Cobalt-catalyzed transfer hydrogenation of C=O and C=N bonds

Article abstract of DOI:10.1039/c3cc45900d

An earth-abundant metal cobalt catalyst has been developed for the transfer hydrogenation of ketones, aldehydes, and imines under mild conditions. Experiments are described which provide insights into the mechanism of the transfer hydrogenation reaction. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3cc45900d

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Cobalt-catalyzed transfer hydrogenation of CQO and
CQN bonds†
Cite this: DOI: 10.1039/c3cc45900d
Guoqi Zhang and Susan K. Hanson*
Received 1st August 2013,
Accepted 13th September 2013
DOI: 10.1039/c3cc45900d
www.rsc.org/chemcomm
An earth-abundant metal cobalt catalyst has been developed for the
transfer hydrogenation of ketones, aldehydes, and imines under
mild conditions. Experiments are described which provide insights
into the mechanism of the transfer hydrogenation reaction.
Transition metal-catalyzed transfer hydrogenation is a simple and
versatile method for the reduction of polar multiple bonds. A
number of high-value chemical products, including alcohols and
amines, can be efficiently produced using transfer hydrogenation
1
processes. Rapid turnover frequencies and high substrate to catalyst
ratios have been achieved using catalysts based on ruthenium,
2–6
iridium, and rhodium metals. However, for more widespread or
industrial applications, catalysts composed of inexpensive, earth-
abundant metals would be preferable. Several iron-based systems
have recently emerged for the transfer hydrogenation of ketones and
Fig. 1 Cobalt precatalysts evaluated for transfer hydrogenation.
7–9
imines, including a highly effective PNNP-ligated Fe catalyst for
10
asymmetric transfer hydrogenation under mild conditions.
1-phenylethanol was obtained in 94% isolated yield after 24 h at
Despite these advances, transfer hydrogenation catalysts composed room temperature using 2 (2 mol%, generated in situ by the reaction
F
4
of first-row transition metals remain scarce relative to their precious of 1 and H[BAr
metal analogues. The discovery of additional examples of earth- reaction.‡
2 2
]ꢀ(Et O) ). No basic additives were required for this
abundant metal transfer hydrogenation catalysts could open new
ground for catalyst design, broadening the scope of potential active cobalt catalyst was homogeneous or heterogeneous in nature.
catalytic systems and mechanisms. The transfer hydrogenation of acetophenone with isopropanol was
Previously, we reported the synthesis of the square planar carried out using 2 (2 mol%) with added Hg metal (100 equiv.). The
Additional experiments were performed to assess whether the
Cy
Cy
cobalt(II) alkyl complexes (PNP )Co(CH SiMe ) (1) and [(PNHP )- catalytic activity was maintained in the presence of mercury, with
2
3
F
Co(CH SiMe )]BAr (2) and their use as pre-catalysts for hydro- the product 1-phenylethanol obtained in 90% GC yield after 24 h at
genation (with H ) (Fig. 1). The efficacy of cobalt complex 2 as a room temperature. Another poisoning experiment was carried out
2
3
4
11
2
hydrogenation catalyst suggested the potential of 2 as a catalyst for using trimethylphosphine, inspired by the recent work of Morris
12
the transfer hydrogenation of polar multiple bonds.
Cobalt complexes 1 and 2 were first tested as catalysts for the iron nanoparticle catalysts for ketone transfer hydrogenation were
transfer hydrogenation of acetophenone with isopropanol. Although unaffected by added Hg metal, but addition of PMe completely
and co-workers. Morris and co-workers found that heterogeneous
3
12
the neutral cobalt(II) alkyl complex 1 showed no activity for the suppressed the catalytic activity. For the cobalt system, catalytic
transfer hydrogenation reaction, complex 2 was found to be an active activity was maintained in the presence of PMe , consistent with a
3
catalyst. In the reaction of acetophenone with isopropanol, homogeneous catalyst. Even with 4 mol% added PMe , the transfer
3
hydrogenation of acetophenone with isopropanol proceeded in 77%
yield using the cobalt complex 2 (2 mol%) as a precatalyst.
