Nickel-Catalyzed Asymmetric Hydrogenation of N-Sulfonyl Imines

Article abstract of DOI:10.1002/anie.201902576

An efficient nickel-catalyzed asymmetric hydrogenation of N-tBu-sulfonyl imines was developed with excellent yields and enantioselectivities using (R,R)-QuinoxP* as a chiral ligand. The use of a much lower catalyst loading (0.0095 mol %, S/C=10500) represents the highest catalytic activity for the Ni-catalyzed asymmetric hydrogenations reported so far. Mechanistic studies suggest that a coordination equilibrium exists between the nickel salt and its complex, and that excess nickel salt promotes the formation of the active Ni-complex, and therefore improved the efficiency of the hydrogenation. The catalytic cycle was also investigated by calculations to determine the origin of the enantioselectivity. An extensive network of numerous weak attractive interactions was found to exist between the catalyst and substrate in the transition state and may also contribute to the high catalytic activity.

Full text of DOI:10.1002/anie.201902576

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Ni-Catalyzed Asymmetric Hydrogenation of N-Sulfonyl Imines
Authors: Bowen Li, Jianzhong Chen, Zhenfeng Zhang, Ilya D. Gridnev,
and Wanbin Zhang
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201902576
Angew. Chem. 10.1002/ange.201902576
Link to VoR: http://dx.doi.org/10.1002/anie.201902576
http://dx.doi.org/10.1002/ange.201902576

10.1002/anie.201902576
Angewandte Chemie International Edition
DOI: 10.1002/anie.200((will be filled in by the editorial staff))
((Catch Phrase))
Ni-Catalyzed Asymmetric Hydrogenation of N-Sulfonyl Imines
Bowen Li, Jianzhong Chen, Zhenfeng Zhang, Ilya D. Gridnev, and Wanbin Zhang*
Abstract: An efficient nickel-catalyzed asymmetric hydrogenation of
N-tBu-sulfonyl imines was developed with excellent yields and
enantioselectivities using (R,R)-QuinoxP* as a chiral ligand. The
use of a much lower catalyst loading (0.0095 mol %, S/C = 10500)
represents the highest catalytic activity for all of the Ni-catalyzed
asymmetric hydrogenations reported so far. Mechanistic studies
suggested that a coordination equilibrium exists between the Ni salt
and its complex, and that excess Ni salt promoted the formation of
the active Ni-complex and therefore improved the efficiency of the
hydrogenation. The catalytic cycle was also investigated using
calculations to determine the origin of enantioselectivity. An
extensive network of numerous weak attractive interactions was
found to exist between the catalyst and substrate in the transition
state which may also contribute to the high catalytic activity.
In contrast, catalysts containing earth-abundant transition metals
possess several advantages in asymmetric catalysis due to being
abundant, inexpensive, and environmentally friendly. In the past few
years, earth-abundant transition metals have looked increasingly
attractive as alternatives to traditionally used transition metals in
asymmetric
hydrogenations.[3]
Although
excellent
enantioselectivities have been obtained for some asymmetric
hydrogenations using earth-abundant transition metal catalysts, to
the best of our knowledge, there are very few examples in which the
ratio of substrate to catalyst (S/C) is more than 1000 with
satisfactory enantioselectivity.[4] The low activities of earth-
abundant transition metal catalysts for asymmetric hydrogenation
prevents their broad adoption in industry because the chiral ligands
are generally expensive even though earth-abundant transition
metals are generally cheap.
Chiral amines are versatile chiral building blocks for the synthesis of
a variety of chiral intermediates and bioactive compounds (Scheme
1).[1] Among many strategies for the large-scale preparation of chiral
amines, the asymmetric catalytic hydrogenation of imines has
emerged as one of the most practical and powerful synthetic
methodologies. In the past decades, traditionally used transition
metal catalysts based on Rh, Ru, Ir, and Pd etc, have been widely
employed in the asymmetric hydrogenation of various imines with
excellent results.[2] However, the reserves of these precious metals
are declining and they are very expensive, limiting their application
in asymmetric catalytic hydrogenations on an industrial scale.
