Manganese Catalyzed Asymmetric Transfer Hydrogenation of Ketones Using Chiral Oxamide Ligands

Article abstract of DOI:10.1055/s-0037-1611669

The asymmetric transfer hydrogenation of ketones using isopropyl alcohol (IPA) as hydrogen donor in the presence of novel manganese catalysts is explored. The selective and active systems are easily generated in situ from [MnBr(CO)₅] and inexpensive C₂-symmeric bisoxalamide ligands. Under the optimized reaction conditions, the Mn-derived catalyst gave higher enantioselectivity compared with the related ruthenium catalyst.

Full text of DOI:10.1055/s-0037-1611669

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
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Georg Thieme Verlag Stuttgart · New York
2019, 30, A–E
letter
A
en
J. Schneekönig et al.
Letter
Synlett
Manganese Catalyzed Asymmetric Transfer Hydrogenation of
Ketones Using Chiral Oxamide Ligands
Jacob Schneekönig
O
O
[MnBr(CO)5] (6 mol%),
L4a (2 mol%)
O
O
Kathrin Junge
0
0
0
0-
0
0
0
1-7
0
4
4-8
8
8
8
OH
*
O
Ph
Ph
Matthias Beller*
0
0
0
0-0
0
0
1-
5
7
0
9-0
9
6
5
MeO
OMe
NH HN
L4a
+
Ph
R
R
KOtBu (20 mol%),
iPrOH (6 mL), 80 °C,
20 h
30–99% yield
15 examples
up to 93% ee
Leibniz-Institut für Katalyse e.V., Albert-Einstein-Str. 29a,
18059 Rostock, Germany
Matthias.Beller@catalysis.de
2
OH
HO
OH
R = Alkyl, Aryl
H2N
Published as part of the 30 Years SYNLETT – Pearl Anniversary
Issue
Received: 14.12.2018
Accepted after revision: 10.01.2018
Published online: 25.01.2019
with up to 85% ee. Very recently, Morris and co-workers
published a manganese pincer complex that enables the
ATH of aromatic ketones with up to 53% ee.9 The group of
Sortais could show that the combination of [MnBr(CO)5]
and a chiral diamine ligand is capable of catalyzing the ATH
of aromatic ketones with up to 90% ee.10 Notably, asymmet-
ric hydrogenations using manganese pincer complexes
were reported by Clarke and co-workers as well as by our
group.11 While the replacement of precious catalyst metals
by non-noble metals is intensively studied, considerably
less effort has focused on the development of readily avail-
able and less sensitive ligands. Here, many catalysts derived
from Fe, Mn or Co and P-based pincer ligands provide out-
standing catalytic performance, but most of their ligands
are very expensive, often not commercially available and/or
air-sensitive. In this respect, the application of phosphorus-
free and easy accessible ligand systems is highly desired
and would be a clear advantage for any possible application
from an economic point of view.
Therefore, we started a program to identify active non-
phosphorous-based manganese catalyst systems for ATH.
As model substrates we chose an aromatic (acetophenone)
and an aliphatic (cyclohexyl methyl ketone) ketone. For
convenience, in the initial activity screening, the catalyst
was derived in situ from a combination of the metal precur-
sor [MnBr(CO)5] and chiral amine derivatives. Remarkably,
in the presence of Jacobsen’s ligand L1 the ATH of acetophe-
none proceeded with 36% ee (Table 1, entry 1). Therefore,
we tested other multidentate ligands, specifically chiral ox-
amides L3–L7,12,13 which were varied with respect to their
electronic and steric properties (Figure 1). Advantageously,
L3–L7 are easy accessible by amidation of dimethyl oxalate
with various amino alcohols.14,15 Nevertheless, to our
knowledge, this type of ligand has never been tested in
asymmetric reductions to date.
DOI: 10.1055/s-0037-1611669; Art ID: st-2018-b0806-l
License terms:
Abstract The asymmetric transfer hydrogenation of ketones using iso-
propyl alcohol (IPA) as hydrogen donor in the presence of novel manga-
nese catalysts is explored. The selective and active systems are easily
generated in situ from [MnBr(CO)5] and inexpensive C2-symmeric bisox-
alamide ligands. Under the optimized reaction conditions, the Mn-de-
rived catalyst gave higher enantioselectivity compared with the related
ruthenium catalyst.
