Highly Efficient and Selective Hydrogenation of Aldehydes: A Well-Defined Fe(II) Catalyst Exhibits Noble-Metal Activity

Article abstract of DOI:10.1021/acscatal.6b00436

The synthesis and application of [Fe(PNP^Me-iPr)(CO)(H)(Br)] and [Fe(PNP^Me-iPr)(H)₂(CO)] as catalysts for the homogeneous hydrogenation of aldehydes is described. These systems were found to be among the most efficient catalysts for this process reported to date and constitute rare examples of a catalytic process which allows selective reduction of aldehydes in the presence of ketones and other reducible functionalities. In some cases, TONs and TOFs of up to 80000 and 20000 h^-1, respectively, were reached. On the basis of stoichiometric experiments and computational studies, a mechanism which proceeds via a trans-dihydride intermediate is proposed. The structure of the hydride complexes was also confirmed by X-ray crystallography.

Full text of DOI:10.1021/acscatal.6b00436

Subscriber access provided by GAZI UNIV
Article
Highly Efficient and Selective Hydrogenation of Aldehydes:
A Well-Defined Fe(II) Catalyst Exhibits Noble Metal Activity
Nikolaus Gorgas, Berthold Stoeger, Luis F. Veiros, and Karl Anton Kirchner
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b00436 • Publication Date (Web): 11 Mar 2016
Downloaded from http://pubs.acs.org on March 13, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
ACS Catalysis is published by the American Chemical Society. 1155 Sixteenth Street
N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 21
ACS Catalysis
1
1
2
3
4
5
6
7
1
2
Highly Efficient and Selective Hydrogenation of Aldehydes: A Wellꢀ
Defined Fe(II) Catalyst Exhibits Noble Metal Activity
3
4
5
6
7
8
9
8
9
Nikolaus Gorgas,† Berthold Stöger,‡ Luis F. Veiros,§ and Karl Kirchner*, †
10
11
12
13
14
15
16
17
†Institute of Applied Synthetic Chemistry and ‡Institute of Chemical Technologies and Analytics,
Vienna University of Technology, Getreidemarkt 9, Aꢀ1060 Vienna, AUSTRIA, and §Centro de Química
Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais No. 1, 1049ꢀ001
Lisboa, PORTUGAL
10
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
11
Abstract
12
13
14
15
16
17
18
19
The synthesis and application of [Fe(PNPMeꢀiPr)(CO)(H)(Br)] and [Fe(PNPMeꢀiPr)(H)2(CO)] as catalysts
for the homogeneous hydrogenation of aldehydes is described. These systems were found to be
among of the most efficient catalysts for this process reported to date and constitutes a rare example
of a catalytic process which allows selective reduction of aldehydes in presence of ketones and other
reducible functionalities. In some cases, TONs and TOFs of up to 80000 and 20000hꢀ1, respectively,
were reached. Based on stoichiometric experiment and computational studies, a mechanism which
proceeds via a transꢀdihydride intermediate is proposed. The structure of the hydride complexes was
also confirmed by Xꢀray crystallography.
20
21
KEYWORDS: Aldehyde hydrogenation, iron pincer complexes, homogeneous catalysis, mechanistic
studies, DFT calculations.
22
Introduction
23
24
25
26
27
28
29
30
31
32
33
34
35
Efficiency and selectivity constitute the decisive factors in the development of sustainable chemical
processes, especially regarding industrial large scale applications. Within this context, the catalytic
reduction of carbonyl compounds using molecular hydrogen represents a green and economic method
in order to access valuable alcohols for the production of a large number of fine and bulk chemicals.1
Over the last decades, a wide variety of highly productive homogeneous catalysts based on noble
metals have been developed for this purpose. However, the selective hydrogenation of carbonyl
compounds over other reducible functional groups is still a challenging task. Although significant
progress has been made concerning the selective reduction of carbonyl groups in presence of C=C
double bonds,2 only few examples for catalyst are known which exhibit full selectivity for aldehydes
over ketones. In particular, such reactions are important for the production of flavors3, fragrances3 and
pharmaceuticals.4 Very recently, Dupau and coworkers reported a general and highly efficient method
for the chemoselective baseꢀfree rutheniumꢀcatalysed hydrogenation of aldehydes in the presence of
ketones. By using the ruthenium complex [Ru(en)(dppe)(OCOtBu)2] (Chart 1) a variety of different
ACS Paragon Plus Environment

ACS Catalysis
Page 2 of 21
2
1
2
3
4
5
6
7
1
2
3
4
ketoaldehydes could by hydrogenated reaching turnover numbers up to 40000.5 Surprisingly, apart
from some quite less effective examples,6 this system remains the only example of a noble metalꢀ
based homogeneous hydrogenation catalyst which allows selective reduction of aldehydes in the
presence of ketones.
8
9
5
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6
7
8
Chart 1. Wellꢀdefined catalysts for the chemoselective reduction of aldehydes 5,11,12,13
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
However, it is a major attractive goal to replace scarce, toxic, and expensive noble metals by
environmental friendly and abundant first row transition metals.7,8 Among them, iron appears as one of
the most attractive alternatives.9 In recent years, significant progress has been achieved in the
development of iron based hydrogenation catalysts.10 Interestingly, some of these systems proved to
be selective for the reduction of aldehydes in the presence of other carbonyl moieties.11,12,13, In 2013,
Beller and coꢀworkers reported on an Fe(II) tetraphos system (Chart 1) which represents the first
example of a homogeneous hydrogenation catalyst exhibiting full chemoselectivity for the reduction of
aldehydes.11 Various substrates including aromatic, aliphatic and α,βꢀunsaturated aldehydes could be
efficiently converted into the corresponding primary alcohols, while other carbonyl moieties such as
ketones and esters were not reduced. Turnover numbers up to 2000 could be achieved at 140°C and
a hydrogen pressure of 40 bar. Even higher TONs were obtained by the group of Milstein using an
Fe(II) hydrido carbonyl pincer complex (Chart 1).12 This complex was found to be highly active also for
the hydrogenation of ketones, while its performance in the reduction of aldehydes was only modest.10g
However, by employing NEt3 as additive in the reaction, the efficiency of this system could be
significantly increased and TONs of up to 4000 were obtained for several substrates under 30 bar H2
and a reaction temperature of 40°C. Interestingly, enhanced productivity was also observed in the
presence of a large excess of acetophenone, which, however, was found to be unaffected under these
conditions. Although briefly mentioned, no further investigations on the chemoselectivity of this
catalyst have been provided. More recently, Hu et al. developed a general method of the
chemoselective hydrogenation and transfer hydrogenation of aldehydes by using a similar iron(II)
pincer complex supported by a 2,6ꢀbis(phosphinito)pyridine ligand (Chart 1).13 This reaction takes
place under very mild conditions (4ꢀ8 bar H2, r.t.), albeit high catalyst loadings (5ꢀ10 mol%) were
required to obtain the primary alcohols in reasonable yields. However, it was remarkable that this
reaction did not proceed via a bifunctional mechanism, i.e. involving the pincer ligand.10b
ACS Paragon Plus Environment

