Catalytic and Mechanistic Developments of the Nickel(II) Pincer Complex-Catalyzed Hydroarsination Reaction

Article abstract of DOI:10.1002/chem.201902138

Synthetic challenges have significantly slowed the development of the catalytic asymmetric hydroarsination reaction despite it being a highly attractive C?As bond formation methodology. In addition, there is a poor understanding of the main reaction steps in such reactions which limit further development in the field. Herein, key intermediates of the hydroarsination reaction catalyzed by a PCP Ni^II-Cl pincer complex are presented upon investigating the reaction with DFT calculations, conductivity measurements, NMR spectroscopy, and catalytic screening. The novel Ni–Cl–As interaction proposed was then contrasted against known Ni^II-catalyzed hydrophosphination reactions to highlight dissimilarities between them even though P and As share a close group relationship. Lastly, the asymmetric hydroarsination of nitroolefins was further developed to furnish a library of chiral organoarsines in up to 99 % yield and 80 % ee under mild conditions (?20 °C to RT) between 5 to 210 mins.

Full text of DOI:10.1002/chem.201902138

A Journal of
Accepted Article
Title: Catalytic and mechanistic developments of the Nickel(II) pincer
complex-catalyzed hydroarsination reaction
Authors: Wee Shan Tay, Yunpeng Lu, Xiang-Yuan Yang, Yongxin Li,
Sumod Pullarkat, and Pak-Hing Leung
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: Chem. Eur. J. 10.1002/chem.201902138
Link to VoR: http://dx.doi.org/10.1002/chem.201902138
Supported by

Chemistry - A European Journal
10.1002/chem.201902138
FULL PAPER
Catalytic and mechanistic developments of the Nickel(II) pincer
complex-catalyzed hydroarsination reaction
Wee Shan Tay, Yunpeng Lu, Xiang-Yuan Yang, Yongxin Li, Sumod A. Pullarkat, and Pak-Hing Leung*[a]
Abstract: Synthetic challenges have significantly slowed the
development of the catalytic asymmetric hydroarsination reaction
despite it being a highly attractive C–As bond formation methodology.
In addition, there is a poor understanding of the main reaction steps
in such reactions which limit further development in the field. Herein,
key intermediates of the hydroarsination reaction catalyzed by a PCP
Ni(II)-Cl pincer complex are presented upon investigating the reaction
with DFT calculations, conductivity measurements, NMR
spectroscopy and catalytic screening. The novel Ni–Cl–As interaction
proposed was then contrasted against known Ni(II)-catalyzed
hydrophosphination reactions to highlight dissimilarities between
them even though P and As share a close group relationship. Lastly,
the asymmetric hydroarsination of nitroolefins was further developed
to furnish a library of chiral organoarsines in up to 99% yield and 80%
ee under mild conditions (-20ºC to RT) between 5 to 210 mins.
useful synthetic tools even in the syntheses of complex natural
products.[7]
In recent years, variants involving As nucleophiles have emerged
in response to the demand for greener synthetic methodologies.[
With traditional organoarsine syntheses violating most,[9] if not all,
of the 12 green chemistry principles,[10] this is clearly a fertile field
for further development. Preceding studies have identified
catalyst design as instrumental to the success of this highly
efficient reaction which achieved excellent yields and ee’s in <5
mins.[8g,h] A better understanding of the reaction mechanism
should spur further developments rapidly, although fast reaction
rates come with a caveat: the difficulty in observing short-lived
intermediates.
8]
Herein, the Ni(II)-mediated asymmetric hydroarsination of
nitroolefins is investigated from several complementary aspects.
Catalytic screening was conducted in conjunction with density
functional theory (DFT) calculations, 31P{ H} NMR studies and
conductivity measurements. In reference to other closely-related
hydrofunctionalization reactions, reported mechanisms of related
1
Introduction
Ni(II)-catalyzed hydrophosphination reactions were also
discussed.[11] Results of this investigation suggest that the key
Catalytic asymmetric hydrofunctionalization reactions offer
virtually limitless alternatives for asymmetric C-heteroatom bond
formation.[ This attractive flexibility has spurred the development
of many catalytic systems to direct the stereoselective addition of
H-X to unsaturated bonds (Scheme 1). Mechanistic aspects of
these reactions have also been well studied, and several
alternative mechanisms have been proposed for most
heteroatoms compatible with the hydrofunctionalization
catalytic intermediate involving the PCP Ni(II) pincer catalyst
interacts with the arsine nucleophile via a Ni–Cl–As interaction.
This “nucleophile association” mechanism has not been
previously reported in the closely-related hydrophosphination
reactions, therefore offering novel insights highlighting the
uniqueness of the hydroarsination reaction.
1]
methodology (eg. B, Si,[3] N,[4] P,[5] S ). Such developments
[
2]
[6]
have paved the way to employ hydrofunctionalization reactions as
Results and Discussion
Solvent effect on catalysis
A primary reaction step of the hydroarsination mechanism
involves activating the H–As bond for subsequent bond breaking.
Previous kinetic studies done by Cullen and Leeder have
concluded that either an ionic or neutral mechanism may facilitate
the proton transfer reaction of secondary arsines, in which the
former involved reversible heterolytic H–As bond cleavage while
the latter proceeded by a four-centered mechanism.[12] In view of
Scheme 1. General scheme of catalytic asymmetric hydrofunctionalizations of
activated olefins.
2
the potentially amphoteric character of HAsPh , catalytic
screening was carried out to observe the potential dissociation of
the H–As bond during the hydroarsination reaction (Table 1).