More recently, pioneering research concerning the Ni-catalyzed
asymmetric hydrogenation of ketones, alkenes, and enamides has
been reported by Hamada,[5] Chirik,[6] and Zhang.[7] Although three
excellent examples relating to the Ni-catalyzed asymmetric transfer
hydrogenation of imines have been reported,[8] the Ni-catalyzed
asymmetric hydrogenation of imines using H2 gas as the hydrogen
source has not been explored, a process which is considered to be
more suitable for industrial application. As part of our study on
asymmetric catalytic hydrogenations,[9] in this paper we report the
first Ni-catalyzed asymmetric hydrogenation of N-sulfonyl imines
using H2 gas as the hydrogen source, with high activity (S/C up to
10500) and excellent enantioselectivity. To the best of our
knowledge, the high reactivity reported using our methodology is
the highest reported to date for Ni-catalyzed asymmetric
hydrogenations.[5-8]
Table 1. Ligand screening
Scheme 1. Representative chiral drugs and bioactive compounds
bearing chiral aryl alkyl amine skeletons.
[]
B. Li, Dr. J. Chen, Dr. Z. Zhang and Prof. W. Zhang
Shanghai Key Laboratory for Molecular Engineering of
Chiral Drugs, School of Chemistry and Chemical
Engineering, Shanghai Jiao Tong University, 800
Dongchuan Road, Shanghai 200240, P. R. China
Fax: (+) 86 21 54743265
E-mail: wanbin@sjtu.edu.cn
Homepage: http://wanbin.sjtu.edu.cn
Prof. Ilya D. Gridnev
Department of Chemistry, Graduate School of Science,
Tohoku University, Aramaki 3-6, Aoba-ku, Sendai
9808578, Japan
Supporting information for this article is available on the WWW
under http://www.angewandte.org
1
This article is protected by copyright. All rights reserved.

10.1002/anie.201902576
Angewandte Chemie International Edition
Initially,
we
selected
(E)-2-methyl-N-(1-
The substrate scope of the catalytic system was explored using
slightly different reaction conditions following optimization (SI for
detials) (Table 2). Substrates bearing either an electron-donating or
electron-withdrawing group at the 2-position on the aromatic ring
were converted to their corresponding products in quantitative
conversions and with excellent enantioselectivities (2b-e, ees: 99%,
98%, 97%, and 99%), albeit the imine 1b required a higher
temperature and 1d/1e required a higher catalyst loading. When the
substituent group was present at the 3- and 4-positions (2f-p), the
corresponding products bearing electron-donating groups (Me, MeO
and Ph) were obtained with excellent yields and enantioselectivities,
while the substrates bearing an electron-withdrawing group (F, Cl,
and Br) afforded moderate to good yields and good
enantioselectivities. Disubstituted substrates were also examined in
the catalytic reaction affording excellent results (2q-u). Similarly,
when the benzene ring was replaced by a furyl or naphthyl group,
good to excellent results were obtained (2v-y). Furthermore,
substrates bearing different alkyl groups were also evaluated with
the catalyst system. Substrates in which the methyl group was
replaced with an ethyl, isopropyl, cyclopropyl, or cyclopentyl were
successfully reduced with full conversions and good to excellent
enantioselectivities (2z-ac). In addition, benzocyclic substrates also
underwent asymmetric hydrogenation using 2.0 mol% catalyst. A
five-membered imine (1ad) was reduced at 70 oC providing the
corresponding product in 99% yield and 92% ee, while the six-
membered imine (1ae) afforded the product with excellent
enantioselectivity (97% ee) but a lower yield (77%).
phenylethylidene)propane-2-sulfonamide (1a) as the model
substrate to optimize the reaction conditions. A number of
commonly used chiral diphosphine ligands, combined with
.
Ni(OAc)2 4H2O, were examined in trifluoroethanol (TFE) under 50
bar of H2 at 50 oC over 24 h (Table 1). When the axial chiral ligands
(S)-BINAP and (S)-SegPhos were employed, the reaction afforded
moderate catalytic activities and low enantioselectivities. (S)-
DTBM-SegPhos, which possesses highly substituted phenyl rings,
showed excellent catalytic activity and better enantioselectivity than
(S)-SegPhos. The more electron-rich ligands, (R,R)-DuanPhos and
(R,R)-QuinoxP*, provided full conversions and to our delight, when
using (R,R)-QuinoxP* as the ligand, the reaction proceeded with an
excellent enantioselectivity of 97% ee.
