Reversible carbon-carbon bond formation between carbonyl compounds and a ruthenium pincer complex

Article abstract of DOI:10.1039/c3cc43517b

This communication describes the reversible reaction of a ruthenium pincer complex with a variety of carbonyl compounds. Both NMR spectroscopic and X-ray crystallographic characterization of isomeric carbonyl adducts are reported, and the equilibrium constants for carbonyl binding have been determined.

Full text of DOI:10.1039/c3cc43517b

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COMMUNICATION
Reversible carbon–carbon bond formation between
carbonyl compounds and a ruthenium pincer
complex†
Cite this: Chem. Commun., 2013,
49, 7147
Received 10th May 2013,
Accepted 21st June 2013
Chelsea A. Huff, Jeff W. Kampf and Melanie S. Sanford*
DOI: 10.1039/c3cc43517b
www.rsc.org/chemcomm
This communication describes the reversible reaction of a ruthenium
pincer complex with a variety of carbonyl compounds. Both NMR
spectroscopic and X-ray crystallographic characterization of isomeric
carbonyl adducts are reported, and the equilibrium constants for
carbonyl binding have been determined.
Ruthenium pincer complexes such as (PNN)Ru(H)(CO) (1; PNN =
6-(di-tert-butylphosphinomethylene)-2-(N,N-diethylaminomethyl)-
1,6-dihydropyridine) are promising catalysts for the hydrogena-
tion of traditionally unreactive carbonyl substrates such as esters,
amides, carbonates, and carbamides.1 Seminal studies by Milstein
and coworkers have shown that the unsaturated arm of the pincer
ligand plays a critical role in these transformations. Specifically,
the ligand accepts a proton during the heterolytic cleavage of H2
and subsequently delivers this proton to the reduced substrate.1e,2
Our group became interested in 1 as a catalyst for the hydrogena-
tion of methyl formate during the cascade conversion of CO2 to
CH3OH.3 In the course of our investigations of this system, we
discovered that the unsaturated pincer ligand arm of 1 can also
add to the electrophilic carbon of CO2.4 As shown in Scheme 1, this
addition initially yields kinetic product 2a, which rapidly converts
to thermodynamic product 2b. Milstein reported an analogous
reversible reaction between CO2 and the symmetric pincer com-
plex (PNP)Ru(H)CO (PNP = 2,6-bis-(di-tert-butylphosphinomethyl)-
pyridine-1,6-dihydropyridine).5,6
Scheme 1 CO2 activation at pincer complex 1.
formate, suggesting that a reaction occurs between these two
species. We also noted a recent report by Milstein demonstrating
that (PNP)Ru(H)CO reacts with aldehydes at À50 1C.7,8 The products
were characterized by low temperature NMR spectroscopy and were
reported to be unstable at room temperature. We report herein that
the PNN complex 1 reacts reversibly with formate esters as well
as aldehydes and ketones to generate room temperature stable
addition products. Detailed investigations of these transformations
(using both NMR spectroscopy and X-ray crystallography) show that
up to three isomeric products are formed and ultimately equilibrate
to a single major stereoisomer.
Initial studies focused on the reaction of 1 with 2.5 equivalents
of methyl formate in C6D6 at 25 1C (Scheme 2a). NMR spectroscopic
analysis of the crude reaction mixture shows signals consistent
with a product in which the pincer ligand has added to methyl
We hypothesized that 1 might react in a similar fashion with
other carbonyl compounds like esters, amides, ketones, and/or
aldehydes. Such reactions would be of significant interest because
these molecules are also substrates for hydrogenation reactions
catalyzed by 1.1 Our hypothesis about this reactivity was predicated
on a key observation made during our studies of the hydrogenation
of methyl formate with catalyst 1.3 We observed a distinctive color
change from brown to yellow upon combining 1 and methyl
Department of Chemistry, University of Michigan, 930 North University Avenue,
Ann Arbor, Michigan 48109, USA. E-mail: mssanfor@umich.edu; Tel: +1 734 615 0451
† Electronic supplementary information (ESI) available: Text, tables, figures, and
spectral details for the synthesis and characterization of new compounds; crystallo-
graphic data for 3, 5, 6B-i and 6B-ii. CCDC 936845–936848. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/c3cc43517b
Scheme 2 Reversible reaction of 1 with methyl formate.
Chem. Commun., 2013, 49, 7147--7149 7147
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Fig. 1 ORTEP diagram (50% probability level) of the molecular drawing of 3. All
H atoms (other than Ru–H and H–COOMe) have been omitted for clarity. Selected
bond lengths (Å) and angles (deg): Ru1–O2 = 2.2022(9), C2–C3 = 1.5678(17),
O2–C2 = 1.3409(15), Ru1–H1 = 1.526(19); Ru1–O2–C2 = 112.65(7), O2–C2–C3 =
112.50(10).
