Mechanism-Based Enantiodivergence in Manganese Reduction Catalysis: A Chiral Pincer Complex for the Highly Enantioselective Hydroboration of Ketones

Article abstract of DOI:10.1002/anie.201704184

A manganese alkyl complex containing a chiral bis(oxazolinyl-methylidene)isoindoline pincer ligand is a precatalyst for a catalytic system of unprecedented activity and selectivity in the enantioselective hydroboration of ketones, thus producing preparatively useful chiral alcohols in excellent yields with up to greater than 99 % ee. It is applicable for both aryl alkyl and dialkyl ketone reduction under mild reaction conditions (TOF >450 h^?1 at ?40 °C). The earth-abundant base-metal catalyst operates at very low catalyst loadings (as low as 0.1 mol %) and with a high level of functional-group tolerance. There is evidence for the existence of two distinct mechanistic pathways for manganese-catalyzed hydride transfer and their role for enantiocontrol in the selectivity-determining step is presented.

Full text of DOI:10.1002/anie.201704184

A Journal of the Gesellschaft Deutscher Chemiker
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Accepted Article
Title: Mechanism-Based Enantiodivergence in Manganese
Reduction Catalysis: A Chiral Pincer Complex for the Highly
Enantioselective Hydroboration of Ketones
Authors: Lutz Gade, Hubert Wadepohl, Vladislav Vasilenko, and
Clemens K Blasius
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201704184
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10.1002/anie.201704184
Angewandte Chemie International Edition
COMMUNICATION
Mechanism-Based Enantiodivergence in Manganese Reduction
Catalysis: A Chiral Pincer Complex for the Highly
Enantioselective Hydroboration of Ketones
Vladislav Vasilenko, Clemens K. Blasius, Hubert Wadepohl and Lutz H. Gade*[a]
Abstract: A manganese alkyl complex containing a chiral “boxmi”
pincer ligand is a precatalyst for a catalyst of unprecedented activity
and selectivity in the enantioselective hydroboration of ketones
producing preparatively useful chiral alcohols in excellent yields and
up to >99 %ee. It is applicable for both aryl alkyl and dialkyl ketone
reduction under mild conditions (TOF >450 h-1 at –40°C) and an
earth-abundant base metal catalyst which operates at very low
catalyst loadings (as low as 0.1 mol%) and with a high level of
functional group tolerance. We provide evidence for the existence of
two distinct mechanistic pathways for manganese-catalyzed hydride
transfer and elaborate their role for enantiocontrol in the selectivity-
determining step.
Recently,[14] we reported the potential of the chiral
bis(oxazolinyl-methylidene)isoindoline (“boxmi”)[15] pincers as
ancillary ligands in iron-based catalysts for the enantioselective
hydrosilylation of ketones. The stability of these chiral catalysts
and the efficiency of the stereodirecting ligands indicated the
possibility to employ the boxmi pincer systems in a more general
way in enantioselective 3d metal reduction catalysis. We herein
present the first manganese-based catalyst for enantioselective
hydroboration of ketones,[16] providing excellent enantiomeric
excess and high conversion efficiency, which renders the
method an attractive alternative to the established
stereoselective reductions. We will also provide evidence for the
nature of the key reactive species in the catalytic hydroboration
which appears to be notably different from that involved in the
corresponding hydrosilylation.
Nature’s metalloenzymes, employing earth-abundant, non-toxic
base metals, in particular iron and manganese,[1] allow for
reactions that are usually considered to be the domain of noble
metal catalysis – even more so when it comes to chiral building
blocks.[2] Recent efforts to use 3d transition metals have
produced highly active homogeneous iron catalysts for
enantioselective oxidations[3] and reductions of a plethora of
substrates.[4] In contrast, manganese complexes have mainly
been employed in oxidation catalysis with reductive
transformations remaining scarce.[5] Nevertheless, the excellent
aptitude of manganese in this field has only just been
demonstrated in seminal contributions by Trovitch,[6] Zhang,[7]
Beller,[8] Kempe,[9] Kirchner,[10] Milstein,[11] and others.[12] Very
recently, Kirchner and Clarke reported the first examples of the
exploitation of chirality for Mn-catalyzed enantioselective
reductive transformations (Scheme 1).[13]
The manganese precatalyst 1 was obtained directly from the
corresponding boxmi-H protioligand and the readily available
dialkylmanganese precursor Mn(CH2SiMe3)2.[17] Alternatively,
complex 1 could be synthesized by alkylation of manganese
chlorido complexes with LiCH2SiMe3 (Scheme 2). In a first assay,
we found that the hydroboration of the test substrate 2a at room
temperature with 5 mol% of
1 (R = Ph, R’ = H) reached
completion within minutes, furnishing the chiral alcohol (S)-3a
after workup with 92 %ee (Table 1, entry 1).
