Transfer Hydrogenation and Hydrogenation of Commercial-Grade Aldehydes to Primary Alcohols Catalyzed by 2-(Aminomethyl)pyridine and Pincer Benzo[h]quinoline Ruthenium Complexes

Article abstract of DOI:10.1002/cctc.201600420

The chemoselective reduction of commercial-grade aldehydes (97–99 %) to primary alcohols is achieved with cis-[RuCl₂(ampy)(PP)] [ampy=2-(aminomethyl)pyridine; PP=1,4-bis(diphenylphosphino)butane, 1,1′-ferrocenediyl-bis(diphenylphosphine)] and pincer [RuCl(CNN^R)(PP)] [PP=1,3-bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, 1,1′-ferrocenediyl-bis(diphenylphosphine); HCNN^R=4-substituted-2-aminomethyl-benzo[h]quinoline; R=Me, Ph] complexes by transfer hydrogenation and hydrogenation reactions. Aromatic, conjugated, and aliphatic aldehydes are converted quantitatively to the corresponding alcohols using 2-propanol with potassium carbonate at substrate/catalyst ratios up to 100 000 by transfer hydrogenation, whereas aldehyde hydrogenation (5–20 atm of H₂) is achieved efficiently in MeOH in the presence of KOtBu at substrate/catalyst ratios up to 40 000.

Full text of DOI:10.1002/cctc.201600420

DOI: 10.1002/cctc.201600420
Full Papers
Transfer Hydrogenation and Hydrogenation of
Commercial-Grade Aldehydes to Primary Alcohols
Catalyzed by 2-(Aminomethyl)pyridine and Pincer
Benzo[h]quinoline Ruthenium Complexes
Salvatore Baldino,[a] Sarah Facchetti,[b] Antonio Zanotti-Gerosa,[b] Hans Gꢀnter Nedden,[b] and
Walter Baratta*[a]
The chemoselective reduction of commercial-grade aldehydes
(97–99%) to primary alcohols is achieved with cis-[Ru-
Cl2(ampy)(PP)] [ampy=2-(aminomethyl)pyridine; PP=1,4-bis-
transfer hydrogenation and hydrogenation reactions. Aromatic,
conjugated, and aliphatic aldehydes are converted quantita-
tively to the corresponding alcohols using 2-propanol with po-
tassium carbonate at substrate/catalyst ratios up to 100000 by
transfer hydrogenation, whereas aldehyde hydrogenation (5–
20 atm of H2) is achieved efficiently in MeOH in the presence
of KOtBu at substrate/catalyst ratios up to 40000.
(diphenylphosphino)butane,
1,1’-ferrocenediyl-bis(diphenyl-
phosphine)] and pincer [RuCl(CNNR)(PP)] [PP=1,3-bis(diphenyl-
phosphino)propane, 1,4-bis(diphenylphosphino)butane, 1,1’-
ferrocenediyl-bis(diphenylphosphine); HCNNR =4-substituted-
2-aminomethyl-benzo[h]quinoline; R=Me, Ph] complexes by
Introduction
The metal-catalyzed hydrogenation (HY)[1] and transfer hydro-
genation (TH)[2] of carbonyl compounds, with particular regard
to ketones, are widely accepted as cost-efficient routes for the
synthesis of alcohols in industry.[3] The HY and TH procedures,
which involve H2 and 2-propanol or formic acid as hydrogen
sources, have a lower environmental impact and an easier
work up with respect to the classical reduction that involves
NaBH4 or boranes still employed in industry.[4] In recent de-
cades great attention has been devoted to the development
of chiral Ru catalysts based on well-designed ligands for the
synthesis of optically active alcohols by the asymmetric reduc-
tion of ketones.[1] In addition to the Noyori-type TH and HY Ru
catalysts,[5] which have an arene or a diphosphane in combina-
tion with a bidentate N ligand with a NH function, a new gen-
eration of highly active pincer Ru catalysts that contain neutral
or anionic tridentate ligands has been reported.[6] These sys-
tems are active in several organic reactions, which include al-
cohol dehydrogenation,[7] ester and amide hydrogenation,[8]
and borrowing hydrogen transformations.[9] In the last decade,
we developed highly active and productive Ru and Os cata-
lysts, which have substituted 2-(aminomethyl)pyridine ligands,
for the TH and HY of carbonyl compounds, and progress in
this area has been reviewed recently.[10] The commercially avail-
able cis-[RuCl2(ampy)(PP)] [ampy=2-(aminomethyl)pyridine; 1:
PP=1,4-bis(diphenylphosphino)butane (dppb),[11] 2: PP=1,1’-
ferrocenediyl-bis(diphenylphosphine) (dppf)][12] and pincer
[RuCl(CNN)(dppb)] (HCNN=6-(p-tolyl)-2-aminomethylpyridine;
3)[13] are practical catalysts for ketone reduction and other or-
ganic transformations, which include the dehydrogenation,
deuteration, and isomerization of alcohols (Figure 1).[12,14]
Figure 1. Ampy and CNN pincer Ru catalysts.
[a] Dr. S. Baldino, Prof. W. Baratta
Dipartimento DI4A
Conversely, for the reduction of simple aldehydes to primary
alcohols, NaBH4 remains the preferred reagent in industry.[3,15]
Several heterogeneous catalysts, such as those based on Pd/C,
are used in the HY of aromatic aldehydes to benzyl alcohols,
and particular attention has been devoted to avoid over-reduc-
tion to methylarenes.[16] Furthermore, heterogeneous catalysts
display a low tolerance to several aromatic substituents, such
as nitro and halide groups, which are hydrogenated easily.
Universitꢀ di Udine
Via Cotonificio 108, 33100 Udine (Italy)
Fax: (+39)0432-558803
E-mail: walter.baratta@uniud.it
[b] Dr. S. Facchetti, Dr. A. Zanotti-Gerosa, Dr. H. G. Nedden
Johnson Matthey Fine Chemicals Division
28 Cambridge Science Park, Milton Road, Cambridge, CB4 0FP (UK)
Supporting information for this article can be found under http://
dx.doi.org/10.1002/cctc.201600420.
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With regard to the reduction of conjugated aldehydes, the
chemoselective HY of cinnamaldehyde at C=O without the re-
duction of the C=C bond has been a challenging target for
heterogeneous catalysts for decades.[17] By contrast to ketone
reduction, the number of catalysts for the TH and HY of alde-
hydes is much lower and the catalysis is usually performed
with a substrate to catalyst ratio (S/C) ꢀ103 to achieve the
complete conversion of the substrate (Scheme 1).[1,2,18]
and phosphane-based Ru complexes[34] were active in the alde-
hyde reduction. Commercial-grade aromatic aldehydes can be
hydrogenated using Will’s tethered catalyst [(C3-teth-TsDpen)-
RuCl] in MeOH/H2O[35] as water shifts the acetal–aldehyde equi-
librium to aldehyde. Recently, Dupau et al. reported that
[Ru(O2CR)2(diamine)(PP)]
(PP=1,2-bis(diphenylphosphino)-
ethane, xantphos), which bears bulky carboxylates, are highly
efficient catalysts for the reduction of redistilled commercially
available aldehydes in alcoholic and nonprotic apolar solvents
in neutral or slightly acidic conditions with S/C=104–105,
whereas ketones lead to a very poor conversion.[36]
A comparison of the properties of the aldehydes versus ke-
tones may suggest that aldehydes can be reduced more easily
to alcohols than ketones because of their higher redox poten-
tials.[37] In addition, aldehydes have lower steric requirements,
which facilitates their approach to the metal center. However,
in practice aldehydes are substrates that are difficult to reduce
selectively, and the catalysis is affected by the substrate quality
and nature and the concentration of the base. As the TH and
HY of carbonyl compounds are usually performed under basic
conditions to allow the formation of the catalytically active
metal hydrides,[38] the control of chemoselectivity is a delicate
point. Aldehydes, which have a formyl group, show a broader
reactivity than ketones. Under basic conditions, aldehydes may
undergo the Claisen–Tishchenko (dimerization)[39] and Canni-
zzaro[40] reactions (Scheme 2).