Table 2. Substrate scope.
Table 3. Benzosultam substrate scope.
To further extend the substrate scope, three types of cyclic N-
sulfonyl imine substrates bearing methyl or phenyl group were
examined in the asymmetric hydrogenation. To our surprise, under 1
bar H2 pressure and with a catalyst loading of 0.5 mol %, the
products shown in Table 3 were obtained in quantitative yields and
excellent enantioselectivities. Five-membered cyclic substrates gave
their corresponding products 2af and 2ag with 94% ee and 90% ee,
respectively. Six-membered cyclic substrates, irrespective of
whether the X was an oxygen or nitrogen atom, were also
hydrogenated to give products (2ah-ak) with excellent
enantioselectivities of 95-97% ee.
2
This article is protected by copyright. All rights reserved.

10.1002/anie.201902576
Angewandte Chemie International Edition
The tBu-sulfonyl group of products 2a and 2g could be removed
using AlCl3 to afford chiral amines 3a and 3g in 95% and 93%
yields, respectively, with no loss of ee (Scheme 2).[11] These chiral
amines could be further transformed to several chiral
pharmaceuticals and bioactive compounds, such as Fendiline, IDH1
inhibitor, NPS R568, and Rivastigmine (Scheme 1).[1]
According to the above coordination behaviors, we envisaged
that the coordination equilibrium between the Ni salt and its
complex most likely has some effect on the asymmetric
.
hydrogenantion. Thus, the effect of the ratio of Ni(OAc)2 4H2O to
(R,R)-QuinoxP* on the asymmetric hydrogenation was explored
(see SI). Additionally, it is interesting to note that the inactive Ni-
complex 4 could be reactivated when excess Ni salt was added (see
SI). These results, as expected, also clearly indicate that a
.
coordination equilibrium exists between Ni(OAc)2 4H2O and its
complex, and excess Ni salt is able to promote the formation of the
active Ni-complex 5 and therefore improve the efficiency of the
hydrogenation.
Scheme 2. Product derivatizations. Reaction conditions: a: 2a, g (1.5
mmol), anisol (2.0 mmol), AlCl3 (3.0 mmol), CH2Cl2 (10 mL), RT, 2 h.
Next, the coordination behaviors of (R,R)-QuinoxP* with
.
Ni(OAc)2 4H2O in d3-TFE were studied in the different ratios using
1H NMR spectroscopy (Figure 1). It can be seen that a coordination
equilibrium exists between the Ni salt and its complex, and the
predominant complexes formed in a ratio of 2/1 and 1/1 (ligand to
Ni salt) should be complexes 4 and 5, respectively (Scheme 3).
HRMS and 31P NMR spectroscopy also shows the existence of the
above complex structures (see SI).
Scheme 4. Study of catalyst loading.
To examine the efficiency of the catalytic system, the
hydrogenation of the standard substrate 1a, substituted substrate 1c
and cyclic substrate 1af were tested with a relatively low catalyst
loading. Anhydrous Ni(OAc)2 was used to avoid the unfavourable
effect of water and a 20/1 ratio of Ni salt to ligand was employed
(see SI). The hydrogenation of 1a proceeded smoothly with 92%
yield and 97% ee at 1000 S/C under 50 bar of H2 at 50 oC over 24 h
(Scheme 4a). The hydrogenation of 1c afforded complete
conversion to the desired product with 97% ee, even at 0.033 mol %
o
catalyst loading (S/C = 3000) at 70 C after 48 h (Scheme 4b). To
our delight, the cyclic substrate 1af, in the presence of a much lower
catalyst loading (0.0095 mol %, S/C = 10500), was hydrogenated
o
completely at 60 C under 10 bar hydrogen pressure over 72 h with
a 10 equivalents Ni salt, affording product 2af with 93% ee (Scheme
4c). This result represents the highest catalytic activity for all of the
Ni-catalyzed asymmetric hydrogenations reported to date. To the
best of knowledge, the highest S/C reported is 570.[7a]
Figure 1 Coordination study.
Scheme 5. Deuterium-labeling experiment.