Page 3 of 21
ACS Catalysis
3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
1
2
3
4
5
6
7
Within this context, our group recently reported on the synthesis and reactivity of iron hydride
complexes containing PNP pincer ligands based on a 2,6ꢀdiaminopyridine scaffold (Chart 2).14 In
these ligands the aromatic pyridine ring and the phosphine moieties are connected via NꢀH or Nꢀ
methyl linkers. The advantage of these ligands is that both substituents on the phosphine and amine
sites can be systematically varied in a modular fashion which has a decisive effect on the outcome of
reactions. Complexes featuring at least one NꢀH spacer in the ligand backbone efficiently catalyze the
hydrogenation of ketones under mild conditions.
8
9
Chart 2. Iron hydride complexes based on the 2,6ꢀdiaminopyridine scaffold (R = iPr)
10
11
12
13
14
15
16
17
18
19
20
21
Based on detailed experimental and computational studies it could be shown that this reaction
proceeds via an innerꢀsphere mechanism in which the catalytically active species is formed by
deprotonation of the NꢀH group. In accordance to the proposed mechanism, no reaction took place
when complex [Fe(PNPMeꢀiPr)(CO)(H)(Br)] (2), which is not capable for this kind of metalꢀligand
cooperation, was tested. Surprisingly, aldehydes could still be reduced with this complex under the
same reaction conditions, thus pointing to an alternative reaction mechanism which allows complete
chemoselectivity of aldehydes over ketones. However, these results were just preliminary and the way
in which complex 2 is able to promote this reaction remained unclear. In this paper, we provide a
detailed catalytic and mechanistic study for the chemoselective reduction of aldehydes using complex
2, which was found to be the most efficient iron based hydrogenation catalyst reported to date
displaying unprecedented high turnover numbers surpassing even noble metal catalysts.
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
22
Results and discussion
23
24
25
26
The monohydride complex [Fe(PNPMeꢀiPr)(CO)(H)(Br)] (2) was prepared as described previously by
the reaction of [Fe(PNPMeꢀiPr)(CO)(Br)2] (1) with Na[HBEt3] (1.1 equivs) in THF (Scheme 1). With this
procedure typically two isomers were formed.11 The major isomer of 2, with the hydride ligand being
trans to the bromide ligand, could be isolated in pure form in 68% isolated yield.
ACS Paragon Plus Environment

ACS Catalysis
Page 4 of 21
4
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
2
Scheme 1. Synthesis of complexes 2 and 3 (mixture of cis and trans isomers)
3
4
Interestingly, by using 2 equivs of Na[HBEt3] the corresponding iron(II) dihydride complexes 3 are
obtained, which exist of a mixture of a cis (major) and a transꢀisomer (minor) in an approximate ratio of
1.0:0.7 (Scheme 1). These new complexes could be isolated in 56% yield and were fully characterised
5
1
6
by a combination of elemental analysis, H, 13C{1H}, 31P{1H} NMR and IR spectroscopy. The 31P{1H}
7
NMR spectrum displays two signals at 191.1 and 189.2 ppm for the cisꢀ and the transꢀisomer
respectively. In the 13C{1H} NMR spectrum two triplets centered at 224.7 and 219.5 ppm were
observed for the carbonyl ligands while only one mutual strong band at 1880 cmꢀ1 was found for the
CO vibration in the IR spectrum. In the 1H NMR spectrum, transꢀ3 exhibits a sharp triplet at ꢀ8.76 ppm
(JPH = 42.9 Hz) while a broad signal centered at ꢀ13.02 ppm is observed for cisꢀ3 due to fast
interchange of the two hydride ligands. This could be proved by recording NMR spectra at variable
temperatures in THFꢀd8 (Figure 1).
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
Figure 1
Upon cooling, the broad signal originated from the cisꢀisomer starts to split into two separate triplets
centered at ꢀ8.82 ppm and ꢀ17.64 ppm respectively while the evolution of a single triplet resonance
was observed at higher temperatures. In addition, all iron hydride complexes described above could
be crystallized and their solid state structure was determined by Xꢀray diffraction. Structural views of 2
and 3 are depicted in Figures 2 and 3 with selected bond distances given in the captions.
Figures 2 and 3
Alternatively, the iron dihydride could also be prepared in situ by the reaction of complex 2
with tBuOK (1.1 equiv.) under an atmosphere of H2. Since 2 is not capable of activating dihydrogen in
a bifunctional manner, the formation of 3 likely involves intermolecular cleavage of H2 with support of
the iron center and the external base. The rate of hydrogen cleavage strongly depends on the solvent.
ACS Paragon Plus Environment

