A Highly Active Manganese Catalyst for Enantioselective Ketone and Ester Hydrogenation

Article abstract of DOI:10.1002/anie.201702406

A new hydrogenation catalyst based on a manganese complex of a chiral P,N,N ligand has been found to be especially active for the hydrogenation of esters down to 0.1 mol % catalyst loading, and gives up to 97 % ee in the hydrogenation of pro-chiral deactivated ketones at 30–50 °C.

Full text of DOI:10.1002/anie.201702406

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Communications
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International Edition: DOI: 10.1002/anie.201702406
German Edition: DOI: 10.1002/ange.201702406
Enantioselective Catalysis
A Highly Active Manganese Catalyst for Enantioselective Ketone and
Ester Hydrogenation
Magnus B. Widegren, Gavin J. Harkness, Alexandra M. Z. Slawin, David B. Cordes, and
Matthew L. Clarke*
Abstract: A new hydrogenation catalyst based on a manganese
complex of a chiral P,N,N ligand has been found to be
especially active for the hydrogenation of esters down to
0.1 mol% catalyst loading, and gives up to 97% ee in the
hydrogenation of pro-chiral deactivated ketones at 30–508C.
T
he hydrogenation of various carbonyl compounds with
ruthenium catalysts is a very effective reduction that is
applicable at commercial scale.[1] While the fine chemicals
catalysis sector is unlikely to seriously deplete the worlds
supply of ruthenium, replacing scarce metal catalysts with an
essentially indefinitely sustainable metal source is desirable,
elegant, and increases fundamental knowledge of catalytic
hydrogenation. Moreover, some precious-metal-catalyzed
hydrogenations can not be optimized to the very low catalyst
loadings needed to make the cost of catalyst and metal
removal from products economically viable; the use of
a metal such as manganese could offer advantages in these
cases (metal contamination limits in pharmaceutical com-
pounds are 250 ppm compared to 10 ppm for Ru). There is an
extensive global effort being expended on developing cata-
lysts with more abundant metals. Fe and Co hydrogenation
catalysts have probably been developed to the greatest
degree,[2] but very recently catalysts based on abundant
manganese[3,4] have appeared (e.g. compounds 1[3a] and 2[3c] in
Figure 1). Further improvements in abundant metal catalysis
are needed since only highly active catalysts will be used to
replace Ru (or Rh and Ir).
Figure 1. Ketone hydrogenation catalysts based on manganese.
importance of facially coordinating TRIPHOS ligands in
hydrogenation catalysis.[7] Here we introduce, to our knowl-
edge, the first enantioselective manganese-catalyzed ketone
hydrogenation, which is based on a facially coordinating
planar chiral P,N,N ligand. In addition to establishing
asymmetric hydrogenation catalysis with manganese, these
catalysts operate well below 1008C and, in the context of
abundant metal catalysts, at highly competitive catalyst
loadings for the hydrogenation of both ketones and esters.
Compared to many ligands used in hydrogenation studies,
ligand (SC,RP)-3 is easily prepared: it can be made in one step
from a commercially available, well-known precursor that is
prepared commercially at significant scale (or in a shorter
time in a two-step process). This ligand is prone to facial
coordination as evidenced by the crystal structure of the Ru
complex 4 (Figure 2). Ligand 3 can be converted to the very
sparingly soluble cationic Mn complex 5a by reaction with
convenient precursor Mn(CO)5Br in toluene at 1108C for
2 hours in 60% yield. In order to get more structural
information on this type of Mn complex, ion exchange
reactions were attempted with various anions in various
solvents (see the Supporting Information (SI)). The complex
containing a BARFanion, 5b had good solubility, and crystals
could be grown such that the complex was structurally
characterized by X-ray crystallography.
The Noyori-type [RuCl2(diphosphine)(diamine)] catalysts
are widely used for ketone hydrogenation,[1] but our long-
standing interest has been seeking to expand the scope of
ketone and ester hydrogenation using ruthenium complexes
of tridentate ligands.[5] While most of the ligands we have
studied coordinate to ruthenium in a meridional fashion, we
also identified a P,N,N ligand that would exhibit facial
coordination.[6] The publication by the Beller group of a Mn
catalyst based on a P,N,P ligand[3b] motivated us to examine
the use of ligand 3 in Mn-catalyzed hydrogenation. Facially
coordinating amino-phosphines have not been used to any
great degree in bifunctional reduction catalysis, despite the
Catalyst 5a was investigated in the hydrogenation of
a range of pro-chiral ketones including those that have proven
difficult to reduce with most common ruthenium catalysts.