Scheme 1. Transfer hydrogenation and hydrogenation of aldehydes.
In addition to Ir complexes,[19] the Ru Noyori system [(arene)-
RuCl(TsDpen)]
(Tsdpen=N-(p-toluenesulfonyl)-1,2-diphenyl-
ethylenediamine),[20] [CpRu(PPh3)(PN)] (PN=diphenyl-2-pyridyl-
phosphine),[21] [RuH2(PPh3)4],[22] [RuCl2(PTA)4] (PTA=1,3,5-triaza-
7-phosphaadamantane),[23]
[RuCl2(mtppms)2]2
(mtppms=
sodium 3-diphenylphosphinobenzenesulfonate),[24] [RuCl2(PO)2]
(PO=(2-methoxyethyl)diphenylphosphine),[25]
[RuCl2(POP)-
(dmso)] (POP=xantphos),[26] [RuCl2(PPh3)(NNN)] (NNN=2-(ben-
zoimidazol-2-yl)-6-(3,5-dimethylpyrazol-1-yl)pyridine),[27]
In addition to alkoxides and hydrides of the main group ele-
ments,[39b,41] [RuH2(PPh3)4],[42] [RuHCl(CO)(PPh3)3],[43] [RuCl(Si-
[RuCl(PPh3)2(MeCN)3][BPh4],[28] [RuCl2(CO)2(PS)] (PS=bis(2-di-
phenylphosphanylphenyl)ether monosulfide and 9,9-dimethyl-
4,5-bis(diphenylphosphanyl)xanthene monosulfide), and Ru
cluster carbonyl derivatives[29] catalyze the aldehyde TH using
2-propanol or formates as hydrogen donors that work at rela-
tively low S/C (100–1000). Complexes 2[12] and 3[30] were active
in the TH of aldehydes with NaOiPr and K2CO3 as the base. To
achieve complete reduction, the aldehydes were distilled
under an inert atmosphere and used rapidly in TH as commer-
cial-grade substrates led to poor or no conversion.[26] Notably,
aldehydes are reduced slowly by alcohols in the presence of
Group 1 alkoxides, hydroxides, or carbonates and aluminum
alkoxides through the Meerwein–Verley–Pondorf (MPV) reac-
tion.[31] With regard to HY, the Shvo-type catalysts,[32] arene-[33]
Me3)(CO)(PPh3)2],[44]
[(h5-C5Ph4O)2HRu2H(CO)4],[45]
[RuCl2(p-
cymene)]2/PR3,[46] and Os, Ir, and Ni complexes catalyze the
Claisen–Tishchenko reaction.[47] Aldehydes that display reactive
a-hydrogen atoms can easily undergo aldol condensation in
basic media.[48] Notably, during the TH of aldehydes in 2-propa-
nol, conjugated mono- and dienones can also be produced by
cross-coupling reactions between the aldehyde and the
formed acetone (vide infra; Scheme 2). Furthermore, aldehydes
can also undergo decarbonylation with Ru[49] and Os[43a] com-
plexes to afford metal carbonyl derivatives, and this reaction is
considered as a deactivation pathway for Ir and Ru catalysts to
result in a low S/C ratio.[19h,i,50] A strategy to achieve both high
productivity and chemoselectivity in aldehyde reduction entails
Scheme 2. Base-mediated aldehyde reactions.
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Figure 2. 4-Functionalized 2-aminomethyl-benzo[h]quinoline ruthenium complexes [RuCl(CNNR)(PP)] 4–9.
the use of both fast and robust catalysts that work in weakly
basic media. In addition, the development of catalysts that can
work with a S/C ratio higher than 1000 to meet industrial re-
quirements and can be employed with commercial-grade sub-
strates and solvents is highly desirable for applications. Recent-
ly, we described that the easily accessible pincer complexes
[RuCl(CNNR)(PP)] (4–9) based on 4-functionalized 2-aminometh-
yl-benzo[h]quinoline ligands (HCNNR) prepared by a scalable
synthesis are highly productive catalysts for both the TH and
HY of ketones (Figure 2).[51a]
We report here the use of the ampy and CNNR pincer Ru
complexes in the TH and HY of aldehydes of commercial-grade
purity at S/C=2000–100000. A comparison of the activity of
the ampy and pincer complexes and the effect of the reaction
parameters are also provided.
Results and Discussion
Catalytic TH of aldehydes catalyzed by 1 and 2
Scheme 3. Transfer hydrogenation of aldehydes catalyzed by 1 and 2 and
4–9.
The commercially available ampy complexes 1 and 2 were
used in the TH of several aldehydes of commercial-grade
purity (Scheme 3).
If benzaldehyde a (assay 99%) was heated to reflux in 2-
propanol with 1 (S/C=2000) and the weak base K2CO3
(5 mol%), 98% conversion was achieved in 1.75 h, which af-
forded 92% of benzyl alcohol (Table 1, entry 1). Complex 2 (S/
C=2000), which bears dppf in place of dppb, afforded 85%
conversion of a with 74% of benzyl alcohol in 4 h, whereas
with S/C=5000, only 49% of the alcohol is obtained (entries 3
and 4). Notably, with the use of freshly distilled a, complex 1
(S/C=2000) with K2CO3 (5 mol%) gives 94% of benzyl alcohol
in 1 h (entry 5), whereas complex 2 (S/C=20000) in the pres-
ence of NaOiPr (2 mol%) gives 95% conversion in 2 h.[12] Com-
plex 1 (S/C=2000) catalyzes the selective reduction of 4-bro-
mobenzaldehyde b (assay 99%) to 4-bromobenzyl alcohol
(>97%) in 30 min (entry 6).
If the reaction was performed at S/1=5000, almost full con-
version was achieved in 1.5 h (92%) but with the formation of
70% of alcohol (entry 7), which indicates that at longer reac-
tion time generally results in a decrease of selectivity. NMR
spectroscopy of the product distribution revealed the forma-
tion of (E)-4-(4-bromophenyl)but-3-en-2-one and (1E,4E)-1,5-
bis(4-bromophenyl)penta-1,4-dien-3-one in an approximately
1:2 molar ratio as the outcome of the condensation between
b and acetone formed during the TH (Scheme 4, see Support-
ing Information).
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Table 1. TH of aldehydes (0.1m) catalyzed by 1 and 2 with K2CO3 (5 mol%) in 2-propanol at 828C.
Entry
Substrate
Complex
Loading
(S/C)
t
[h]
Conv[a]
[%]
Alcohol[a]
[%]
Byproducts[a]
[%]
1
2
3
4
5[b]
6
7
8
a
a
a
a
a
b
b
b
c
c
c
c
c
e
e
f
f
f
f
f
g
g
h
h
i
1
1
2
2
1
1
1
2
1
1
1
2
2
1
2
1
1
2
2
2
1
2
1
2
1
2
2000
5000
2000
5000
2000
2000
5000
2000
2000
5000
10000
2000
5000
2000
2000
2000
5000
2000
5000
2000
2000
2000
2000
2000
2000
2000
1.75
5
4
5
1
0.5
1.5
2.5
0.5
1
4.5
0.5
4
2
2
3
3
0.5
4
0.5
3.5
3
98
43
85
59
95
98
92
92
98
99
95
99
52
36
42
78
11
98
52
95
60
98
89
95
>99
94
92
39
74
6
4
11
10
<1
<1
22
30
<1
<1
6
49
>94
>97
70
62
9
>97
>98
89
98
49
10
11
12
13
14
15
16
17
18
19
20[c]
21
22
23
24
25
26
1
3
21
28
15
14
<1
<1
<1
2
<1
18
5
23
66
30
24
>77
>10
>97
50
>94
42
93
66
29
70
4
4
3
3
i
70
[a] The conversion and the amount of byproducts were determined by using GC analysis or 1H NMR spectroscopy. [b] Substrate was distilled. [c] Substrate
and 2-propanol were distilled and NaOiPr (2 mol%) was used as base (see Ref. [12]).