Los Alamos National Laboratory, Chemistry Division, Los Alamos, NM, 87545, USA.
Several different cobalt complexes were compared as precatalysts
E-mail: skhanson@lanl.gov
for the transfer hydrogenation reaction. In combination with
†
Electronic supplementary information (ESI) available. See DOI: 10.1039/
F
c3cc45900d
H[BAr
4 2 2
]ꢀ(Et O) , the phenyl substituted PNP cobalt(II) alkyl
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Ph
11b
a
derivative (PNP )Co(CH SiMe
2 3
) (3) was slightly less active than Table 1 Substrate scope of the transfer hydrogenation reaction
cyclohexyl-substituted 2, affording 1-phenylethanol in 81% yield
Entry
1
Substrate
Product
Isolated yield (%)
94
after 24 h at room temperature. Complex 4, having a BPh counter-
4
F
4
ion instead of BAr , displayed comparable activity for the transfer
hydrogenation of acetophenone and isopropanol (1-phenylethanol
11b
was obtained in 92% isolated yield). The cobalt(III) complex 5
was also tested as a catalyst for the transfer hydrogenation of
acetophenone and isopropanol, but it was found to be less effective,
affording 1-phenylethanol in only 62% yield.
The substrate scope of the most active cobalt precatalyst 2 was
then evaluated (Table 1 and Table S1, ESI†). Complex 2 (2 mol%)
was a viable precatalyst for the transfer hydrogenation of aromatic
ketones bearing electron donating or electron withdrawing sub-
stituents (Table 1, entries 1–4, Table S1, ESI†). The transfer
2
3
4
95
99
98
95
98
0
0
hydrogenations of 2 -bromoacetophenone and 4 -methoxyaceto-
phenone proceeded in high conversions within 24 h at room
temperature, affording 1-(2-bromophenyl)ethanol and 1-(4-methoxy-
phenyl)ethanol in 95% and 99% isolated yields, respectively (entries
b
5
2
and 3). Aliphatic ketones were effectively reduced using a similar
6
procedure; 2-hexanol was obtained in 95% GC yield from the
transfer hydrogenation of 2-hexanone and isopropanol at 80 1C
(
entry 8). 4-tert-Butyl-cyclohexanone was reduced with 96% conver-
sion, affording a mixture of cis- and trans-4-tert-butylcyclohexanol
33 : 67 ratio of cis :trans, entry 9).
b
c
7
99
(
Cobalt complex 2 was also an active precatalyst for the
transfer hydrogenation of aldehydes. For aromatic aldehydes,
transfer hydrogenation with isopropanol proceeded smoothly
within 24 h at room temperature or 80 1C. For instance, benzyl
alcohol and 2-fluorobenzyl alcohol were obtained in high yields
c
8
9
95
c,d
96
1
0
95
92
97
(95% and 92% isolated yields, respectively) upon the transfer
hydrogenation of benzaldehyde and 2-fluorobenzaldehyde with
isopropanol using 2 (2 mol%). For conjugated substrates, such
b
as trans-4-phenyl-3-buten-2-one or cinnamaldehyde, transfer 11
hydrogenation with isopropanol resulted in the complete
reduction of both CQC and CQO bonds.
The transfer hydrogenation of imines was also possible upon 12
heating to 80 1C with pre-catalyst 2 (2 mol%). Several different
aldimines underwent transfer hydrogenation with isopropanol,
b
b
b
b
13
95
98
96
95
affording the corresponding amines in high yields within 24 h
95–98%, entries 14–16). Transfer hydrogenation of a ketimine, the
(
N-benzyl imine of acetophenone, was unsuccessful, affording the 14
reduced product in only 9% GC yield. Imine transfer hydrogenation
has attracted considerable recent attention and has applications in 15
1d
the synthesis of amines. Despite the importance of this reaction,
there have been few prior examples of base metal catalysts for the 16
7a,10b,13
transfer hydrogenation of imines.
