.
Angewandte
Communications
given in the Supporting Information and only the essential
results are discussed and compared here. In our previous
study on the hydrogenation of nitriles to amines by using
catalyst 4, we identified an outer-sphere mechanism by
a simultaneous transfer of the hydride from the iron center
and the proton from the nitrogen to the nitrile to give the
corresponding imine, based on experimental and computa-
[
14b]
tional analyses.
The most important feature in this reaction
is the reversible process between the hydrogenation and
dehydrogenation of catalyst 9 and its amido intermediate 11.
The barrier for the addition of hydrogen to 11 to give 9 is
À1
1
0
7.14 kcalmol and the reaction is slightly exergonic by
À1
.33 kcalmol . For the formation of the hemiacetal, the
computed free energy barrier of methyl benzoate and methyl
À1
acetate is 21.51 and 22.98 kcalmol , respectively. However,
this reaction step is endergonic by 11.93 and 10.61 kcalmol ,
respectively. For the dissociation of the hemiacetal to the
À1
Scheme 3. Proposed mechanism for the Fe-catalyzed ester hydrogena-
tion: Methyl benzoate (5a) serves as a representative example.
corresponding aldehyde and methanol, the reaction is exer-
À1
gonic by 8.21 and 4.05 kcalmol
for methoxy(phenyl)-
methanol and 1-methoxyethanol, respectively. The hydro-
genation of benzaldehyde to benzyl alcohol has a free energy
11. Next, the dissociation of hemiacetal 10 to benzaldehyde
(12) and methanol takes place, while 9 is regenerated from 11
À1
À1
barrier of 6.60 kcalmol and is exergonic by 3.30 kcalmol .
In contrast, the activation of acetaldehyde to ethanol is
by addition of H . In the final step, benzaldehyde (12) is
2
[
20]
hydrogenated to give benzyl alcohol 6.
À1
barrierless and exergonic by 6.49 kcalmol . Such small
In summary, the first base-free iron-based catalyst system
for the hydrogenation of various carboxylic acid esters and
lactones was developed and showed high efficiency. The
practical importance of the new catalyst system is demon-
strated in the challenging reduction of the pharmaceutical
intermediate 7. Based on computations, an outer-sphere
mechanism is proposed involving simultaneous hydrogen
transfer from the iron center and the ligand.
differences in free energy connecting aldehyde and alcohol
reveal the reversibility between hydrogenation and dehydro-
genation when the reaction conditions are changedby chang-
ing the reaction conditions. Noteworthy, the first step of the
hemiacetal formation is the rate-determining step on the
whole potential surface. In order to support the assumption of
an outer-sphere mechanism, which is based on the critical role
of the N-H group of the PNHPiPr ligand, iron(II) complexes
analogous to 4 and 9 (Me-4 and Me-9) were prepared. Me-4
and Me-9, containing the ligand PNMePiPr (PNMePiPr= Experimental Section
bis[(2-diisopropylphosphino)ethyl]methyl amine), where the
hydrogen of the central nitrogen of the pincer ligand is
replaced by a methyl group, should not be active.
As expected, no conversion of methyl benzoate under the
standard conditions described in Table 2 was achieved with
either of the two iron complexes (Scheme 2).This demon-
strates clearly that a cooperative interaction involving the N-
Unless otherwise stated, all catalytic hydrogenation experiments
using molecular hydrogen were carried out in a Parr Instruments
autoclave (300 mL).
Representative experiment: Under an argon atmosphere, a vial
was charged with 4 (0.005 or 0.025 mmol), which was dissolved in
[19]
1
mL of anhydrous THF. The yellow solution was stirred slowly for 3–
5 min before the ester (0.5 mmol) was added. The vial was placed in
the alloy plate, which was then placed into the autoclave. Once sealed,
the autoclave was purged three times with hydrogen, then pressurized
to 30 bar, and heated at 1008C or 1208C for 6, 19, or 20 h. Afterwards,
the autoclave was cooled to room temperature and depressurized,
and the reaction mixture was analyzed by GC or as an isolated
product (column chromatography: n-pentane/ethyl acetate 2:1) by
NMR spectroscopy, GCMS, and HRMS.
Received: February 18, 2014
Published online: && &&, &&&&
Scheme 2. Hydrogenation of methyl benzoate with complexes Me-4
and Me-9.
Keywords: alcohols · esters · homogeneous catalysis ·
.
H unit of the pincer ligand and the Fe-H group is required for
catalytic hydrogenation.
Based on these results we propose the following mecha-
nism for the hydrogenation of methyl benzoate (5a)
hydrogenation · iron
[
1] a) P. N. Rylander, Catalytic Hydrogenation in Organic Syntheses,
Academic Press, New York, 1979; b) Handbook of Heteroge-
neous Hydrogenation for Ogranic Synthesis (Ed.: S. Nishimura),
Wiley, New York, 2001; c) Handbook of Homogeneous Hydro-
genation (Eds.: J. G. de Vries, C. J. Elsevier), Wiley-VCH,
(
Scheme 3). The ester is hydrogenated in a concerted way
by the simultaneous transfer of the hydride from the iron
center and the proton from the nitrogen ligand in complex 9
to give the corresponding hemiacetal 10 and amido complex
4
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Angew. Chem. Int. Ed. 2014, 53, 1 – 6
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