SiMe3
Mn(CH2
)
O
O
2
∗
∗
∗
∗
toluene
R
R
R
N
N
R'
R'
R'
R'
NH
N
Mn
N
SiMe3
N
R
1. LDA, MnCl2 thf
,
O
O
2. LiCH2SiMe3 toluene
,
work
previous
R,R'boxmi-H
1
= =
Ph, R' H)
(R
active
precatalyst
O
C
Ph
N
N
N
SiMe3
SiMe3
PPh2
N
H
CO
N
PPh2
CO
N
Mn
N
R
N
Mn
N
Mn
Mn
Br
Scheme 2. One- and two-step access to the active precatalyst 1 (for variation
of R, R’, see Table 1).
CO
Br
PPh2
P
Ph2
P
Ph2
CO
Fe
Fe
2014
2016
2017
2017
Kirchner
Trovitch
Zhang
Clarke
transfer
KOtBu, iPrOH
hydrosilylation
hydroboration
hydrogenation
hydrogenation
The rapid conversion in the catalytic reaction at room
temperature led us to investigate the hydroboration of
acetophenone at reduced temperature. The addition of neat
pinacolborane to a substrate/catalyst mixture at –40°C gave the
secondary alcohol in 96 %ee and full conversion after 2 h
(Table 1, entry 2). Following the same protocol, we then varied
the substitution pattern of the boxmi ligand. Whilst alteration of
the backbone moiety R’ had no significant impact on the
selectivity of the catalyst, only modest enantiomeric excess was
detected upon exchange of the oxazoline R groups from phenyl
to isopropyl, tert-butyl or benzyl. Moreover, these derivatives led
to the formation of the (R)-enantiomer as the major product,
indicating the presence of two distinct, enantiodivergent
mechanistic pathways (vide infra). Notably, the activity of the
catalyst was mostly unaffected by these ligand variations, with
full conversions observed in all cases (see SI for a complete list
of ligands).
,
,
,
,
,
,
PhSiH3 C6H6
HBPin Et
2O
50 bar H2 KOtBu,
EtOH,
50°C
or
rt 80°C
rt
rt
61-97 %ee
20-86 %ee
O
this study
∗
R
N
Mn
OH
O
R'
R'
-
∗
N
Mn
N
SiMe3
HBPin, 40°C to rt, 2 h
then SiO2
R
R'
R
R'
∗
R
to >99
%ee
conv.
up
and
>99 %
O
Scheme 1. Selected example of previously reported manganese catalysts for
ketone reduction and our approach for enantioselective hydroboration.
[a]
V. Vasilenko, C. K. Blasius, Prof. H. Wadepohl, Prof. L. H. Gade
Anorganisch-Chemisches Institut, Universität Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
E-mail: lutz.gade@uni-heidelberg.de
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201704184
Angewandte Chemie International Edition
COMMUNICATION
Table 1. Screening of reaction conditions for the enantioselective
hydroboration of ketones.
Despite their highly active nature, the in situ generated pre-
catalysts were found to be readily accessible in pure form and
could be stored as such, so that isolated complex 1 was used in
all further studies. In addition, we were able to obtain X-ray
quality crystals of the pyridine adduct 1⋅(py), featuring a trigonal-
R,R'boxmi-MnCH2SiMe
mol%)
3 (5
O
OH
borane
(2 equiv.)
∗
solvent, -40°C to rt, 2 h
then SiO2
2a
3a
bipyramidal coordination environment with a meridionally-
coordinating pincer attached to the manganese center (Figure 1).