Several additional experiments focused on gaining insights
into the mechanism of the transfer hydrogenation reaction.
B ¨a ckvall and coworkers have identified ‘‘monohydride’’ and cis : trans alcohol = 33 : 67.
a
Conditions: substrate (0.5 mmol) in isopropanol–THF (3 : 1 (v/v),
mL), 25 1C, 24 h. Reactions run at 80 1C. GC yield. Ratio of
b
c
d
2
‘
‘dihydride’’ pathways for transition-metal catalyzed transfer
1
4
hydrogenation reactions. To distinguish between these two transfer hydrogenation proceeds by a monohydride pathway,
possibilities, the transfer hydrogenation of acetophenone was as scrambling of the deuterium into both the C–H and O–H
carried out with both isopropanol-d and isopropanol-OD (Fig. 2). positions would be expected for the dihydride pathway.
8
While the reaction with isopropanol-d
8
afforded 1-phenylethanol-d
2
,
A number of precious metal transfer hydrogenation catalysts
the reaction with isopropanol-OD afforded 1-phenylethanol-OD, are proposed to operate by metal–ligand cooperativity, where
where less than 2% of deuterium was incorporated into the catalysis is facilitated by a cooperative interaction between the
1
5
benzylic C–H position of the product. This suggests that the metal center and an N–H group on the ligand. The proposed
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1
0304–10310; (c) S. E. Clapham, A. Hadzovic and R. H. Morris,
Coord. Chem. Rev., 2004, 248, 2201–2237; (d) J. Wu, F. Wang, Y. Ma,
X. Cui, L. Cun, J. Zhu, J. Deng and B. Yu, Chem. Commun., 2006,
1
766–1768.
2
3
(a) S. Hashiguchi, A. Fujii, J. Takehara, T. Ikariya and R. Noyori,
J. Am. Chem. Soc., 1995, 117, 7562–7563; (b) N. Uematsu, A. Fujii,
S. Hashiguchi, T. Ikariya and R. Noyori, J. Am. Chem. Soc., 1996, 118,
4
916–4917.
(a) C. M. Moore and N. K. Szymczak, Chem. Commun., 2013, 49,
400–402; (b) R. Soni, J. M. Collinson, G. C. Clarkson and M. Wills,
Org. Lett., 2011, 13, 4304–4307; (c) R. Guo, C. Elpelt, X. Chen, D. Song
and R. H. Morris, Chem. Commun., 2005, 3050–3052; (d) S. E.
Clapham, A. Hadzovic and R. H. Morris, Coord. Chem. Rev., 2004,
Fig. 2 Deuterium labelling experiments support a ‘‘monohydride’’ pathway for
the transfer hydrogenation reaction.
2
48, 2201–2237.
mechanisms typically involve outer-sphere reduction of the
CQO or CQN bond in either a concerted or step-wise fashion.
To evaluate the potential role of metal–ligand cooperativity in the
cobalt transfer hydrogenation catalysis, the reactivity of 2 was
compared with the analogue 6, where the central N–H group on
the pincer ligand has been replaced with a methyl group. Complex
4
(a) M. Watanabe, Y. Kashiwame, S. Kuwata and T. Ikariya, Eur.
J. Inorg. Chem., 2012, 504–511; (b) A. Azua, S. Sanz and E. Peris,
Chem.–Eur. J., 2011, 17, 3963–3967; (c) H. V ´a zquez-Villa, S. Reber,
M. A. Ariger and E. M. Carreira, Angew. Chem., Int. Ed., 2011, 50,
15
8
979–8981; (d) F. E. Hahn, C. Holtgrewe, T. Pape, M. Martin, E. Sola
and L. A. Oro, Organometallics, 2005, 24, 2203–2209; (e) Z. R. Dong,
Y. Y. Li, J. S. Chen, B. Z. Li, Y. Xing and J. X. Gao, Org. Lett., 2005, 7,
1
043–1045.