Key words transfer hydrogenation, asymmetric, manganese, chiral
ligands, ketones
Enantiomerically pure alcohols are of significant impor-
tance for the pharmaceutical, fine-chemical and fragrance
industries. Although numerous precious-metal complexes
have been reported for the asymmetric reduction of car-
bonyl compounds, there is a continuing interest in the de-
velopment of less expensive, more efficient catalysts. In ad-
dition to classic hydrogenations, the asymmetric transfer
hydrogenation (ATH) of prochiral ketones represents a con-
venient approach towards enantiomerically enriched alco-
hols. In recent years, remarkable progress has been made in
replacing noble metals such as ruthenium or iridium with
more abundant base metals such as iron or cobalt in such
transformations.1–4
As part of the recent development in homogenous man-
ganese-catalyzed reductions,5,6 the first manganese-based
catalysts for non-enantioselective transfer hydrogenation
have been published by Darcel and Sortais as well as by our
group.7 In addition, Kirchner has described a Mn catalyst
containing a chiral ferrocenyl-based pincer ligand for ATH
of ketones,8 which produced the corresponding alcohols
Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–E

B
J. Schneekönig et al.
Letter
Synlett
Entry
Ligand
Conv. [%]
R = Ph
ee [%]
Conv. [%]
R = Cy
ee [%]
N
N
OH
R
NH HN
PPh2
R
PPh2
4
5
L2c
L3a
32
63
–
–
6
0
tBu
OH
tBu
14
0
77
10
tBu
tBu
6
7
L3b
L3c
92
40
10
53
20
L1 (S,S)-Jacobsen´s ligand
L2a: R = (CH2)
L2b: R = (C=O); (S,S) Trost ligand
L2c: R = (C=O); (S,S) Trost naphthyl ligand
9
8
9
L4a
L4b
65
–
26
43
15
82
rac.
–
O
O
O
O
O
O
R
R
Ph
Ph
Ph
Ph
10
11
12
13
L5
–
15
46
14
73
rac.
–
NH HN
NH HN
NH HN
L6a
L6b
L7
66
25
73
30
5
OH
HO
OR
RO
25
6
L3a: R = iBu
L3b: R = Bn
L3c: R = tBu
L4a: R = H
L4b: R = Me
L5
rac.
4
a Standard reaction conditions: ketone (1 mmol), [MnBr(CO)5]
(0.01 mmol, 1 mol%), ligand (0.01 mmol, 1 mol%), KOtBu (0.1 mmol,
10 mol%), iPrOH (5 mL), 70 °C, 16 h.
O
O
O
O
R
R
NH HN
NH HN
Ph
Ph
Interestingly, when cyclohexyl methyl ketone was used
as substrate, improved enantioselectivities were achieved.
Here, the benzyl (L3b) and the phenyl (L4a) substituted ox-
amide ligands gave 53% and 82% ee, respectively (Table 1,
entries 6 and 8). To elucidate the influence of the free OH
group, ligands L4b and L5 were tested, producing racemic
1-cyclohexylethanol in low conversion. The phosphorus-
containing ligands L2a–c were also applied, with the ali-
phatic ketone showing no reactivity at all. Clearly, the in
situ generated Mn catalyst system using oxamide ligand
L4a is especially suited for ATH of aliphatic ketones and was
chosen for further optimization of the reaction parameters.
Next to temperature and time (see the Supporting Infor-
mation) different metal precursors such as Mn(0), Mn(I)
and Mn(II) salts were investigated to improve the catalyst
activity and product yield (Figure 2 and Table S1). Besides
[MnBr(CO)5], especially [Mn2(CO)10] and [Mn(OTf)(CO)5]
produced the chiral alcohol in high enantiomeric excess of
76% and 84% ee. The tested Mn(II) precursors did not con-
vert cyclohexyl methyl ketone under the applied condi-
tions.