The observed Mn-N bond lengths are all within the expected
range for 3d metal boxmi complexes, and the Mn-C bond
distance is similar to other Mn(II) alkyl compounds with
tridentate nitrogen ligands.[7,14,18]
#
R’
H
R[a]
Ph
Ph
Ph
Ph
iPr
borane
HBPin
HBPin
HBPin
HBPin
HBPin
HBPin
HBPin
solvent
toluene
toluene
toluene
toluene
toluene
toluene
toluene
conv. (%)[b]
>99
%ee[b]
92 (S)
96 (S)
96 (S)
96 (S)
22 (R)
12 (R)
14 (R)
1[c]
2
H
>99
3
Me
Ph
H
>99
In order to evaluate the general applicability of the novel
catalyst platform, we subjected a wide range of substrates to our
standard protocol at 2.5 mol% catalyst loading. Excellent
conversions and enantioselectivities were obtained for all aryl
methyl ketones (up to >99 %ee) with only subtle changes in
enantiodiscrimination depending on the substitution pattern
(Scheme 3, 3a–k). Polycycles were found to be equally suitable,
whereas replacement of the methyl group by longer alkyl chains
gave slightly diminished enantiomeric excess (3l–n and 3o,p,
respectively). Similarly, heterocyclic ketones were reduced with
good to excellent enantiodiscrimination (3q,r).
4
>99
5
>99
6
H
tBu
Bn
>99
7
Me
>99
8
H
H
H
Ph
Ph
Ph
HBCat
toluene
toluene
toluene
45
97
78
6 (R)
10 (R)
0
9
9-BBN
10
BH3 ∙THF
11
12
13
14
H
H
H
H
H
Ph
Ph
Ph
Ph
Ph
HBPin
HBPin
HBPin
HBPin
HBPin
THF
>99
>99
>99
>99
>99
84 (S)
95 (S)
85 (S)
70 (S)
94 (S)
Et2O
1
HBPin
(2 equiv.)
mol%),
toluene, -40°C to rt, 2 h
(2.5
O
OH
CH2Cl2
MeCN
Hexane
∗
R
R'
R
R'
then SiO2
2
3
OH
OH
3b
OH
OH
3d
OH
3e
15
Ph
F
Cl
Br
[a] (S)-enantiomers of all ligands were employed. [b] Determined by HPLC or
GC analysis. [c] Performed at rt. Identical results were obtained for isolated
and in situ generated precatalysts.
3a
3c
>99
94 %ee
>99
94
%ee
%,
>99
>99
>99
96 %ee
>99
>99
96 %ee
>99
>99
97 %ee
OH
%,
%,
%,
%,
%,
%,
%,
%,
%,
%,
OH
OH
MeO
OH
OH
MeO2C
MeO
Attempts to arrive at similar results with commercially
available ligands such as pybox remained unsuccessful,
producing exclusively racemic or poorly enantioenriched
mixtures of 3a (see SI). A further study of the reaction conditions
revealed that the selectivity of the reduction is strongly affected
by the reducing agent. In fact, boranes other than HBPin
3f
3g
3h
3i
94
3j
98 %ee
OH
96 %ee
OH
95 %ee
OH
>99
>99
%ee
>99
>99 %ee
%,
%,
%,
OH
OH
C6H13
F5
MeO
3k
3l
3m
3n
96 %ee
3o
>99
O
95 %ee
>99
S
95 %ee
>99
86 %ee
93 %ee
%,
%,
%,
OH
OH
OH
OH
OH
(Table 1,
entries 8-10)
gave lower
conversions
and
Ph
unsatisfactory enantioselectivities. Solvent screening revealed
excellent enantiodiscrimination for low polarity solvents such as
toluene, Et2O and hexane. Slightly lower selectivities were
observed for THF, MeCN, and CH2Cl2.
3p
3q
3r
94 %ee
3s
3t
>99
>99
>99
80 %ee
>99
Ph
83 %ee
%,
>99
>99
70 %ee
>99
86 %ee
%,
%,
%,
%,
%,
%,
OH
OH
OH
OH
OH
Hex
Ph
3u
3v
3w
3x
3y
>99
87 %ee
28 %ee
>99
16 %ee
78 %ee
>99
90 %ee
%,
Scheme 3. Substrate scope of the manganese-catalyzed hydroboration of
ketones.
Notably, we observed that direct attachment of the aryl
group to the carbonyl function was no prerequisite for a high
selectivity. In fact, vinyl and alkynyl ketones (3s,t) were
converted to the corresponding alcohols with respectable
enantiomeric excess and excellent chemoselectivity, i.e. no
detectable hydroboration of the unsaturated carbon-carbon bond.
