and serves as a precatalyst for C-H bond halogenation. As such, this represents a new class of tunable supporting ligand systems in Pd^IV catalysis.

Full text of DOI:10.1021/ja905713t

Published on Web 09/10/2009
Chelating N-Heterocyclic Carbene Alkoxide as a Supporting Ligand for PdII/IV
C-H Bond Functionalization Catalysis
Polly L. Arnold,*,† Melanie S. Sanford,*,‡ and Stephen M. Pearson†
School of Chemistry, UniVersity of Edinburgh, Edinburgh, United Kingdom EH9 3JJ, and Department of Chemistry,
UniVersity of Michigan, Ann Arbor, Michigan 48109-1055
Received July 10, 2009; E-mail: Polly.Arnold@ed.ac.uk; mssanfor@umich.edu
Palladium(IV) complexes have been proposed as key intermediates in
the catalytic ligand-directed functionalization of arene and alkane C-H
bonds.1 The best current methods for CH halogenation reactions of this
type employ Pd(OAc)2 as a catalyst in conjunction with a terminal oxidant
such as PhICl2 or an N-halosuccinimide.2 In the proposed PdII/PdIV cycle
for these transformations, ligand-directed C-H activation (step a in
Scheme 1) is followed by oxidation of PdII to PdIV in the presence of a
strong oxidant (step b). The resulting PdIV complex can then undergo C-Cl
bond-forming reductive elimination (step c) to generate the product.
Recently, similar PdIV or closely related dimeric PdIII intermediates have
been proposed in many different Pd-catalyzed reactions, including C-H
functionalizations, amino functionalizations of alkenes, the construction
of cyclopropanes from enynes, and the aryl halogenation of olefins.3
The Arnold group has previously used N-heterocyclic carbene (NHC)
ligands functionalized with tethered anionic alkoxy or amido groups to
stabilize high oxidation state metal cations.7 Such ligands are attractive
candidates for accessing the target PdIV species because NHC-PdII
complexes are known to be stable in acidic reaction media and in the
presence of strong oxidants.8 Based on these considerations, we set out
to synthesize PdII complexes containing chelating carbene ligands that
could participate in key steps of the catalytic cycle in Scheme 1.
Complex 1, PdL(bzq) (L ) OCMe2CH2(1-C{NCHCHNiPr});
bzq ) benzo[h]quinoline) (eq 1), can be envisioned as the product of
ligand-directed C-H activation (step a in Scheme 1). Here, it was
prepared in 88% yield by treatment of [Pd(bzq)Cl]29a with KL9b in
THF at -35 °C. It is an orange solid and has been fully characterized.
The metal-bound carbene is evident in the 13C NMR spectrum from
the deshielded resonance at 174.1 ppm.
Scheme 1. Pd(OAc)2-Catalyzed Chlorination of Benzo[h]quinolinea
Treatment of 1 with equimolar PhICl2 in MeCN-d3 at -35 °C results
in the oxidative addition of two chloride ligands to the Pd center to
give 2 (eq 1), step b in Scheme 1. Rapid, essentially quantitative
formation of 2 can be observed by 1H NMR spectroscopy. Complex
2 is stable in the solid state for at least one week and has been fully
characterized. The resonance for the proton on C16 (Figure 1a) is
shifted to higher frequency (9.80 ppm), and the carbene resonance is
now observed at 150.6 ppm in the 13C NMR spectrum. To the best of
our knowledge, 2 is the first PdIV-NHC and also the first isolated
PdIV alkoxide.
a (a) Ligand-directed C-H activation; (b) oxidation of PdII to PdIV by
PhICl2; (c) C-Cl bond-forming reductive elimination; (d) ligand exchange.
While PdII/IV-catalyzed processes are efficient and selective for certain
classes of substrates, significant challenges remain in this field. In particular,
the development of novel catalysts with enhanced activity, broader scope,
and chiral ligand environments would be highly desirable. However,
catalyst design for this mechanistic manifold has been extremely limited
due to the relatively small subset of ancillary ligands (predominantly sp2
N-donors and carboxylates)4,5 that are known to support high oxidation
state Pd centers. This Communication describes the first implementation
of robust, modular chelating N-heterocyclic carbene ligands for PdII/IV
-
catalyzed processes.
Several key features must be considered in the design of ancillary
ligands for these oxidative transformations. First, suitable ligands should
be strong σ-donors (it is unlikely that a d6 PdIV center has orbitals low
enough in energy to accept electrons via π-donation) and sufficiently
bulky and/or chelating to help stabilize the higher palladium oxidation
states.4,5 Second, the ligands must be resistant to decomposition under
the highly oxidizing reaction conditions. Third, it is essential that the
supporting ligands do not participate in reductive elimination reactions
that compete with functionalization of the desired substrate. Finally,
the ideal ancillary ligands would be modular, in order to facilitate the
design of new catalysts for regio- and stereoselective reactions.6
Figure 1. Molecular structure of 2 (a) and 4 (b). Ellipsoids drawn at the
50% probability level. Hydrogen atoms except alcohol omitted for clarity.
