10.1002/cctc.201901871
ChemCatChem
COMMUNICATION
the metal centre to the carbonyl C atom of D (XIII) and then one
of the H2 molecules generated earlier in the reaction takes part
aim to destabilize them in order to minimize the overall activation
barrier/energy span that is ultimately determining the apparent
in the first re-hydrogenation step (XIV) leading the reaction to XV. turnover frequency. Like in a clockwork, it is the wheel that is
After dissociation of the unsaturated alcohol E from XV the
active species is regenerated (I’’’) while E isomerizes base
catalyzed to ketone F,[9] which associates to I’’’ and forms XVI. It
should be noted that in principle the olefinic C-C-double bond of
E could also be hydrogenated. However, experimentally E was
not observed in the reaction mixture, while F was detected in
significant amounts. It is therefore plausible to assume a fast
isomerization of E and the subsequent hydrogenation of the
C=O bond of F is favored. In subcycle E the keto group of F is
hydrogenated following the same principle steps as in subcycle
D.
hardest to turn that defines the rate of the overall movement.
Computational and Experimental Details
The DFT calculations and all experiments are described in detail in the SI.
Cartesian coordinates of the compounds computed are provided by the
authors upon request.
Acknowledgements
With regard to the overall Gibbs free activation energy it is
worthwhile noting that all single barriers are either low or of
moderate height throughout the whole catalytic cycle and
therefore can easily be overcome. However, it was observed
experimentally that reasonable reaction rates can be achieved
only at temperatures of around 150°C. The requirement of high
reaction temperatures results from the fact that the TDTS
(C-C bond forming step in subcycle C; TSXXIV, see SI) lies at
26.9 kcal/mol on the hyper surface while the TDI (XIX, subcycle
E) has a pronounced stability at -15.4 kcal/mol. Accordingly, the
overall Gibbs free activation energy (i.e. the energy span) is
calculated as the sum of the absolute values of TDI and TDTS
(15.4 + 26.9 kcal/mol) subtracted by the Gibbs free reaction
energy Gr (-13.1 kcal/mol) amounting to a value of G# = 29.2
kcal/mol. This value compares reasonably well with the
experimentally determined value of G# = 26.1 +/- 0.5 kcal/mol
estimated from conversion/time-experiments and in this way
supports the derived mechanism.[10]
A.K. is grateful for a stipend from the Erasmus-Mundus-Action-
1-program (SINCHEM; FPA2013-0037).
Key words: Methanol • Homogeneous Catalysis • Mechanism •
DFT • Hydrogen borrowing
[1]
[2]
A. Kaithal, M. Schmitz, M. Hölscher, W. Leitner,
ChemCatChem 2019, DOI: 10.1002/cctc.201900788.
a) P. T. Anastas, I. J. Levy, K. E. Parent, Green Chemistry
Education, Changing the Course of Chemistry 2009, 1011; b)
P. T. Anastas, R. H. Crabtree, Handbook of Green Chemistry,
Volume 1., Green Catalysis, Homogeneous Catalysis 2013;
c) S. Wesselbaum, T. vom Stein, J. Klankermayer, W. Leitner,
Angew. Chem. Int. Ed. 2012, 51, 7499-7502; d) K. Natte, H.
Neumann, M. Beller, R. V. Jagadeesh, Angew. Chem. Int. Ed.
2017, 56, 6384-6394; e) K. Oikawa, S. Itoh, H. Yano, H.
Kawasaki, Y. Obora, Chem Commun (Camb) 2017, 53, 1080-
1083; f) S. M. A. H. Siddiki, A. S. Touchy, M. A. R. Jamil, T.
Toyao, K.-i. Shimizu, ACS Catal. 2018, 8, 3091-3103; g) Q.
Liu, G. Xu, Z. Wang, X. Liu, X. Wang, L. Dong, X. Mu, H. Liu,
ChemSusChem 2017, 10, 4748-4755; h) Y. Li, H. Li, H. Junge,
M. Beller, Chem. Commun. 2014, 50, 14991-14994.
Conclusions
[3]
[4]
A. Kaithal, P. v. Bonn, M. Hölscher, W. Leitner, Angew. Chem.
Int. Ed. 2019, DOI: 10.1002/anie.201909035.
In summary, the various reaction pathways of a complete
reaction network of a Guerbet-type C-C methylation using
methanol as C1 source has been analyzed computationally
using density functional theory. Based on experimental evidence
for organometallic and organic intermediates involved in the
individual cycles, the frequently postulated combination of
de-hydrogenation, aldol coupling, and re-hydrogenation was
evaluated for the specific case of the Ru-MACHO-BH catalyst. It
was found that the metal catalyzed de- and re-hydrogenation
cycles are characterized by moderate barriers in the range of
around ca. 10-15 kcal/mol. Also the base catalyzed C-C bond
formation has only a moderate barrier of 13.6 kcal/mol, but
involves the highest transition state on the energy surface at
26.9 kcal/mol relative to the reference point. Together with the
high stability of the dihydride complexes in presence of the
alcohol/ketone substrates (particularly XVI, XVII and XI), this
results in a significant energy span of 29.2 kcal/mol that
correlates well with the observed high reaction temperatures.
The insight obtained from this study may provide valuable
information for the design of effective catalysts for this general
reaction type. It is generally assumed that the activity and hence
the transition states of the metal catalyst dehydrogenation are
limiting factors for the rate of product formation. However, the
present analysis indicates that the intermediate adducts with
substrates in the re-hydrogenation should be targeted with the
a) M. Nielsen, E. Alberico, W. Baumann, H.-J. Drexler, H.
Junge, S. Gladiali, M. Beller, Nature 2013, 495, 85; b) E.
Alberico, A. J. J. Lennox, L. K. Vogt, H. Jiao, W. Baumann, H.-
J. Drexler, M. Nielsen, A. Spannenberg, M. P. Checinski, H.
Junge, M. Beller, J. Am. Chem. Soc. 2016, 138, 14890-14904;
c) C. Gunanathan, D. Milstein, Chem. Rev. 2014, 114, 12024-
12087; d) X. Yang, ACS Catal. 2013, 3, 2684-2688.
[5]
[6]
a) A. T. Nielsen, W. J. Houlihan, in Organic Reactions, 2011,
pp. 1-438; b) A. Balog, C. Harris, K. Savin, X.-G. Zhang, T.-C.
Chou, S. J. Danishefsky, Angew. Chem. Int. Ed. 1998, 37,
2675-2678.
a) J. Neumann, C. Bornschein, H. Jiao, K. Junge, M. Beller,
Eur. J. Org. Chem. 2015, 2015, 5944-5948; b) D. H. Nguyen,
G. Raffa, Y. Morin, S. Desset, F. Capet, V. Nardello-Rataj, F.
Dumeignil, R. M. Gauvin, Green Chemistry 2017, 19, 5665-
5673.
[7]
[8]
[9]
B. Chatterjee, C. Gunanathan, Org. Lett. 2015, 17, 4794-4797.
S. Kozuch, S. Shaik, Acc. Chem. Res. 2011, 44, 101-110.
B. Suchand, G. Satyanarayana, Eur. J. Org. Chem. 2017,
2017, 3886-3895.
[10]
A more detailed comparison between the experimental and
the computed Gibbs free activation barrier can be obtained by
conducting a thorough experimental kinetic analysis together
with a detailed microkinetic modeling study.[11] However, the
challenges associated with the kinetic analysis in such a
complex experimental system are significant, prompting us to
refrain from performing such a study.
[11]
Recent leading references on microkinetic modeling and the
challenges
associated
with
combined
computational/experimental analysis in mechanistic studies
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