Additionally, 1,1-diphenylacetone was reduced with good
stereodiscrimination, whilst an increased linker length only
produced modest selectivity (3u,v). Likewise, 2-octanone (3w)
was reduced with a high activity but only poor stereoselectivity,
regardless of the boxmi derivative employed as the
stereodirecting ligand. Importantly, good to excellent
stereodiscrimination was observed for dialkyl ketones with
Figure 1. Molecular structure of the precatalyst pyridine adduct 1·(py),
determined by X-ray diffraction (disorder involving part of one oxazoline ring
and attached phenyl group not shown). Displacement ellipsoids set at 30 %
probability level, hydrogen atoms omitted for clarity. Selected bond lengths
(Å): Mn-C29 2.158(5), Mn-N1 2.293(3), Mn-N2 2.185(4), Mn-N3
2.285(13)/2.294(14), Mn-N4 2.245(4).
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10.1002/anie.201704184
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COMMUNICATION
sterically sufficiently dissimilar substituents (3x,y), highlighting
the role of steric effects for enantiocontrol.
is a potent hydrogen transfer agent in its own right (Scheme 4d).
To discriminate between the manganese- and the boron-
mediated hydrogen addition, we pre-generated the manganese
hydride and added a mixture of the substrate and DBPin. Since
the resulting product featured a high deuterium incorporation, a
direct hydride migration from the boron rather than the metal
atom appears to be favored in the hydroboration pathway
(Scheme 4e). This is reminiscent of Guan’s mechanism for the
iron-catalyzed hydrogenation, in which the hydride exerts the
role of a directing spectator ligand.[19]
To further assess the catalytic activity of the hydroboration,
we gradually lowered catalyst loadings (down to 0.1 mol%, for
details see SI). At room temperature, concentrations as low as
0.25 mol% facilitated a smooth conversion of 2c within less than
5 minutes, indicating a lower limit for the turnover frequency of
4800 h-1. For the standard conditions (2.5 mol% catalyst loading
and -40°C) TOF values of at least 450 h-1 were achieved. The
excellent scalability of our protocol was further corroborated by
applying it to a gram scale synthesis of 1-phenylethanol. Using
1 mol% of precatalyst 1, 1 g of acetophenone 2a was reduced in
quantitative yield and 95 %ee.
Source
(a) Hydrogen
1
mol%)
1
mol%)
(2.5
(2.5
HBPin
R SiH
(2 equiv.)
(2 equiv.)
3
O
OH
Ph
OH
rt
toluene,
rt
toluene,
Ph
Ph
then SiO2
then K2CO3/MeOH
various silanes
2a
-3a
R
)-
3a
S
(
)
(
92 %ee
70-71 %ee
The remarkable performance of the manganese catalyst
directed our attention toward the mechanism of the
hydroboration. Notably, neither the activity nor the selectivity of
the catalyst were affected by the presence of the common
radical traps triphenylmethane and 9,10-dihydroanthracene (0.1
and 1.0 equiv.), rendering radical processes unlikely. In order to
gain more detailed insights into the catalytic cycle and
precatalyst activation pathways, we performed a range of control
experiments (see Scheme 4, and SI). In view of the strong
influence of the borane on the reduction process (vide supra),
and
Adduct Formation
HBPin Loading
(b)
OH
O
OH
1
HBPin
TMEDA
(x equiv.)
mol%),
(2.5
(x equiv.),
then SiO2
Ph
Ph
Ph
2a
with 0
TMEDA
with 2
HBPin
equiv.
equiv.
Deuterium Labeling
(c)
(d)
O
D
OH
1
D
BPin
toluene, rt, 5 min
mol%),
(2.5
(2 equiv.)