In order to probe the reaction pathway of the asymmetric
hydrogenation, a deuterium labeling experiment was conducted
using D2 and it was shown that deuterium adds to the prochiral
carbon atom (Scheme 5). This result suggests that the reaction
mechanism for the Ni catalysis is similar to that of the Pd-catalyzed
Scheme 3. Coordination equilibrium.
3
This article is protected by copyright. All rights reserved.

10.1002/anie.201902576
Angewandte Chemie International Edition
asymmetric hydrogenation of imines.[9f] Accordingly, we computed
complex C1 as an active catalyst (Scheme 6).[9f]
a viable catalytic cycle for the hydrogenation of 1a using Ni–H
Scheme 6. Computed catalytic cycles for 1a. Relative Gibbs free energies in kcal/mol are shown (WB97XD/6-31g(d,p)/SMD(2,2,2-
trifluoroethanol, 298.15 K. 1 atm).
substrate are shown in red (CH…HC), green (CH…π), violet (CH…O)
and blue (with transferred hydride) dotted lines. TS(R) has 12 CH…HC
interactions in the range 2.15-2.82 Å, 4 CH…π interactions (2.49-2.71
Å), one CH…O interaction (2.60 Å) and 6 stabilizing interactions with
the transferred hydride (2.24-2.71 Å). The network of stabilizing
interactions is significantly less pronounced in TS(S): 6 CH…HC
interactions in the range 2.36-2.90 Å, 4 CH…π interactions (2.70-2.95
Å), two CH…O interaction (2.67 and 2.77 Å) and 1 stabilizing
interaction with the transferred hydride (2.30 Å).
The catalyst C1 readily coordinates with the substrate 1a via
either of its prochiral planes. Unlike in the case of the Pd-catalyst in
a similar reaction where the formation of similar adducts was
slightly endoergic,[9f] coordination of 1a to C1 is significantly
exoergic in both cases. Similar to the Pd example, the structures of
R1 and S1 are significantly different. In R1, a coplanar orientation
of Ni-H and C=N bonds creates a favorable environment for facile
hydride transfer with a free activation barrier less than 1 kcal/mol.
On the other hand, steric restrictions do not allow the formation of
the same adduct using the opposite prochiral plane of 1a. Instead, a
six-membered ring involving the hydride S1 is formed, which is
slightly more stable than R1, but significantly less reactive; this
results in a difference of 5.0 kcal/mol of free energy between the
competing transition states TS(R) and TS(S) due to a much more
Figure 2. Optimized Transition states for the enantiodetermining
extensive network of stabilizing intramolecular interactions in
TS(R) (Figure 2). This is a stereodetermining stage that cannot be
hydride transfer stage. Close contacts between the catalyst and
4
This article is protected by copyright. All rights reserved.

10.1002/anie.201902576
Angewandte Chemie International Edition
Q.-A. Chen, Z.-S. Ye, Y. Duan, Y.-G. Zhou, Chem. Soc. Rev. 2013,
42, 497. l) P. Etayo, A. Vidal-Ferran, Chem. Soc. Rev. 2013, 42, 728.
m) K. H. Hopmann, A. Bayer, Coord. Chem. Rev. 2014, 268, 59. n)
Z. Zhang, N. A. Butt, W. Zhang, Chem. Rev. 2016, 116, 14769. o) P.-
G. Echeverria, T. Ayad, P. Phansavath, V. Ratovelomanana-Vidal,
Synthesis 2016, 48, 2523. p) C. S. G. Seo, R. H. Morris,
Organometallics 2019, 38, 47.
affected by the second hydrogenation step, which is also preferable
for the R-catalytic cycle by 4.5 kcal/mol (Scheme 6, note that the S-
cycle also requires an additional isomerization step). Furthermore,
the extensive network of numerous weak attractive interactions
between the catalyst and substrate in TS(R) may also contribute to
the high catalytic activity.
[3] For reviews: a) R. H. Morris, Chem. Soc. Rev. 2009, 38, 2282. b) K.
Gopalaiah, Chem. Rev. 2013, 113, 3248. c) H. Pellissier, H. Clavier,
Chem. Rev. 2014, 114, 2775. d) R. H. Morris, Acc. Chem. Res. 2015,
48, 1494. e) Y.-Y. Li, S.-L. Yu, W.-Y. Shen, J.-X. Gao, Acc. Chem.