Page 5 of 21
ACS Catalysis
5
1
2
3
4
5
1
2
3
Immediate formation of 3 was observed in EtOH (1 bar H2), while the same reaction carried out in THF
required, even under a hydrogen pressure of 5 bar, up to 3 days in order to achieve complete
conversion.
6
7
8
4
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5
6
7
Scheme 2. Reaction of 3 with benzaldehyde in C6D6.
8
9
Stoichiometric experiments revealed that 3 readily reacts with aldehydes. Again, significant
differences were observed depending on the choice of the solvent. The addition of 1 equiv of
benzaldehyde to a solution of the iron dihydride in an aprotic solvent (Scheme 2) resulted in the
formation of a new iron hydride species which was, however, present only in small concentrations.
This new compound, exhibiting a characteristic triplet resonance at ꢀ23.55 ppm (JPH = 55.5 Hz) in the
10
11
12
13
14
15
16
17
18
19
20
1
hydride region of the H spectrum together with a singlet at 164.9 ppm in the 31P{1H} NMR spectrum,
was identified as the alkoxide complex 4 generated by the insertion of the aldehyde into one of the
metal hydride bonds of 3 (Figure 4). The intensity of this signal did not change over time but grew by
increasing the amount of added substrate. Thus, addition of up to 20 equivs of aldehyde was
necessary to observe complete conversion of the iron dihydride. Moreover, no reaction took place
when the solution of the in situ generated hydrido alkoxide complex was exposed to dihydrogen (24h,
6 bar).
21
22
Figure 4
23
24
25
26
27
28
29
30
31
32
In contrast to this, the iron dihydride immediately disappeared after the addition of 1 equiv
benzaldehyde when the reaction was carried out in ethanol (Scheme 3). In this case, two new
1
complexes were observed in the H and 31P{1H} NMR spectra. The first complex was again found to
be the hydrido alkoxide 4 resulting from substrate insertion, displaying just slightly deviating chemical
shifts due to the different solvent. The second complex exhibits a triplet resonance at ꢀ26.38 ppm (JPH
= 58.9 Hz) in the 1H spectrum which correlates to a signal at 159.4 ppm in the 31P{1H} NMR spectrum
and was identified as a cationic species, in which the alkoxide trans to the hydride is replaced by a
solvent molecule (4’). This complex could be independently synthesized by treatment of 2 with silver
salts in ethanol. Purging this mixture with dihydrogen leads immediately to the reformation of the iron
dihydride 3. These finding strongly indicate that the use of a protic solvents is essential for the
ACS Paragon Plus Environment

ACS Catalysis
Page 6 of 21
6
1
2
3
1
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2
3
4
5
Scheme 3. Reaction of 3 with 1 equiv of benzaldehyde in EtOH (inset: Hydride region of the 1H NMR
spectra of cisꢀ and transꢀ3 as well as the akoxide and ethanol complexes 4 and 4’, respectively, at
room temperature).
6
7
hydrogenation reaction by labilizing and solvatizing the alkoxo ligand trans to the hydride. In particular,
this effect appears to be responsible for the irreversibility of the insertion step by preventing βꢀhydride
elimination of the coordinated alkoxide. In the same way, the coordination of dihydrogen to the iron
metal center might be facilitated, thus accelerating the rate of H2 activation. Noteworthy, complex 3 did
not react with acetophenone, presumably to the lower electrophilicity of ketones.
8
9
10
11
12
13
Scheme 4. Reaction of 3 with benzaldehyde in EtOH (see Figure 5)
ACS Paragon Plus Environment

Page 7 of 21
ACS Catalysis
7
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1
2
3
4
5
6
7
8
9
Since the reactivity of a transition metal hydride is mainly affected by its coꢀligand in the transꢀ
position, we therefore expected that only the transꢀisomer is reactive towards aldehydes and that both
isomers are in equilibrium with one another (Scheme 4).15
The cis/trans isomerisation was supposed to take place within minutes, since no exchange could
be observed on the NMR time scale (1Hꢀ1H EXSY). Thus, another experiment was performed by
adding only 0.5 equivs benzaldehyde to a solution of 3 in ethanol and the reaction was continuously
monitored by 31P{1H} NMR spectroscopy. As depicted in Figure 5, the signal of transꢀ3 immediately
disappeared and a new signal was found again for the ethanol complex 4’, whereas the concentration
of cisꢀ3 remained almost unaffected. In this case, the hydrido alkoxide complex was not observed
which might be attributed to the lower substrate concentration in comparison to the previous
experiments (Scheme 4, Figure 4). As expected, we observed recovery of the transꢀdihydride as a
result of the slow isomerisation process which required several minutes to reach again its equilibrium
state.
10
11
12
13
14
15
16
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 5
17
18
19
Based on the observations described above, a simplified catalytic cycle is depicted in Scheme 5.
The preꢀcatalyst 2 readily forms complex transꢀ3 as a result of heterolytic cleavage of dihydrogen
20
21
22
Scheme 5. Proposed simplified catalytic cycle for the chemoselective hydrogenation of aldehydes with
dihydrogen to give alcohols based on experimental findings.
ACS Paragon Plus Environment

ACS Catalysis
Page 8 of 21
8
1
2
3
4
5
6
7
8
9
1
2
promoted by the iron metal center and the external base. Substrate insertion proceeds presumably
through an outer sphere mechanism in which the nucleophilic dihydride directly attacks the aldehyde’s
carbonyl group to give the alkoxide intermediate 4. The compound is labile and the alkoxide ligand
may be replaced either by the solvent (ethanol) to form 4’ or by dihydrogen to form complex 5 which
features an η2ꢀH2 bound dihydrogen ligand. Subsequent deprotonation of the coordinated H2 finally
leads to the regeneration of transꢀ3 and liberation of the product alcohol. Intermediate 5 may be also
formed by replacement of solvent in 4’ by H2. However, since intermediates 4 and 4’ could be
detected by NMR spectroscopy, the question arises whether or not these species are indeed part of
the catalytic cycle or merely resting states.
Accordingly, the reaction mechanism was explored in detail by means of DFT calculations.16 In the
model used for the calculations, acetaldehyde was taken as substrate and transꢀ3 as actives species.
Also, an explicit ethanol molecule (solvent) was considered, providing a proton shuttle and Hꢀbond
stabilization of the intermediates. The free energy profile obtained for the reaction is represented in
Scheme 6.17 The mechanism starts with nucleophilic attack of one hydride ligand of transꢀ3 to the
carbonyl Cꢀatom of acetaldehyde (in A), with formation of an ethoxide ion that coordinates the metal
weakly in a CꢀH σꢀcomplex (B). This species is further stabilized by an EtOH———OHꢀbond with the
neighbor ethanol molecule. The process is endergonic, with ∆G = 6.3 kcal/mol, and the corresponding
barrier (∆G‡ = 12.0 kcal/mol) indicates a facile process.
3
4
5
6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
7
8
9
10
11
12
13
14
15
16
17
18
19
1.68
2.86
2.74
4.72
1.41
1.73
2.40
2.07
1.43
12.0
1.50
1.97
1.45
10.3
+ H2
TSAB
8.9
TSDE
7.4
TSBC
7.3
6.6
D
6.4
6.3
C
Me
3.0
TSEF
2.5
TSGH
H
G
B
H
C
O
H
O
E
H
H
O
Me
1.48
H
0
H
H
O
2
.
1.42
Me
O
C
C
H
Me
O
C
O
H
H
7
2
A
H
O
H
H
1.44
O
1.53
H
1.89
2.20
PR2
H
4.62
PR2
H
2.01
C
N
N
PR2
O
N
1.41
Me
H
H
N
Fe
CO
O
4.31
PR2
CO
H
N
N
Fe
H
CO
1.88
O
N
Fe
CO
ꢀ9.3
N
PR2
N
PR2
N
N
C
N
PR2
N
PR2
H
N
Fe
CO
H
Me
3.39
Fe
ꢀ12.7
H
C
H
D
N
PR2
H
Me
H
O
B
N
PR2
H
H
1.53
O
F
H
H
C
PR2
E
Me
G
H
N
Fe
H
CO
N
PR2
CO
H
C
H
N
PR2
1.79
H
N
Fe
H
A
O
O
N
PR2
1.64
H
H
N
PR2
N
Fe
H
CO
N
PR2
F
20
21
Scheme 6. Free energy profile calculated (DFT) for the hydrogenation of acetaldehyde by H2,
catalyzed by transꢀ3. The free energy values (kcal/mol, solvent corrected, EtOH) are referred to the
initial reactants (A) and relevant distances (Å) are indicated.
22
23
ACS Paragon Plus Environment

