Cobalt-Catalyzed Hydrogenation of Esters to Alcohols: Unexpected Reactivity Trend Indicates Ester Enolate Intermediacy

Article abstract of DOI:10.1002/anie.201502418

The atom-efficient and environmentally benign catalytic hydrogenation of carboxylic acid esters to alcohols has been accomplished in recent years mainly with precious-metal-based catalysts, with few exceptions. Presented here is the first cobalt-catalyzed hydrogenation of esters to the corresponding alcohols. Unexpectedly, the evidence indicates the unprecedented involvement of ester enolate intermediates. Getting involved: The atom-efficient and environmentally benign catalytic hydrogenation of carboxylic acid esters to alcohols has been accomplished in recent years mainly with precious-metal-based catalysts. Presented here is the first cobalt-catalyzed hydrogenation of esters to alcohols. Unexpectedly, the evidence indicates the unprecedented involvement of ester enolate intermediates.

Full text of DOI:10.1002/anie.201502418

Angewandte
Chemie
International Edition: DOI: 10.1002/anie.201502418
German Edition: DOI: 10.1002/ange.201502418
Homogeneous Catalysis
Hot Paper
Cobalt-Catalyzed Hydrogenation of Esters to Alcohols: Unexpected
Reactivity Trend Indicates Ester Enolate Intermediacy**
Dipankar Srimani, Arup Mukherjee, Alexander F. G. Goldberg, Gregory Leitus, Yael Diskin-
Posner, Linda J. W. Shimon, Yehoshoa Ben David, and David Milstein*
Abstract: The atom-efficient and environmentally benign
catalytic hydrogenation of carboxylic acid esters to alcohols
has been accomplished in recent years mainly with precious-
metal-based catalysts, with few exceptions. Presented here is the
first cobalt-catalyzed hydrogenation of esters to the corre-
sponding alcohols. Unexpectedly, the evidence indicates the
unprecedented involvement of ester enolate intermediates.
The replacement of expensive noble-metal catalysts by
earth-abundant metal catalysts is an important goal. How-
ever, the tendency of first-row transition-metal complexes to
react by one-electron pathways, rather than by the prevailing
two-electron transformations of second- and third-row
metals, can make it difficult to envisage and control catalytic
reactivity.[9] Nevertheless, noteworthy progress has been
made in the area of homogeneous earth-abundant metal
hydrogenation catalysts.[10–12] Recently we and other groups
have developed several iron-based catalysts for the hydro-
genation of alkynes, ketones, aldehydes, and esters.[13] Very
recently, substantial efforts were made towards the develop-
ment of cobalt catalysts for homogeneous hydrogenation.[14,15]
Chirik and co-workers developed diiminopyridine cobalt
catalysts for olefin hydrogenation at room temperature,[14c]
and for asymmetric hydrogenation of substituted styrenes.[14d]
Hanson and co-workers developed an aliphatic PNP pincer
cobalt(II) alkyl catalyst for the hydrogenation of aldehydes,
ketones, imines, and alkenes, and dehydrogenation of secon-
dary alcohols to ketones.[14a,b] However, the more demanding
hydrogenation of ester derivatives by cobalt complexes has
not been accomplished so far. Herein we report the first
hydrogenation of esters catalyzed by a cobalt pincer complex.
Unexpectedly, a mechanism involving ester enolate interme-
diacy is likely operative.
R
eduction of esters to alcohols is a key industrial process for
the production of agrochemicals, pharmaceuticals, flavors,
and fragrances.[1] The reduction generally involves the use of
stoichiometric amounts of metal hydride reagents, such as
LiAlH4, NaBH4, and their derivatives, thus resulting in the
generation of stoichiometric amounts of waste, low func-
tional-group tolerance, and hazardous reagents.[2] In contrast,
the catalytic hydrogenation of esters to alcohols is environ-
mentally benign, waste-free, and fully atom-economical.