Res. 2015, 48, 2587. f) P. J. Chirik, Acc. Chem. Res. 2015, 48, 1687.
g) I. Bauer, H.-J. Knölker, Chem. Rev. 2015, 115, 3170. h) R. Bigler,
A. Mezzetti, Org. Process Res. Dev. 2016, 20, 253. i) Z. Zhang, N. A.
Butt, M. Zhou, D. Liu, W. Zhang, Chin. J. Chem. 2018, 36, 443.
[4] a) P. O. Lagaditis, P. E. Sues, J. F. Sonnenberg, K. Y. Wan, A. J.
Lough, R. H. Morris, J. Am. Chem. Soc. 2014, 136, 1367. b) M. R.
Friedfeld, H. Zhong, R. T. Ruck, M. Shevlin, P. J. Chirik, Science
2018, 360, 888. c) L. Zhang, Y. Tang, Z. Han, K. Ding, Angew.
Chem., Int. Ed. 2019, 58, doi: 10.1002/anie.201814751.
In conclusion, a Ni-catalyzed asymmetric hydrogenation of N-
tBu-sulfonyl imines was developed to afford chiral tBu-sulfonyl
amines with excellent catalytic activities and enantioselectivities
based on the founding of a coordination equilibrium between the Ni
salt and its complex. A much lower catalyst loading (0.0095 mol %,
S/C = 10500) for a cyclic substrate 1af represents the highest
catalytic activity for all the Ni-catalyzed asymmetric hydrogenations
reported to date. Computations suggested that the enantioselectivity
originates from the significant structural differences between the S-
and R-pathways. Furthermore, the computations also suggested that
the very high catalytic activities of the hydrogenation may be partly
due to the numerous weak attractive interactions between the
substrate and catalyst in the transition state.
[5] (a) Y. Hamada, Y. Koseki, T. Fujii, T. Maeda, T. Hibino, K. Makino,
Chem. Commun. 2008, 46, 6206. (b) T. Hibino, K. Makino, T.
Sugiyama, Y. Hamada, ChemCatChem 2009, 1, 237.
[6] M. Shevlin, M. R. Friedfeld, H. Sheng, N. A. Pierson, J. M. Hoyt,
L.-C. Campeau, P. J. Chirik, J. Am. Chem. Soc. 2016, 138, 3562.
[7] a) W. Gao, H. Lv, T. Zhang, Y. Yang, L. W. Chung, Y.-D. Wu, X.
Zhang, Chem. Sci. 2017, 8, 6419. b) X. Li, C. You, S. Li, H. Lv, X.
Zhang, Org. Lett. 2017, 19, 5130. c) J. Long, W. Gao, Y. Guan, H.
Lv, X. Zhang, Org. Lett. 2018, 20, 5914. d) Y.-Q. Guan, Z. Han, X.
Li, C. You, X. Tan, H. Lv, X. Zhang, Chem. Sci. 2019, 10, 252.
[8] a) H. Xu, P. Yang, P. Chuanprasit, H. Hirao, J. Zhou, Angew. Chem.,
Int. Ed. 2015, 54, 5112; Angew. Chem. 2015, 127, 5201. b) P. Yang,
L. H. Lim, P. Chuanprasit, H. Hirao, J. Zhou, Angew. Chem., Int. Ed.
2016, 55, 12083; Angew. Chem. 2016, 128, 12262. c) X. Zhao, H.
Xu, X. Huang, J. S. Zhou, Angew. Chem. Int. Ed. 2019, 58, 292;
Angew. Chem. 2019, 131, 298.
Acknowledgments
We would like to thank Shanghai Municipal Education
Commission (No. 201701070002E00030), National Natural Science
Foundation of China (Nos. 21620102003, 21702134 and 21772119)
and Science and Technology Commission of Shanghai Municipality
(No. 17ZR1415200) for financial support. We thank the
Instrumental Analysis Center of SJTU for characterization.
[9] For representative papers: a) F. Tian, D. Yao, Y. Liu, F. Xie, W.