OH
HO
OH
HO
L6a: R = (S)-Ph
L6b: R = (R)-Ph
L7
Figure 1 Tested ligands for the manganese-catalyzed ATH of ketones
using IPA
As shown in Table 1, manganese catalysts derived from
alkyl-, benzyl- or phenyl-substituted N,N′-bis(2-hy-
droxyethyl)oxamides L3a–c and L4a achieved only low se-
lectivities in the ATH of the aromatic model compound ace-
tophenone (entries 5–8). The introduction of an additional
phenyl group in the -position to the alcohol moiety of the
ligand motif (L6a and L6b) did not result in a significant
improvement of the selectivity. Here, 30% ee were obtained
for acetophenone, when the phenyl groups are arranged cis
to each other (L6a). The sterically demanding ligand L7 de-
rived from (1R,2R)-(–)-trans-1-aminoindanol was active,
but only racemic 1-phenylethanol was obtained as a prod-
uct. For comparison, phosphorus containing ligands L2a–c
with a related structure motive were also applied for the
ATH of acetophenone, leading to moderate activities and
poor or no chiral induction (entries 2–4).
Table 1 Ligand Screening for the ATH of Ketonesa
O
[MnBr(CO)5], L1–L7
OH
KOtBu, iPrOH
70 °C, 16 h
R
R
Entry
Ligand
Conv. [%]
R = Ph
ee [%]
Conv. [%]
R = Cy
ee [%]
1
2
3
L1
50
65
35
36
4
10
24
Figure 2 Metal precursor screening for ATH of cyclohexyl methyl
ketone
L2a
L2b
35
28
rac.
0
–
Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–E

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J. Schneekönig et al.
Letter
Synlett
The influence of the other metal precursors in the in
situ catalyst system was also studied in the ATH reaction of
cyclohexyl methyl ketone under the optimized conditions.
Applying different iron and ruthenium salts, 95% conver-
sion of the model substrate was achieved by combining di-
chloro(p-cymene)ruthenium(II) dimer with L4a. The tested
iron precursors showed no activity at all for the desired re-
action (see the Supporting Information). Notably, none of
the tested noble metal precursors led to a higher selectivity
compared with the results of the catalyst system generated
from [MnBr(CO)5] and L4a. This is one of the rare cases in
which a non-noble metal-based catalyst leads to higher en-
antioselectivities than its noble-metal analogues.
The influence of the metal to ligand to base ratios
(M/L/B) and loadings were then investigated. For the ali-
phatic benchmark substrate the initial ratio of M/L/B =
1:1:10 yielded 48% of the product after 20 h at 80 °C (Table
2, entry 1). To our surprise, with 2 or 5 mol% metal and li-
gand loadings at a constant base loading (10 mol%) no con-
version of the substrate was observed (entries 2 and 3). Ap-
parently, the amount of base is not sufficient to activate the
catalytic systems, which demonstrates the importance of
the free base for general reactivity.
dination mode of the catalyst. Attempts to grow crystals
were unsuccessful because of the propensity of oxamide li-
gands to form hydrogels.16 Therefore, the real nature of this
in situ formed catalyst remains unclear.
With the optimized conditions in hand,17 the general
catalytic activity of the catalyst system was explored for the
ATH for 15 prochiral ketones (Scheme 1). Given the good re-
sults obtained with the cyclic aliphatic model substrate,
other cyclic ketones were considered as a priority. While
cyclopropyl methyl ketone (1) gave only 46% yield and 59%
ee, cyclic ketones with increasing ring size (2–4) were re-
duced in good yields and high enantioselectivities of up to
88% ee. Furthermore, the influence of functional groups on
the cyclohexyl ring was investigated. Thus, the heterocyclic
4-acetyltetrahydropyran (5) was transformed with a high
yield (88%) and excellent selectivity of 93% ee. The ,-un-
saturated 1-acetyl-1-cyclohexene (6) was chemoselectively
reduced to the desired 1-(1-cyclohexenyl)ethanol but only
with poor yield (23%; 74% ee). Attempts to improve the
yield with longer reaction time (48 h) led to the respective
saturated alcohol. Moreover, 1-tetralol was obtained in 35%
yield with 50% ee. Additionally, the linear aliphatic ketone 8
was converted in 63% yield into the desired alcohol with an
ee of 85%. The branched ketone 1,1-diphenyl-2-propanone
(9) reacted only in moderate yield but with excellent selec-
tivity of 92% ee.
Table 2 Optimization of M/L/B Ratioa
O
OH
[MnBr(CO)5], L4a
Although the initial results with the aromatic model ke-
tone were not very promising, a number of substituted ace-
tophenones were applied in the manganese-catalyzed ATH.