Preliminary results revealed a strong dependence on alcohols for
good catalytic activity (Entries 5-7). Amongst several solvents
screened, only alcoholic solvents allowed complete conversion of
nitrostyrene 1a within 2 h, albeit with moderate ee’s of 33-59%
(Entries 5-7). Increasing the hydrophobicity of the alcohol resulted
in increased reaction times and decreased stereoselectivities
correspondingly (Entries 5-7). Varying the water present in the
[
a]
W. S. Tay, Dr Y. Lu, Dr X.-Y. Yang, Dr Y. Li, Dr S. A. Pullarkat, Prof
P.-H. Leung
Division of Chemistry and Biological Chemistry, School of Physical
and Mathematical Sciences
Nanyang Technological University
21 Nanyang Link, Singapore 637371
E-mail: pakhing@ntu.edu.sg
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.

Chemistry - A European Journal
10.1002/chem.201902138
FULL PAPER
In addition, H–As bond cleavage may indeed occur in the absence
of catalyst, particularly in highly polar protic environments such as
Table 1. Solvent screening for the Ni(II)-mediated hydroarsination
reaction.
2
MeOH/H O (10% v/v).
[
a]
Investigating C-H bond formation
In catalytic asymmetric hydrofunctionalization reactions, up to two
chiral carbon centers may be controlled during C*–H and C*–E
bond formations. Excellent stereoselectivities rely on close
interactions with the chiral catalyst during bond formation steps.
In particular, the stereoselective formation of C*–H bonds are
notably challenging in the presence of highly protic environments
such as aqueous or semi-aqueous/alcoholic conditions. To that
effect, α-nitrostyrenes 4 were specially designed to evaluate the
effectiveness of catalyst 3 in controlling C*–H bond formations
under optimized conditions.[ C–As bond formation occurs at a
terminal alkene instead, while C–H bond formation results in a
newly-generated chiral center at the tertiary carbon atom. Solvent
screening for α-nitrostyrene 4a revealed reactivities and
stereoselectivities comparable to nitrostyrene 1a (Table 2). Under
optimal conditions, arsine 5a was afforded in 91% yield with 71%
ee at RT (Entry 1). Clearly, C*–H bond formation was efficiently
controlled by chiral catalyst 3, even in the presence of a highly
protic environment.
t[b]
(min)
1440
Yield[c]
(%)
NR
ee[d]
(%)
-
Entry
Solvent
CHCl
T
(ºC)
1
2
3
4
5
6
7
8
9
3
RT
16]
Acetone
MeCN
THF
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
-20
-40
1440
1440
1440
30
NR
NR
NR
87
-
-
-
MeOH
EtOH
59
40
33
-
90
84
iPrOH
120
1440
<5
97
AcOH
NR
89
MeOH/H
MeOH/H
MeOH/H
2
2
2
O (5%)[e]
O (10%)[f]
O (15%)[g]
39
75
45
-
1
1
1
1
1
0
<5
99
1
<5
90
2
MeOH/AcOH (10%)[h]
1440
15
NR
76
Table 2. Investigating C–H bond formation.[a]
3[i]
MeOH/H
MeOH/H
O (10%)[f]
O (10%)[f]
80
80
2
4
2
75
99
[
a] Reaction conditions: nitrostyrene 1 (7.46 mg, 0.05 mmol, 1.0 eq.),
HAsPh (13.80 mg, 0.06 mmol, 1.2 eq.), cat. (R,R)-3 (0.83 mg, 1.00 μmol, 2
2
mol %), solvent (2 mL). [b] Complete conversion was observed via TLC. [c]
Determined by HPLC at 254 nm. NR = no reaction. [d] Determined by chiral
HPLC of the crude reaction mixture. [e] H
added. [f] H O (200 μL, 10 % v/v of solvent) was added. [g] H
5 % v/v of solvent) was added. [h] AcOH (200 μL, 10 % v/v of solvent) was
2
O (100 μL, 5 % v/v of solvent) was
Entry
Solvent
T
t[b]
(min)
15
Yield[c]
(%)
ee[d]
(%)
71
2
2
O (300 μL,
(ºC)
1
1
2
3
4
5
6
7
8
9
MeOH
RT
91
added. [i] 5 mol % of cat. (2.08 mg, 2.50 μmol) was used instead.
EtOH
RT
RT
RT
RT
RT
RT
0
30
98
85
92
86
91
83
68
NR
48
25
61
50
40
53
79
-
iPrOH
30
Dry MeOH
30
MeOH/H
2
O (5%)[e]
15
reaction also affected the reaction in terms of rate and
stereoselectivities (Entries 9-11). The heterolytic cleavage of the
H–As bond was supported by the absence of arsine 2a when the
reaction was conducted in protic but acidic conditions such as
MeOH/AcOH (10% v/v) (Entry 12). The acid-base behavior of
MeOH/H O (10%)[f]
2
15
O (15%)[g]
MeOH/H
MeOH
2
15
15
MeOH
-20
1440
HAsPh
pH of the solvent.
= 20.3 in THF)[14] suggests that spontaneous
HAsPh (pK
dissociation of the proton is unlikely, which may explain the lack
of reactivity observed in THF (Entry 4), whereas no data was
2
was considered in account of the dielectric constant and
[
13]
A quick literature review for the pK
a
of
[a] Reaction conditions: nitroolefin 4 (0.05 mmol, 1.0 eq.), HAsPh
2
(13.80
mg, 0.06 mmol, 1.2 eq.), cat. (R,R)-3 (0.83 mg, 1.00 μmol, 2 mol %), solvent
2 mL). [b] Complete conversion was observed via TLC. [c] Determined by
HPLC at 254 nm. [d] Determined by chiral HPLC of the crude reaction
mixture. [e] H O (100 μL, 5 % v/v of solvent) was added. [f] H O (200 μL,
O (300 μL, 15 % v/v of solvent) was
2
a
(
2
2
available for the pK
knowledge. To supplement pK
a
of HAsPh
2
in MeOH to the best of our
values, an NMR study was
10 % v/v of solvent) was added. [g] H
2
added.