we hypothesized that HBPin is
involved in the
then SiO2
F
F
stereodescriminating step of the catalytic cycle. In order to probe
the existence of a common manganese hydride intermediate as
the hydrogen transfer agent, we performed the reduction with a
range of other reductants (see SI for further details). Surprisingly,
the corresponding hydrosilylation produced an inverted
stereoinduction in favor of the (R)-alcohol while the observed
enantioselectivity proved to be independent of the silane
employed (Scheme 4a). This finding indicates that a hydride
transfer from the reducing agent might be a critical step in
manganese-catalyzed reductions, and strongly contrasts with
the behavior of the related iron catalysts, where the same
enantiomer is formed preferentially, irrespective of the reducing
agent employed.[14] This discovery lead us to the assumption that
the boxmi manganese catalyst can operate via two distinct
pathways, i.e. involving a direct hydrogen transfer for the
hydrosilylation or via a borane-mediated reduction for the
hydroboration. As expected for a competition between these
enantiodivergent pathways, we observed a strong correlation of
the product enantioselectivity with the amount of HBPin added –
with an increasing fraction of (R)-enantiomer formed at low
pinacol borane concentrations (Scheme 4b). Importantly, an
inversion of the stereochemistry of the manganese-catalyzed
hydroboration was also observed, when the reaction was carried
out in the presence of TMEDA, providing an additional indication
2c
3c-D1
D
>99%
BPin
incorporation
Precatalyst Activation
Ph,Hboxmi-H
H
Ph,H
Ph,Hboxmi-MnCH2SiMe3
H
boxmi-Mn
Mn(CH2SiMe3
)
2
Me3 CH2BPin
Si
SiMe4
11
and 29
internal reference
identified
B
Si NMR
1H NMR
by
quantified by
vs.
Mn-H
B-H Transfer
(e)
+
2c
D
BPin
D
OH
H
BPin
rt, 5 min
Ph,Hboxmi-MnCH2SiMe3
boxmi-Mn
Ph,H
H
Ar
3c-D1
incorporation
then SiO2
Me3SiCH2BPin
D
>85 %
Scheme 4. Mechanistic control experiments.
Based on these findings, we propose for the hydroboration a
catalytic cycle similar to the hydrosilylation catalyzed by weak
Lewis acids (Scheme 5, left).[20] After coordination of HBPin and
the substrate (steps I and II), hydrogen transfer takes place
(step III), a process that is critical to the stereoselectivity of the
reaction. Elimination of the boronic ester finally regenerates the
catalyst (step IV). The tendency of manganese borane adducts
to undergo bridging is well-documented for carbonyl and
cyclopentadienyl complexes,[21] as is the analogous affinity of the
low-coordinate highly thermally unstable π-acceptor free
manganese hydrides to undergo dimerization.[22] Therefore, we
expect the borane-manganese adduct to be a key intermediate
in the hydroboration cycle. This pathway is significantly faster
than the corresponding direct migration of the hydrogen from the
manganese hydride (Scheme 5, right), allowing for an excellent
enantiocontrol in the hydroboration at sufficiently high pinacol
borane loadings and in the absence of strongly coordinating co-
ligands. However, our results also indicate that the direct hydride
transfer is favored for manganese-catalyzed hydrosilylations,
thus following a catalytic cycle similar to the iron-catalyzed
process.[14]
of the occurrence of
a
catalyst-borane adduct in the
stereoselectivity determining step of the hydroboration.
We then set out to determine the origin of the C-1 hydrogen
atom: The reaction of deuterated pinacol borane DBPin with
ketone 2c led to the exclusive formation of the C1-labelled
alcohol 3c-D1 after silica work-up – evidence for the role of the
borane as the sole hydrogen source (Scheme 4c). However, the
precatalyst instantly reacts with HBPin to form Me3SiCH2BPin
and, presumably, a transient manganese hydride species, which
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10.1002/anie.201704184
Angewandte Chemie International Edition
COMMUNICATION
O
Ed. 2014, 53, 8722–8726; e) R. Bigler, R. Huber, A. Mezzetti, Angew.
Chem. Int. Ed. 2015, 54, 5171–5174.
H
BPin
R3SiOR*
Ar
LigMn
H
PinB-OR*
S
O(
)
I
H
O
IV
III
Ar
σ
[5]
a) W. Zhang, J. L. Loebach, S. R. Wilson, E. N. Jacobsen, J. Am.
Chem. Soc. 1990, 112, 2801–2803; b) T. Katsuki, Coord. Chem. Rev.
1995, 140, 189–214; c) S. Liao, B. List, Angew. Chem. Int. Ed. 2010, 49,
628–631; d) S. M. Paradine, J. R. Griffin, J. Zhao, A. L. Petronico, S. M.
Miller, M. Christina White, Nat. Chem. 2015, 7, 1–8; e) D. Shen, C.
Saracini, Y.-M. Lee, W. Sun, S. Fukuzumi, W. Nam, J. Am. Chem. Soc.