Industrially, hydrogenations of fatty acid esters are achieved
by using heterogeneous catalysts which require very high
temperatures and pressures. To overcome these limitations
some homogeneous catalytic systems for the hydrogenation
of esters were reported.[3–5] In 2006, we reported the first mild,
low-pressure hydrogenation of non-activated aromatic and
aliphatic esters, catalyzed by a pincer ruthenium complex.[6]
A
year later, Firmenich researchers reported the hydrogenation
of esters using bidentate amino phosphine or tetradentate
imino phosphine ligands.[7] Since then, the catalytic hydro-
genation of activated and non-activated esters and lactones
has progressed rapidly and several bifunctional catalysts for
this reaction have been developed.[8]
The complexes 1,[16] 2, and 3 (Figure 1) were synthesized
by the treatment of CoCl2 with 1.2 equivalents of the
corresponding pincer ligand in THF. The new cobalt(II)
[*] Dr. D. Srimani, Dr. A. Mukherjee, Dr. A. F. G. Goldberg,
Y. Ben David, Prof. Dr. D. Milstein
Department of Organic Chemistry, Weizmann Institute of Science
Rehovot, 76100 (Israel)
E-mail: david.milstein@weizmann.ac.il
Figure 1. Cobalt pincer complexes.
Dr. D. Srimani
Department of Chemistry, Indian Institute of Technology Guwahati
Guwahati 781039, Assam (India)
Dr. G. Leitus, Dr. Y. Diskin-Posner, Dr. L. J. W. Shimon
Chemical Research Support, Weizmann Institute of Science
76100 Rehovot (Israel)
complexes 2 and 3 were crystallographically characterized
(Figure 2; see the Supporting Information for details). The
complex 2 exhibits a trigonal bipyramidal structure, while the
structure of 3 is close to a square pyramid, probably because
of steric reasons involving the NEt2 group.
Our initial attempts were focused on assessing the
catalytic activity of the cobalt pincer complexes, upon
activation with NaHBEt3, for the hydrogenation of esters.
Thus, the precatalyst 1 (2 mol%) was treated with 2 equiv-
alents of NaHBEt3 and used for the hydrogenation of
[**] This research was supported by the European Research Council
under the FP7 framework (ERC No 246837) and by the Israel
Science Foundation. D.M. holds the Israel Matz Professorial Chair
of Organic Chemistry. D.S. is thankful to DST-INSPIRE Grant (DST/
INSPIRE/04/2014/001130). A.F.G.G. thanks the Azrieli Foundation
for the award of an Azrieli Postdoctoral Fellowship.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201502418.
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a precatalyst for the hydrogenation of cyclohexyl hexanoate.
To our delight, under similar reaction conditions used for the
precatalyst 1, 2 gave 85% yield of cyclohexanol with the
formation of 79% hexanol (Table 1, entry 2). The complex 3,
under the same reaction conditions, gave a lower yield (67%)
of cyclohexanol (entry 3). Increasing the loading of 2 to
4 mol% and the reaction time to 65 hours did not result in
significantly higher yield of cyclohexanol (88%; entry 4).
Activation of the 2 with only 1 equivalent of NaHBEt3 gave
a lower yield of cyclohexanol under similar hydrogenation
conditions (entry 5). The amount of the base has a significant
effect on the yield of the ester hydrogenation reaction.
Increasing the precatalyst/base ratio to 1:12.5 increased the
yield of cyclohexanol (99%), whereas decreasing the ratio to
1:2 gave only 20% product (entries 7 and 8). Without reacting
the pre-catalyst with NaHBEt3 only a moderate yield (50%)
was obtained even at high precatalyst/base ratio (1:12.5;
entry 9). Decreasing the precatalyst loading to 1 mol% gave
54% yield after 70 hours in the presence of 14 mol% base
(entry 10). Among the different bases, tBuOK was found to
be better than NaOMe, NaOEt, and potassium bis(trimethyl-
silyl)amide (KHMDS), and among the solvents screened,
THF was a better choice than toluene or 1,4-dioxane
(entries 11–15).