a
designed to reflect the nature of the H–As bond in various
solvents.[15] Results obtained were in close agreement with the
solvent screening conducted and it was determined that the
Key intermediate of the hydroarsination reaction
fastest H/D exchange occurred in MeOD/D
2
O (10% v/v). It was
It was previously established that interactions were present
inferred that the addition of D O may encourage H/D exchange in
2
between Ni(II)-pincer 3 and HAsPh
2
whereas they were absent
certain solvents (eg. MeCN, MeOD), although it may be
insufficient to promote H/D exchange in others (eg. acetone, THF).
between Ni(II)-pincer 3 and nitrostyrene 1a.[
8g] 31
P{ H} NMR
1
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201902138
FULL PAPER
Table 3. Summary of selected data from DFT calculations.[a]
Charge
Anionic
Neutral
Anionic
Free energy/Hartree
-7570.6511
-7071.8305
-9684.4982
G(formation)
-55.7
24244.4
-52.3
/kcal mol-1
Ni–X bond length/Å
As–X bond length/Å
As–C bond length/Å
2.415
2.289
1.945
-
-
2.514
2.419
1.949
[
a] All values were obtained in the gas phase at 298.15K.
studies revealed that these interactions exist in equilibrium and
were thus not useful in revealing more structural information of
the intermediate species.[15] Due to the inability of NMR studies to
shed light on structural information of the intermediates, we turned
to DFT calculations to explore interactions between Ni(II)-catalyst
favorable axial interactions leading to the formation of 5
coordinate intermediates were derived by DFT calculations,
transient axial interactions remain a possibility. However, these
axial interactions should be minor considering the high percent
buried volume (%Vbur) of Ni(II) complex 3 in which the bulky ligand
limits access of reagents to the metal center.[18]
3
and HAsPh
phase reflected a Ni–Cl–As type interaction between Ni(II)-
catalyst 3 and HAsPh at 298.15 K (Table 3). 4-coordinate
2
(Table 3).[17] Optimized DFT calculations in the gas
In fact, this Ni–X–As type interaction was not unique to only
chlorides. DFT calculations were also attempted for Ni–Br–As
complex A1’ and G(formation) values were similarly
2
intermediate A1 was spontaneously formed over intermediate A2,
and no 5-coordinate intermediates were derived. DFT
calculations of the known Ni(II) complex 3 were first benchmarked
against bond lengths and angles determined by X-ray
crystallography. The reliability of gas-phase DFT calculations in
this instance was reflected by the close agreement between
theoretical and experimental bond lengths (eg. For the Ni–Cl bond
length, calc.: 2.218 Å, experimental: 2.2075(8) Å).[18] The
theoretical Ni–Cl bond length of complex 3 also highly resembled
-1
spontaneous at -52.3 kcal mol (Table 3). Longer theoretical Ni–
X and As–X bonds observed for X = Br were reasonable upon
accounting for the larger bromide ionic radius. The bromide
variant of Ni-Cl catalyst 3 was also catalytically active in the
hydroarsination reaction.[15] Both percentage yields and ee’s
obtained were within 5% of that furnished by Ni-Cl catalyst 3.
Excellent correlation was also observed between the longer Ni–
Br and As–Br bonds and the stereoselectivities of the
transformation. Arsine 2a was obtained in a slightly lower ee (Cl:
75%, Br: 70%) understandably due to the further distance
between the chiral ligand and reaction site on intermediate A1’.
Unfortunately, the Ni-F variant of catalyst 3 could not be
successfully prepared to further observe other Ni–X–As
interactions.[21]
that of other similar square planar PCP-Ni(II) pincer complexes
between 2.20-2.24 Å.[19] Interaction with AsPh
-
lengthened the
2
Ni–Cl bond of catalyst 3 to 2.415 Å in intermediate A1. A thorough
literature search of other As–Cl bonds in trivalent organoarsine
chlorides of the type R
2
AsCl were determined to be 2.19-2.34
Å.[20] Theoretical calculations for intermediate A1 revealed an As–
Cl bond length of 2.289 Å, closely resembling that of Ph
2
AsCl
The spontaneous formation of intermediate A1 was calculated
2.26 Å).[
20k]
In determining the relevance of theoretical
upon considering the existing presence of AsPh
-
under reaction
(
2
predictions, intermediate A1 was then investigated empirically.
The hydroarsination of nitrostyrene 1a catalyzed by Ni-Cl complex
conditions. It seems worthy to note here that the generation of
-1
intermediate A1 was strongly unfavourable (293.4 kcal mol )
without prior deprotonation of HAsPh
.[17] Unlike other
hydrofunctionalization (hydrophosphination) reactions in which
coordination of HEPh to the transition metal catalyst acidified the
3
was conducted in a large excess of chloride ions to suppress
2
[
15]
any equilibrium dissociation of the Ni–Cl bond. As expected, the
reaction proceeded with no notable difference in rate and afforded
arsine 2a in comparable yield and ee, within 5% that of the control
reaction. Unlike intermediate A2, the formation of Ni–Cl–As
intermediate A1 remained favorable even in the presence of
2
H–E bond for subsequent deprotonation,[5] theoretical
calculations involving the current unprecedented Ni–Cl–As
interaction suggest otherwise. Instead, the H–As bond was
-
excess Cl . In addition to the described Ni–Cl–As interaction, other
interactions between the AsPh
expected to exhibit a degree of lability even in the absence of
-
-
2
anion and the electropositive
catalyst 3 to afford an equilibrium concentration of AsPh
2
in
[15]
MeOH (vide supra, determined by 31P{ H} NMR spectroscopy).