Pleasingly, 5a was found to reduce ketone 6b to complete
conversion with 82% ee at just 508C. As has been observed
with ruthenium catalysts derived from P,N,N ligands, some
steric bulk on the substrate[4b,g] is required to get the best
enantioselectivity. In this case both secondary alkyl and (often
challenging)[3c,5b] tertiary alkyl substitution gives good ee
(Table 1 and Scheme 1).[5f]
[*] M. B. Widegren, G. J. Harkness, Prof. Dr. A. M. Z. Slawin,
Dr. D. B. Cordes, Dr. M. L. Clarke
School of Chemistry, University of St Andrews
EaStCHEM, St Andrews, Fife, KY16 9ST (UK)
E-mail: mc28@st-andrews.ac.uk
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under https://doi.org/10.
1002/anie.201702406.
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Figure 2. fac-Ru and fac-Mn complexes of ligand (Sc,Rp)-3; X-ray
structure of complex 4 and 5b with hydrogen atoms (and BARF
counterion) omitted for clarity.[12] BARF=tetrakis(3,5-bis(trifluoro-
methyl)phenyl)borate.
In the context of establishing the best ligand classes to
further develop Mn-catalyzed hydrogenation, we carried out
Table 1: Enantioselective reduction of ketones.[a]
Scheme 1. A range of functionalized ketones hydrogenated in presence
of the chiral Mn catalyst 5a. Typical reaction conditions: 0.34 mmol
substrate, 0.003 mmol catalyst, 0.034 mmol base and internal standard
(0.06 mmol) in 1.6 mL ethanol (0.2m) under 50 bar of H2 at 508C for
16 h.
Entry
No.
R1
R2
Conversion
[%][b]
ee
[%][c]
1
2
6a
6b
6b
6b
6b
6c
6c
6d
6d
6d
6d
6d
Ph
Ph
Ph
Ph
CH3
99 (80)
99 (87)
99 (n.d.)
99 (89)
99 (91)
99 (90)
99 (n.d.)
99 (85)
99 (n.d.)
99 (n.d.)
99 (n.d.)
99 (87)
20 (R)
82 (R)
84 (R)
80 (R)
85 (R)
23 (R)
27 (R)
58 (R)
58 (R)
58 (R)
57 (R)
53 (R)
one experiment at low catalyst loading of 0.1 mol%, and were
pleased to find complete conversion of the ortho-substituted
ketone 6d within 16 hours at just 508C. Given that bulky
ketones can also be reduced within 16 hours at 508C, (and are
still reduced at 308C), it seems very likely that this type of
catalyst is more active than the previous benchmarks
(Figure 1). Table S4 (SI) shows that at least 30 bar hydrogen
pressure is desired; A reaction run without hydrogen using
ethanol as potential reductant[8] only gave 16% yield under
otherwise standard conditions. Transfer hydrogenation using
isopropanol as solvent and hydrogen source is possible with
complete conversion, but not with good enantioselectivity.
Stable pre-catalysts that can reduce carbonyls with cheap
weak bases are desired and rare. Preliminary experiments
using catalyst 5a show that the weak bases K3PO4 or K2CO3
can be used and, where examined, give similar results under
otherwise standard conditions (see SI and Table 1, entries 4
and 10).
CH(CH3)2
CH(CH3)2
CH(CH3)2
CH(CH3)2
CH3
CH3
CH3
CH3
CH3
3[d]
4[e]
5[f]
6
Ph
4-Cl-Ph
4-Cl-Ph
2-Cl-Ph
2-Cl-Ph
2-Cl-Ph
2-Cl-Ph
2-Cl-Ph
7[d]
8
9[e]
10[g]
11[d]
12[h]
CH3
CH3
[a] Typical reaction conditions: 0.34 mmol substrate, 0.003 mmol cata-
lyst, 0.034 mmol base and internal standard (0.06 mmol) in 1.6 mL
ethanol (0.2m) under 50 bar of H2 at 508C for 16 h. [b] Conversion was
estimated by 1H-NMR using 1-methylnaphthalene as internal standard
(8–10 mL). Isolated yield in brackets. [c] ee was measured using chiral
HPLC, known absolute configuration in brackets. [d] Reaction run at
308C for 65 h. [e] 0.034 mmol K3PO4 as base. [f] Reaction run using
30 bar H2, reaction time 4 h. [g] 0.034 mmol K2CO3 as base. [h] 0.1 mol%
5a, 16 h reaction time; n.d.=not determined.