Next, the scope of the reaction was examined with various
esters, including primary, secondary, and tertiary aliphatic
esters. Thus, 1 mmol of cyclohexyl hexanoate under 50 bar
pressure of H2 at 1308C in THF, in the presence of 2 (2 mol%)
gave 85% yield of cyclohexanol and 79% yield of hexanol
after 38 hours (Table 2, entry 1). A small amount of hexyl
hexanoate was also observed as a result of the transesterifi-
cation reaction between the formed hexanol and cyclohexyl
hexanoate. Under similar reaction conditions, hexyl hexa-
noate gave 67% yield of hexanol after 43 hours. By increasing
the precatalyst loading to 4 mol%, the yield of hexanol
increased to 87% (entry 2). Similarly, pentyl pentanoate gave
67 and 85% pentanol by using 2 and 4 mol% precatalyst,
respectively (entry 3). Under similar reaction conditions,
other aliphatic esters also gave good yields of the hydro-
genated product. g-Valerolactone gave a moderate yield
(50%) of 1,4-pentanediol (entry 11).
Aliphatic esters are normally considered to be more
challenging substrates for catalytic hydrogenation than aro-
matic ones because of the generally higher electophilicity of
the carbonyl carbon atom in the latter, thus making hydride
transfer to the carbonyl group of aromatic esters more facile.
Very surprisingly, this was not the case in the reactions
reported here. Thus, methyl benzoate was not hydrogenated
at all under similar reaction conditions. (Table 2, entry 12).
Also, 2,2,2-trifluoroethyl trifluoroacetate, which is expected
to be even more activated towards hydride transfer to the
carbonyl group, remained unreacted (entry 13). In light of this
unexpected inverse reactivity in the hydrogenation reaction
we envisioned that the hydrogenation reaction might proceed
by the enolate form of the ester, which is in equilibrium with
the ester under the basic reaction conditions, and hence non-
enolizable esters do not react. Mechanistically, the enolate
can undergo hydrogenation to generate the salt of a hemi-
acetal intermediate which can form an aldehyde and alkoxide,
Figure 2. a) Molecular structure of 2 with thermal ellipsoids set at
50% probability. Hydrogens except H2 on the amine were omitted for
clarity.[21] Selected bond lengths [ꢀ] and angles [8]: Co1–N1 2.0902(13),
Co1–N2 2.2679(12) Co1–Cl2 2.2938(5), Co1–Cl1 2.3027(5), Co1–P1
2.4938(4), N2–H2 0.85(2); N1-Co1-N2 76.71(5), N1-Co1-Cl2 128.81(4),
N2-Co1-Cl2 97.28(4), N1-Co1-Cl1 104.02(4), N2-Co1-Cl1 89.38(4), Cl2-
Co1-Cl1 126.934(17), N1-Co1-P1 79.83(4), N2-Co1-P1 156.49(3),
Cl2-Co1-P1 96.295(16), Cl1-Co1-P1 97.656(16). b) Molecular structure
of 3 with thermal ellipsoids set at 50% probability. Hydrogens were
omitted for clarity. Selected bond lengths [ꢀ] and angles [8]: Co1–N1
2.1783(11), Co1–N2 2.2430(12), Co1–Cl2 2.3081(4), Co1–Cl1
2.3244(4), Co1–P1 2.4724(4); N1-Co1-N2 75.88(4), N1-Co1-Cl2
160.77(3), N2-Co1-Cl2 97.72(3), N1-Co1-Cl1 95.99(3), N2-Co1-Cl1
97.71(3), Cl2-Co1-Cl1 102.877(14), N1-Co1-P1 78.04(3), N2-Co1-P1
142.37(3), Cl2-Co1-P1 98.075(14), Cl1-Co1-P1 111.639(14).
cyclohexyl hexanoate under 50 bar H2 pressure at 1308C in
THF in the presence of 25 mol% tBuOK. Only 27% yield of
cyclohexanol and 11% yield of 1-hexanol were obtained after
38 hours (Table 1, entry 1).