Page 9 of 21
ACS Catalysis
9
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1
2
3
4
5
6
7
8
9
The second step of the mechanism corresponds to dissociation of the CꢀH coordinated ethoxide,
yielding a cationic Feꢀcomplex with one free coordination position (C). The process has a small barrier
of 1.1 kcal/mol and is essentially thermoneutral (∆G = 1.0 kcal/mol). The free coordination position in
C may be occupied by three different species. One possibility is, naturally, a solvent molecule
(ethanol) producing complex 4’ as depicted in Schemes 4 and 5. This a facile process with a barrier of
only 2.7 kcal/mol and a free energy balance of ∆G = ꢀ2.4 kcal/mol (see supporting information, Figure
S1). Alternatively, there can be Oꢀcoordination of the recently formed ethoxide ion, resulting in
complex H (4) and exhibits a negligible barrier (0.2 kcal/mol), being a considerably exergonic process
(∆G = ꢀ15.7 kcal/mol). In fact, the alkoxide complex H is 9.3 kcal/mol more stable than the initial
reactants, being by far the most stable intermediate along the reaction mechanism and, thus,
representing the catalyst resting state. Finally, the free coordination position in C can be occupied by
one dihydrogen molecule giving rise to formation of dihydrogen complex E. This process is clearly
exergonic (∆G = ꢀ7.8 kcal/mol) and essentially barrierless. The final step corresponds to the breaking
of the H–H bond in the dihydrogen complex E, with protonation of the nearby ethoxide ion and
regeneration of the dihydride species (in F). This is a facile process with a barrier of only 0.5 kcal/mol,
being largely exergonic (∆G = ꢀ15.2 kcal/mol). Overall, the reaction is exergonic with ∆G = ꢀ12.7
kcal/mol, and closing the cycle exchanging one ethanol molecule (the reaction product) with a new
acetaldehyde molecule (the substrate), from F back to A, is slightly endergonic, with a free energy
balance of ∆G = 4.1 kcal/mol. The highest barrier of the entire process corresponds to substitution of
ethoxide in H by one H2 molecule, in order to allow the reaction to continue. Therefore, the overall
barrier for the process is the difference between the free energy values of H and TSDE, being ca. 20
kcal/mol, in good agreement with the experimental conditions used for the reaction. It has to be noted
that a similar mechanism was proposed recently by Yang, albeit for the reduction of ketones rather
than aldehydes.18
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Since the preliminary catalytic reactions were obtained with high catalyst loadings, more extensive
test reactions were performed here in order to investigate the catalytic performance of complex 2.
Initial experiments were conducted in EtOH using 4ꢀfluorobenzaldehyde as substrate (Table 1). In
presence of 0.05 mol% of 2 together with 1.0 mol% of tBuOK, full conversion to the corresponding
primary alcohol was achieved within 30 min at room temperature and a hydrogen pressure of 6 bar. In
accordance to our observations on a stoichiometric level, no reaction took place in aprotic solvents
such as THF or toluene. A possible transferꢀhydrogenation mechanism in EtOH could be excluded,
since the reduction of 4ꢀfluorobenzaldehyde was not observed in absence of dihydrogen.
Decreasing the catalyst loading led to significantly lower reaction rates. Nevertheless, although a
much longer reaction time was required, full conversion could still be accomplished at a catalyst to
substrate ratio of 1:10000, demonstrating the high efficiency and robustness of this system (entry 2).
As expected, the catalytic activity increased dramatically by applying higher hydrogen pressures. For
example, performing the same reaction at 30 bar reduced the reaction time from 24 to less than one
hour (entry 3) and even 73% of the primary alcohol were obtained at a catalyst to substrate ration of
1:20000 (entry 9).
ACS Paragon Plus Environment