2016, 138, 15857–15860.
coordination
LigMn
H transfer
-bond
metathesis
O
B
Ar
H
O
O
H
Ar
-H
LigMn
LigMn
"fast"
"slow"
hydroboration
hydrosilylation
transfer
borane-mediated
transfer
direct
II
H transfer
coordination
coordination
σ
II
I
-bond
HBPin
metathesis
H
O
O
LigMn
III
H
B
LigMn
R
)
O(
O
H
[6]
[7]
[8]
T. K. Mukhopadhyay, M. Flores, T. L. Groy, R. J. Trovitch, J. Am. Chem.
Soc. 2014, 136, 882–885.
Ar
Ar
R3SiH
G. Zhang, H. Zeng, J. Wu, Z. Yin, S. Zheng, J. C. Fettinger, Angew.
Chem. Int. Ed. 2016, 55, 14369–14372.
Scheme 5. Tentative mechanistic proposal for the manganese-catalyzed
hydroboration and hydcrosilylation of ketones.
a) S. Elangovan, C. Topf, S. Fischer, H. Jiao, A. Spannenberg, W.
Baumann, R. Ludwig, K. Junge, M. Beller, J. Am. Chem. Soc. 2016,
138, 8809–8814; b) S. Elangovan, M. Garbe, H. Jiao, A. Spannenberg,
K. Junge, M. Beller, Angew. Chem. Int. Ed. 2016, 55, 15364–15368;
c) M. Peña-López, P. Piehl, S. Elangovan, H. Neumann, M. Beller,
Angew. Chem. Int. Ed. 2016, 55, 14967–14971; d) S. Elangovan, J.
Neumann, J.-B. Sortais, K. Junge, C. Darcel, M. Beller, Nat. Commun.
2016, 7, 12641; e) Andérez-Fernández, M.; Vogt, L. K.; Fischer, S.;
Zhou, W.; Jiao, H.; Garbe, M.; Elangovan, S.; Junge, K.; Junge, H.;
Ludwig, R.; Beller, M. Angew. Chem. Int. Ed. 2016, 56, 559–562;
f) Neumann, A. J.; Elangovan, S.; Spannenberg, A.; Junge, K.; Beller,
M. Chem. Eur. J. 2017, 23, 5410–5413; g) Papa, V.; Cabrero-Antonino,
J. R.; Alberico, E.; Spannenberg, A.; Junge, K.; Junge, H.; Beller, M.
Chem. Sci. 2017, 8, 3576–3585.
In conclusion, we have developed a manganese(II)-based
molecular catalyst for the stereoselective reduction of a broad
range of ketone substrates under very mild conditions. In
contrast to other active Mn catalysts that most likely operate
through a radical mechanism,[6] preliminary experiments indicate
that boxmi manganese complexes are expected to facilitate a
heterolytic rather than a homolytic bond activation. Our system
provides an example of the potential of enantioselective base
metal catalysis and, in particular, the applicability of manganese
catalysts in organic synthesis. It also highlights the role of
enantiodivergent mechanistic pathways for enantioselective 3d
metal catalysis.
[9]
a) Kallmeier, F.; Irrgang, T.; Dietel, T.; Kempe, R. Angew. Chem. Int.
Ed. 2016, 55 (39), 11806–11809; b) Deibl, N.; Kempe, R. Angew.
Chem. Int. Ed. 2017, 56, 1663–1666.
[10] a) Mastalir, M.; Glatz, M.; Gorgas, N.; Stöger, B.; Pittenauer, E.;
Allmaier, G.; Veiros, L. F.; Kirchner, K. Chem. Eur. J. 2016, 22 (35),
12316–12320; b) Mastalir, M.; Glatz, M.; Pittenauer, E.; Allmaier, G.;
Kirchner, K. J. Am. Chem. Soc. 2016, 138 (48), 15543–15546;
c) Mastalir, M.; Glatz, M.; Stöger, B.; Weil, M.; Pittenauer, E.; Allmaier,
G.; Kirchner, K. Inorg. Chim. Acta 2017, 455, 707–714.
Acknowledgements
We acknowledge the award of a predoctoral fellowship to V. V.
from the Landesgraduiertenförderung of the state of Baden-
Württemberg and generous funding by the University of
Heidelberg as well as the Deutsche Forschungsgemeinschaft
(DFG-Ga488/9-1). The authors thank Dr. Torsten Roth for
helpful suggestions.