2
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Further examples of ketones that can be reduced with
Mn-hydride is proposed that can be formed after CO loss;
good enantioselectivity are shown in Scheme 1. The level of
enantioselectivity observed for the hydrogenation of 6 f, 6h,
and 6i exceeds previous best reports in the literature for these
substrates using precious-metal-catalyzed hydrogena-
tions.[5b,c,f] Methylketones containing aromatic rings with
ortho-substituents give higher selectivity, which allowed
promising levels of selectivity for producing the drug inter-
mediate 7l.[9]
while we have not been able to isolate such a species, we
assume that an analagous complex reduces the substrates,
with the NH group likely to be involved in hydrogen splitting
and control of stereochemistry in some way.[11] The tuning of
this ligand structure to further lower catalyst cost and enhance
activity for achiral processes, or to tune catalyst structure to
deliver broad scope or improved enantioselectivity in asym-
metric hydrogenation, is underway.
The results described above suggest this catalyst is
unusually reactive in the hydrogenation of carbonyl deriva-
tives. We therefore examined the hydrogenation of esters[5e,10]
using catalyst 5a, and found considerable success.
Acknowledgements
While this work was in progress, the first examples of Mn-
catalyzed ester hydrogenation were reported: typical condi-
tions were 110–1208C for 24 hours using 2 mol% of Mn
catalyst.[3b] The use of 1 mol% of catalyst 5a at just 758C to
deliver similar yields of products in slightly shorter reaction
times suggests that this type of ligand may be more promising
to develop Mn-catalyzed ester hydrogenation further
(Table 2). A variety of esters were reduced with good yield
We thank the EPSRC for DTG funding for M.B.W. and G.J.H.
and for the use of the National Mass Spectrometry Service.
The technical support staff at St Andrews are also gratefully
acknowledged. The research data underpinning this paper can
be accessed at: https://doi.org/10.17630/91ab7775-867c-4b21-
97c7-7c9117269ada.
Conflict of interest
Table 2: Hydrogenation of esters.[a]
The authors declare no conflict of interest.
Keywords: enantioselective catalysis · ester hydrogenation ·
ferrocene · manganese · reduction
Entry
R1
R2
Conversion[b]
[%]
1
2
3
4
5
6
7
8
8a
8b
8c
8d
8e
8 f
4-F-Ph
2-Br-Ph
Ph(CH2)2-
4-H2N-Ph
4-O2N-Ph
2-Naphth
CH3
CH3
CH2CH3
CH3
CH2CH3
CH3
99 (86)
99 (90)
99 (84)
91 (80)
0
99 (87)
99 (n.d)[c]
82[d]
[1] Selected publications: a) T. Ohkuma, S. Hashaguchi, T. Ikariya,
R. Noyori, J. Am. Chem. Soc. 1995, 117, 2675; b) R. Noyori, T.
Ohkuma, Angew. Chem. Int. Ed. 2001, 40, 40; Angew. Chem.
2001, 113, 40; c) The Handbook of Homogeneous Hydrogena-
tion (Eds.: C. J. Elsevier, J. G. De Vries), Wiley-VCH, Wein-
heim, 2007; d) T. Ohkuma, C. A. Sandoval, R. Srinivasan, Q. Lin,
Y. Wei, K. MuÇiz, R. Noyori, J. Am. Chem. Soc. 2005, 127, 8288;
e) T. Ohkuma, N. Utsumi, K. Tsutsumi, K. Murata, C. Sandoval,
R. Noyori, J. Am. Chem. Soc. 2006, 128, 8724.
ꢀ
8g
8h
4-(Ph-C C)-C6H4
nPr
CH3
nBu
9
8i
99 (86)[e]
[a] Typical reaction conditions: 0.34 mmol substrate, 0.003 mmol cata-
lyst, 0.034 mmol base and internal standard (0.06 mmol) in 1.6 mL
isopropanol (0.2m) under 50 bar of H2 at 758C for 16 h. [b] Conversion
was estimated by 1H-NMR using 1-methylnaphthalene as internal
standard (8–10 mL). Isolated yield in brackets. [c] 1H-NMR analysis
showed the presence of ꢁ20% alkene. [d] Reaction run neat with
0.1 mol% 5a and 2 mol% base at 908C for 15 h. [e] A 50:50 mixture of cis
and trans isomers.