1
Ni(II) center were also considered. While no energetically
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201902138
FULL PAPER
-
1
This was easily observed with solvent screening (Table 1): (1) an
acidic environment hindered the hydroarsination reaction, and (2)
increasing the aqueous character of the solvent resulted in a
remarkable decrease in reaction times. Concurrently, theoretical
calculations were utilized to evaluate the feasibility of an
significantly smaller than that of KCl (195 S cm ) under the same
conditions. Further attempts to confirm the weak dissociation
equilibrium by obtaining more molar conductivity values of Ni
catalyst 3 were unsuccessful. Experiments repeated at higher
concentrations (>5 mM) were hindered by the limited solubility of
equilibrium dissociation of H–AsPh
determined that dissociation of H–AsPh
and in MeOH were non-spontaneous, although solvent effects of
2
(Table 4).[17] Calculations
in both the gas phase
2
the catalyst in MeOH/H O (10% v/v). Concentrations less than
2
2mM were avoided to minimize error affecting the accuracy of
measurements obtained. Despite these limitations, it was clear
that the Ni–Cl bond of Ni catalyst 3 does not dissociate
-1
MeOH considerably reduced the 
spontaneity was expected, considering the high pK
r
G to 62.7 kcal mol . This non-
of HAsPh
.[14]
a
2
Proton transfer process proceeding by an extended proton
network, although more likely, could not be modelled due to
constraints imposed by the extended solvent model. Nevertheless,
these calculations of the direct proton transfer provide another
perspective regarding dissociation of the H–As bond in different
Table 5. Conductivity measurements in MeOH/H
2
O (10% v/v).[a]
Entry
1
Sample
Concentration
/ mM
-
Conductivity
/ S cm-
2
1[b]
2
10% H O/
90% MeOH (solvent)
2
solvents. The effect of MeOH on the spontaneity of H–AsPh bond
cleavage is clearly observable with the following evidence.
2
3
4
KCl
KCl
2
20
2
195
1022
5
Ni-Cl complex 3
[
a] Measurements were conducted at 212 ºC. [b] Values were averaged
G in gaseous and methanolic states.[a]
r
over 3 runs and reported to the nearest whole number.
Table 4. 
Reaction
Condition
r
 G /
-
1
kcal mol
349.1
62.7
Gaseous
MeOH
THF
appreciably and, together with the theoretical and experimental
evidence collected, support the formation intermediate A1.
217.5
It may be erroneous to immediately assume that the Ni–Cl–As
intermediate A1 exhibits reactivity typical of in situ-generated
arsenous halides because the overall anionic charge precludes
nucleophilic attack at the As atom. Molecular orbital (MO) surface
plots for intermediate A1 suggest -type bonding between Ni–Cl
and Cl–As, although it appeared that no delocalized bonding over
the Ni–Cl–As motif was present. An in-depth NBO analysis for the
Ni–Cl–As bonding is of great interest, and certainly deserves
specialized attention in future work. Also, the -donating/-
accepting nature of the Ni–Cl–As interaction remains a subject for
Gaseous
MeOH
-55.7
-46.6
[
a] All values were obtained at 298.15K.
Firstly, other solvents did not result in a significant reduction of
G. Even with similar oxygen-containing solvents such as THF,
G calculated for the H–As bond dissociation was only 217.5 kcal


r
further study and
a
literature search revealed limited
r
[22]
understanding on similar Ni–Cl–E interactions. Firstly, the role
of a halide ligand in transition metal catalysis is often discounted
and most discussions revolve around their removal from the
coordination sphere (such as with silver salts bearing weakly
-1
mol , suggesting that the reported pK
be loosely taken as a reference for the ionization of H–AsPh
MeOH. Secondly, significantly lower  G values in MeOH was
only uniquely observed for the dissociation of H–AsPh . When the
a
of HAsPh
2
in THF can only
2
in
r
2
coordinating anions eg. -BF
-ClO
-PF ).[11a,b,23] Secondly,
4
,
4
,
6
formation of intermediate A1 was taken as a reference reaction,
the solvent effect exhibited was several orders smaller and
electronic factors are complicated even when attempts are made
to predict the nature of metal-halide interactions. These
interactions may rely on factors such as the oxidation state,
electron density, coordinated ligands and geometry of the metal
center, thus requiring a synergistic evaluation of the entire
complex instead of a single bond in isolation. Similar M–X–E type
-
1
calculated 
to 286.4 kcal mol for H–As dissociation. Interestingly, the
catalysis proceeded smoothly in MeOH/H O (10% v/v) even at -
0ºC (Table 1 Entry 14), suggesting that the H–As bond
r
G values differed only by 9.2 kcal mol as opposed
-1
2
4
-1
dissociation energy of 62.7 kcal mol could be further reduced
with an increase in the solvent’s aqueous character under actual
experimental conditions.
interactions are most commonly observed in transition metal
fluoride catalysis.[24] This has been attributed to the unique
electronegativity and van der Waals radii of fluoride anions. How
Ni(II)–Cl complex 3 increases the reactivity of the arsenide
nucleophile warrants a further in-depth study regarding the
electronic nature of the Ni–Cl–As interaction. Empirically,
intermediate A1 is supported by a series of carefully-designed
experiments (vide infra) and nevertheless represents a crucial
intermediate of the Ni(II)-mediated asymmetric hydroarsination
reaction.