Complex 2 was less active and selective than 1 for b and led
to 62% of alcohol (entry 8). The substrate 4-(dimethylamino)-
benzaldehyde c (assay 99%) is reduced efficiently with 1 at S/
C=5000 and 10000 to afford 99 and 89% of 4-(dimethylami-
no)benzyl alcohol in 1 and 4.5 h, respectively (entries 10 and
11). With 2 (S/C=2000) 98% of alcohol was attained in 0.5 h,
whereas at S/C=5000 incomplete conversion was achieved
(entries 12 and 13). The TH of iso-propyl 4-formylbenzoate
e with 1 and 2 (S/C=2000) attained a moderate conversion
(36 and 42%, entries 14 and 15) with the formation of the
aldol condensation dienone product with acetone (Scheme 4,
see Supporting Information), which indicates that the presence
of the carboxylate function inhibits the catalytic activity of 1.
Complexes 1 and 2 catalyze the chemoselective reduction of
conjugated aldehydes. With 1 (S/C=2000), trans-cinnamalde-
hyde f (assay 98%) was converted to the corresponding allylic
alcohol (77%) in 3 h, whereas 2 gave 97% in 0.5 h without re-
duction at the C=C bond (entries 16 and 18). This result is simi-
lar to that obtained if we used freshly distilled f with 2 in the
presence of NaOiPr (entry 20).[12] At a lower loading of 1 and 2
(S/C=5000), incomplete conversion was observed (entries 17
and 19). The TH of a-methylcinnamaldehyde g (assay 97%,
predominantly the E isomer) with 1 gave 60% conversion with
42% of a-methylcinnamol, whereas the chemoselective forma-
tion of alcohol (93%) was attained with 2 (entries 21 and 22).
Hexanal h (assay 98%) with 1 and 2 led to 1-hexanol (66 and
29%) with the formation of aldol condensation byproducts
(entries 23 and 24). The TH of the heteroaromatic thiophene-2-
carbaldehyde i (assay 98%) with 1 and 2 gave quantitative
conversions in 3 h to afford 70% of 2-thienylmethanol with
the formation of enone and dienone side products in an ap-
proximately 2:1 molar ratio (entries 25 and 26, see Supporting
Information).
These results indicate that the commercially available ampy
complexes 1 and 2 can be employed in the TH of commercial-
grade aromatic and conjugated aldehydes at S/C=2000–
10000. For aromatic aldehydes, chemoselective TH was ach-
ieved using the dppb-containing complex 1. Conversely, conju-
gated aldehydes can be converted selectively to allylic alcohols
with the less basic dppf derivative 2.
Catalytic TH of aldehydes catalyzed by 4–9
The easily accessible pincer complexes 4–9 obtained from 4-
functionalized 2-aminomethyl-benzo[h]quinoline ligands[47a]
have been studied in the TH of aldehydes of commercial-grade
purity in basic 2-propanol. Benzaldehyde a (assay 99%) was re-
duced quantitatively and selectively to benzyl alcohol (98-
99%) with complexes 4–9 (S/C=2000) in the presence of
K2CO3 (5 mol%) within 1.25–6.5 h, the dppf-containing cata-
lysts 6 and 9 being more active than the dppp and dppb
derivatives (Table 2, entries 1–6).
Notably, under the same conditions but using distilled a, the
pincer 5 (S/C=2000) affords 97% of alcohol in 35 min, where-
as quantitative conversion is achieved in 30 s with 3.[26] The
bromo aldehyde b was converted quantitatively with 4–6, 8,
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Table 2. TH of aromatic aldehydes (0.1m) catalyzed by 4–9 with K2CO3 (5 mol%) in 2-propanol at 828C.
Entry
Substrate
Complex
Loading
(S/C)
t
[h]
Conv.[a]
[%]
Alcohol[a]
[%]
Byproducts[a]
[%]
1
2
3
4
5
6
7
8
a
a[b]
a
a
a
a
b
b
b
b
b
b
b
c
c
c
c
c
c
c
c
c
4
5
6
7
8
9
4
5
5
6
7
8
9
4
4
5
5
5
5
5
5
6
6
7
8
9
–
5
5
–
4
5
6
7
8
9
2000
2000
2000
2000
2000
2000
2000
2000
5000
2000
2000
2000
2000
5000
10000
2000
5000
10000
20000
40000
100000
5000
10000
2000
2000
2000
–
2
1.5
1.25
5
5
1.25
0.5
2
3
0.5
3
100
100
99
99
99
99
98
100
66
98
99
>99
98
98
98
98
78
82
36
1
<1
1
1
1
1
20
18
19
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
>97
44
81
<1
23
19
67
1
100
>99
95
98
98
98
97
98
>99
>99
92
98
98
99
98
–
41
80
31
52
75
95
33
53
96
0.5
1.5
3
0.5
0.5
1.5
3
7
20
1.5
3
2
2
2
10
2
2
2
5
5
>98
>94
>97
>97
>97
>96
>97
>99
>99
>91
>97
>97
>98
>97
–
36
65
17
>51
>74
>94
>32
>52
>95
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
–
c
c
c
c
c
d
d
d
e
e
e
e
e
e
2000
500
5
15[c]
14
–
2000
2000
2000
2000
2000
2000
<1
<1
<1
<1
<1
<1
0.75
6
5
1
1
[a] The conversion and the amount of byproducts were determined by using GC analysis or H NMR spectroscopy. [b] By using distilled a, 97% of benzyl al-
cohol is formed in 35 min. [c] (1E,4E)-1,5-Bis(4-nitrophenyl)penta-1,4-dien-3-one and iso-propyl 4-nitrobenzoate in 2:3 ratio.
and 9 (S/C=2000) in a shorter time than that required for a. A
high selectivity was achieved with the dppf-containing com-
plexes 6 and 9 to lead to 98–99% of 4-bromobenzyl alcohol
(entries 10 and 13), whereas the dppp-bearing complexes 4
and 7 and dppb-containing 5 and 8 gave 44–82% of alcohol.
The NMR spectra of the isolated products of the TH of b with
5 (S/C=5000, entry 9) after 3 h showed the formation of 4-bro-
mobenzyl alcohol (36%) and (1E,4E)-1,5-bis(4-bromophenyl)-
penta-1,4-dien-3-one (18%) in a 2:1 molar ratio with a small
amount of iso-propyl 4-bromobenzoate (1%; Scheme 4, see
Supporting Information). The iso-propyl benzoate is likely pro-
duced from b by a cross-Claisen–Tischenko or Claisen–Tischen-
ko reaction followed by transesterification. These results indi-
cate that with a high S/C (ꢁ5000) and longer reaction time,
CÀC coupling reactions compete significantly with TH to result
in a low selectivity. Initial attempts to inhibit the aldol conden-
sation by the fractional distillation of acetone (b.p.=568C)
failed.[52] The effect of substrate concentration has also been in-
vestigated. As aldehydes show a higher reduction potential
than ketones,[33] a higher substrate concentration could be em-
ployed in TH, which is a significant advantage for industrial ap-
plications. However, by increasing the concentration of b from
0.1 to 1m (b/5=10000, 5 mol% K2CO3) the conversion de-
creased from 69 to 33% (16 h) with the formation of 37, 27,
and 22% of alcohol at 0.1, 0.2, and 1m, respectively. Com-
plexes 4–9 efficiently catalyzed the chemoselective TH of 4-(di-
methylamino)benzaldehyde c (0.1m) to alcohol. With 4 at S/
C=5000 and 10000, 4-(dimethylamino)benzyl alcohol was at-
tained in 94 and 97% (1.5 and 3 h, respectively; entries 14 and
15), whereas 99% conversion was achieved at a remarkably
high S/C=100000 in 20 h with 5 with no erosion of the selec-
tivity (entries 16–21). Without a Ru catalyst and in the presence
of K2CO3, no reduction occurred (entry 27). The strong elec-
tron-donating properties of the dimethylamino group of c lead
to a low electrophilic formyl functionality, which hinders the
CÀC coupling reactions. However, the TH of p-nitrobenzalde-
hyde d with 5 (S/C=2000) affords a poor conversion (41% in
2 h) with 36% of alcohol (entry 28). The analysis of the prod-
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Scheme 4. Transfer hydrogenation of b, d, and e in 2-propanol.
ucts at S/5=500 revealed the formation of 4-nitrobenzyl alco-
hol A (65%), (1E,4E)-1,5-bis(4-nitrophenyl)penta-1,4-dien-3-one
B (2%), and iso-propyl 4-nitrobenzoate C (13%; Scheme 4,
entry 29). Without 5 and in the presence of K2CO3 (5 mol%), d
undergoes 31% conversion in 2 h to form A/B/C in an approxi-
mately 6:2:3 molar ratio (entry 30, see Supporting Information).