[11] a) A. Nerush, M. Vogt, U. Gellrich, G. Leitus, Y. Ben-David, D. Milstein,
J. Am. Chem. Soc. 2016, 138, 6985–6997; b) A. Mukherjee, A. Nerush,
G. Leitus, L. J. W. Shimon, Y. Ben David, N. A. Espinosa Jalapa, D.
Milstein, J. Am. Chem. Soc. 2016, 138, 4298–4301; c) Espinosa-Jalapa,
N. A.; Nerush, A.; Shimon, L.; Leitus, G.; Avram, L.; Ben-David, Y.;
Milstein, D. Chem. Eur. J. 2017, 23, 5934–5938.
Keywords: enantioselective catalysis • hydroboration •
[12] a) J. Zheng, S. Elangovan, D. A. Valyaev, R. Brousses, V. César, J.-B.
B. Sortais, C. Darcel, N. Lugan, G. Lavigne, Adv. Synth. Catal. 2014,
356, 1093–1097; b) V. K. Chidara, G. Du, Organometallics 2013, 32,
5034–5037; c) Nguyen, D. H.; Trivelli, X.; Capet, F.; Paul, J.-F.;
Dumeignil, F.; Gauvin, R. M. ACS Catal. 2017, 7, 2022–2032.
reduction • manganese • enantiodivergence
[1]
a) V. L. Schramm, F. C. Wedler, Manganese in Metabolism and
Enzyme Function, Academic Press, 1986; b) W. Kaim, B. Schwederski,
A. Klein, Bioinorganic Chemistry: Inorganic Elements in the Chemstry
of Life, 2013; c) J. D. Crowley, D. A. Traynor, D. C. Weatherburn, Met.
Ions Biol. Syst. 2000, 37, 209–78; d) J. Rittle, M. T. Green, Science
2010, 330, 933–7.
[13] a) Zirakzadeh, A.; de Aguiar, S. R. M. M.; Stöger, B.; Widhalm, M.
ChemCatChem 2017, DOI: 10.1002/cctc.201700042; b) M. B.
Widegren, G. J. Harkness, A. M. Z. Slawin, D. B. Cordes, M. L. Clarke,
Angew. Chem. Int. Ed. 2017, DOI 10.1002/anie.201702406.
[14] a) T. Bleith, H. Wadepohl, L. H. Gade, J. Am. Chem. Soc. 2015, 137,
2456–2459; b) T. Bleith, L. H. Gade, J. Am. Chem. Soc. 2016, 138,
4972–4983.
[2]
[3]
M. Yoshimura, S. Tanaka, M. Kitamura, Tetrahedron Lett. 2014, 55,
3635–3640.
a) E. Rose, B. Andrioletti, S. Zrig, M. Quelquejeu-Ethève, Chem. Soc.
Rev. 2005, 34, 573; b) F. G. Gelalcha, B. Bitterlich, G. Anilkumar, M. K.
Tse, M. Beller, Angew. Chem. Int. Ed. 2007, 46, 7293–7296; c) T. Niwa,
M. Nakada, J. Am. Chem. Soc. 2012, 134, 13538–13541; d) Cussó, X.
Ribas, J. Lloret-Fillol, M. Costas, Angew. Chem. Int. Ed. 2015, 54,
2729–2733; e) O. Cussó, M. Cianfanelli, X. Ribas, R. J. M. Klein
Gebbink, M. Costas, J. Am. Chem. Soc. 2016, 138, 2732–2738.
a) C. P. Casey, H. Guan, J. Am. Chem. Soc. 2007, 129, 5816–5817;
b) G. Bauer, K. A. Kirchner, Angew. Chem. Int. Ed. 2011, 50, 5798–
5800; c) W. Zuo, A. J. Lough, Y. F. Li, R. H. Morris, Science 2013, 342,
1080–1083; d) S. Werkmeister, K. Junge, B. Wendt, E. Alberico, H.
Jiao, W. Baumann, H. Junge, F. Gallou, M. Beller, Angew. Chem. Int.
[15] a) Q. H. Deng, H. Wadepohl, L. H. Gade, Chem. - A Eur. J. 2011, 17,
14922–14928; b) Q. H. Deng, H. Wadepohl, L. H. Gade, J. Am. Chem.
Soc. 2012, 134, 2946–2949; c) Q. H. Deng, H. Wadepohl, L. H. Gade, J.
Am. Chem. Soc. 2012, 134, 10769–10772; d) Q. H. Deng, T. Bleith, H.