Lastly, establishing the inertness of the Ni–Cl bond in catalyst 3
under highly polar conditions was of paramount importance to
affirm the structure of intermediate A1. Molar conductivity
measurements were conducted to investigate the degree of Ni–
Cl bond ionization of Ni catalyst 3 (Table 5). It was concluded that
Ni catalyst 3 exhibited a weak ionization equilibrium at best,
observed from a conductivity of 4.90 S cm-1 which closely
resembled the blank solvent (Entries 1 and 4). This was
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201902138
FULL PAPER
Proposed mechanism
product dissociation from intermediate C regenerates 4-
Majority of known Ni-mediated reactions have unknown active
catalysts due to their flexibility in accessing several oxidation
states.[25] However, it is important to understand key reaction
steps to assist further developments of catalytic organoarsenic
synthetic methodologies. The insights derived above may be
succinctly summarized in a proposed catalytic cycle as presented
coordinate Ni complex 3 and releases the desired product. The
highly polar solvent environment may assist concurrent proton
transfer between several potential shuttles such as water, MeOH,
diphenylarsine and/or the nitroolefin. As such, the identity of the
proton donor cannot be concluded in this study. Previous attempts
at deuterium labelling were also unsuccessful.[ Other minor 4-
membered intermediates are possibly formed along with the
proposed intermediates. Nevertheless, no paramagnetic species
were observed spectroscopically, indicating the unlikely
occurrence of 4-membered tetrahedral derivatives of Ni(II)-
catalyst 3. Figure 1 summarizes the overall free energy changes
8g]
in Scheme 2. The overall mechanism can be outlined in 4 key
-
steps: (1) Ni–Cl–As association between catalyst 3 and AsPh
2
,
(
2) intermolecular attack on the activated olefin, (3)
stereoselective protonation and (4) dissociation to release the
product and regenerate the active catalyst (Scheme 2).
-
[17]
Interaction of AsPh
2
to 4-coordinate Ni(II)-complex 3 generates
of key intermediates in the proposed catalytic cycle (in MeOH).
Ni–Cl–As intermediate A1. A 1,4-nucleophilic attack of
The overall 
kcal mol-1 which closely agrees with other olefin
hydrophosphinations and hydroamination reactions in which 
r
G was determined by DFT calculations to be -10.9
r
G
are calculated to be close to zero or even slightly
endergonic.[11b,26]
Evaluating
reactions
against
Ni-catalyzed
hydrophosphination
To the best of our knowledge, this constitutes the first proposed
mechanism for the Ni-mediated hydroarsination reaction.
However, mechanisms for the Ni-catalyzed hydrophosphination
reactions have since been established by both experimental and
theoretical methods.[11] Togni and coworkers identified a Lewis
acidic interaction between a PPP-Ni(II) pincer complex and the
electron-deficient olefin substrate.[11a,b] On the other hand, purely
theoretical investigations in the absence of experimental support
by Downey and coworkers led to an alternative mechanism in
which the active Ni–PPh
2
catalytic species was generated by
displacing the Ni–Cl bond of the POCOP Ni(II)-Cl pre-catalyst.[
Notably, direct participation of the Ni(II) center was involved in
both proposed catalytic cycles and the active catalytic species
were only generated in-situ under reaction conditions. Due to
11e]
different -donating/-accepting natures of arsines as compared
to phosphines,[
27]
mechanisms for the hydrophosphination
Scheme 2. Proposed mechanism of the Ni(II)-mediated asymmetric
hydroarsination reaction.
reaction cannot be assumed to be immediately applicable to the
hydroarsination reaction. For comparison, the relevance of the
mechanisms proposed by Togni and Downey were evaluated in
context of the hydroarsination reaction. Interaction between Ni(II)-
catalyst 3 and the electron-deficient olefin substrate was deemed
absent by a series of low temperature NMR studies.[ Similarly,
experimental evidence suggest that the Ni–Cl bond of Ni(II)-
catalyst 3 remains inert under hydroarsination conditions and the
catalysis proceeded smoothly even in the presence of a large
intermediate A1 on nitroolefin 1 generates the arsine-nitronate
species B. As evidenced by the excellent 1,4-regioselectivities
observed for arsines 2/5, the intermolecular attack is proposed to
resemble a Michael-type reaction instead of typical transition
metal-catalyzed oxidative addition/reductive elimination pathways.
Sequential protonation of intermediate B occurs within the
catalyst sphere to generate intermediate C. Potentially, arsine
dissociation in intermediate B may be a competing pathway prior
to subsequent racemic protonation. This was supported by
variations in ee’s (40% to 61%) observed when different ratios of
water were present (Table 2, Entries 4-7). Even so, high overall
ee’s suggest that excellent control is exerted over the C*–H bond
formation process, signaling the preference for the
stereoselective proton transfer step. Intermediates B and C
consequently resulted in good stereoselectivities observed at the
C*–As and C*–H chiral centers (Tables 1 and 2). Subsequent
8g]
-
excess of Cl ions.
Substrate scope
To develop the methodology further, a series of functionalized
nitroolefins were selected to explore the electronic and steric
effects of substituents on the catalytic pathway (Table 6).
Generally, Ni-catalyst 3 exhibited good tolerance for a range of
functionalized nitroolefins. Olefins 1b-e bearing electron-deficient
aryl rings achieved complete conversion within 5 mins (Entries 1-
4) while olefins bearing electron-rich tolyl rings required 30 mins
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201902138
FULL PAPER
Figure 1. DFT calculations of the reaction profile for the Ni(II)-mediated hydroarsination reaction at 298.15 K in MeOH.[17]
Table 6. Electronic and steric effects on the hydroarsination reaction.[a]
(
Entries 5 and 6). Olefins with electron- donating methoxy
substituents 1h and 1i required higher temperature and
achieved complete conversion at 0 ºC after 60 and 210 mins
respectively (Entries 7 and 8). Overall, stereoselectivities were
not significantly affected by substituents and a range of
functionalized arsines could be obtained in 70-75% ee’s
(
7
Entries 1-8) except 2-methoxy-functionalized arsine 2h (Entry
). Sterically-bulkier naphthyl moieties were also tolerated and
afforded arsine 2j with 68% ee at 0 ºC (Entry 9). Notably
challenging nitroolefins were also generated with appreciable
yields and ee’s. Alkyl-substituted olefin 2k was generated in
57% yield with 34% ee even with the less-rigid alkyl substituent
(
Entry 10). 2-pyridyl arsine 2l was obtained in a moderate yield
t[b] (min)
Yield[c]
ee[d] (%)
Entry
Arsine
T (ºC)
of 69% with 32% ee despite bearing potential catalyst-
poisoning heteroatoms (Entry 11). The low stereoselectivity
could be due to the presence of a basic pyridyl group which
(%)
1
2
3
4
5
6
7
8
9
2b
2c
2d
2e
2f
-20
-20
-20
-20
-20
-20
0
<5
<5
<5
<5
30
74
91
75
78
95
70
94
79
73
57[e]
69
94
62
74
71
73
75
73
70
53
70
68
34
32
72
72
2
encouraged the undesirable formation of Ni–AsPh /Ni-pyridyl
species that led to alternative reaction pathways or side
reactions that decreased the yield and selectivity of the
reaction. Lastly, the hydroarsination reaction of other
challenging terminal nitroolefins also proceeded smoothly to
afford arsines 5b and 5c in 94% and 62% yields respectively
with 72% ee (Entries 12 and 13). Ni(II)-catalyst 3 was
concluded to be sensitive to the electron density of the olefin,
favouring electron-deficient olefins as expected from the
proposed arsa-Michael reaction mechanism. Electron-rich
olefins either required longer reaction times or higher
temperatures to achieve comparable yields.