Thus, the Ru-catalyzed TH of d, which has a highly electrophilic
formyl group, leads to the alcohol through both ruthenium hy-
dride and potassium alkoxide species[53] and the products of
the aldol condensation and Claisen–Tischenko reactions. By
contrast to the ampy complexes 1 and 2, the pincer complexes
4–9 (S/C=2000) promote the selective reduction of iso-propyl
4-formylbenzoate e to alcohol (up to 95%). With the dppf de-
rivatives 6 and 9, the corresponding hydroxymethyl benzoate
is obtained in 94 and 95% (entries 33 and 36), whereas the
dppp and dppb catalysts gave a lower conversion. trans-Cinna-
maldehyde f has been reduced to trans-3-phenyl-2-propen-1-ol
with 4–9 (S/C=5000–10000) with conversions in the range of
52–98% in 0.5–6.5 h (Table 3, entries 1–12). Complex 5 at S/C=
10000 gave 84% of the allylic alcohol in the presence of
a small amount of 3-phenylpropan-1-ol (4%, entry 4). As the
pincer catalysts 4–9 show a high activity for C=O but not C=C
bond reduction, it is likely that the saturated alcohol is formed
through an isomerization of the allylic alcohol to the saturated
aldehyde.[12] Notably, with 1 and 2 the TH of f gave allylic
alcohol with nearly no byproducts (Table 1, entries 16–19).
Table 3. TH of conjugated and aliphatic aldehydes (0.1m) catalyzed by 4–9 with K2CO3 (5 mol%) in 2-propanol at 828C.
Entry
Substrate
Complex
Loading
(S/C)
t
[h]
Conv.[a]
[%]
Alcohol[a]
[%]
Byproducts[a]
[%]
1
2
3
4
5
6
7
8
f
f
f
f
f
f
f
f
f
f
f
f
g
g
g
g
g
g
g
h
h
h
h
h
h
h
h
h
4
4
5
5
6
6
7
7
8
8
9
9
4
4
5
5
6
6
6
4
4
5
5
5
5
6
6
6
5000
10000
5000
10000
5000
10000
5000
10000
5000
10000
5000
10000
5000
10000
5000
10000
5000
1
6.5
1
6.5
0.5
4
4
4
4
4
99
68
99
98
96
98
93
96
93
96
98
57
95
92
92
96
97
89
59
90
84
77
80
73
77
73
10 (10)[b]
9 (1)[b]
9 (7)[b]
14 (4)[b]
19 (19)[b]
18 (3)[b]
20 (3)[b]
19 (4)[b]
20 (3)[b]
19 (4)[b]
14 (5)[b]
13 (2)[b]
<1
<1
<1
<1
<1
<1
<1
<1
<1
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
77
84
44
1
4
0.25
2.75
0.25
1.75
0.25
0.5
2.75
0.25
0.67
0.1
0.33
0.8
3
>95
>91
>91
>95
>96
>96
>95
>99
>99
>99
>99
>99
54
10000
20000
2000
5000
2000
97
96
>99
>99
>99
>99
>99
94
>99
>99
>99
<1
<1
<1
40
<1
<1
<1
5000
10000
20000
2000
5000
10000
0.15
0.33
1
>99
>99
>99
[a] The conversion and the amount of byproducts were determined by using GC analysis or 1H NMR spectroscopy. [b] Percentage of the saturated alcohol
3-phenylpropan-1-ol in brackets.
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a-Methylcinnamaldehyde
g
was reduced rapidly to a-
purity (98–99%) using methanol as the solvent and with S/C
up to 40000 (Scheme 3). Complex 2 (S/C=2000) catalyzed the
quantitative HY of benzaldehyde a (2m) into benzyl alcohol
(98%) in 16 h at 508C in the presence of 2 mol% of KOtBu
(Table 4, entry 3), whereas 1 shows poor activity (entries 1 and
2). Notably, with distilled a, complex 2 (S/C=5000) afforded
benzyl alcohol in 10 min.[12] The pincer complexes 4–6 were
more active than 1 and 2 and led to quantitative conversion at
a higher S/C ratio. The HY of a with 4 (S/C=10000 and 20000)
gave the selective reduction to benzyl alcohol (97 and 99%) in
8 h (entries 4 and 5). In a gram-scale reaction, 5 g of a (3.3m)
was converted to alcohol (92%, 20 h) by using a Parr autoclave
(20 atm of H2) at S/4=25000 (entry 6). With complex 5 (S/C=
20000), 98% of alcohol is obtained in 16 h (entry 8), whereas
less basic 6 was less active than 4 and 5 and afforded 60% of
alcohol (entry 9). Interestingly, with complex 4 and under
5 atm of H2, the electron-rich aldehyde c is reduced quantita-
tively and chemoselectively to 4-(dimethylamino)benzyl alco-
hol (>97%) at high S/C=10000–40000 in 1–22 h (entries 10–
12).
methylcinnamol (92–97%) with 4–6 (S/C=5000–20000) in
a shorter time (0.25–2.75 h) than f without the hydrogenation
of the C=C bond (Table 3, entries 13–19). The aliphatic alde-
hyde h was reduced rapidly and selectively to 1-hexanol (>
99%) by 4–6 (S/C=2000–10000) in 6 min to 1 h (entries 20–24
and 26–28). At higher S/5=20000, 94% conversion is achieved
in 3 h, but with a lower selectivity because of the formation of
condensation products (entry 25, see Supporting Information).
These results indicate that for aromatic and aliphatic alde-
hydes, the pincer complexes 4–9 are superior to the ampy
complexes 1 and 2 and can afford a high selectivity at a high
S/C ratio (2000–100000) and in a shorter time. The pincer com-
plexes 6 and 9 that bear dppf gave generally better results
compared to the catalysts with the more basic dppp and dppb
phosphanes. The presence of the orthometallated CNN terden-
tate ligand makes these complexes[47] thermally more stable
and catalytically more productive compared to the related
ampy catalysts. With regard to a,b-unsaturated aldehydes,
a high selectivity toward the formation of the allylic alcohol
was achieved with 2. Aldol condensation with acetone and
Claisen–Tischenko side reactions were observed mainly for aro-
matic aldehydes with electron-withdrawing groups, whereas
those with electron-donating groups gave chemoselective TH
to alcohols.
Cinnamaldehyde f was hydrogenated with 1 and 2 (S/C=
1000 and 2000) to cinnamol (87 and 89%, respectively) in 3
and 8 h (entries 13 and 14). Conversely, complexes 4 and 5
gave 89 and 90% of alcohol at a higher S/C (10000; entries 15
and 17). For substrate a, less basic 6 was less active than 4 and
5 and led to poor selectivity in the reduction of f (entry 18).