Zhang, Adv. Synth. Catal. 2010, 352, 1841. b) Y. Liu, W. Zhang,
Angew. Chem. Int. Ed. 2013, 52, 2203; Angew. Chem. 2013, 125,
2259. c) J. Chen, D. Liu, N. Butt, C. Li, D. Fan, Y. Liu, W. Zhang,
Angew. Chem. Int. Ed. 2013, 52, 11632; Angew. Chem. 2013, 125,
11846. d) Y. Liu, I. D. Gridnev, W. Zhang, Angew. Chem. Int. Ed.
2014, 53, 1901; Angew. Chem. 2014, 126, 1932. e) Q. Hu, Z. Zhang,
Y. Liu, T. Imamoto, and W. Zhang, Angew. Chem. Int. Ed. 2015, 54,
2260; Angew. Chem. 2015, 127, 2288. f) J. Chen, Z. Zhang, D. Liu,
W. Zhang, Angew. Chem. Int. Ed. 2016, 55, 8444; Angew. Chem.
2016, 128, 8584. g) J. Chen, Z. Zhang, B. Li, F. Li, Y. Wang, M.
Zhao, I. D. Gridnev, T. Imamoto, W. Zhang, Nat. Commun. 2018, 9,
5000.
Keywords: nickel-catalyst asymmetric hydrogenation chiral amines
(R,R)-QuinoxP*
[1] Chiral Amine Synthesis: Methods, Developments and Applications
(Ed.: T. C. Nugent), Wiley-VCH, Weinheim, 2010.
[2] For representative reviews: a) H.-U. Blaser, C. Malan, B. Pugin, F.
Spindler, H. Steiner, M. Studer, Adv. Synth. Catal. 2003, 345, 103. b)
W. Tang, X. Zhang, Chem. Rev. 2003, 103, 3029. c) W. Zhang, Y.
Chi, X. Zhang, Acc. Chem. Res. 2007, 40, 1278. d) N. B. Johnson, I.
C. Lennon, P. H. Moran, J. A. Ramsden, Acc. Chem. Res. 2007, 40,
1291. e) N. Fleury-Brꢀgeot, V. de la Fuente, S. Castillꢁn, C. Claver,
ChemCatChem 2010, 2, 1346. f) C. Wang, B. Villa-Marcos, J. Xiao,
Chem. Commun. 2011, 47, 9773. g) J.-H. Xie, S.-F. Zhu, Q.-L. Zhou,
Chem. Rev. 2011, 111, 1713. h) D. J. Ager, A. H. M. de Vries, J. G.
de Vries, Chem. Soc. Rev. 2012, 41, 3340. i) Z. Yu, W. Jin, Q. Jiang,
Angew. Chem. Int. Ed. 2012, 51, 6060. Angew. Chem. 2012, 124,
6164. j) J.-H. Xie, Q.-L. Zhou, Acta Chim. Sinica 2012, 70, 1427. k)
[10] Y. -C. Chen, T.-F. Wu, J.-G. Deng, H. Liu, X. Cui, J. Zhu, Y.-Z. Jiang,
M. C. K. Choi, A. S. C. Chan, J. Org, Chem. 2002, 67, 5301.
[11] D. Enders, M. Seppelt, T. Beck, Adv. Synth. Catal. 2010, 352, 1413.
5
This article is protected by copyright. All rights reserved.

10.1002/anie.201902576
Angewandte Chemie International Edition
Entry for the Table of Contents (Please choose one layout)
Layout 1:
((Catch Phrase))
((Text for Table of Contents, max. 450
characters))
((Author(s), Corresponding Author(s)*))
__________ Page – Page
((Title Text))
((TOC Graphic))
Layout 2:
((Catch Phrase))
Bowen Li, Jianzhong Chen, Zhenfeng
Zhang, Ilya D. Gridnev, and Wanbin
Zhang __________ Page – Page
Ni-Catalyzed Asymmetric Hydrogenation of
N-Sulfonyl Imines
The first Ni-catalyzed asymmetric hydrogenation of N-sulfonyl imines using H2 gas as a
hydrogen source has been realized with excellent enantioselectivities (up to 99.7% ee) and
high catalytic activities (S/C up to 10500). Mechanistic studies suggested that the presence
of excess earth-abundant cheap Ni salt with respect to the ligand promoted the formation of
the active Ni-catalyst and therefore improved the efficiency of the hydrogenation.
This article is protected by copyright. All rights reserved.