Table 1: Optimization of the reaction conditions for cobalt-catalyzed
hydrogenation of esters.[a]
Entry Precatalyst NaHBEt3 Base
t [h] Solvent Base
Yield
[%][b]
(mol%)
(mol%) (mol%)
1
2
3
4
5
6
7
8
9
1 (2)
2 (2)
3 (2)
2 (4)
2 (2)
2 (4)
2 (4)
2 (4)
2 (4)
2 (1)
2 (2)
2 (2)
4
4
4
8
2
8
8
8
–
2
4
4
25
25
25
25
25
16
50
8
50
14
25
25
38 THF
38 THF
38 THF
65 THF
38 THF
65 THF
48 THF
65 THF
48 THF
72 THF
tBuOK
27
85
67
88
65
70
99
20
50
54
41
32
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
10
11
12
38 toluene tBuOK
38 1,4- tBuOK
dioxane
13
14
15
2 (2)
2 (2)
2 (2)
4
4
4
25
25
25
38 THF
38 THF
38 THF
KHMDS 38
NaOMe 28
NaOEt
32
[a] Reaction conditions: ester (1.0 mmol), THF (1 mL), H2 (50 bar),
1308C. [b] Determined by GC with respect to cyclohexanol. THF=te-
trahydrofuran.
Recently, we developed a pyridine-based PNNH/Ru
complex with the potential for dual-mode metal–ligand
cooperation, and it catalyzes the hydrogenation of esters at
room temperature and low pressure.[17] Following this obser-
vation, the PNNH-based cobalt complex 2 was studied as
2
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Table 2: Catalytic hydrogenation of esters using the cobalt precatalyst 2.[a]
of ester hydrogenation was not indicated before. It is
particularly surprising, considering the very low concentra-
Entry
Ester
t [h] Mol% Product
Yield
[%][b]
tion of the ester enol tautomer of simple esters.[18]
Regarding the active cobalt catalyst, we believe that under
the reactions conditions a cobalt(I) hydride complex is
formed. Indeed, Chirik and co-workers has shown that
treatment of the complex [(PNP)CoCl2] (1) with one equiv-
alent and two equivalents of NaHBEt3 gave the cobalt(I)
complexes [(PNP)CoICl] and [(PNP)CoH], respectively.[19]
We observed similar reactivity in the case of complexes 2
and 3. Thus, treatment of 2 and 3 with one equivalent of
NaHBEt3 at room temperature gave the paramagnetic
[(PNNH)CoICl] and [(PNNEt2)CoICl]. The complexes were
characterized by X-ray crystallography (see the Supporting
Information). Although we were not able to isolate the active
catalyst in the ester hydrogenation reactions, we believe that
in situ a catalytically active cobalt hydride pincer complex was
formed by reaction with two equivalents of the hydride source
and under H2 pressure.[20]
In conclusion, we have demonstrated the first hydro-
genation of esters into alcohols catalyzed by a cobalt complex.
New PNNEt2 and PNNH cobalt pincer complexes were
prepared. The PNNH-based cobalt pincer complex was found
to be the best catalyst. An unprecedented mechanism for
ester hydrogenation, involving enolate intermediates, is
indicated, thus suggesting selectivity for enolizable esters.
The synthetic implications of this finding and the detailed
mechanism of the reaction are being explored.
cyclohexanol
hexanol
hexanol
hexanol
pentanol
pentanol
85
79
67
87
67
85
1
38
2
43
43
48
48
2
4
2
4
2
3
4[c]
5[c]
48
48
2
2
cyclohexanol
61
67
tert-butanol
6[c]
48
48
4
4
cycloheptanol
83
7[c]
8
cyclohexylmethanol 51
48
70
4
4
3-methylbutan-1-ol
3-methylbutan-1-ol
65
80
9[c]
48
4
2-heptanol
52
10[c]
11
48
70
4
4
phenol
65
50
1,4-pentanediol
12
13
48
48
4
4
no reaction
no reaction
–
–
[a] Reaction conditions: substrate (1.0 mmol), precatalyst 2 (4 mol%),
NaHBEt3 (8 mol%), tBuOK (25 mol%), THF (1.0 mL), H2 (50 bar), 1308C.
[b] Yields were determined by GC. [c] Yields of methanol and ethanol are
not reported.
Keywords: alcohols · cobalt · esters · homogeneous catalysis ·
hydrogenation
followed by hydrogenation of the aldehyde into the corre-
sponding alcohol and regeneration of the catalytic base
(Figure 3). This result also indicates that the organometallic
[1] P. G. Andersson, I. J. Munslo, Modern Reduction Methods,
Wiley, New York, 2008.