2g
2h
2i
30
60
0
210
60
2j
0
1
0
1
2k
2l
RT
0
1440
60
1
1 [
1 [
2
f]
f]
5b
5c
0
15
3
0
15
[
a] Reaction conditions: nitroolefin 1 (0.05 mmol, 1.0 eq.), HAsPh
mg, 0.06 mmol, 1.2 eq.), cat. (R,R)-3 (0.83 mg, 1.00 μmol, 2 mol %), MeOH
2 mL), H O (200 μL). [b] Complete conversion was observed via TLC. [c]
2
(13.80
(
2
Determined by HPLC at 254 nm. [d] Determined by chiral HPLC of the
crude reaction mixture. [e] Incomplete conversion after 24 h. [f] Reaction
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201902138
FULL PAPER
conditions: nitroolefin 4 (0.05 mmol, 1.0 eq.), HAsPh
mmol, 1.2 eq.), cat. (R,R)-3 (0.83 mg, 1.00 μmol, 2 mol %), MeOH (2 mL).
2
(13.80 mg, 0.06
DEE: Merck, toluene, n-hexane Avantor, Acetone: Sigma-Aldrich, THF:
Tedia) and used as supplied. DCM and THF were dried and distilled.
Where necessary, solvents were degassed prior to use. A Low Temp
Pairstirrer PSL-1400 was used for controlling low temperature
reactions. Column chromatography was done on Silica gel 60 (Merck).
Melting points were measured using SRS Optimelt Automated Point
System SRS MPA100. Optical rotations were measured with JASCO
o
P-1030 Polarimeter in the specified solvent in a 0.1 dm cell at 22.0 C.
NMR spectra were recorded on Bruker AV 300, AV 400 and AV 500
spectrometers. Chemical shifts were reported in ppm and referenced
Conclusions
1
to an internal SiMe
4
standard (0 ppm) for H NMR, chloroform-d (77.23
ppm) or acetonitrile-d (1.39 ppm) for 13C NMR, and an external 85%
In conclusion,
a
catalytic cycle for the asymmetric
H PO
3 4
for 31P{ H} NMR. Due to their instability in solution, arsine
1
hydroarsination reaction catalyzed by a PCP Ni(II)-Cl pincer
complex was proposed. As an important development to drive
the greener syntheses of complex arsenic-containing
compounds, the proposed pathway highlighted a novel Ni–Cl–
As interaction as a key catalytic intermediate. This was
proposed in conjunction with a series of carefully-designed
arsines 2 and 5 were characterized by 1H NMR, HRMS, HPLC and
optical rotation measurements except arsines 2a, 2c, 2g, 2i and 5c
which were characterized fully.
General procedure for catalytic hydroarsination reaction
3
1
1
experiments, DFT calculations, P{ H} NMR studies and
conductivity measurements. Two contrasting Ni(II)-catalyzed
Catalyst (R,R)-3 (1.00 μmol, 2 mol %) was added to a solution of
diphenylarsine (13.80 mg, 0.06 mmol, 1.2 equiv.) in the stated solvent
hydrophosphination mechanisms were highlighted as
reference to the newly proposed hydroarsination mechanism.
Even as the mechanisms for Ni(II)-catalyzed
hydrophosphination reactions were highly varied, none
reflected the developments proposed in this study. It is
imperative that the hydroarsination reaction should not be
a
(
1 mL) and brought to the desired temperature. Nitroolefin (0.05 mmol,
1.0 equiv.) was subsequently added and washed down with the stated
solvent to make 2 mL. The reaction was stirred at the indicated
temperature and checked every 15 mins by TLC to monitor the
consumption of the substrate. The arsine product could be crystallized
from a mixture of DCM/MeOH to afford the pure products 2a, 2c, 2g, 2i
and 5c as crystalline needles.
taken as
a simple extension of the well-established
hydrophosphination reaction.
2a White solid. The ee was determined on a Daicel Chiralpak ID column
Several implications stand out regarding the proposed Ni–Cl–
As interaction. Firstly, the transient nature of the Ni–Cl–As
interaction could be related to the rapid generation of desired
arsine products. Even without vigorous heating, reactions
conducted under mild conditions (RT to -20ºC) could afford
arsine products almost quantitatively in <5 mins (Tables 1 and
with n-hexane/2-propanol = 99/1, flow = 0.8 mL/min, wavelength = 254
nm. Retention times: 8.7 min (minor), 9.5 min (major). [α]D = -45.2 (c
1
2.75, MeOH)(measured for Table 1 Entry 14). Mp: 88- 90ºC.