The para-substituted derivatives 10 and 11 were both re-
duced to the corresponding alcohols with 55% ee. p-Methyl
acetophenone (12) and o-methoxy acetophenone (13) were
converted into the respective products with decreased
yields and moderate chiral induction. Finally, the catalyst
system [MnBrCO5]/L4a was also active for the transfer hy-
drogenation of the heterocyclic ketones 4-acetylpyridine
(14) and 2-acetylfuran (15) with moderate yields and enan-
tioselectivities.
In summary, we have developed a convenient protocol
for asymmetric transfer hydrogenation of ketones derived
from manganese and readily available N,N′-bis(2-hy-
droxyethyl)oxamide ligands. The in situ generated catalyst
system [MnBrCO5]/L4a is especially active for the reduction
of aliphatic ketones with up to 93% ee. Although this ligand
class is scarcely explored, its combination with manga-
nese(I) precursors represents a potential alternative to es-
tablished noble-metal catalysts based on chiral phosphorus
containing ligands. Further work to generalize this concept
and to determine the actual nature of the formed catalyst is
under way.
KOtBu, iPrOH
70 °C, 16 h
Cy
Cy
Entry
[MnBr(CO)5] [mol%]
M:L:B
Conv. [%]
ee [%]
1
2
1
2
1:1:10
1:1:5
48
0
82
–
3
4
5
6
7
8
5
1:1:2
0
–
2
1:1:10
2:1:10
3:1:10
4:1:10
5:1:10
73
80
84
65
0
83
86
88
90
–
4
6
8
10
a Standard reaction conditions: ketone (1 mmol), [MnBr(CO)5], ligand,
KOtBu, iPrOH (6 mL), 70 °C, 16 h.
On the other hand, formation of the desired alcohol was
achieved in significantly higher yield (73%), when the
amounts of metal, ligand and base were doubled (Table 2,
entry 4). The highest yield of 84% and a very good ee was
observed with 6 mol% loading of the metal precursor [Mn-
Br(CO)5] as an optimum (entry 6). A further increase of the
metal loading led to decreased yields, although up to 90% ee
was detected (entries 7 and 8). This rather unusual metal to
ligand ratio raised the question of the real coordination
mode of the ligand to the metal. NMR spectroscopy and
mass spectrometry did not provide an insight into the coor-
Funding Information
This work was supported by the state of Mecklenburg Vorpommern.()
Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–E

D
J. Schneekönig et al.
Letter
Synlett
Stöckli, M.; Mezzetti, A. ACS Catal. 2016, 6, 6455. (i) De Luca, L.;
Mezzetti, A. Angew. Chem. Int. Ed. 2017, 56, 11949. (j) De Luca,
L.; Mezzetti, A. CHIMIA 2018, 72, 233.
[MnBr(CO)5] (6 mol%),
O
OH
L4a (2 mol%)
*
KOtBu (20 mol%), iPrOH
(5 mL), 80 °C, 20 h
R
O
R
(3) Li, Y.-Y.; Yu, S.-L.; Shen, W.-Y.; Gao, J.-X. Acc. Chem. Res. 2015, For
a recent review on ATH including cobalt, see: 48, 2587.
(4) Zhang, G.; Hanson, S. K. Chem. Commun. 2013, 10151.
(5) For recent reviews on manganese-catalysed (de)hydrogenative
reactions, see: (a) Maji, B.; Barman, M. K. Synthesis 2017, 49,
3377. (b) Garbe, M.; Junge, K.; Beller, M. Eur. J. Org. Chem. 2017,
4344. (c) Kallmeier, F.; Kempe, R. Angew. Chem. Int. Ed. 2018, 57,
46; Angew. Chem. 2018, 130, 48.
O
O
O
1: 46%
(59% ee)
2: 87%
3: 85%
4: 84%
(88% ee)
(77% ee)
(88% ee)
(6) (a) Elangovan, S.; Topf, C.; Fischer, S.; Jiao, H.; Spannenberg, A.;
Baumann, W.; Ludwig, R.; Junge, K.; Beller, M. J. Am. Chem. Soc.