Complex 4 catalyzes the highly chemoselective HY of a-meth-
ylcinnamaldehyde g (S/C=15000) to attain the unsaturated al-
cohol (>99%) in 24 h (entry 19). With 4, hexanal h (S/C=5000)
is reduced rapidly to 1-hexanol with good selectivity (90%,
entry 20) in 1.5 h. In addition, thiophene-2-carbaldehyde i (1m)
Catalytic HY of aldehydes catalyzed by 1 and 2 and 4–6
The Ru derivatives 1 and 2 and 4–6 in the presence of KOtBu
were active in the hydrogenation (5–20 atm of H2) of aromatic,
conjugated, and aliphatic aldehydes of commercial-grade
Table 4. HY aldehydes (2m) catalyzed by 1 and 2 and 4–6 with KOtBu (2 mol%) in methanol at 508C (Biotageꢂ Endeavor).
Entry
Substrate
Complex
Loading
(S/C)
PH
[atm]
t
[h]
Conv.[a]
[%]
Alcohol[a]
[%]
Byproducts[a]
[%]
2
1
2
3
4
5
6
7
8
a
a
a
a
1
1
2
4
4
4
5
5
6
4
4
4
1
2
4
4
5
6
4
4
4
4
1000
2000
2000
10
10
10
10
10
20
10
10
13
5
3
8
16
8
35
22
100
100
100
92
98
99
63
100
98
98
95
98
99
96
99
80
100
99
33
7
98
97
99
92
98
98
60
>99
>97
>97
87
89
89
75
90
20
>99
90
2
15
2
3
1
0
2
1
3
<1
<1
<1
8
10000
20000
25000
10000
20000
10000
10000
20000
40000
1000
a
8
a[b]
a
20
16
16
16
1
7
22
3
8
8
8
8
a
a
c[c,d]
c[c,d]
c[c,d]
f
f
f
f
f
9
10
11
12
13
14
15
16
17
18
19
20
21
22
5
5
10
10
10
10
10
10
5
5
5
5
2000
9
10000
20000
10000
10000
15000
5000
10
21
11
60
<1
9
f
8
24
1.5
1
g[c]
h[c,d]
i[c,d]
i[c]
10000
5000
100
100
99
95
1
5
0.66
[a] Conversion and product distribution were determined by using GC analysis or 1H NMR spectroscopy. [b] [S]=3.3m, 5 g scale reaction in a Parr auto-
clave. [c] Parr autoclave. [d] [S]=1m.
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is transformed selectively to 2-thienylmethanol (99%) with S/
4=10000 (1 h), whereas at a higher substrate concentration
(2m) 95% of alcohol was formed (entries 21 and 22). The influ-
ence of the solvent in the HY of a was investigated for 4–6.
With 4 (S/C=10000) under 13 atm of H2 in MeOH, a is convert-
ed to alcohol (96%) in 16 h at 508C with 2 mol% of KOtBu
(Table 5, entry 1).
Conclusions
We have demonstrated that the easily accessible 2-(amino-
methyl)pyridine (ampy) complexes cis-[RuCl2(ampy)(PP)] [1 and
2; PP=1,4-bis(diphenylphosphino)butane, 1,1’-ferrocenediyl-
bis(diphenylphosphine)] and pincer [RuCl(CNNR)(PP)] [4–9;
PP=1,3-bis(diphenylphosphino)propane, 1,4-bis(diphenylphos-
phino)butane,
1,1’-ferrocenediyl-bis(diphenylphosphine);
HCNNR =4-substituted-2-aminomethyl-benzo[h]quinoline; R=
Me, Ph] are highly active catalysts for the reduction of com-
mercial-grade (97–99%) aromatic, aliphatic, and conjugated al-
dehydes to their corresponding primary alcohols through both
transfer hydrogenation (TH) with 2-propanol and hydrogena-
tion (HY; 5–20 atm of H2) in MeOH. The pincer catalysts 4–9
display a generally higher productivity than 1 and 2 for both
TH (substrate to catalyst ratio (S/C) up to 100000) and HY (S/C
up to 40000) of aromatic and aliphatic aldehydes. Conversely,
the ampy complexes 1 and 2 were more efficient for the che-
moselective reduction of unsaturated aldehydes, which thus
indicates that the best performance in terms of selectivity and
productivity can be achieved by the correct matching of the
substrate and catalyst. For both the ampy and pincer com-
plexes the type of diphosphine affects the aldehyde TH and
HY reactions strongly. On account of the formation of acetone
in the TH, cross aldol-condensation side products may form
during the catalysis, which depends on the electrophilic char-
acter of the formyl group. The ability of the pincer complexes
to catalyze the reduction of undistilled substrates at a high S/C
ratio makes them suitable systems for applications in the re-
duction of industrially relevant aldehydes. Further studies are
currently in progress to extend the use of ampy and pincer Ru
catalysts in other organic transformations.
Table 5. Effect of the solvent in the HY of a (2m) catalyzed by 4–6 (S/C=
10000) with 2 mol% of KOtBu under 13 atm of H2 in 16 h at 508C (Biot-
ageꢂ Endeavor).
[a]
Entry Complex Solvent
Conv.[a] Alcohol
Byproducts[a]
[%]
[%]
[%]
1
2
3
4
5
6
7
8
4
4
4
4
4
4
5
5
5
5
5
5
6
6
6
6
6
MeOH
100
96
93
88
86
58
10
98
97
97
80
82
6
60
19
18
16
18
4
7
12
11
21
1
2
3
3
10
18
0
3
4
5
3
11
MeOH/EtOH=3:1 100
MeOH/EtOH=1:1 100
MeOH/EtOH=1:3 100
EtOH
79
11
100
toluene[b]
MeOH
MeOH/EtOH=3:1 100
MeOH/EtOH=1:1 100
MeOH/EtOH=1:3
EtOH
toluene[b]
9
10
11
12
13
14
15
16
17
90
100
6
63
23
23
19
29
MeOH
MeOH/EtOH=3:1
MeOH/EtOH=1:1
MeOH/EtOH=1:3
EtOH
[a] Conversion was determined by using GC analysis or 1H NMR spectros-
copy. [b] The reaction was run for 32 h.
If we used MeOH/EtOH mixtures, complete conversion was
observed, but with a decrease of selectivity (93–86%, en-
tries 2–4), whereas in EtOH both lower conversion (79%) and
selectivity (58% of alcohol) were attained (entry 5). In toluene,
4 displays poor activity with the formation of only 10% of al-
cohol after 32 h (entry 6). A similar behavior was observed with
5, for which methanol was the solvent of choice, which led to
98% of alcohol in 16 h (entry 7), and 6% conversion was ach-
ieved in toluene (entry 12). Finally, complex 6 was less active
and led to 60 and 18% of alcohol in MeOH and EtOH, respec-
tively (entries 13 and 17). These data indicate that in the HY of
aldehydes with the pincer complexes[13b] the alcohol medium
plays a crucial role, and methanol is the solvent of choice. The
use of KOtBu in methanol results in the formation of the
weaker base KOMe, which is involved in the formation of the
catalytically active ruthenium hydride species from H2 via
a ruthenium-alkoxide-amide species.[13b] The comparison of the
activity of the ampy and pincer complexes in HY shows that al-
though the ampy dppf complex 2 is more active than the
dppb complex 1, for the pincer complexes the reverse behav-
ior is observed, and the dppp and dppb complexes 4 and 5
are superior to the dppf derivative 6.
Experimental Section
General: All reactions were performed under an Ar atmosphere
using standard Schlenk techniques. The aldehydes a (99%), f
(98%), g (97%), and h (98%) were purchased from Alfa Aesar;
b (99%) and d (98%) were from Aldrich; and c (99%) was from
Merck and used without further purification, whereas e was pre-
pared from 4-formylbenzoic acid.[54] Methanol (100%), ethanol
(99.7%), and toluene (99%) were from VWR, whereas 2-propanol
(99.7%) was from Alfa Aesar and used as received. All other chemi-
cals were from Aldrich and Alfa Aesar. Complexes 1 and 2 were ob-
tained from Alfa Aesar, whereas 4–9 were prepared according to
a procedure reported previously.[51a] NMR spectra were recorded by
using a Bruker AC 200, and the chemical shifts [ppm] are relative
to TMS for 1H and 13C{1H} NMR spectra. GC analyses were per-
formed by using a Varian GP-3380 gas chromatograph with a MEG-
ADEX-ETTBDMS-b column of 25 m of length, internal diameter
0.25 mm, column pressure 5 psi, H2 as carrier gas, and a flame ioni-
zation detector (FID). The injector and detector temperature was
2508C. Program used: initial T=1508C ramped to 1908C at
38CminÀ1 and then to 2208C at 208CminÀ1. The hydrogenation ex-
periments were performed by using a Biotageꢂ Endeavor and
a Parr autoclave.