[2] S. N. Ege, Organic Chemistry, D.C. Health Company, Lexington,
1989, p. 596.
[3] a) A. R. Grey, G. P. Pez, A. Wallo, J. Am. Chem. Soc. 1981, 103,
7536; b) U. Matteoli, G. Mechi, M. Bianchi, F. Piacenti, J.
Organomet. Chem. 1986, 299, 233.
=
mechanism likely involves insertion of the C C bond into
À
Co H, rather than the expected hydride transfer to the
carbonyl carbon atom. To our knowledge, such a mechanism
[4] a) U. Matteoli, G. Mechi, M. Bianchi, F. Piacenti, J. Mol. Catal.
1988, 44, 347; b) U. Matteoli, G. Mechi, M. Bianchi, F. Piacenti, S.
Ianelli, M. Nardelli, J. Organomet. Chem. 1995, 498, 177.
[5] a) Y. Hara, H. Inagaki, S. Nishimura, K. Wada, Chem. Lett. 1992,
1983; b) H. T. Teunissen, C. J. Elsevier, Chem. Commun. 1997,
667; c) H. T. Teunissen, C. J. Elsevier, Chem. Commun. 1998,
1367; d) K. Nomura, H. Ogura, Y. Imanishi, J. Mol. Catal. A
2001, 166, 345; e) M. C. Van Engelen, H. T. Teunissen, J. G.
de Vries, C. J. Elsevier, J. Mol. Catal. A 2003, 206, 185; f) M. J.
Hanton, S. Tin, B. J. Boardman, P. Miller, J. Mol. Catal. A 2011,
346, 70.
[6] J. Zhang, G. Leitus, Y. Ben-David, D. Milstein, Angew. Chem.
Int. Ed. 2006, 45, 1113; Angew. Chem. 2006, 118, 1131.
[7] L. A. Saudan, C. M. Saudan, C. Debieux, P. Wyss, Angew. Chem.
Int. Ed. 2007, 46, 7473; Angew. Chem. 2007, 119, 7617.
[8] a) E. Fogler, E. Balaraman, Y. Ben-David, G. Leitus, L. J. W.
Shimon, D. Milstein, Organometallics 2011, 30, 3826; b) J.
Zhang, E. Balaraman, G. Leitus, D. Milstein, Organometallics
2011, 30, 5716; c) S. Takebayashi, S. H. Bergens, Organometallics
2009, 28, 2349 – 2351; d) W. W. N. O, A. J. Lough, R. H. Morris,
Figure 3. Plausible mechanism of ester hydrogenation via an ester
enolate intermediate.
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These are not the final page numbers!

.
Angewandte
Communications
Chem. Commun. 2010, 46, 8240; e) Y. Sun, C. Koehler, R. Tan,
V. T. Annibale, D. Song, Chem. Commun. 2011, 47, 8349; f) D.
Spasyuk, S. Smith, D. G. Gusev, Angew. Chem. Int. Ed. 2012, 51,
2772; Angew. Chem. 2012, 124, 2826; g) D. Spasyuk, S. Smith,
D. G. Gusev, Angew. Chem. Int. Ed. 2013, 52, 2538; Angew.
Chem. 2013, 125, 2598; h) M. Ito, T. Ootsuka, R. Watari, A.
Shiibashi, A. Himizu, T. Ikariya, J. Am. Chem. Soc. 2011, 133,
4240; i) T. Touge, T. Hakamata, H. Nara, T. Kobayashi, N. Sayo,
T. Saito, Y. Kayaki, T. Ikariya, J. Am. Chem. Soc. 2011, 133,
14960; j) K. Junge, B. Wendt, F. A. Westerhaus, A. Spannenberg,
H. Jiao, M. Beller, Chem. Eur. J. 2012, 18, 9011; k) C. Liu, J.-H.
Xie, Y.-L. Li, J.-Q. Chen, Q.-L. Zhou, Angew. Chem. Int. Ed.
2013, 52, 593; Angew. Chem. 2013, 125, 621; l) P. A. Dub, T.