ACS Catalysis
Page 10 of 21
10
1
2
3
4
5
6
7
8
9
1
2
The presence of a strong base appeared mandatory for the reaction to occur. By comparing
turnover frequencies after one hour, we found that a certain amount of tBuOK is substantial in order to
maintain the catalyst in its active state. When the baseꢀloading was reduced below 1.0 mol% the initial
reaction rates dropped significantly (entries 4ꢀ7). On the other hand, larger quantities of tBuOK also
resulted in lower activity (entry 11). In light of the common sensitivity of aldehydes towards highly
basic conditions, this result might be attributed to ongoing side reactions of the substrate, which may
potentially cause catalyst deactivation. Therefore, also weaker bases were considered. At a substrate
to base ratio of 1:100, amines such as NEt3 or diisopropylꢀethylamine were not effective, whereas
DBU (1,8ꢀdiazaꢀbicyclo[5.4.0]undecꢀ7ꢀene) was found to be a suitable coꢀcatalyst. Although the
catalytic activity was lower in comparison to tBuOK at room temperature, similar initial turnover
frequencies were observed when the reaction temperature was raised to 40°C and higher base
loadings did not diminish the catalytic performance of complex 2 (entries 12ꢀ14). Even when a catalyst
to substrate ratio of only 1:20000 was used, 73% of the primary alcohol were formed within 1 h and
>99% after the same time when the pressure was increased to 60 bar (entry 16), which corresponds
to a turnover frequency of more than 20000 hꢀ1.
3
4
5
6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
Finally, by using this protocol a turnover number of 40000 could be reached within 16 hours (entry
17) and, most impressive, applying a long reaction time of 48 hours full conversion was still achieved
at a catalyst to substrate ratio of 1:80000 (corresponds to 12.5 ppm catalyst loading, entry 18), which
stands for one of the highest turnover numbers reached for a selective aldehyde reduction catalyst to
date.19
In order to prove the general applicability of 2 a scope of various substrates has been tested (Table
2). The catalytic experiments were conducted in presence of 50ꢀ100 ppm of catalyst together with 1
mol% of DBU at 40°C and 30 bar hydrogen pressure, to ensure quantitative conversion for all
substrates in a reasonable reaction time (16 h). Best results could be obtained for heteroaromatic
substrates and aromatic aldehydes bearing electron withdrawing halogen substituents on the phenyl
ring, while the reduction of benzaldehyde and derivatives with electron donating groups such as 4ꢀ
anisaldehyde and 4ꢀtolylaldehyde was slightly slower. Even sterically demanding as well as aliphatic
29
30
31
32
33
Scheme 7. Hydrogenation of 4ꢀfluorobenzaldehyde in presence of different coꢀsubstrates bearing
other reducible functionalities
ACS Paragon Plus Environment

Page 11 of 21
ACS Catalysis
11
1
2
3
4
5
6
7
8
9
1
aldehydes could be reduced quantitatively at low catalyst loadings. If present, C=C double bonds
remained unaffected, even in the case of challenging α,βꢀunsaturated substrates such as
cinnamaldehydes or the industrial important citral, emphasizing the high selectivity of this system. It
has to be noted that the hydrogenation of cinnamaldehyde did not proceed in presence of tBuOK,
revealing the benefits of employing DBU as base in the reaction. Again, higher turnover numbers can
be obtained by increasing the hydrogen pressure. This was exemplarily shown for cinnamaldehyde
which was quantitatively converted into the corresponding primary alcohol at a catalyst to substrate
ratio of 1:20000 at 60 bar H2.
2
3
4
5
6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
7
8
9
Additional tests were carried out in order to investigate the catalyst’s selectivity towards other
reducible functionalities (Scheme 7). For this purpose, competitive experiments were performed using
an equimolar mixture of 4ꢀfluorobenzaldehyde and the respective coꢀsubstrate at a catalyst to
substrate ratio of 1:5000 with respect to the aldehyde. Gratifyingly, ketones, esters, epoxides, alkynes
and nitro groups were not hydrogenated and did also not show to interfere the reaction.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Since the iron(II) dihydride is supposed to be a key intermediate in the catalytic hydrogenation, we
finally conducted a series of test reactions in which the isolated complex 3 was directly used as the
catalyst (Table 3). In this case, the addition of an external base is not required. Using cinnamaldehyde
as the substrate resulted in full conversion to the corresponding primary alcohol at a catalyst loading
of 0.5 mol% within one hour (30 bar, r.t.), but no reaction took place when the amount of 3 was
lowered to 0.1 mol%. This is in accordance to our findings on the influence of the base loading on the
catalytic activity, since the overall basicity of the reaction solution now exclusively depends on the
amount of the product alkoxide which is initially formed by the insertion of the aldehyde into the metal
hydride bond. However, quantitative formation of cinnamyl alcohol was achieved when the same
reaction was carried out in a 2:1 mixture of EtOH and NEt3.
25
26
Conclusion
27
28
29
30
31
32
33
34
35
36
37
38
39
In sum, an inexpensive robust homogeneous preꢀcatalyst and catalyst using earthꢀabundant iron,
[Fe(PNPMeꢀiPr)(CO)(H)(Br)] and [Fe(PNPMeꢀiPr)(H)2(CO)] (mixture of trans and cis isomers) based on
the 2,6ꢀdiaminiopyridine scaffold where the PiPr2 moieties of the PNP ligand connect to the pyridine
ring via NMe spacers, was developed and applied for the hydrogenation of several aldehydes to
alcohols in the presence of DBU as base. This methodology proceeds with high chemoselectivity even
in the presence of other reducible functional groups like ketones, esters, alkynes, olefins, and α,βꢀ
unsaturated double bonds. The yields and chemoselectivities under mild conditions are exceptional
compared with previous iron catalysts and even noble metal catalysts. In some cases, full conversion
was achieved even at a catalyst to substrate ratio of 1:80000 (12.5 ppm catalyst loading). Accordingly,
[Fe(PNPMeꢀiPr)(CO)(H)(Br)] and [Fe(PNPMeꢀiPr)(H)2(CO)] are one of the most efficient hydrogenation
catalysts for this process to date. Based on stoichiometric experiment and computational studies, a
mechanism which proceeds indeed via the transꢀdihydrideꢀcomplex [Fe(PNPMeꢀiPr)(H)2(CO)] is
proposed. Thus, the lowꢀcatalyst loadings (typically 50 ppm), mild reaction conditions (40oC, 30 bar
ACS Paragon Plus Environment

ACS Catalysis
Page 12 of 21
12
1
2
3
4
5
1
2
H2), the broad applicability and the mild reaction conditions make these catalysts and this procedure
interesting for the synthesis of fine and bulk chemicals.3
3
6
7
4
8
9
5
Associated Content
6
Complete crystallographic data, 1H, 13C{1H}, and 31P{1H} NMR spectra of all complexes, and technical
details in CIF format for 2 and 3 (CCDC entries CCDC: 1433576 (2), 1433577 (3), Computational
Details and coordinates of all optimized species. This material is available free of charge via the
Internet at http://pubs.acs.org.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
Author Information
Corresponding Author
*Eꢀmail: kkirch@mail.tuwien.ac.at
Notes
The authors declare no competing financial interests.
Acknowledgements
Financial support by the Austrian Science Fund (FWF) is gratefully acknowledged (Project No.
P24583ꢀN28). LFV acknowledges Fundação para a Ciência e Tecnologia, Projecto Estratégico ꢀ PEstꢀ
OE/QUI/UI0100/2013. The Xꢀray center of the Vienna University of Technology is acknowledged for
financial support and for providing access to the singleꢀcrystal diffractometer.
22
ACS Paragon Plus Environment

