Secondary Substrate–Ligand Transition-State Stabilization
FULL PAPER
has enabled us to draw impor-
tant conclusions concerning
structure–activity relationships.
A mechanistic study of one par-
ticular case—regioselective hy-
droformylation of 2—revealed
that the experimentally ob-
served enhancement in activity
and selectivity brought about
by the ligand is a result of the
selective supramolecular transi-
tion-state stabilization within
our system. Furthermore, the
transition-state geometry and
the nature of the supramolec-
ular catalyst–substrate interac-
tion were identified by using
Figure 7. DFT calculations on the reaction mechanism of directed hydroformylation of 2. a) Catalyst–substrate
complex; b) transition state of hydrometalation; c) catalyst–product complex; d, e) alternative transition states.
E+ZPE=electronic energy+zero point energy (relative to structure a).
tion in the transition state. This movement is assisted by a
supramolecular interaction, which becomes optimal at the
transition state with hydrogen bonds pointing directly
DFT calculations. These calculations have led to a refine-
ment of our originally proposed supramolecular interaction
geometry and enabled a better understanding of the factors
involved in transition-state stabilization.
We hope that a detailed understanding of the reaction
mechanism will encourage future designs of supramolecular
and biomimetic catalysts for a broad variety of synthetically
relevant transformations.
ꢀ
toward the lone pairs of the carboxylate (d(N3 H···O5)=
ꢀ
ꢀ
2.012 ꢃ, d(N4 H···O5)=1.857 ꢃ, d(N5 H···O4)=1.569 ꢃ,
ꢀ
d(N6 H···O4)=1.583 ꢃ). This binding motif closely resem-
bles the so-called “oxanion hole” structures that are known
in enzymes and clearly stabilizes the formation of the car-
boxylate anion.[19] Additionally, this coordination mode min-
imizes repulsion between the lone pair of the pyridine nitro-
gen and the anionic carboxylate oxygen. For the hydrometa-
lation product (alkyl rhodium intermediate), the calculation
predicts a complex network of hydrogen bonding both be-
tween the ligand and the substrate and also between ligands
(Figure 7c). Additionally, a rhodium–carboxylate interaction
Experimental Section
General procedure for hydroformylation experiments: Experiments were
performed either in
a Premex stainless steel autoclave Medimex
(100 mL) equipped with a glass liner containing a magnetic stirring bar
(1000 rpm) or in an Argonaut Endeavour reactor system consisting of
eight parallel mechanically stirred (500 rpm) pressure reactors with indi-
vidual temperature and pressure controls. The hydroformylation solution
(dACHTUNGTRENNUNG(Rh···O)=2.463 ꢃ) was also identified. All attempts to
find an alternative catalyst–substrate interaction mode (e.g.,
one ligand bonding as shown in Figure 7d; or hydrogen
was prepared by charging a Schlenk flask with [RhACTHNUTRGEN(UNG acac)(CO)2], ligand,
1,3,5-trimethoxybenzene (internal standard 1H NMR) and solvent, under
argon. Then, the substrate was added and the mixture was stirred for
5 min under argon. The solution was transferred to the autoclave with a
syringe under an argon atmosphere. The autoclave was purged three
times with synthesis gas CO/H2 (1:1) and the reaction was conducted as
specified in the text. Runs were stopped by cooling the system (if appro-
priate), venting, and purging with argon. Reaction kinetics were moni-
bonding only as shown in Fig
higher activation energies.
ACHTUNGERTNuNUNG re 7e) resulted in much
Although the hydrometalation step is supposed to be
rate- and selectivity-determining, the catalytic cycle cannot
be reduced to this step only. The system based on the mono-
dentate receptor ligands is quite flexible and the binding ge-
ometry may vary during the catalytic cycle to accommodate
further reaction intermediates. The guanidine ligand might
also participate in CO dissociation (see Figure 7e), alkene
coordination or the hydrogenolysis of the acyl–rhodium in-
termediate.
1
tored either from the gas consumption curve or by H NMR spectroscop-
ic analysis of reaction samples.
Acknowledgements
This work was supported by the Fonds der Chemischen Industrie, the
Deutsche Forschungsgemeinschaft (GRK 1038), and an Alfried Krupp
Award for young university teachers of the Krupp foundation (to B.B.).
Conclusion
A library of phosphane ligands bearing guanidine receptor
units for carboxylates was prepared and tested in the hydro-
formylation of unsaturated carboxylic acids. This study has
led to the identification of some new ligand structures that
could even surmount the activity and selectivity of the origi-
nally published supramolecular catalyst [Rh]/1. Notably, a
direct comparison of the performance of various catalysts
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