Selected bond lengths (Å) and angles (deg): for 2, Pd1-C1 1.993(2),
Pd1-O1 1.993(1), Pd1-N3 2.105(2), Pd1-C27 2.045(2), Pd1-Cl1
2.464(2), Pd1-Cl2 2.342(1), C27-Pd1-C1-N1 60.4(2); for 4: Pd1-C1
1.981(3), Pd1-N3 2.085(3), Pd1-C27 2.000(3), Pd1-Cl1 2.413(4),
C27-Pd1-C1-N1 92.8(2).
† University of Edinburgh.
‡ University of Michigan.
9
13912 J. AM. CHEM. SOC. 2009, 131, 13912–13913
10.1021/ja905713t CCC: $40.75  2009 American Chemical Society

C O M M U N I C A T I O N S
Single crystals of 2 suitable for X-ray analysis were grown by diffusion
of pentanes into an acetone solution of 2 at -35 °C; the molecular structure
is shown in Figure 1a. The palladium center in 2 is approximately
octahedral. The Pd-Ccarbene bond is long (1.981(3) Å), and comparison
of the Pd-Caryl, Pd-O, and Pd-Cl distances with those in a handful of
other PdIV complexes suggests that they are also long in 2,4,5,10 in
accordance with significant steric congestion at the octahedral metal center.
The high-frequency chemical shift of the proton on C26 in the 1H NMR
spectrum of 2 (6.12 ppm) as well as nOe interactions between it and the
isopropyl and methyl protons on the alkoxycarbene ligand suggest that
the solid-state structure is retained in solution.
additional PdIV bromide complexes relevant to the catalytic systems
have also been characterized (see SI). Notably, these reactions are slow
relative to those catalyzed by Pd(OAc)2, which are complete within
12 h under identical conditions. This is not unexpected since the current
system was optimized for the stabilization of PdIV, and cyclopalladation
(typically the rate-determining step) is expected to be sluggish at a
more electron-rich PdII center.11 Importantly, at the end of catalytic
reactions, no protonated/unbound carbene ligand was observed by 1H
NMR spectroscopy (see SI for details), suggesting the stability of the
Pd-carbene bond to prolonged heating under oxidizing conditions.
While 2 is stable at -35 °C in acetonitrile and at room temperature in
the solid state, we were delighted to find that it undergoes C-Cl bond-
forming reductive elimination upon warming in solution. As shown in eq
2, warming a 5.3 × 10-4 M solution of 2 in MeCN from -30 to 33 °C
over 24 h afforded yellow 3 as the major product in 75% isolated yield.
This represents a rare example of directly observable carbon-halogen
bond-forming reductive elimination from a PdIV complex.5 Notably, we
did not detect reductive elimination products containing the carbene ligand
under any conditions. This is remarkable because many side reactions
(e.g., Ccarbene-Cbzq, Cbzq-O, or Ccarbene-Cl bond-forming reductive
elimination) are possible in this system.
In conclusion, this Communication describes the synthesis of a new
PdIV complex that undergoes C-Cl bond-forming reductive elimination
and serves as an effective precatalyst for the selective halogenation of C-H
bonds. Complex 2 is, to the best of our knowledge, the first example of
a PdIV-NHC or PdIV-alkoxide adduct. The complex contains tunable
ligands that appear to be inert to the strongly oxidizing reaction conditions,
implying that related systems that can impart regio- or stereocontrol over
the C-H functionalization reaction should be accessible. Investigation into
the use of the pendant alcohol to facilitate substrate activation, the use of
other oxidants, and the design of asymmetric ligand structures is ongoing
and will be reported in due course.
Acknowledgment. We thank EaStCHEM, the UK EPSRC
(studentship for S.M.P.), and the US NSF (CHE-0754639) for funding.
We thank Dr. J. Kampf for help with crystallography.
Interestingly, changing the reaction concentration had a significant
impact on the products resulting from thermal decomposition of 2. When
the reaction was conducted at a higher concentration (1.1 × 10-2 M),
product 3 was formed as only 46% of total Pd-containing products, along
with equimolar quantities of 4 and a complex assigned as 3′ (eq 3). The
ratio of these two products was readily determined by integration of the
Supporting Information Available: Full experimental details and
X-ray crystallographic data (PDF, CIF). This material is available free
of charge via the Internet at http://pubs.acs.org.
References
(1) (a) Daugulis, O.; Zaitsev, V. G.; Shabashov, D.; Pham, Q. N.; Lazareva,
A. Synlett 2006, 3382. (b) Yu, J. Q.; Giri, R.; Chen, X. Org. Biomol. Chem.
2006, 4, 4041. (c) Dick, A. R.; Sanford, M. S. Tetrahedron 2006, 62, 2439.
(d) Yoneyama, T.; Crabtree, R. H. J. Mol. Catal. A. 1994, 108, 35.