Procedure for the TH of aldehydes: The selected aldehyde
(1 mmol), K2CO3 (6.9 mg; 0.05 mmol), and 2-propanol (8 mL) were
introduced into a Schlenk, subjected to three vacuum–Ar cycles,
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Full Papers
bereiner, R. H. Crabtree, Chem. Rev. 2010, 110, 681; e) J. Zhang, M. Gan-
delman, L. J. W. Shimon, D. Milstein, Dalton Trans. 2007, 107.
[8] a) N. T. Fairweather, M. S. Gibson, H. Guan, Organometallics 2015, 34,
335; b) S. Werkmeister, K. Junge, M. Beller, Org. Process Res. Dev. 2014,
18, 289; c) A. P. Dub, T. Ikarya, ACS Catal. 2012, 2, 1718; d) E. Balaraman,
C. Gunanathan, J. Zhang, L. J. W. Shimon, D. Milstein, Nat. Chem. 2011,
3, 609; e) E. Fogler, E. Balaraman, Y. Ben-David, G. Leitus, L. J. W. Shimon,
D. Milstein, Organometallics 2011, 30, 3826.
[9] a) J. Leonard, A. J. Blacker, S. P. Marsden, M. F. Jones, K. R. Mulholland, R.
Newton, Org. Process Res. Dev. 2015, 19, 1400; b) D. Spasyuk, C. Vicent,
D. G. Gusev, J. Am. Chem. Soc. 2015, 137, 3743; c) E. J. Derrah, M. Hana-
uer, P. N. Plessow, M. Schelwies, M. K. da Silva, T. Schaub, Organometal-
lics 2015, 34, 1872; d) A. J. A. Watson, B. N. Atkinson, A. C. Maxwell,
J. M. J. Williams, Adv. Synth. Catal. 2013, 355, 734; e) J. R. Zbieg, E. L.
McInturff, M. J. Krische, Org. Lett. 2010, 12, 2514; f) A. Denichoux, T. Fu-
kuyama, T. Doi, J. Horiguchi, I. Ryu, Org. Lett. 2010, 12, 1.
[10] a) G. Chelucci, S. Baldino, W. Baratta, Coord. Chem. Rev. 2015, 300, 29;
b) G. Chelucci, S. Baldino, W. Baratta, Acc. Chem. Res. 2015, 48, 363.
[11] W. Baratta, E. Herdtweck, K. Siega, M. Toniutti, P. Rigo, Organometallics
2005, 24, 1660.
[12] E. Putignano, G. Bossi, P. Rigo, W. Baratta, Organometallics 2012, 31,
1133.
[13] a) W. Baratta, G. Chelucci, S. Gladiali, K. Siega, M. Toniutti, M. Zanette, E.
Zangrando, P. Rigo, Angew. Chem. Int. Ed. 2005, 44, 6214; Angew. Chem.
2005, 117, 6370; b) W. Baratta, S. Baldino, M. J. Calhorda, P. J. Costa, G.
Esposito, E. Herdtweck, S. Magnolia, C. Mealli, A. Messaoudi, S. A.
Mason, L. F. Veiros, Chem. Eur. J. 2014, 20, 13603.
and the system was put in an oil bath at 908C. From a 250 mm so-
lution of the Ru complex in 2-propanol, 2 mL (0.5 mmol of Ru) was
added to the mixture heated to reflux to reach a final volume of
10 mL. The reaction was sampled by the removal of an aliquot of
the reaction mixture, the addition of diethyl ether (1:1 in volume),
and filtration through a short silica pad before the conversion was
determined by GC analysis. For solid and high-boiling compounds,
the solvent was evaporated by gentle heating under vacuum, and
1
the crude mixture was dissolved in CDCl3 and analyzed by H NMR
spectroscopy; S/C=2000, K2CO3 5 mol%.
Procedure for the HY of aldehydes: In a 10 mL glass tube, the se-
lected Ru catalyst (0.001 mmol) and aldehyde (10 mmol) were dis-
solved in MeOH (4 mL) and 0.2 mL of a 1.0m solution of KOtBu
(0.2 mmol) in tert-butanol was added. The tube was put in an En-
deavour apparatus, the system was filled and vented under stirring
four times with N2, then four times with H2 (without stirring), and
finally charged to the desired H2 pressure. The system was kept at
508C for the appropriate time, and the reaction was sampled by
the removal of an aliquot of the reaction mixture (approximately
0.5 mL), followed by the addition of diethyl ether (2.5 mL). After fil-
tration through a short silica pad, the conversion was determined
by GC analysis; S/C=10000, KOtBu 2 mol%, aldehyde 2m.
[14] a) W. Baratta, G. Bossi, E. Putignano, P. Rigo, Chem. Eur. J. 2011, 17,
3474; b) G. Bossi, E. Putignano, P. Rigo, W. Baratta, Dalton Trans. 2011,
40, 8986.
Acknowledgements
We thank Dr. P. Martinuzzi (Universitꢀ di Udine) for assistance
with NMR spectroscopy.
[15] J. Seyden-Penne, Reductions by the Alumino- and Borohydrides in Organ-
ic Synthesis, VCH, New York, 1991.
[16] S. Nishimura, Handbook of Heterogeneous Catalytic Hydrogenation for
Organic Synthesis, Wiley-VCH, New York, 2001, 700 pp..
[17] a) H. Chen, D. A. Cullen, J. Z. Larese, J. Phys. Chem. C 2015, 119, 28885;
b) H. Liu, Z. Li, Y. Li, Ind. Eng. Chem. Res. 2015, 54, 1487; c) L. J. Malobela,
J. Heveling, W. G. Augustyn, L. M. Cele, Ind. Eng. Chem. Res. 2014, 53,
13910; d) J. Hꢃjek, N. Kumar, T. Salmi, D. Yu. Murzin, H. Karhu, J. Vayry-
nen, L. Cerveny, I. Paseka, Ind. Eng. Chem. Res. 2003, 42, 295; e) G. Neri,
L. Bonaccorsi, L. Mercadante, S. Galvagno, Ind. Eng. Chem. Res. 1997, 36,
3554.
[18] a) M. L. Clarke, G. J. Roff, Handbook of Homogeneous Hydrogenation,
Vol. 1 (Eds.: J. G. de Vries, C. J. Elsevier), Wiley-VCH, Weinheim, 2007,
pp. 413; b) L. A. Saudan, Acc. Chem. Res. 2007, 40, 1309.
[19] a) J. R. Miecznikowski, R. H. Crabtree, Organometallics 2004, 23, 629;
b) Y.-M. He, Q.-H. Fan, ChemCatChem 2015, 7, 398; c) D. Talwar, X. Wu,
O. Saidi, N. Poyatos Salguero, J. Xiao, Chem. Eur. J. 2014, 20, 12835; d) Y.
Wei, D. Xue, Q. Lei, C. Wang, J. Xiao, Green Chem. 2013, 15, 629; e) M. V.
Jimꢅnez, J. Fernꢃndez-Tornos, J. J. Pꢅrez-Torrente, F. J. Modrego, S. Win-
terle, C. Cunchillos, F. J. Lahoz, L. A. Oro, Organometallics 2011, 30,
5493; f) Y. Himeda, N. Onozawa-Komatsuzaki, S. Miyazawa, H. Sugihara,
T. Hirose, K. Kasuga, Chem. Eur. J. 2008, 14, 11076; g) X. Wu, C. Corcoran,
S. Yang, J. Xiao, ChemSusChem 2008, 1, 71; h) X. Wu, J. Liu, X. Li, A. Za-
notti-Gerosa, F. Hancock, D. Vinci, J. Ruan, J. Xiao, Angew. Chem. Int. Ed.