Ikariya, ACS Catal. 2012, 2, 1718; m) “Hydrogenation of
Esters”: L. A. Saudan in Sustainable Catalysis: Challenges and
Practices for the Pharmaceutical and Fine Chemical Industries
(Eds.: P. J. Dunn, K. K. Hii, M. J. Krische, M. T. Williams),
Wiley, Hoboken, NJ, 2013, chap. 2.
Milstein, Angew. Chem. Int. Ed. 2014, 53, 4685; Angew. Chem.
2014, 126, 4773; e) T. Zell, Y. Ben-David, D. Milstein, Catal. Sci.
Technol. 2015, 5, 822; f) S. Werkmeister, K. Junge, B. Wendt, E.
Alberico, H. Jiao, W. Baumann, H. Junge, F. Gallou, M. Beller,
Angew. Chem. Int. Ed. 2014, 53, 8722; Angew. Chem. 2014, 126,
8867; g) S. Chakraborty, H. Dai, P. Bhattacharya, N. T. Fair-
weather, M. S. Gibson, J. A. Krause, H. Guan, J. Am. Chem. Soc.
2014, 136, 7869; h) C. Bornschein, S. Werkmeister, B. Wendt, H.
Jiao, E. Alberico, W. Baumann, H. Junge, K. Junge, M. Beller,
Nat. Commun. 2014, 5, 4111.
[14] a) G. Zhang, B. L. Scott, S. K. Hanson, Angew. Chem. Int. Ed.
2012, 51, 12102; Angew. Chem. 2012, 124, 12268; b) G. Zhang,
K. V. Vasudevan, B. L. Scott, S. K. Hanson, J. Am. Chem. Soc.
2013, 135, 8668; c) S. C. Bart, E. Lobkovsky, P. J. Chirik, J. Am.
Chem. Soc. 2004, 126, 13794; d) S. Monfette, Z. R. Turner, S. P.
Semproni, P. J. Chirik, J. Am. Chem. Soc. 2012, 134, 4561; e) R. P.
Yu, J. M. Darmon, C. Milsmann, G. W. Margulieux, S. C. E.
Stieber, S. DeBeer, P. J. Chirik, J. Am. Chem. Soc. 2013, 135,
13168; f) Q. Knijnenburg, A. D. Horton, H. van den Heijden,
T. M. Kooistra, D. G. H. Hetterscheid, J. M. M. Smits, B. den
Bruin, P. H. M. Budzelaar, A. W. Gal, J. Mol. Catal. A 2005, 232,
151.
[15] a) G. F. Ferrari, A. Andreetta, G. F. Pregaglia, R. Ugo, J.
Organomet. Chem. 1972, 43, 209; b) G. F. Pregaglia, A.
Andreetta, G. F. Ferrari, R. Ugo, J. Organomet. Chem. 1971,
30, 387; c) H. M. Feder, J. Halpern, J. Am. Chem. Soc. 1975, 97,
7186.
[16] E. Khaskin, Y. D. Posner, L. Weiner, G. Leitus, D. Milstein,
Chem. Commun. 2013, 49, 2771.
[17] E. Fogler, J. A. Garg, P. Hu, G. Leitus, L. J. W. Shimon, D.
Milstein, Chem. Eur. J. 2014, 20, 15727.
[18] Involvement of the enol tautomer of the activated b-keto group
(not the ester group) in hydrogenation of b-keto esters was
reported: Y. Hamada, K. Makino, J. Synth. Org. Chem. Jpn.
2008, 66, 1057.
[9] a) M. D. Fryzuk, J. B. Ng, S. J. Rettig, J. C. Huffman, K. Jonas,
Inorg. Chem. 1991, 30, 2437; b) J. L. Kersten, A. L. Rheingold,
K. H. Theopold, C. P. Casey, R. A. Widenhoefer, C. E. C. A.
Hop, Angew. Chem. Int. Ed. Engl.Angew. Chem. Int. Ed. 1992,
31, 1341; Angew. Chem. 1992, 104, 1364.
[10] Selected examples: a) A. A. Mikhailine, M. I. Maishan, A. J.
Lough, R. H. Morris, J. Am. Chem. Soc. 2012, 134, 12266; b) A.
Mikhailine, A. J. Lough, R. H. Morris, J. Am. Chem. Soc. 2009,
131, 1394; c) A. A. Mikhailine, M. I. Maishan, R. H. Morris, Org.