2016, 138, 8809. (b) Elangovan, S.; Garbe, M.; Jiao, H.;
Spannenberg, A.; Junge, K.; Beller, M. Angew. Chem. Int. Ed.
2016, 55, 15184. (c) Kallmeier, F.; Irrgang, T.; Dietel, T.; Kempe,
R. Angew. Chem. Int. Ed. 2016, 55, 11806. (d) van Putten, R.;
Uslamin, E. A.; Garbe, M.; Liu, C.; Gonzalez-de-Castro, A.; Lutz,
M.; Junge, K.; Hensen, E. J. M.; Beller, M.; Lefort, L.; Pidko, E. A.
Angew. Chem. Int. Ed. 2017, 56, 7679. (e) Garbe, M.; Junge, K.;
Walker, S.; Wei, Z.; Jiao, H.; Spannenberg, A.; Bachmann, S.;
Scalone, M.; Beller, M. Angew. Chem. Int. Ed. 2017, 56, 11237.
(f) Papa, V.; Cabrero-Antonino, J. R.; Alberico, E.; Spannenberg,
A.; Junge, K.; Junge, H.; Beller, M. Chem. Sci. 2017, 8, 3576.
(g) Espinosa-Jalapa, N. A. Nerush A.; Shimon, L. J. W.; Leitus, G.;
Avram, L.; Ben-David, Y.; Milstein, D. Chem. Eur. J. 2017, 23,
5934. (h) Fu, S.; Shao, Z.; Wang, Y.; Liu, Q. J. Am. Chem. Soc. 2017,
139, 11941. (i) Glatz, M.; Stöger, B.; Himmelbauer, D.; Veiros, L.
F.; Kirchner, K. ACS Catal. 2018, 8, 4009. (j) Kumar, A.; Janes, T.;
Espinosa-Jalapa, N. A.; Milstein, D. Angew. Chem. Int. Ed. 2018,
57, 12076. (k) Zou, Y.-Q.; Chakraborty, S.; Nerush, A.; Oren, D.;
Diskin-Posner, Y.; Ben-David, Y.; Milstein, D. ACS Catal. 2018, 8,
8014.
O
O
O
O
O
5: 88%
6: 23%
(74% ee)
7: 35%
(47% ee)
8: 63%
(85% ee)
(93% ee)
O
O
Ph
p-Cl 96% (55% ee)
p-CF3 99% (55% ee)
p-Me 78% (36% ee)
o-MeO 30% (19% ee)
10: R =
11:
Ph
12:
13:
R
9: 42%
(92% ee)
O
O
14: 40%
(32% ee)
15: 50%
(40% ee)
O
N
Scheme 1 Substrate scope for the ATH of ketones
Acknowledgment
(7) (a) Perez, M.; Elangovan, S.; Spannenberg, A.; Junge, K.; Beller,
M. ChemSusChem 2017, 10, 83. (b) Bruneau-Voisine, A.; Wang,
D.; Dorcet, V.; Roisnel, T.; Darcel, C.; Sortais, J.-B. Org. Lett. 2017,
19, 3656.
We thank Dr. C. Fischer, S. Buchholz, S. Schareina and E. Gerova-
Martin (all at LIKAT) for their excellent technical and analytical sup-
port.
(8) Zirakzadeh, A.; de Aguiar, S. R. M. M.; Stöger, B.; Widhalm, M.;
Kirchner, K. ChemCatChem 2017, 9, 1744.
Supporting Information
(9) Demmans, K. Z.; Olson, M. E.; Morris, R. H. Organometallics
2018, 37, 4608.
(10) Wang, D.; Bruneau-Voisine, A.; Sortais, J.-B. Catal. Commun.
2018, 105, 31.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611669.
S
u
p
p
orti
n
gInformati
o
n
S
u
p
p
orit
n
gInformati
o
n
(11) (a) Widegren, M. B.; Harkness, G. J.; Slawin, A. M. Z.; Cordes, D.
B.; Clarke, M. L. Angew. Chem. Int. Ed. 2017, 56, 5825. (b) Garbe,
M.; Junge, K.; Walker, S.; Wie, Z.; Jiao, H.; Spannenberg, A.;
Bachmann, S.; Scalone, M.; Beller, M. Angew. Chem. Int. Ed. 2017,
56, 11237; Angew. Chem. 2017, 129, 11389.