Wadepohl, L. H. Gade, J. Am. Chem. Soc. 2013, 135, 5356–5359;
e) Q. H. Deng, C. Rettenmeier, H. Wadepohl, L. H. Gade, Chem. - A
Eur. J. 2014, 20, 93–97; f) T. Bleith, Q. H. Deng, H. Wadepohl, L. H.
Gade, Angew. Chem. Int. Ed. 2016, 55, 7852–7856.
[4]
[16] For a selection of other recent transition metal catalyzed hydroborations
see for example: a) Guo, J.; Chen, J.; Lu, Z. Chem. Commun. 2015, 51
(26), 5725–5727; b) Weidner, V. L.; Barger, C. J.; Delferro, M.; Lohr, T.
L.; Marks, T. J. ACS Catal. 2017, 7, 1244–1247.
This article is protected by copyright. All rights reserved.

10.1002/anie.201704184
Angewandte Chemie International Edition
COMMUNICATION
[17] a) R. A. Andersen, E. Carmona-Guzman, J. F. Gibson, G. Wilkinson, J.
Chem. Soc. Dalt. Trans. 1976, 21, 2204; b) A. Alberola, V. L. Blair, L. M.
Carrella, W. Clegg, A. R. Kennedy, J. Klett, R. E. Mulvey, S. Newton, E.
Rentschler, L. Russo, Organometallics 2009, 28, 2112–2118.
[18] a) D. Reardon, G. Aharonian, S. Gambarotta, G. P. A. Yap,
Organometallics 2002, 21, 786–788; b) C. M. Pérez, A. Rodríguez-
Delgado, P. Palma, E. Álvarez, E. Gutiérrez-Puebla, J. Cámpora, Chem.
- A Eur. J. 2010, 16, 13834–13842.
[19] a) P. Bhattacharya, J. A. Krause, H. Guan, Organometallics 2011, 30,
4720–4729; b) P. Bhattacharya, J. A. Krause, H. Guan, J. Am. Chem.
Soc. 2014, 136, 11153–11161; c) P. Bhattacharya, J. A. Krause, H.
Guan, Organometallics 2014, 33, 6113–6121.
[20] a) A. L. Liberman-Martin, R. G. Bergman, T. D. Tilley, J. Am. Chem.
Soc. 2015, 137, 5328–5331; b) M. C. Lipke, A. L. Liberman-Martin, T. D.
Tilley, Angew. Chem. Int. Ed. 2017, 56, 2260–2294.
[21] a) X.-M. Liu, C.-Y. Wang, Q.-S. Li, Y. Xie, R. B. King, H. F. Schaefer III,
Dalt. Trans. 2009, 3774; b) S. Schlecht, J. F. Hartwig, J. Am. Chem.
Soc. 2000, 122, 9435–9443; c) K. K. Pandey, J. Organomet. Chem.
2007, 692, 1997–2005.
[22] a) V. L. Blair, L. M. Carrella, W. Clegg, J. Klett, R. E. Mulvey, E.
Rentschler, L. Russo, Chem. - A Eur. J. 2009, 15, 856–863; b) W. A.
Chomitz, J. Arnold, Dalt. Trans. 2009, 120, 1714; c) S. Yao, Y. Xiong,
M. Driess, Chem. - A Eur. J. 2012, 18, 11356–11361.
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Entry for the Table of Contents
COMMUNICATION
HBPin, then SiO2
OH
O
Vladislav Vasilenko, Clemens K.
Mn
∗
R
R'
R
R'
Blasius, Hubert Wadepohl, Lutz H.
Gade*
O
B


Mn
to >99
broad
%ee
scope
scale
up
H
O


O
LigMn


H
R
gram
TOF >450 h
-1 (-40°C)
Page No. – Page No.


active
precatalyst
Mechanism-Based Enantiodivergence
in Manganese Reduction Catalysis: A
Chiral Pincer Complex for the Mild
and Highly Enantioselective
Direct or indirect: Two distinct mechanistic pathways are operative for
manganese-catalyzed hydride transfer in the selectivity-determining step in the
enantioselective hydroboration of ketones producing preparatively useful chiral
alcohols in excellent yields and enantioselectivity (up to >99 %ee) with very low
catalyst loadings and a high level of functional group tolerance.
Hydroboration of Ketones
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