Fig. 2 ORTEP diagram (50% probability level) of the molecular drawing of 5. All
H atoms (other than Ru–H) have been omitted for clarity. Selected bond lengths (Å)
and angles (deg): Ru1–O2 = 2.1991(9), C2–C7 = 1.5816(17), O2–C2 = 1.3867(14),
Ru1–H1 = 1.534(19); Ru1–O2–C2 = 113.59(7), O2–C2–C7 = 109.79(9).
formate to form a single detectable product, 3. Removal of the
volatiles from this mixture under high vacuum resulted in clean
regeneration of complex 1, indicating that the reaction is fully
reversible. Analytically pure samples were obtained in 94% yield by
slow evaporation of solvent from a solution of 3 in methyl formate.
1H and 13C NMR spectroscopic experiments clearly show that 3
contains a C–C bond between the carbonyl carbon of methyl formate
and the nitrogen arm of the pincer ligand (see ESI† for full details).
As highlighted in red, NOESY NMR analysis shows cross-peaks
consistent with the stereoisomer depicted in Scheme 2. X-ray quality
crystals were obtained by crystallization from a mixture of methyl
formate and pentane, and the solid state structure of 3 is shown in
Fig. 1. The X-ray structure shows the same stereoisomer as that
characterized in solution via NMR analysis.
A survey of carbonyl compounds revealed that other formate
esters (e.g., ethyl formate) as well as ketones and aldehydes (e.g.,
cyclopentanone and benzaldehyde) undergo analogous reactions
with 1 (Scheme 3). In most cases these transformations were
reversible, and removal of the volatiles followed by redissolution in
C6D6 resulted in clean regeneration of 1.9 Products 4–6 were isolated
in 65–88% yield via an analogous procedure to that described
for 3 (see ESI† for full details). Complex 5 was also characterized
by X-ray crystallography (Fig. 2).
Scheme 4 Four possible isomeric products from the reaction of 1 with unsym-
metrical carbonyl compounds.
standard conditions (30 min, rt). In contrast, the reaction of 1
with benzaldehyde at rt yielded 6 as an B85 : 15 mixture of two
isomeric products. As a result, a more detailed investigation of
the latter transformation was conducted.
When the reaction of Ru complex 1 with benzaldehyde was
conducted at À50 1C for 5 min in toluene-d8, the P-side adduct,
6A-i, was formed as a single diastereomer (Scheme 5).10 Warming
this mixture to room temperature and allowing it to equilibrate
for 5 min resulted in complete disappearance of 6A-i along with
the formation of a 90 : 10 mixture of the two N-side diastereomers
6B-i :6B-ii. Finally, allowing this solution to stand for 24 h at rt
resulted in a 15 : 85 ratio of 6B-i :6B-ii. This ratio did not change
further after longer times at room temperature, suggesting that it
represents the equilibrium isomer mixture. All of the isomeric
products were completely characterized via NMR spectroscopic
experiments, and the full details are described in the ESI.†
The reaction of 1 with unsymmetrical carbonyl compounds
could, in principle, lead to four products (Scheme 4). These
include two pairs of regioisomers [A (P-side)/B (N-side)], with
each pair being a set of diastereomers (A-i/A-ii and B-i/B-ii).
Despite this potential complexity, products 3–5 were formed as
>95% of the isomer reported in Schemes 2 and 3 under the
Scheme 5 Reactivity of 1 with benzaldehyde.
Scheme 3 Reaction of 1 with different carbonyl compounds.
7148 Chem. Commun., 2013, 49, 7147--7149
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at room temperature. The observed C–C bond and Ru–O bond
forming reactions are reversible. Numerous isomeric products
can be formed, but they eventually equilibrate to a single major
isomer in all cases examined. This study reveals that there is
a rich complexation chemistry of 1 that competes with H2
addition and may impact hydrogenation catalysis. Further
investigations to probe the role of these reactions in catalysis
are underway.
This work was supported by the US National Science
Foundation under the CCI Center for Enabling New Technologies
Through Catalysis (CENTC) Phase II Renewal, CHE-1205189. CAH
was supported by a NSF Research Fellowship and by a Rackham
Merit Fellowship. We also acknowledge funding from NSF Grant
CHE-0840456 for X-ray instrumentation. Finally, we thank Alex
Miller (UNC) and Karen Goldberg (UW) for helpful discussions.
Notes and references
1 (a) J. Zhang, G. Leitus, Y. Ben-David and D. Milstein, Angew. Chem.,
Int. Ed., 2006, 45, 1113; (b) E. Balaraman, B. Gnanaprakasam,
L. J. W. Shimon and D. Milstein, J. Am. Chem. Soc., 2010,
132, 16756; (c) E. Fogler, E. Balaraman, Y. Ben-David, G. Leitus,
L. J. W. Shimon and D. Milstein, Organometallics, 2011, 30, 3826;
(d) E. Balaraman, Y. Ben-David and D. Milstein, Angew. Chem., Int.