(12) Ligands L3b, L4a, L4b, L5, L6a and L6b were synthesized analo-
gously to procedures described for related compounds, see:
Şeker, S.; Barış, D.; Arslan, N.; Turgut, Y.; Pirinççioğlu, N.; Toğrul,
M. Tetrahedron: Asymmetry 2014, 25, 411; To a solution of the
corresponding amino alcohol (2 mmol) in MeOH (4 mL) was
added a solution dimethyl oxalate (1 mmol) in MeOH (2 mL)
dropwise at room temperature. The resulting mixture was
stirred for 30 min. Within this time, a cloudy white solid was
formed. The solid was filtered off and washed with cold MeOH
(2 × 2 mL) to give the analytically pure product.
References and Notes
(1) For recent reviews on iron-catalysed ATH of ketones, see:
(a) Morris, R. H. Acc. Chem. Res. 2015, 48, 1494. (b) Bigler, R.;
Huber, R.; Mezzetti, A. Synlett 2016, 27, 831. (c) Prokopchuk, D.
E.; Smith, S. A. M.; Morris, R. H. In Ligands for Iron-Based Homo-
geneous Catalysts for the Asymmetric Hydrogenation of Ketones
and Imines; John Wiley & Sons, Ltd: Weinheim, 2016, pp. 20.
(2) (a) Demmans, K. Z.; Ko, O. W. K.; Morris, R. H. RSC Adv. 2016, 6,
88580. (b) De Luca, L.; Mezzetti, A. Angew. Chem. Int. Ed. 2017,
56, 11949. (c) Demmans, K. Z.; Seo, C. S. G.; Lough, A. J.; Morris,
R. H. Chem. Sci. 2017, 8, 6531. (d) Bigler, R.; Mezzetti, A. Org.
Process Res. Dev. 2016, 20, 253. (e) Zuo, W.; Lough, A. J.; Li, Y. F.;
Morris, R. H. Science 2013, 342, 1080. (f) Bigler, R.; Mezzetti, A.
Org. Lett. 2014, 16, 6460. (g) Bigler, R.; Huber, R.; Mezzetti, A.
Angew. Chem. Int. Ed. 2015, 54, 5171. (h) Bigler, R.; Huber, R.;
Analytical data found for L4b
1H NMR (300 MHz, DMSO-d6):  = 7.96 (d, J = 8.2 Hz, 2 H), 7.29–
7.19 (m, 10 H), 5.07–4.98 (m, 2 H), 3.60 (d, J = 5.3 Hz, 4 H), 3.29
(s, 6 H).13C NMR (75 MHz, DMSO-d6):  = 159.30, 138.50,
Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–E

E
J. Schneekönig et al.
Letter
Synlett
128.66, 127.88, 126.86, 74.79, 59.12, 53.50.MS (ESI-TOF): m/z
calcd 357.1814 [M+H]+, 379.1627 [M+Na]+; found: 357.1804
[M+H]+, 379.1627 [M+Na]+.
18 H).13C NMR (75 MHz, DMSO-d6):  = 160.21, 59.90, 59.41,
33.93, 26.86.MS (ESI-TOF): m/z calcd 289.2127 [M+H]+,
311.1941 [M+Na]+; found: 289.2120 [M+H]+, 311.1944 [M+Na]+.
L7
L5
1H NMR (300 MHz, DMSO-d6):  = 9.07 (d, J = 9.0 Hz, 2 H), 7.41–
7.10 (m, 10 H), 4.79–4.56 (m, 2 H), 2.03–1.60 (m, 4 H), 0.82 (t,
J = 7.3 Hz, 6 H).
1H NMR (300 MHz, DMSO-d6):  = 9.10 (s, 2 H), 7.30–6.94 (m, 8
H), 5.16–5.03 (m, 2 H), 4.58–4.41 (m, 2 H), 3.21–3.12 (m, 2 H),
2.78–2.69 (m, 2 H).
13C NMR (75 MHz, DMSO-d6):  = 159.69, 142.88, 128.20,
126.89, 126.73, 54.99, 28.22, 11.20.MS (ESI-TOF): m/z calcd
347.1730 [M+Na]+; found: 347.1727 [M+Na]+.