H NMR
(CD CN, 400 MHz): δ 7.68-7.65 (m, 2H, Ar), 7.48-7.47 (m, 2H, Ar),
3
7.29-7.27 (m, 3H, Ar), 7.25-7.21 (m, 6H, Ar), 7.19-7.16 (m, 1H, Ar), 4.99
(
1
dd, 1H, 3
J
HH = 13.0 Hz, 3
J
HH = 12.8 Hz, AsCH), 4.60 (dd, 1H, 3
J
HH
=
3.0 Hz, JHH = 4.0 Hz, NCH), 4.37 (dd, 1H, JHH = 12.6 Hz, 2JHH = 4.0
2
3
6). Secondly, this is the first reported instance with catalysts
Hz, NCH); 13C NMR (CD
CN, 100 MHz): δ 134.5-128.1 (18C, Ar), 79.7
s, 1C, AsC), 43.8 (s, 1C, NC). HRMS (+ESI) m/z: (M + H)+ calcd for
As, 380.0632; found, 380.0625.
3
bearing the same PCP chiral ligand that excellent
stereoselectivity could still be obtained without direct
interaction with the metal center.[8h,28] By extension, this may
also reduce the risk of catalyst poisoning that is typically of
concern with hydrofunctionalization reactions involving soft
donor atoms such as P and As. Lastly, this mode of interaction
was relatively robust and generated a library of nitro-
functionalized arsines in up to 80% ee’s. This represents a
remarkable progress in the arsenal of As–C bond forming
methodologies, most of which rely on toxic reagents and/or
harsh conditions thus resulting in a heavy burden on human
health and the environment. The chiral induction model by
catalyst 3 may be of interest and will be further investigated in
detail in subsequent studies. Further work is also in progress
to employ more complex olefin frameworks in hydroarsination
reactions towards the synthesis of valuable pharmaceutical
compounds.
(
20 2
C H19NO
2
b White solid. The ee was determined on a Daicel Chiralpak ID
column with n-hexane/2-propanol 99/1, flow 0.8 mL/min,
wavelength = 250 nm. Retention times: 8.3 min (minor), 8.9 min (major).
=
=
1H NMR (CD
3JHH = 13.0 Hz, 3
CN, 400 MHz): δ 7.66-7.14 (m, 14H, Ar), 5.02 (dd, 1H,
3
3
J
HH = 12.9 Hz, AsCH), 4.63 (dd, 1H, JHH = 13.4 Hz,
2JHH = 3.8 Hz, NCH), 4.36 (dd, 1H, JHH = 12.6 Hz, 2JHH = 3.5 Hz, NCH).
HRMS (+ESI) m/z: (M + H) calcd for C20
3
+
2
H18ClNO As, 414.0242; found,
414.0231.
2c White solid. The ee was determined on a Daicel Chiralpak ID column
with n-hexane/2-propanol = 99/1, flow = 0.8 mL/min, wavelength = 250
nm. Retention times: 8.2 min (minor), 8.9 min (major). [α]D = -1.62 (c
1
0
.38, MeOH)(measured for Table 6 Entry 2). Mp: 96.5-97.2ºC. H NMR
(CD CN, 400 MHz): δ 7.67-7.65 (m, 2H, Ar), 7.49-7.47 (m, 3H, Ar),
3
7.32-7.24 (m, 5H, Ar), 7.22-7.20 (m, 2H, Ar), 7.17-7.15 (m, 2H, Ar), 4.98
(
1
dd, 1H, 3
J
HH = 13.4 Hz, 3
J
HH = 12.8 Hz, AsCH), 4.62 (dd, 1H, 3
J
HH
=
3.4 Hz, JHH = 4.0 Hz, NCH), 4.37 (dd, 1H, JHH = 12.8 Hz, 2JHH = 4.0
2
3
Hz, NCH); 13C NMR (CD
CN, 100 MHz): δ 134.5-129.6 (18C, Ar), 79.4
1C, AsC), 43.1 (s, 1C, NC). HRMS (+ESI) m/z: (M + H)+ calcd for
18AsClNO , 414.0242; found, 414.0228.
3
Experimental Section
(
C
20
H
2
All reactions were carried out under a positive pressure of nitrogen
using standard Schlenk techniques. Solvents were purchased from
their respective companies (ACN, MeOH, DCM: VWR Chemicals,
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201902138
FULL PAPER
2
d White solid. The ee was determined on a Daicel Chiralpak ID
column with n-hexane/2-propanol 99/1, flow 0.8 mL/min,
wavelength = 254 nm. Retention times: 7.8 min (minor), 8.5 min (major).
1H NMR (CD
CN, 400 MHz): δ 7.69-7.67 (m, 2H, Ar), 7.53-7.53 (m, 3H,
2j White solid. The ee was determined on a Daicel Chiralpak ID column
=
=
with n-hexane/2-propanol = 99/1, flow = 0.8 mL/min, wavelength = 280
1
nm. Retention times: 8.6 min (minor), 9.4 min (major). H NMR (CD
3
CN,
3
400 MHz): δ 8.16-8.16 (m, 1H, Ar), 7.84-7.82 (m, 1H, Ar), 7.75-7.71 (m,
3H, Ar), 7.56-7.51 (m, 4H, Ar), 7.46-7.46 (m, 3H, Ar), 7.17-7.13 (m, 2H,
Ar), 7.11-7.09 (m, 1H, Ar), 7.05-7.01 (m, 2H, Ar), 5.28-5.28 (m, 1H,
Ar), 7.39-7.36 (m, 4H, Ar), 7.29-7.12 (m, 4H, Ar), 5.03-4.96 (m, 2H,
AsCH and NCH), 4.71-4.69 (m, 1H, NCH). HRMS (+ESI) m/z: (M + H)+
calcd for C20
AsCH), 5.11-5.11 (m, 1H, NCH), 4.81 (dd, 1H, 3JHH = 13.3 Hz, 2
J
=
As,
2 2
H17Cl NO As, 447.9852; found, 447.9847.