Ed., 2011, 50, 11702; (e) Y. Sun, C. Koehler, R. Tan, V. T. Annibale
and D. Song, Chem. Commun., 2011, 47, 8349; ( f ) E. Balaraman,
C. Gunanathan, J. Zhang, L. J. W. Shimon and D. Milstein, Nat.
Chem., 2011, 3, 609; (g) E. Balaraman, E. Fogler and D. Milstein,
Chem. Commun., 2012, 48, 1111; (h) D. Spasyuk, S. Smith and
D. G. Gusev, Angew. Chem., Int. Ed., 2013, 52, 2538; (i) Z. Han,
L. Rong, J. Wu, L. Zhang, Z. Wang and K. Ding, Angew. Chem., Int.
Ed., 2012, 51, 13041.
Scheme 6 Keq for reaction of 1 with carbonyl compounds.
Additionally, both 6B-i and 6B-ii were characterized by X-ray
crystallography.11 Overall this system exemplifies the potential
complexity of the reactions of 1 with unsymmetrical carbonyl
compounds.12
2 (a) H. Li, X. Wang, F. Huang, G. Lu, J. Jiang and Z.-X. Wang,
Organometallics, 2011, 30, 5233; (b) G. Zeng and S. Li, Inorg. Chem.,
2011, 50, 10572; (c) X. Yang, ACS Catal., 2012, 2, 964.
The equilibrium constants (Keq) for the reactions of 1 with all of
the carbonyl substrates were determined via H NMR integration
3 C. A. Huff and M. S. Sanford, J. Am. Chem. Soc., 2011, 133, 18122.
4 C. A. Huff, J. W. Kampf and M. S. Sanford, Organometallics, 2012,
31, 4643.
1
(Scheme 6). Keq appears to be particularly sensitive to the steric
properties of the carbonyl substrate. For example, Keq drops from
2.7 Â 102 to 1.5 Â 102 upon moving from methyl to ethyl formate,
likely reflecting the increased size of the ethyl substituent. Electronic
effects also play an important role in this equilibrium. For example,
aldehydes are similar in size to formate esters but have a signifi-
cantly more electrophilic carbonyl carbon. This results in a large
value of Keq for the reaction of 1 with benzaldehyde (Keq > 103 at rt).
Ketones are also more electrophilic than formate esters, but the
carbonyl carbon is more sterically encumbered. With these
substrates, steric factors appear to dominate the binding
equilibrium. For example, Keq for cyclopentanone is 5.0 Â
101, while acetone (which does not have the alkyl groups tied
back in a ring) barely reacts (Keq estimated to be o10À2 at rt).
Similarly, no product was detected in the presence of up to
20 equivalents of methyl acetate or N,N-dimethylformamide,
5 M. Vogt, M. Gargir, M. A. Iron, Y. Diskin-Posner, Y. Ben-David and
D. Milstein, Chem.–Eur. J., 2012, 18, 9194.
6 For other examples of metal–ligand cooperative activation of CO2
involving the ligand framework: (a) A. M. Chapman, M. F. Haddow
and D. F. Wass, J. Am. Chem. Soc., 2011, 133, 18463; (b) M. J. Sgro
and D. W. Stephan, Angew. Chem., Int. Ed., 2012, 51, 11343;
(c) M. J. Sgro and D. W. Stephan, Chem. Commun., 2013, 49, 2610;
(d) F. A. LeBlanc, A. Berkefeld, W. E. Piers and M. Parvez, Organo-
metallics, 2012, 31, 810; (e) X. Xu, G. Kehr, C. G. Daniliuc and
G. Erker, J. Am. Chem. Soc., 2013, 135, 6465; ( f ) D. A. Dickie,
R. P. Ulibarri-Sanchez III, P. J. Jarman and R. A. Kemp, Polyhedron,
2013, 58, 92; (g) V. T. Annibale and D. Song, Chem. Commun., 2012,
48, 5416; (h) M. Vogt, O. Rivada-Wheelaghan, M. A. Iron, G. Leitus,
Y. Diskin-Posner, L. J. W. Shimon, Y. Ben-David and D. Milstein,
Organometallics, 2013, 32, 300.
7 M. Montag, J. Zhang and D. Milstein, J. Am. Chem. Soc., 2012, 134, 10325.
8 For other examples of aldehyde activation involving the ligand
framework: see 6b and S. Ogoshi, K.-I. Tonomori, M.-A. Oka and
H. Kurosawa, J. Am. Chem. Soc., 2006, 128, 7077.
9 The reaction with benzaldehyde was the only reaction that was not
reversible by this method.
indicating that Keq for these substrates is o10À3
.
10 The other P-side isomer (6A-ii) was not detected. We hypothesize
that this is due to the sterically large nature of the tert-butyl groups
attached to the phosphine. Notably, Milstein reported a single
isomeric product in the low temperature reaction of (PNP)Ru(H)CO
with benzaldehyde.
11 The crystal structure of 6B-ii was also obtained and details can be
found in ESI†.
Overall, the work described in this communication shows
that the reactivity of 1 with carbonyl compounds is more
complex than was previously appreciated. While prior work
focused primarily on 1 as a catalyst for the hydrogenation of
CQO derivatives, this report describes the first example of the
addition of a Ru-bound pincer ligand to a carbonyl compound
12 The P side regioisomer of 5 was also fully characterized by NMR
spectroscopy at À40 1C (5A). See ESI† for more details.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 7147--7149 7149