2006, 45, 6718; Angew. Chem. 2006, 118, 6870; i) C. M. Beck, S. E. Rath-
mill, Y. J. Park, J. Chen, R. H. Crabtree, L. M. Liable-Sands, A. L. Rheingold,
Organometallics 1999, 18, 5311.
Keywords: alcohols
hydrogenation · ruthenium
·
aldehydes
·
hydrogen transfer
·
[1] a) M. Yoshimura, S. Tanaka, M. Kitamura, Tetrahedron Lett. 2014, 55,
3635; b) G. Shang, W. Li, X. Zhang, Catalytic Asymmetric Synthesis 3rd ed.
(Ed.: I. Ojima), Wiley, Hoboken, 2010, Chap. 7; c) The Handbook of Ho-
mogeneous Hydrogenation, Vols. 1–3 (Eds.: J. G. de Vries, C. J. Elsevier),
Wiley-VCH, Weinheim, 2007; d) Transition Metals for Organic Synthesis
2nd ed. (Eds. M. Beller, C. Bolm), Wiley-VCH, Weinheim, 2004, p. 29;
e) Asymmetric Catalysis on Industrial Scale (Eds.: H.-U. Blaser, E. Schmidt),
Wiley-VCH, Weinheim, 2004.
[2] a) D. Wang, D. Astruc, Chem. Rev. 2015, 115, 6621; b) F. Foubelo, C.
Nꢃjera, M. Yus, Tetrahedron: Asymmetry 2015, 26, 769; c) J. Ito, H. Nish-
iyama, Tetrahedron Lett. 2014, 55, 3133; d) R. H. Morris, Chem. Soc. Rev.
2009, 38, 2282; e) W. Baratta, P. Rigo, Eur. J. Inorg. Chem. 2008, 4041;
f) C. Wang, X. Wu, J. Xiao, Chem. Asian J. 2008, 3, 1750; g) T. Ikariya, A. J.
Blacker, Acc. Chem. Res. 2007, 40, 1300; h) J. S. M. Samec, J. E. Bꢄckvall,
P. G. Andersson, P. Brandt, Chem. Soc. Rev. 2006, 35, 237.
[3] J. Magano, J. R. Dunetz, Org. Process Res. Dev. 2012, 16, 1156.
[4] a) M. V. Nora de Souza, T. R. A. Vasconcelos, Appl. Organomet. Chem.
2006, 20, 798; b) E. R. Burkhardt, K. Matos, Chem. Rev. 2006, 106, 2617.
[5] a) K. J. Haack, S. Hashiguchi, A. Fujii, T. Ikariya, R. Noyori, Angew. Chem.
Int. Ed. Engl. 1997, 36, 285; Angew. Chem. 1997, 109, 297; b) H. Doucet,
T. Ohkuma, K. Murata, T. Yokozawa, M. Kozawa, E. Katayama, A. F. Eng-
land, T. Ikariya, R. Noyori, Angew. Chem. Int. Ed. 1998, 37, 1703; Angew.
Chem. 1998, 110, 1792.
[20] a) J. W. Faller, A. R. Lavoie, Organometallics 2002, 21, 3493; b) I. Yamada,
R. Noyori, Org. Lett. 2000, 2, 3425.
[21] P. Kumar, A. K. Singh, S. Sharma, D. S. Pandey, J. Organomet. Chem.
2009, 694, 3643.
[6] a) H. A. Younus, W. Su, N. Ahmad, S. Chen, F. Verpoort, Adv. Synth. Catal.
2015, 357, 283; b) C. Gunanathan, D. Milstein, Chem. Rev. 2014, 114,
12024; c) H. A. Younus, N. Ahmad, W. Su, F. Verpoort, Coord. Chem. Rev.
2014, 276, 112; d) S. Schneider, J. Meiners, B. Askevold, Eur. J. Inorg.
Chem. 2012, 412; e) J. M. Serrano-Becerra, D. Morales-Morales, Curr. Org.
Synth. 2009, 6, 169; f) D. Benito-Garagorri, K. Kirchner, Acc. Chem. Res.
2008, 41, 201.
[7] a) K-N. T. Tseng, J. W. Kampf, N. K. Szymczak, ACS Catal. 2015, 5, 5468;
b) S. Muthaiah, S. H. Hong, Adv. Synth. Catal. 2012, 354, 3045; c) T. C.
Johnson, D. J. Morris, M. Wills, Chem. Soc. Rev. 2010, 39, 81; d) G. E. Do-
[22] H. Imai, T. Nishiguchi, K. Fukuzumi, J. Org. Chem. 1976, 41, 665.
[23] D. J. Darensbourg, F. Joo, M. Kannisto, A. Katho, J. H. Reibenspies, Orga-
nometallics 1992, 11, 1990.
[24] I. Szatmꢃri, G. Papp, F. Joꢆ, ꢇ. Kathꢆ, Catal. Today 2015, 247, 14.
ˇ
[25] S. Sabata, J. Vcelak, J. Hetflejs, Collect. Czech. Chem. Commun. 1995, 60,
127.
[26] A. N. Kharat, A. Bakhoda, B. T. Jahromi, Inorg. Chem. Commun. 2011, 14,
1161.
[27] M. Zhao, Z. Yu, S. Yan, Y. Li, Tetrahedron Lett. 2009, 50, 4624.
[28] S. Naskar, M. Bhattacharjee, J. Organomet. Chem. 2005, 690, 5006.
ChemCatChem 2016, 8, 1 – 11
www.chemcatchem.org
9
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
These are not the final page numbers! ÞÞ

Full Papers
[29] a) B. Deb, P. P. Sarmah, D. K. Dutta, Eur. J. Inorg. Chem. 2010, 1710; b) B.
Deb, B. J. Borah, B. J. Sarmah, B. Das, D. K. Dutta, Inorg. Chem. Commun.
2009, 12, 868; c) S. Bhaduri, K. Sharma, D. Mukesh, J. Chem. Soc. Dalton
Trans. 1992, 77; d) S. Bhaduri, K. Sharma, J. Chem. Soc. Chem. Commun.
1988, 173.
[30] W. Baratta, K. Siega, P. Rigo, Adv. Synth. Catal. 2007, 349, 1633.
[31] For MPV reductions see: a) A. L. Wilds, Org. React. 1944, 2, 178; b) B.
Verley, Bull. Soc. Chim. Fr. 1925, 37, 537; c) B. Verley, Bull. Soc. Chim. Fr.
1927, 41, 788; d) W. Ponndorf, Angew. Chem. 1926, 39, 138. For reviews
on MPV see: e) J. S. Cha, Org. Process Res. Dev. 2006, 10, 1032; f) C. R.
Graves, E. J. Campbell, S. T. Nguyen, Tetrahedron: Asymmetry 2005, 16,
3460.
[32] a) C. P. Casey, H. Guan, Organometallics 2012, 31, 2631; b) C. P. Casey,
S. E. Beetner, J. B. Johnson, J. Am. Chem. Soc. 2008, 130, 2285; c) Y.
Blum, D. Czarkie, Y. Rahamin, Y. Shvo, Organometallics 1985, 4, 1459.
[33] A. B. Chaplin, P. J. Dyson, Organometallics 2007, 26, 4357.
[34] a) T. Miyada, E. H. Kwan, M. Yamashita, Organometallics 2014, 33, 6760;
b) I. Warad, H. Al-Hussain, R. Al-Far, R. Mahfouz, B. Hammouti, T. Ben
Hadda, Spectrochim. Acta Part A 2012, 95, 374; c) L. G. Melean, M. Rodri-
guez, A. Gonzꢃlez, B. Gonzꢃlez, M. Rosales, P. J. Baricelli, Catal. Lett.
2011, 141, 709; d) S. Jimꢅnez, J. A. Lꢆpez, M. A. Ciriano, C. Tejel, A. Martꢈ-
nez, R. A. Sꢃnchez-Delgado, Organometallics 2009, 28, 3193.