Page 13 of 21
ACS Catalysis
13
1
2
3
1
Table 1. Hydrogenation of 4ꢀfluoro benzaldehyde with catalyst 2.a
4
5
conversion
(%)b
entry
S/C
P (bar)
t (h)
TON
TOF (hꢀ1)
T [°C]
base (mol%)
6
7
8
9
1
2
2000
6
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
40
r.t.
r.t.
40
40
40
40
40
40
tBuOK (1.0)
tBuOK (1.0)
tBuOK (1.0)
tBuOK (0.5)
tBuOK (0.4)
tBuOK (0.3)
tBuOK (0.2)
tBuOK (0.5)
tBuOK (1.0)
tBuOK (1.0)
tBuOK (2.5)
DBU (1.0)
0.5
24
1
>99
>99
>99
>99
50
2000
10000
10000
10000
5000
4000
417
10000
10000
10000
10000
10000
10000
20000
20000
20000
20000
20000
20000
20000
20000
20000
40000
80000
6
3
30
30
30
30
30
30
30
30
30
30
30
30
30
60
60
60
10000
10000
5000
1800
0
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4
1
5
1
6
1
18
1800
7
1
<1
0
8
1
62
12300
14600
18600
6600
12300
14600
18600
6600
9200
17000
18200
1250
20000
2500
1667
9
1
73
10
11
12
13
14
15
16
17c
18d
1
93
1
33
1
46
9200
DBU (1.0)
1
85
17000
18200
20000
20000
40000
80000
DBU (5.0)
1
91
DBU (1.0)
16
1
>99
>99
>99
>99
DBU (1.0)
DBU (1.0)
16
48
DBU (1.0)
2
3
4
5
Reaction conditions: a) 2 (0.1ꢀ1.0 ꢁmol, 50ꢀ500 ppm), 4ꢀfluoro benzaldehyde (2 mmol), base (0.2ꢀ5.0 mol%),
EtOH (1 mL); b) determined by 19F NMR spectroscopy; average of two runs; c) 4ꢀfluoro benzaldehyde (4 mmol),
EtOH (2 mL); d) 4ꢀfluoro benzaldehyde (8 mmol), EtOH (4 mL).
6
7
8
ACS Paragon Plus Environment

ACS Catalysis
Page 14 of 21
14
1
2
3
4
5
1
2
Table 2. Hydrogenation of aldehydes A1ꢀA14 with catalysts 2a
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3
4
conversion
entry
S/C
subst.
yield (%)c
(%)b
1
2
20000
20000
15000
15000
20000
20000
20000
10000
10000
10000
20000
10000
10000
10000
10000
A1
A2
> 99%
> 99%
> 99%
98%
96%
> 99%
> 99%
98%
3
A3
4
A4
5
A5
> 99%
> 99%
> 99%
97%
97%
6
A6
> 99%
> 99%
96%
7
A7
8
A8
9
A9
98%
> 99%
> 99%
>99%
>99%
> 99%
97%
10
11d
12
13
14
15
A10
A10
A11
A12
A13
A14
> 99%
>99%
>99%
> 99%
> 99%
> 99%
99%
5
6
Reaction conditions: a) catalyst 2 (0.1ꢀ0.2 ꢁmol, 50ꢀ100 ppm),
aldehyde (2 mmol), DBU (20 ꢁmol, 1.0 mol%), EtOH (1 mL), 30
bar H2; 40°C; 16h b) determined by integration of 1H NMR
spectra; c) based on integration of 1H spectra using mesitylene as
internal standard; d) 60 bar H2.
7
8
9
10
11
12
ACS Paragon Plus Environment

Page 15 of 21
ACS Catalysis
15
1
2
3
1
Table 3. Hydrogenation of cinnamaldehyde using 3 as catalysta
4
5
6
7
8
9
catalyst
(mol%)
conversion
(%)b
yield
(%)c
entry
base
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
2
0.5
0.1
0.1
none
none
NEt3
> 99%
0
> 99%
0
3 d
> 99%
> 99%
2
3
4
5
Reaction conditions: a) catalyst 3, cinnamaldehyde (2.0 mmol),
EtOH (1 mL), 30 bar H2, r.t.; b) determined by integration of 1H
spectra; c) based on integration of 1H NMR spectra using
mesitylene as internal standard; d) EtOH (0.8 mL), NEt3 (0.4 mL).
ACS Paragon Plus Environment

ACS Catalysis
Page 16 of 21
16
1
2
3
1
Figures
4
5
6
7
8
transꢀ3
HB
Fe
HA
Me
Me
N
PR2
HA
N
PR2
HB
N
N
Fe
N
N
PR2
PR2
9
Me
Me
CO
CO
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
cisꢀ3
50
30
40
30
0
-10
-20
-30
-40
-50
T (°C)
-8 -9 -10 -11 -12 -13 -14 -15 -16 -17 -18 -19
2
3
4
5
6
7
8
1
Figure 1. Variable temperature H NMR spectra of complexes 3 (300 MHz, THFꢀd8, hydride region).
Complex cisꢀ3 gives rise to signals at ꢀ8.82 (HA) and ꢀ17.64 ppm (HB) at ꢀ50oC. At this temperature the
signal of HA is superimposed with that of the hydrides of transꢀ3 (ꢀ8.76 ppm).
9
10
11
12
13
14
15
Figure 2. Structural view [Fe(PNPMeꢀiPr)(CO)(H)(Br)] (2) showing 50% thermal ellipsoids (most H
atoms and second independent molecule omitted for clarity). Selected bond lengths (Å) and angles (o):
Fe1ꢀBr1 2.5159(4), Fe1ꢀP1 2.1679(6), Fe1ꢀP2 2.1764(6), Fe1ꢀN1 2.0097(16), Fe1ꢀC20 1.749(2), Fe1ꢀ
H1 1.46(3), P1ꢀFe1ꢀP2 161.99(2), N1ꢀFe1ꢀC20 177.64(9).
ACS Paragon Plus Environment