[2] a) Os catalysts: W. Baratta, M. Ballico, G. Chelucci, K. Siega, P.
Rigo, Angew. Chem. Int. Ed. 2008, 47, 4362; Angew. Chem. 2008,
120, 4434; b) D. Spasyuk, C. Vicent, D. G. Gusev, J. Am. Chem.
Soc. 2015, 137, 3743; c) J. P. C. Coverdale, C. Sanchez-Cano, G. J.
Clarkson, R. Soni, M. Wills, P. J. Sadler, Chem. Eur. J. 2015, 21,
8043; d) G. Chelucci, S. Baldino, W. Baratta, Acc. Chem. Res.
2015, 48, 363; Fe catalysts: e) R. H. Morris, Chem. Soc. Rev.
2009, 38, 2282, and references therein; f) S. Chakraborty, H. Dai,
P. Bhattacharya, N. T. Fairweather, M. S. Gibson, J. A. Krause,
H. Guan, J. Am. Chem. Soc. 2014, 136, 1869; g) W. W. Zuo, A. J.
Lough, Y. F. Li, R. H. Morris, Science 2013, 342, 6162; h) R. P.
Yu, J. M. Damon, J. M. Hoyt, G. W. Margulieux, Z. R. Turner,
P. J. Chirik, ACS Catal. 2012, 2, 1760; i) P. J. Chirik, Acc. Chem.
Res. 2015, 48, 1687; j) J. A. Garg, S. Chakraborty, Y. Ben-David,
D. Milstein, Chem. Commun. 2016, 52, 5285; k) S. Chakraborty,
G. Leitus, D. Milstein, Chem. Commun. 2016, 52, 1812; l) T. Zell,
D. Milstein, Acc. Chem. Res. 2015, 48, 1979; m) Y. Y. Li, S. L. Yu,
X. F. Wu, J. L. Xiao, W. Y. Shen, Z. R. Dong, J. X. Gao, J. Am.
Chem. Soc. 2014, 136, 4031; Cu catalysts: n) H. Shimuzu, D.
Igarashi, W. Kuriyama, Y. Yusa, N. Sayo, T. Saito, Org. Lett.
2007, 9, 1755; o) K. Junge, B. Wendt, D. Addis, S. L. Zhou, S.
Das, S. Fleischer, M. Beller, Chem. Eur. J. 2011, 17, 101, and
references therein; Co catalysts: p) M. R. Friedfeld, M. Shevlin,
under these milder conditions, including 8d, containing an
often problematic[5d] free amino group. We also carried out
a single example of an ester hydrogenation using just
0.1 mol% catalyst, giving good conversion at 908C (Table 2,
entry 8).
In conclusion, we have shown that enantioselective
ketone hydrogenation is possible using manganese. The
catalyst seems to display enhanced activity relative to recent
important benchmarks for achiral Mn catalysts (Figure 1).
The mechanism of Mn catalysis is beginning to attract
attention,[3b,4f,o,p] and in achiral Mn PNP systems, a neutral
Angew. Chem. Int. Ed. 2017, 56, 1 – 5
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Angewandte
Communications
Chemie
G. W. Margulieux, L. C. Campeau, P. J. Chirik, J. Am. Chem.
Soc. 2016, 138, 3314, and references therein; q) M. R. Friedfeld,
M. Shevlin, J. M. Hoyt, S. W. Krska, M. T. Tudge, P. J. Chirik,
Science 2013, 342, 1076; r) S. Rçsler, J. Obenauf, R. Kempe, J.
Am. Chem. Soc. 2015, 137, 7998; Ni catalysts: s) M. Shevlin,
M. R. Friedfeld, H. M. Sheng, N. A. Pierson, J. M. Hoyt, L. C.
Campeau, P. J. Chirik, J. Am. Chem. Soc. 2016, 138, 3562; t) R.
Bigler, R. Huber, A. Mezzeti, Angew. Chem. Int. Ed. 2015, 54,
5171; Angew. Chem. 2015, 127, 5260.
ketone 6q with 97% ee); d) I. Carpenter, S. C. Eckelmann, M. T.