Lett. 2012, 14, 4638; d) A. M. Tondreau, C. Milsmann, A. D.
Patrick, H. M. Hoyt, E. Lobkovsky, K. Wieghardt, P. J. Chirik, J.
Am. Chem. Soc. 2010, 132, 15046; e) K. T. Sylvester, P. J. Chirik,
J. Am. Chem. Soc. 2009, 131, 8772; f) M. M. Rodriguez, E. Bill,
W. W. Brennessel, P. L. Holland, Science 2011, 334, 780; g) R. E.
Cowley, N. A. Eckert, S. Vaddadi, T. M. Figg, T. R. Cundari, P. L.
Holland, J. Am. Chem. Soc. 2011, 133, 9796; h) L.-Q. Lu, Y. Li,
K. Junge, M. Beller, Angew. Chem. Int. Ed. 2013, 52, 8382;
Angew. Chem. 2013, 125, 8540; i) S. Das, B. Wendt, K. Mçller, K.
Junge, M. Beller, Angew. Chem.Int. Ed. 2012, 51, 1662; Angew.
Chem. 2012, 124, 1694; j) W. H. Harman, J. C. Peters, J. Am.
Chem. Soc. 2012, 134, 5080.
[11] a) R. J. Trovitch, E. Lobkovsky, M. W. Bouwkamp, P. J. Chirik,
Organometallics 2008, 27, 6264; b) R. P. Yu, J. M. Darmon, J. M.
Hoyt, G. W. Margulieux, Z. R. Turner, P. J. Chirik, ACS Catal.
2012, 2, 1760 – 1764.
[12] a) C. P. Casey, H. Guan, J. Am. Chem. Soc. 2007, 129, 5816;
b) C. P. Casey, H. Guan, J. Am. Chem. Soc. 2009, 131, 2499.
[13] a) D. Srimani, Y. Diskin-Posner, Y. Ben-David, D. Milstein,
Angew. Chem. Int. Ed. 2013, 52, 14131; Angew. Chem. 2013, 125,
14381; b) R. Langer, G. Leitus, Y. Ben-David, D. Milstein,
Angew. Chem. Int. Ed. 2011, 50, 2120; Angew. Chem. 2011, 123,
2168; c) R. Langer, Y. Diskin-Posner, G. Leitus, L. J. W. Shimon,
Y. Ben-David, D. Milstein, Angew. Chem. Int. Ed. 2011, 50, 9948;
Angew. Chem. 2011, 123, 10122; d) T. Zell, Y. Ben-David, D.
[19] a) S. P. Semproni, C. C. H. Atienza, P. J. Chirik, Chem. Sci. 2014,
5, 1956; b) S. P. Semproni, C. Milsmann, P. J. Chirik, J. Am.
Chem. Soc. 2014, 136, 9211.
[20] [(PNNH)CoICl] catalyzes the hydrogenation of cyclohexyl
hexanoate less efficiently than the presumably formed in situ
cobalt(I) catalyst (68% yield of cyclohexanol under the same
conditions).
[21] CCDC 1048654 (3), 1048655 (2), 1048656 [(PNNH)CoCl], and
1048657 [(PNNEt2)CoCl] contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Received: March 15, 2015
Published online: && &&, &&&&
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ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Homogeneous Catalysis
D. Srimani, A. Mukherjee,
A. F. G. Goldberg, G. Leitus,
Y. Diskin-Posner, L. J. W. Shimon,
Y. Ben David,
D. Milstein*
&&&& — &&&&
Getting involved: The atom-efficient and
environmentally benign catalytic hydro-
genation of carboxylic acid esters to
alcohols has been accomplished in recent
years mainly with precious-metal-based
catalysts. Presented here is the first
cobalt-catalyzed hydrogenation of esters
to alcohols. Unexpectedly, the evidence
indicates the unprecedented involvement
of ester enolate intermediates.
Cobalt-Catalyzed Hydrogenation of Esters
to Alcohols: Unexpected Reactivity Trend
Indicates Ester Enolate Intermediacy
Angew. Chem. Int. Ed. 2015, 54, 1 – 5
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!