L6a
13C NMR: (75 MHz, DMSO-d6):  = 160.60, 141.16, 139.79,
127.66, 126.63, 124.66, 123.59, 76.91, 61.43, 40.20 (shoulder of
DMSO signal).
MS (ESI-TOF): m/z calcd 352.1423 [M]+; found: 352.1429 [M]+.
(14) Denmark, S. C.; Stavenger, R. A.; Faucher, A.-M.; Edwards, J. P.
J. Org. Chem. 1997, 62, 3375.
1H NMR (300 MHz, DMSO-d6):  = 8.86 (d, 2 H), 7.38–7.03 (m,
20 H), 5.06–4.91 (m, 2 H), 4.91–4.81 (m, 2 H).
13C NMR (75 MHz, DMSO-d6):  = 159.74, 140.25, 128.16,
127.05, 127.01, 63.95, 55.74.MS (ESI-TOF): m/z calcd 503.1941
[M+Na]+; found: 503.1945 [M+Na]+.
(15) Gao, J.-X.; Ikariya, T.; Noyori, R. Organometallics 1996, 15, 1087.
(16) (a) Makarević, J.; Jokić, M.; Raza, Z.; Štefanić, Z.; Kojić-Prodić, B.;
Žinić, M. Chem. Eur. J. 2003, 9, 5567. (b) Dzolic, Z.; Wolsperger,
K.; Zinic, M. New J. Chem. 2006, 30, 1411. (c) Sunkur, M.; Baris,
D.; Hosgoren, H.; Togrul, M. J. Org. Chem. 2008, 73, 2570.
(17) General procedure for the ATH of prochiral ketones: Ligand L4a
(6.6 mg, 0.02 mmol, 2 mol%) and MnBr(CO)5 (16.2 mg, 0.06
mmol, 6 mol%) were placed in a flame-dried 25 mL Schlenk
tube equipped with a PTFE-coated stirring bar, followed by
anhydrous degassed isopropyl alcohol (2 mL). The suspension
was stirred for 10 min at room temperature. A solution of potas-
sium tert-butoxide (22.4 mg, 0.2 mmol, 20 mol% in 2 mL iPrOH)
was added and the resulting yellowish solution was stirred for a
further 10 min at room temperature. A solution of the desired
ketone (1 mmol in 2 mL iPrOH) was then added and the mixture
was heated to 80 °C and kept at this temperature for 20 h. The
reaction solution was allowed to cool to room temperature and
filtered through a plug of silica and washed with iPrOH (3 × 5
mL). Hexadecane (20 mg) was added to the reaction solution.
The yield of the desired alcohol was determined by GC analysis
using hexadecane as internal standard, and the ee was deter-
mined either by GC or HPLC analysis using an appropriate sepa-
ration method (see the Supporting Information for further
information).
L6b
1H NMR (300 MHz, DMSO-d6):  = 8.90–8.68 (m, 2 H), 7.41–7.05
(m, 20 H), 5.03–4.74 (m, 4 H).
13C NMR (75 MHz, DMSO-d6):  = 158.99, 142.87, 140.13,
128.60, 128.05, 127.54, 127.36, 127.09, 74.10, 59.46, 74.10,
59.46.
MS (ESI-TOF): m/z calcd 503.1941 [M+Na]+; found 503.1949
[M+Na]+.
(13) Ligands L3a, L3c, and L7 were synthesized analogously to the
procedure described for related compounds, see: Woods, B. P.;
Orlandi, M.; Huang, C. Y.; Sigman, M. S.; Doyle, A. G. J. Am. Chem.
Soc. 2017, 139, 5688; The corresponding amino alcohol (1
mmol) and dimethyl oxalate (1 mmol) were added under a flow
of argon into a flame-dried 25 mL Schlenk tube containing a
PTFE-coated stirring bar. Toluene (10 mL) was added by using a
syringe and the suspension was heated to 90 °C. After 3 h, the
mixture was allowed to cool to room temperature and the vola-
tiles were removed in vacuo. The resulting solid was washed
with cold toluene (2 × 2 mL) to give the analytically pure prod-
uct.
Analytical data found for L3c
1H NMR:  = 8.05 (d, J = 9.8 Hz, 2 H), 3.74–3.40 (m, 6 H), 0.87 (s,
Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–E