Page 17 of 21
ACS Catalysis
17
1
2
3
1
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2
3
4
5
6
7
8
Figure 3. Structural views of transꢀ[Fe(PNPMeꢀiPr)(H)2(CO)] (transꢀ3) (left) and cisꢀ[Fe(PNPMe
ꢀ
iPr)(H)2(CO)] (cisꢀ3) (right) showing 50% thermal ellipsoids (most H atoms omitted for clarity).
Selected bond lengths (Å) and angles (o): Fe1ꢀP1 2.1270(4), Fe1ꢀP2 2.1258(4), Fe1ꢀN1 1.9920(8),
Fe1ꢀC20 1.683(3), Fe1ꢀC20' 1.815(3), Fe1ꢀH1 1.46(2), Fe1ꢀH2 1.46(4), Fe1ꢀH2' 1.46(2), P1ꢀFe1ꢀP2
164.09(2), N1ꢀFe1ꢀC20 177.3(1), N1ꢀFe1ꢀC20' 104.7(1).
4
3
transꢀ
3
cisꢀ
20
10
5
1
equiv. of
subst. added
0
ꢀ7
ꢀ8
ꢀ9 ꢀ10 ꢀ11 ꢀ12 ꢀ13 ꢀ14 ꢀ15 ꢀ16 ꢀ22 ꢀ23 ꢀ24 ꢀ25
9
10
11
Figure 4. 1H NMR spectra (250 MHz, C6D6, hydride region) of 3 in presence of increasing amounts of
benzaldehyde showing the formation of the corresponding alkoxide complex 4.
ACS Paragon Plus Environment

ACS Catalysis
Page 18 of 21
18
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
2
3
4
5
6
7
8
Figure 5. 31P{1H} spectra (101 MHz, EtOH/C6D6) of 3 before (red) and over a period of 30 min after
addition of 0.5 equivs of benzaldehyde (black) showing immediate complete conversion of transꢀ3 into
the ethanol complex 4’ followed by recovery of transꢀ3 via isomerization of cisꢀ3 (due to incomplete
proton decoupling the signal of 4’ shows a slight residual coupling to the corresponding hydride
ligand).
9
ACS Paragon Plus Environment

Page 19 of 21
ACS Catalysis
19
1
2
3
4
5
1
2
TOC
6
7
8
9
3
4
Highly Efficient and Selective Hydrogenation of Aldehydes: A Wellꢀ
Defined Fe(II) Catalyst Exhibits Noble Metal Activity
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5
6
7
Nikolaus Gorgas, Berthold Stöger, Luis F. Veiros, and Karl Kirchner
8
9
ACS Paragon Plus Environment

ACS Catalysis
Page 20 of 21
20
1
2
3
4
1
References
1
(a) de Vries, J. G., Elsevier, C. J. Eds. Handbook of Homogeneous Hydrogenation; WileyꢀVCH:
Weinheim, 2007. (b) Dupau, P. In Organometallics as Catalysts in the Fine Chemical Industry;
Beller, M., Blaser, H. U., Eds.; SpringerꢀVerlag: Berlin, 2012. c) Johnson, N. B.; Lennon, I. C.;
Moran, P. H.; Ramsden, J. A., Acc. Chem. Res. 2007, 40, 1291ꢀ1299. d) Dub, P. A.; Ikariya, T.,
ACS Catal 2012, 2, 1718ꢀ1741.
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2
(a) Noyori, R.; Ohkuma, T., Pure Appl. Chem. 1999, 71; 1493ꢀ1501. (b) Noyori, R.; Ohkuma, T.,
Angew. Chem., Int. Ed. 2001, 40; 40ꢀ73. (c) Noyori, R., Angew. Chem., Int. Ed. 2002, 41; 2008ꢀ
2022. (d) Ohkuma, H.; Ooka, T.; Ikariya, R.; Noyori, J. Am. Chem. Soc. 1995, 117, 10417ꢀ
10418.
3
4
(a) Surburg, H.; Panten, J.; Eds., Common Fragrance and Flavor Materials; WILEYꢀVCH:
Weinheim, 2006. (b) Saudan, L. A.; Acc. Chem. Res. 2007, 40, 1309ꢀ1319.
(a) Smith, A. B.; Barbosa, J.; Wong, W.; Wood, J. L., J. Am. Chem. Soc. 1996, 118, 8316ꢀ8328.
(b) Kobayakawa, Y.; Nakada, M., J. Antibiot. 2014, 67, 483ꢀ485.
5
6
Bonomo, L.; Kermorvan, L.; Dupau, P., ChemCatchem 2015, 7; 907ꢀ910.
(a) Casey, C. P.; Strotman, N. A.; Beetner, S. E.; Johnson, J. B.; Priebe, D. C.; Guzei, I. A.,
Organometallics 2006, 25, 1236ꢀ1244. (b) Diab, L.; Mejkal, T.; Geier, J.; Breit, B., Angew.
Chem. Int. Ed. 2009, 48, 8022ꢀ8026; Angew. Chem. 2009, 121, 8166ꢀ8170.
7
8
9
Bullock, R. M., Ed. Catalysis Without Precious Metals, WileyꢀVCH: Weinheim, 2010.
Roesler, S.; Obenauf, J.; Kempe, R. J. Am. Chem. Soc. 2015, 137, 7998ꢀ8001.
(a) Morris, R. H. Chem. Soc. Rev. 2009, 38, 2282ꢀ2291. (b) Enthaler, S.; Junge, K.; Beller, M.
Angew. Chem., Int. Ed. 2008, 47, 3317ꢀ3321. (c) Gaillard, S.; Renaud, J.ꢀL. ChemSusChem
2008, 1, 505ꢀ509. (d) Bauer, G.; Kirchner, K. A. Angew. Chem., Int. Ed., 2011, 50, 5798ꢀ5800.
(e) Bullock, R. M. Science 2013, 342, 1054ꢀ1055. (f) Sues, P. E.; Demmans, Z.; Morris, R. H.
Dalton Trans. 2014, 43, 7650ꢀ7667. (g) Bauer, I.; Knölker, H.ꢀJ., Chem. Rev. 2015, 115; 3170ꢀ
3387.
10
(a) Bart, S. C.; Lobkovsky, E.; Chirik, P. J., J. Am. Chem. Soc. 2004, 126; 13794ꢀ13807. (b)
Bart, S. C.; Hawrelak, E. J.; Lobkovsky, E.; Chirik, P. J., Organometallics 2005, 24; 5518ꢀ5527.
(c) Trovitch, R. J.; Lobkovsky, E.; Chirik, P. J. Inorg. Chem. 2006, 45; 7252ꢀ7260. (d) Casey, C.
P.; Guan, H., J. Am. Chem. Soc. 2007, 129; 5816ꢀ5817. (e) Trovitch, R. J.; Lobkovsky, E.; Bill,
E.; Chirik, P. J., Organometallics 2008, 27; 1470ꢀ1478. (f) Federsel, C.; Boddien, A.; Jackstell,
R.; Jennerjahn, R.; Dyson, P. J.; Scopelliti, R.; Laurenczy, G.; Beller, M., Angew. Chem. Int. Ed.
2010, 49; 9777ꢀ9780. (g) Langer, R.; Leitus, G.; BenꢀDavid, Y.; Milstein, D., Angew. Chem. Int.
Ed. Engl. 2011, 50; 2120ꢀ2124. (h) Langer, R.; Iron, M. A.; Konstantinovski, L.; DiskinꢀPosner,
Y.; Leitus, G.; BenꢀDavid, Y.; Milstein, D., Chemistry 2012, 18; 7196ꢀ7209. (i) Yu, R. P.;
Darmon, J. M.; Hoyt, J. M.; Margulieux, G. W.; Turner, Z. R.; Chirik, P. J., ACS Catal. 2012, 2;
1760ꢀ1764; (j) Ziebart, C.; Federsel, C.; Anbarasan, P.; Jackstell, R.; Baumann, W.;
Spannenberg, A.; Beller, M., J. Am. Chem. Soc. 2012, 134; 20701ꢀ20704. (k) Fleischer, S.;
Zhou, S.; Junge, K.; Beller, M., Angew. Chem., Int. Ed. 2013, 52; 5120ꢀ5124. (l) Srimani, D.;
DiskinꢀPosner, Y.; BenꢀDavid, Y.; Milstein, D., Angew. Chem., Int Ed 2013, 52; 14131ꢀ14134;
ACS Paragon Plus Environment