Kuntz, J. A. Fuentes, M. B. France, M. L. Clarke, Dalton Trans.
2012, 41, 10136; e) J. A. Fuentes, S. M. Smith, M. T. Scharbert, I.
Carpenter, D. B. Cordes, A. M. Z. Slawin, M. L. Clarke, Chem.
Eur. J. 2015, 21, 10851, and references therein; f) J. A. Fuentes, I.
Carpenter, N. Kann, M. L. Clarke, Chem. Commun. 2013, 49,
10245 (including hydrogenation of ketone 6p with 71% ee);
g) S. D. Phillips, K. H. O. Anderson, N. Kann, M. T. Kuntz, M. B.
France, P. Wawryzniak, M. L. Clarke, Catal. Sci. Technol. 2011, 1,
1336.
[3] a) S. Elangovan, C. Topf, S. Fisher, H. Jiao, A. Spannenberg, W.
Baumann, R. Ludwig, K. Junge, M. Beller, J. Am. Chem. Soc.
2016, 138, 8809; b) S. Elangovan, M. Garbe, H. Jiao, A.
Spannenberg, K. Junge, M. Beller, Angew. Chem. Int. Ed.
2016, 55, 15364; Angew. Chem. 2016, 128, 15590; c) F. Kallmeier,
T. Irrgang, T. Dietel, R. Kempe, Angew. Chem. Int. Ed. 2016, 55,
11806; Angew. Chem. 2016, 128, 11984; d) M. Perez, S. Elango-
van, A. Spannenberg, K. Junge, M. Beller, ChemSusChem 2016,
10, 83.
[6] a) Ligand 3 was not reported previously (see the SI for more
data on Ru/3). An iridium hydrogenation catalyst with a very
similar type of ligand was recently reported, see: H. Nie, G.
Zhou, Q. Wang, W. Chen, S. Zhang, Tetrahedron: Asymmetry
2013, 24, 1567; b) Other examples of various P,N,N ligands
recently studied in asymmetric hydrogenation of ketones: W.
Wu, S. Liu, M. Duan, X. Tan, C. Chen, Y. Xie, Y. Lan, X.-Q.
Dong, X. Zhang, Org. Lett. 2016, 18, 2938; c) J. H. Xie, X. Y. Liu,
J. B. Xie, L. X. Wang, Q. L. Zhou, Angew. Chem. Int. Ed. 2011,
50, 7329; Angew. Chem. 2011, 123, 7467.
[7] a) T. vom Stein, M. Meuresch, D. Limper, M. Schmitz, M.
Hçlscher, J. Coetzee, D. J. Cole-Hamilton, J. Klankermayer, W.
Leitner, J. Am. Chem. Soc. 2014, 136, 13217; b) X. Cui, Y. Li, C.
Topf, K. Junge, M. Beller, Angew. Chem. Int. Ed. 2015, 54, 10596;
Angew. Chem. 2015, 127, 10742; c) T. Korstanje, J. I. van der V-
lugt, C. J. Elsevier, B. de Bruin, Science 2015, 350, 298; d) H. T.
Teunissen, C. J. Elsevier, Chem. Commun. 1998, 1367; e) L.
Deng, B. Kang, U. Englert, J. Klankermayer, R. Palkovits,
ChemSusChem 2016, 9, 177; f) J. Coetzee, D. L. Dodds, J.
Klankermayer, S. Brosinski, W. Leitner, A. M. Z. Slawin, D. J.
Cole-Hamilton, Chem. Eur. J. 2013, 19, 11039.
[4] a) J. R. Carney, B. R. Dillon, S. P. Thomas, Eur. J. Org. Chem.
2016, 3912; b) D. A. Valyaev, G. Lavigne, N. Lugan, Coord.
Chem. Rev. 2016, 308, 191; c) W. Liu, D. Zall, M. John, L.
Ackermann, Angew. Chem. Int. Ed. 2015, 54, 4092; Angew.
Chem. 2015, 127, 4165; d) W. Liu, J. T. Groves, Acc. Chem. Res.
2015, 48, 1727; e) A. Nerush, M. Vogt, U. Gellrich, G. Leitus, Y.
Ben-David, D. Milstein, J. Am. Chem. Soc. 2016, 138, 6985; f) M.
Mastalir, M. Glatz, N. Gorgas, B. Stçger, E. Pittenauer, G.