[35] K. E. Jolley, A. Zanotti-Gerosa, F. Hancock, A. Dyke, D. M. Grainger, J. A.
Medlock, H. G. Nedden, J. J. M. Le Paih, S. J. Roseblade, A. Seger, V. Siva-
kumar, I. Prokes, D. J. Morris, M. Wills, Adv. Synth. Catal. 2012, 354, 2545.
[36] a) P. Dupau, L. Bonomo, L. Kermorvan, Angew. Chem. Int. Ed. 2013, 52,
11347; Angew. Chem. 2013, 125, 11557; b) L. Bonomo, L. Kermorvan, P.
Dupau, ChemCatChem 2015, 7, 907.
Jpn. 1982, 55, 504; c) H. Horino, T. Ito, A. Yamamoto, Chem. Lett. 1978,
17.
[43] S. Omura, T. Fukuyama, Y. Murakami, H. Okamoto, I. Ryu, Chem.
Commun. 2009, 6741.
[44] A. Sorkau, K. Schwarzer, C. Wagner, E. Poetsch, D. Steinborn, J. Mol.
Catal. A 2004, 224, 105.
[45] N. Menashe, Y. Shvo, Organometallics 1991, 10, 3885.
[46] M.-O. Simon, S. Darses, Adv. Synth. Catal. 2010, 352, 305.
[47] B. Liu, F. Hu, B.-F. Shi, ACS Catal. 2015, 5, 1863. Osmium: a) P. Barrio,
M. A. Esteruelas, E. Onate, Organometallics 2004, 23, 1340; iridium: b) C.
Tejel, M. A. Ciriano, V. Passarelli, Chem. Eur. J. 2011, 17, 91; c) T. Suzuki, T.
Yamada, T. Matsuo, K. Watanabe, T. Katoh, Synlett 2005, 1450; d) T.
Suzuki, T. Yamada, K. Watanabe, T. Katoh, Bioorg. Med. Chem. Lett. 2005,
15, 2583; e) S. H. Bergens, D. P. Fairlie, B. Bosnich, Organometallics 1990,
9, 566; nickel: f) S. Ogoshi, Y. Hoshimoto, M. Ohashi, Chem. Commun.
2010, 46, 3354; g) Y. Hoshimoto, M. Ohashi, S. Ogoshi, J. Am. Chem. Soc.
2011, 133, 4668.
[48] M. B. Smith, J. March, Advanced Organic Chemistry, 5th ed., New York,
Wiley Interscience, 2001, p. 1218.
[49] a) P. D. Bolton, M. Grellier, N. Vautravers, L. Vendier, S. Sabo-Etienne, Or-
ganometallics 2008, 27, 5088; b) W. Baratta, A. Del Zotto, G. Esposito, A.
Sechi, M. Toniutti, E. Zangrando, P. Rigo, Organometallics 2004, 23,
6264; c) J. N. Coalter III, J. C. Huffman, K. G. Caulton, Organometallics
2000, 19, 3569.
[50] L. A. Saudan, C. M. Saudan, C. Debieux, P. Wyss, Angew. Chem. Int. Ed.
2007, 46, 7473; Angew. Chem. 2007, 119, 7617.
[51] a) S. Facchetti, V. Jurcik, S. Baldino, S. Giboulot, H. G. Nedden, A. Zanot-
ti-Gerosa, A. Blackaby, R. Bryan, A. Boogaard, D. B. McLaren, E. Moya, S.
Reynolds, K. S. Sandham, P. Martinuzzi, W. Baratta, Organometallics
2016, 35, 277; b) W. Baratta, L. Fanfoni, S. Magnolia, K. Siega, P. Rigo,
Eur. J. Inorg. Chem. 2010, 1419; c) W. Baratta, M. Ballico, S. Baldino, G.
Chelucci, E. Herdtweck, K. Siega, S. Magnolia, P. Rigo, Chem. Eur. J. 2008,
14, 9148.
[52] The separation of acetone and 2-propanol is a key operation in industri-
al biocatalysis. See: J. Tao, G. Q. Lin, A. Liese, Biocatalysis for the Pharma-
ceutical Industry: Discovery, Development, and Manufacturing, Wiley,
Weinheim, 2009, Chap. 4.
[53] a) C. F. de Graauw, J. A. Peters, H. Bekkum, J. Huskens, Synthesis 1994,
1007; b) D. Wang, C. Deraedt, J. Ruiz, D. Astruc, J. Mol. Catal. A 2015,
400, 14.
[54] Compound e was prepared following the procedure for the synthesis
of a tBu ester (see Supporting Information): S. E. Bode, D. Drochner, M.
Mꢀller, Angew. Chem. Int. Ed. 2007, 46, 5916; Angew. Chem. 2007, 119,
6020.
[37] H. Adkins, R. M. Elofson, A. G. Rossow, C. C. Robinson, J. Am. Chem. Soc.
1949, 71, 3622.
[38] a) S. E. Clapham, A. Hadzovic, R. H. Morris, Coord. Chem. Rev. 2004, 248,
2201; b) P. Espinet, A. C. Albꢅniz, Fundamentals of Molecular Catalysis,
Current Methods in Inorganic Chemistry, Vol. 3 (Eds. H. Kurosawa, A. Ya-
mamoto), Elsevier, Amsterdam, 2003, Chap. 6, p. 328; c) Recent Advan-
ces in Hydride Chemistry (Eds.: M. Peruzzini, R. Poli), Elsevier, Amsterdam,
2001.
[39] a) A. M. P. Koskinen, A. O. Kataja, Org. React. 2015, DOI: 10.1002/
0471264180.or086.02; b) T. Werner, J. Koch, Eur. J. Org. Chem. 2010,
6904; c) K. Ekoue-Kovi, C. Wolf, Chem. Eur. J. 2008, 14, 6302; d) T. Seki, T.
Nakajo, M. Onaka, Chem. Lett. 2006, 35, 824; e) R. Mahrwald, Curr. Org.
Chem. 2003, 7, 1713; f) O. L. Toermaenkangas, A. M. P. Koskinen, Recent
Res. Dev. Org. Chem. 2001, 5, 115; g) L. Claisen, Chem. Ber. 1887, 20, 646.
[40] T. A. Geissman, Org. React. 1944, 2, 94.
[41] a) S. P. Curran, S. J. Connon, Org. Lett. 2012, 14, 1074; b) B. M. Day, N. E.
Mansfield, M. P. Coles, P. B. Hitchcock, Chem. Commun. 2011, 47, 4995;
c) L. Cronin, F. Manoni, C. J. O’Connor, S. J. Connon, Angew. Chem. Int.
Ed. 2010, 49, 3045; Angew. Chem. 2010, 122, 3109; d) M. R. Crimmin,
A. G. M. Barrett, M. S. Hill, P. A. Procopiou, Org. Lett. 2007, 9, 331.
[42] a) S.-I. Murahashi, T. Naota, K. Ito, Y. Maeda, H. Taki, J. Org. Chem. 1987,
52, 4319; b) T. Ito, H. Horino, Y. Koshiro, A. Yamamoto, Bull. Chem. Soc.
Received: April 10, 2016
Published online on && &&, 0000
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S. Baldino, S. Facchetti, A. Zanotti-Gerosa,
H. G. Nedden, W. Baratta*
&& – &&
Transfer Hydrogenation and
Hydrogenation of Commercial-Grade
Aldehydes to Primary Alcohols
Catalyzed by 2-(Aminomethyl)pyridine
and Pincer Benzo[h]quinoline
Ruthenium Complexes
Transfer Hydrogenation and Hydroge-
nation: Ruthenium 2-(aminomethyl)pyr-
idine and benzo[h]quinoline pincer
alcohols by transfer hydrogenation with
2-propanol and hydrogenation with H2
at substrate/catalyst ratios up to
100000.
complexes efficiently catalyze the reduc-
tion of commercial-grade aldehydes to
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