Page 21 of 21
ACS Catalysis
21
1
2
3
4
5
6
7
8
9
(m) Wienhofer, G.; BasedaꢀKruger, M.; Ziebart, C.; Westerhaus, F. A.; Baumann, W.; Jackstell,
R.; Junge, K.; Beller, M., Chem. Comm. 2013, 49; 9089ꢀ9091. (n) Bornschein, C.; Werkmeister,
S.; Wendt, B.; Jiao, H.; Alberico, E.; Baumann, W.; Junge, H.; Junge, K.; Beller, M., Nat.
Commun. 2014, 5; 4111. (o) Chakraborty, S.; Dai, H.; Bhattacharya, P.; Fairweather, N. T.;
Gibson, M. S.; Krause, J. A.; Guan, H., J. Am. Chem. Soc. 2014, 136; 7869ꢀ7872. (p)
Chakraborty, S.; Lagaditis, P. O.; Förster, M.; Bielinski, E. A.; Hazari, N.; Holthausen, M. C.;
Jones, W. D.; Schneider, S., ACS Catal. 2014, 4; 3994ꢀ4003. (q) Lagaditis, P. O.; Sues, P. E.;
Sonnenberg, J. F.; Wan, K. Y.; Lough, A. J.; Morris, R. H., J. Am. Chem. Soc. 2014, 136; 1367ꢀ
1380. (r) Werkmeister, S.; Junge, K.; Wendt, B.; Alberico, E.; Jiao, H.; Baumann, W.; Junge, H.;
Gallou, F.; Beller, M., Angew. Chem., Int. Ed. 2014, 53; 8722ꢀ8726. (s) Bertini, F.; Mellone, I.;
Ienco, A.; Peruzzini, M.; Gonsalvi, L., ACS Catal. 2015, 5; 1254ꢀ1265. (t) RivadaꢀWheelaghan,
O.; Dauth, A.; Leitus, G.; DiskinꢀPosner, Y.; Milstein, D., Inorg. Chem. 2015, 54; 4526ꢀ4538. (u)
Zhang, Y.; MacIntosh, A. D.; Wong, J. L.; Bielinski, E. A.; Williard, P. G.; Mercado, B. Q.; Hazari,
N.; Bernskoetter, W. H., Chem. Sci. 2015, 6; 4291ꢀ4299.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
11
Wienhofer, G.; Westerhaus, F. A.; Junge, K.; Ludwig, R.; Beller, M., Chem. Eur. J. 2013, 19;
7701ꢀ7707.
12
13
14
Zell, T.; BenꢀDavid, Y.; Milstein, D., Catal. Sci. Technol. 2015, 5; 822ꢀ826.
Mazza, S.; Scopelliti, R.; Hu, X., Organometallics 2015, 34; 1538ꢀ1545;
Gorgas, N.; Stöger, B.; Veiros, L. F.; Pittenauer, E.; Allmaier, G.; Kirchner, K., Organometallics
2014, 33; 6905ꢀ9614.
15
16
Eisenstein, O.; Crabtree, R. H., New J. Chem. 2013, 37, 21ꢀ27.
Parr, R. G.; Yang, W. Density Functional Theory of Atoms and Molecules, Oxford University
Press, New York, 1989.
17
Intermediate D is 1.4 kcal/mol less stable than TSDE. This feature is the result of single point
energy calculations in species of similar stability. In fact, at the theory level used in the
geometry optimizations, D is 4.2 kcal/mol below TSDE.
18
19
Yang, X., Inorg. Chem. 2011, 50; 12836ꢀ12843.
Strohmeier, W.; Weigelt, L. J. Organomet. Chem. 1978, 145, 189ꢀ194.
ACS Paragon Plus Environment