6
displayed similar, although slightly diminished activity relative
to 2 for the transfer hydrogenation of acetophenone, affording
-phenylethanol in 85% isolated yield after 24 h at RT. These
5
(a) T. Zweifel, J. V. Naubron, T. B u¨ ttner, T. Ott and H. Gr u¨ tzmacher,
Angew. Chem., Int. Ed., 2008, 47, 3245–3249; (b) W. B. Cross,
C. G. Daly, Y. Boutadla and K. Singh, Dalton Trans., 2011, 40,
1
9
722–9730; (c) V. Gierz, A. Urbanite, A. Seyboldt and D. Kunz,
Organometallics, 2012, 31, 7532–7538.
6 (a) E. Vega, E. Lastra and M. P. Gamasa, Inorg. Chem., 2013, 52,
193–6198; (b) D. Carmona, F. J. Lahoz, P. Garc ´ı a-Ordu n˜ a and
results suggest that a metal–ligand cooperative interaction is not
essential for the transfer hydrogenation catalysis. In addition, no
chemoselectivity was exhibited by 2 in the transfer hydrogenation
of conjugated substrates. In previous reports, a lack of chemo-
selectivity has often been associated with transfer hydrogenation
6
L. A. Oro, Organometallics, 2012, 31, 3333–3345.
7
(a) S. Zhou, S. Fleischer, K. Junge, S. Das, D. Addis and M. Beller,
Angew. Chem., Int. Ed., 2010, 49, 8121–8125; (b) S. Enthaler,
B. Hagemann, G. Erre, K. Junge and M. Beller, Chem.–Asian J.,
1c
catalysts that operate by an inner-sphere mechanism. Overall,
these results suggest that the mechanism of the cobalt-catalyzed
transfer hydrogenation differs significantly from previously
reported iron systems, which are proposed to react by an outer-
2
006, 1, 598–604; (c) S. Enthaler, G. Erre, M. K. Tse, K. Junge and
M. Beller, Tetrahedron Lett., 2006, 47, 8095–8099; (d) G. Wienh ¨o fer,
I. Sorribes, A. Boddien, F. Westerhaus, K. Junge, H. Junge, R. Llusar and
M. Beller, J. Am. Chem. Soc., 2011, 133, 12875–12879; (e) G. Wienh o¨ fer,
F. A. Westerhaus, R. V. Jagadeesh, K. Junge, H. Junge and M. Beller,
Chem. Commun., 2012, 48, 4827–4829; ( f ) G. Wienh ¨o fer, F. A.
Westerhaus, K. Junge and M. Beller, J. Organomet. Chem., 2013,
10,16
sphere pathway involving metal–ligand cooperativity.
The
differences in mechanism between the cobalt catalyst and related
iron catalysts may have important ramifications for future catalyst
design.
7
44, 156–159.
8
9
(a) C. Sui-Seng, F. N. Haque, A. Hadzovic, A. M. P u¨ tz, V. Reuss,
N. Meyer, A. J. Lough, M. Zimmer-De luliis and R. H. Morris, Inorg.
Chem., 2009, 48, 735–743; (b) N. Meyer, A. Lough and R. H. Morris,
Chem.–Eur. J., 2009, 15, 5606–5610.