(2) With PhICl2 and N-halosuccinimides: (a) Kalyani, D.; Dick, A. R.; Anani, W. Q.;
Sanford, M. S. Tetrahedron 2006, 62, 11483. (b) Kodama, H.; Katsuhira, T.;
Nishida, T.; Hino, T.; Tsubata, K. US Patent 2003181759, 2003 [Chem. Abstr.
2001, 135 344284]; With XOAc: Li, J. J.; Giri, R.; Yu, J. Q. Tetrahedron 2008,
64, 6979.
(3) For some recent examples, see: (a) Deprez, N. R.; Sanford, M. S. J. Am.
Chem. Soc. 2009, 131, 11234. (b) Powers, D. C.; Ritter, T. Nat. Chem.
2009, 1, 302. (c) Lyons, T. W.; Sanford, M. S. Tetrahedron 2009, 65, 3211.
(d) Muniz, K.; Hovelmann, C. H.; Streuff, J. J. Am. Chem. Soc. 2008, 130,
763. (e) Kalyani, D.; Sanford, M. S. J. Am. Chem. Soc. 2008, 130, 2150.
(f) Li, Y.; Song, D.; Dong, V. M. J. Am. Chem. Soc. 2008, 130, 2962. (g)
Liu, G.; Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 7179.
1
diagnostic H NMR resonances for the proton vicinal to N3 (9.03 and
9.42 ppm, respectively), and 4 was further characterized by single-crystal
X-ray analysis; the structure is shown in Figure 1b. Complex 4 can also
be converted back to 1 by the addition of base, for example KHMDS
(see SI). The formation of 3′ and 4 suggests that intermolecular
decomposition pathways (presumably involving electrophilic aromatic
substitution on the bzq ligand and protonolysis of the alkoxide) can be
competitive for PdIV complex 2 under some conditions. This is particularly
interesting because intramolecular C-X bond-forming reductive elimina-
tion from PdIV has typically been assumed to be fast in such systems.4,5
(4) Canty, A. J. In Handbook of Organopalladium Chemistry for Organic
Synthesis; Negishi, E.-i., Ed.; John Wiley & Sons, Inc.: Hoboken, NJ, 2002;
Vol. 1, p 189, and references therein.
(5) (a) Racowski, J. M.; Dick, A. R.; Sanford, M. S. J. Am. Chem. Soc. 2009,
131, 10974. (b) Ball, N. D.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131,
3796. (c) Furuya, T.; Ritter, T. J. Am. Chem. Soc. 2008, 130, 10060. (d)
Whitfield, S. R.; Sanford, M. S. J. Am. Chem. Soc. 2007, 129, 15142.
(6) (a) Asymmetric Pd-catalyzed C-H functionalization: Shi, B. F.; Maugel,
N.; Zhang, Y. H.; Yu, J. Q Angew. Chem., Int. Ed. 2008, 47, 4882. (b) An
asymmetric PdII/IV-catalyzed process: Tsujihara, T.; Takenaka, K.; Onitsuka,
K.; Hatanaka, M.; Sasai, H. J. Am. Chem. Soc. 2009, 131, 3452.
(7) (a) Arnold, P. L.; Casely, I. J. Chem. ReV. 2009, 109, 3599. (b) Arnold, P. L.;
Mungur, S. A.; Blake, A. J.; Wilson, C. Angew. Chem., Int. Ed. 2003, 42, 5981.
(8) (a) Meyer, D.; Taige, M. A.; Zeller, A.; Hohlfeld, K.; Ahrens, S.; Strassner,
T. Organometallics 2009, 28, 2142, and references therein. (b) Viciu, M. S.;
Stevens, E. D.; Petersen, J. L.; Nolan, S. P. Organometallics 2004, 23, 3752.
(9) (a) Pugliese, T.; Godbert, N.; Aiello, I.; Ghedini, M.; La Deda, M. Inorg. Chem.
Commun. 2006, 9, 93. (b) Arnold, P. L.; Rodden, M.; Wilson, C. Chem.
Commun. 2005, 1743.
The data presented herein suggests that L could be a viable
supporting ligand for catalytic halogenation reactions involving PdIV
intermediates. Due to the low thermal stability of PhICl2,2 we examined
the activity of 1 in directed C-H bromination used N-bromosuccin-
imide as the electrophilic halogenating reagent. We were pleased to
find that 1 is an effective precatalyst for the bromination of benzo-
[h]quinoline, providing 10-bromobenzo[h]quinoline in 74% yield after
48 h at 100 °C in MeCN (eq 4). Other arylpyridine derivatives also
undergo ortho-bromination in good yield with this catalyst, and two
(10) Canty, A. J.; Patel, J.; Pfeffer, M.; Skelton, B. W.; White, A. H. Inorg.
Chim. Acta 2002, 327, 20.
(11) For example, see: Desai, L. V.; Stowers, K. J.; Sanford, M. S. J. Am. Chem.
Soc. 2008, 130, 13285, and references therein.
JA905713T
9
J. AM. CHEM. SOC. VOL. 131, NO. 39, 2009 13913