Allmaier, L. F. Veiros, K. Kirchner, Chem. Eur. J. 2016, 22,
12316; g) M. PeÇa Lꢀpez, P. Piehl, S. Elangovan, H. Neumann,
M. Beller, Angew. Chem. Int. Ed. 2016, 55, 14967; Angew. Chem.
2016, 128, 15191; h) S. Elangovan, J. Neumann, J.-B. Sortais, K.
Junge, C. Darcel, M. Beller, Nat. Commun. 2016, 7, 12641;
i) D. H. Nguyen, X. Trivelli, F. Capet, J.-F. Paul, F. Dumeignil,
R. M. Gauvin, ACS Catal. 2017, 7, 2022; j) J. Zheng, S. Chevance,
C. Darcel, J.-B. Sortais, Chem. Commun. 2013, 49, 10010;
k) A. M. Tondreau, J. M. Boncella, Organometallics 2016, 35,
2049; l) A. M. Tondreau, J. M. Boncella, Polyhedron 2016, 116,
96; m) A. Mukherjee, A. Nerush, G. Leitus, L. J. W. Shimon, T.
Ben-David, N. A. E. Jalapa, D. Milstein, J. Am. Chem. Soc. 2016,
138, 4298; n) A. Bruneau-Voisine, D. Wang, T. Roisnel, C.
Darcel, J.-B. Sortais, Catal. Commun. 2017, 92, 1; o) N. P.
Yahaya, K. M. Appleby, M. The, C. Wagner, E. Troschke,
J. J. W. Bray, S. B. Duckett, L. Anders Hammarback, J. S. Ward,
J. Milani, N. E. Pridmore, A. C. Whitwood, J. M. Lynam, I. J. S.
Fairlamb, Angew. Chem. Int. Ed. 2016, 55, 12455; Angew. Chem.
2016, 128, 12643; p) D. H. Nguyen, X. Trivelli, F. Capet, J.-F.
Paul, F. Dumeignol, R. M. Gauvin, ACS Catal. 2017, 7, 2022.
[5] a) M. L. Clarke, M. B. Diaz-Valenzuela, A. M. Z. Slawin, Orga-
nometallics 2007, 26, 16; b) M. B. Dꢁaz-Valenzuela, S. D. Phillips,
M. B. France, M. E. Gunn, M. L. Clarke, Chem. Eur. J. 2009, 15,
1227 (including hydrogenation of ketone 6 f with 69% ee, and
ketone 6i with 84% ee); c) S. D. Phillips, J. A. Fuentes, M. L.
Clarke, Chem. Eur. J. 2010, 16, 8002 (including hydrogenation of
[8] T. Zweifel, J.-V. Naubron, T. Bꢂttner, T. Ott, H. Grꢂtzmacher,
Angew. Chem. Int. Ed. 2008, 47, 3245; Angew. Chem. 2008, 120,
3289.
[9] P. D. de Koning, D. McAndrew, R. Moore, I. B. Moses, D. C.
Boyles, K. Kissick, C. L. Stanchina, T. Cuthbertson, A. Kama-
tani, L. Rahman, R. Rodriguez, A. Urbina, A. Sandoval
(nee Accacia), P. R. Rose, Org. Process Res. Dev. 2011, 15, 1018.
[10] Reviews: a) S. Werkmeister, K. Junge, M. Beller, Org. Process
Res. Dev. 2014, 18, 289 – 302; b) M. L. Clarke, Catal. Sci. Technol.
2012, 2, 2418; c) P. A. Dub, T. Ikarija, ACS Catal. 2012, 2, 1718.
[11] Comments on the NH effect: P. A. Dub, J. C. Gordon, Dalton
Trans. 2016, 45, 6756.
[12] CCDC 1517612 (4) and 1531517 (5b) contain the supplemen-
tary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre.
Manuscript received: March 6, 2017
Final Article published: && &&, &&&&
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Enantioselective Catalysis
Non-precious metal for valuable cataly-
sis: A new manganese catalyst for enan-
tioselective ketone hydrogenation has
been developed (see scheme). This cata-
lyst also hydrogenates esters at low
catalyst loadings for an earth-abundant
metal system.
M. B. Widegren, G. J. Harkness,
A. M. Z. Slawin, D. B. Cordes,
M. L. Clarke*
&&&& — &&&&
A Highly Active Manganese Catalyst for
Enantioselective Ketone and Ester
Hydrogenation
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