T. Hashimoto, S. Urban, R. Hoshino, Y. Ohki, K. Tatsumi and
F. Glorius, Organometallics, 2012, 31, 4474–4479.
Finally, when the transfer hydrogenation reaction was carried
1
out in isopropanol-d
8
and monitored by H NMR spectroscopy, no
diamagnetic cobalt species were detected. This result, together with
the lower activity of the cobalt(III) complex 5 in the transfer 10 (a) A. A. Mikhailine, M. I. Maishan, A. J. Lough and R. H. Morris,
J. Am. Chem. Soc., 2012, 134, 12266–12280; (b) A. A. Mikhailine,
M. I. Maishan and R. H. Morris, Org. Lett., 2012, 14, 4638–4641;
hydrogenation reaction, suggests that complex 5 is unlikely to be
a catalyst resting state in the transfer hydrogenation reaction.
(
c) P. Sues, A. Lough and R. H. Morris, Organometallics, 2011, 30,
In conclusion, we have found that cobalt complex 2 is an
active catalyst for the transfer hydrogenation of CQO and CQN
bonds. Metal–ligand cooperativity is not required for the catalysis,
which likely proceeds through a cobalt monohydride intermediate.
This example of a homogeneous cobalt catalyst for transfer hydro-
genation underscores the potential of cobalt complexes to be
effective catalysts and expands the scope of possibilities for earth-
abundant metal catalyst design.
4418–4431; (d) P. O. Lagaditis, A. J. Lough and R. H. Morris, J. Am.
Chem. Soc., 2011, 133, 9662–9665.
1 (a) G. Zhang, B. L. Scott and S. K. Hanson, Angew. Chem., Int. Ed.,
1
2012, 51, 12102–12106; (b) G. Zhang, K. V. Vasudevan, B. L. Scott and
S. K. Hanson, J. Am. Chem. Soc., 2013, 135, 8668–8681.
2 (a) J. F. Sonnenberg, N. Coombs, P. A. Dube and R. H. Morris, J. Am.
Chem. Soc., 2012, 134, 5893–5899; (b) C. Sui-Seng, F. Freutel,
A. J. Lough and R. H. Morris, Angew. Chem., Int. Ed., 2008, 47,
940–943.
1
1
3 (a) S. Kuhl, R. Schneider and Y. Fort, Organometallics, 2003, 22,
4
184–4186; (b) M. Botta, F. De Angelis, A. Gambacorta, L. Labbiento
This work was funded by Los Alamos National Laboratory
LDRD Early Career Award (20110537ER).
and R. Nicoletti, J. Org. Chem., 1985, 50, 1916–1919.
14 (a) J. S. M. Samec, J. E. B ¨a ckvall, P. G. Andersson and P. Brandt,
Chem. Soc. Rev., 2006, 35, 237–248; (b) J. E. B ¨a ckvall, J. Organomet.
Chem., 2002, 652, 105–111.
5 For representative examples, see: (a) M. Yamakawa, H. Ito and
R. Noyori, J. Am. Chem. Soc., 2000, 122, 1466–1478; (b) V. Rautenstrauch,
X. Hoang-Cong, R. Churlaud, K. Abdur-Rashid and R. H. Morris,
Chem.–Eur. J., 2003, 9, 4954–4967; (c) C. P. Casey, G. A. Bikzhanova,
Q. Cui and I. A. Guzei, J. Am. Chem. Soc., 2005, 127, 14062–14071;
(d) S. Takebayashi, N. Dabral, M. Miskolzie and S. H. Bergens, J. Am.
Chem. Soc., 2011, 133, 9666–9669 and references therein.
Notes and references
1
‡
The addition of base did not promote cobalt catalyst 2. Only 30%
conversion was observed in the transfer hydrogenation of acetophe-
none and isopropanol with added KO Bu (4 mol%). A 95% yield of
t
1
-phenylethanol was obtained under the same reaction conditions
using K CO (4 mol%).
2
3
1
(a) S. Gladiali and E. Alberico, Chem. Soc. Rev., 2006, 35, 226–236; 16 D. E. Prokopchuk and R. H. Morris, Organometallics, 2012, 31,
b) A. Robertson, T. Matsumoto and S. Ogo, Dalton Trans., 2011, 40, 7375–7385.
(
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