HH
3
4
.9 Hz, NCH). HRMS (+ESI) m/z: (M + H)+ calcd for C24
H21NO
2
30.0788; found, 430.0786.
2e White solid. The ee was determined on a Daicel Chiralpak ID column
with n-hexane/2-propanol = 99/1, flow = 0.6 mL/min, wavelength = 240
nm. Retention times: 10.3 min (minor), 11.0 min (major). 1H NMR
2k White solid. The ee was determined on a Daicel Chiralpak ID column
with n-hexane/2-propanol = 99.5/0.5, flow = 0.6 mL/min, wavelength =
230 nm. Retention times: 7.8 min (minor), 8.0 min (major). 1H NMR
(CDCl , 400 MHz): δ 7.53-7.53 (m, 2H, Ar), 7.41-7.38 (m, 4H, Ar), 7.34-
3
7.33 (m, 4H, Ar), 4.32-4.21 (m, 2H, NCH), 3.16-3.11 (m, 1H, AsCH),
1.80-0.84 (m, 11H, cyclohexyl). HRMS (+ESI) m/z: (M + H)+ calcd for
3
(CD CN, 400 MHz): δ 7.67-7.65 (m, 2H, Ar), 7.49-7.47 (m, 3H, Ar),
7
.31-7.19 (m, 6H, Ar), 7.02-7.00 (m, 1H, Ar), 6.92-6.90 (m, 2H, Ar), 5.01
(
1
dd, 1H, 3
J
2
HH = 13.0 Hz, 3
J
HH = 13.0 Hz, AsCH), 4.63 (dd, 1H, 3JHH
=
3.5 Hz, JHH = 4.0 Hz, NCH), 4.39 (dd, 1H, JHH = 12.7 Hz, 2JHH = 3.8
3
19
1
Hz, NCH); F{ H} NMR (CD
3
CN, 377 MHz): δ -113.73 (s, 1F). HRMS
(
+ESI) m/z: (M + H)+ calcd for C20
H18FNO
2
As, 398.0538; found,
20 2
C H25NO As, 386.1101; found, 386.1097.
398.0540.
2l White solid. The ee was determined on a Daicel Chiralpak ID column
2
f White solid. The ee was determined on a Daicel Chiralpak IC column
with n-hexane/2-propanol = 85/15, flow = 0.8 mL/min, wavelength =
210 nm. Retention times: 10.8 min (major), 11.3 min (minor). H NMR
1
with n-hexane/2-propanol = 99.5/0.5, flow = 0.6 mL/min, wavelength =
10 nm. Retention times: 14.8 min (major), 16.3 min (minor). 1H NMR
CD CN, 400 MHz): δ 7.65-7.64 (m, 2H, Ar), 7.46-7.46 (m, 3H, Ar),
2
(
(CD
3
CN, 400 MHz): δ 7.64-7.25 (m, 12H, Ar), 7.10-7.07 (m, 1H, Ar),
HH = 12.2 Hz,
6.95-6.93 (m, 1H, Ar), 5.32 (dd, 1H, 3JHH = 13.6 Hz, 3
J
3
7
.28-7.22 (m, 5H, Ar), 7.13-7.09 (m, 1H, Ar), 7.01-6.98 (m, 3H, Ar), 4.98
AsCH), 4.64 (dd, 1H, 3JHH = 13.8 Hz, 2
1H, 3JHH = 12.0 Hz, 2JHH = 3.5 Hz, NCH). HRMS (+ESI) m/z: (M + H)
J
HH = 3.5 Hz, NCH), 4.52 (dd,
dd, 1H, 3
J
2
HH = 13.0 Hz, 3
J
HH = 12.9 Hz, AsCH), 4.59 (dd, 1H, 3JHH
=
+
(
3.2 Hz, JHH = 3.8 Hz, NCH), 4.32 (dd, 1H, JHH = 12.6 Hz, 2JHH = 3.7
3
calcd for C19
a White solid. The ee was determined on a Daicel Chiralpak ID column
1
18 2 2
H N O As, 381.0584; found, 381.0581.
+
Hz, NCH). HRMS (+ESI) m/z: (M + H) calcd for C21
2
H21NO As,
394.0788; found, 394.0781.
5
with n-hexane/2-propanol = 99/1, flow = 0.8 mL/min, wavelength = 254
1
2
g White solid. The ee was determined on a Daicel Chiralpak ID
99/1, flow 0.8 mL/min,
wavelength = 280 nm. Retention times: 7.6 min (minor), 8.3 min (major).
nm. Retention times: 8.4 min (minor), 9.4 min (major). H NMR (CD
3
CN,
column with n-hexane/2-propanol
=
=
400 MHz): δ 7.67-7.67 (m, 2H, Ar), 7.48-7.46 (m, 3H, Ar), 7.29-7.16 (m,
10H, Ar), 4.99 (dd, 1H, 3JHH = 12.8 Hz, 3JHH = 12.8 Hz, AsCH), 4.60 (dd,
1H, 3JHH = 13.2 Hz, 2JHH = 4.0 Hz, NCH), 4.37 (dd, 1H, 3JHH = 12.6 Hz,
[
α]D = +0.01 (c 0.98, MeOH)(measured for Table 6 Entry 6). Mp: 86.7-
1
2JHH = 4.0 Hz, NCH). HRMS (+ESI) m/z: (M
20 2
C H19NO As, 380.0632; found, 380.0635.
+
H)+ calcd for
87.9ºC. H NMR (CD
3
CN, 400 MHz): δ 7.66-7.64 (m, 2H, Ar), 7.47-7.45
(m, 3H, Ar), 7.33-7.24 (m, 5H, Ar), 7.12-7.10 (m, 2H, Ar), 7.05-7.03 (m,
2
H, Ar), 4.94 (dd, 1H, 3JHH = 12.8 Hz, 3JHH = 12.8 Hz, AsCH), 4.56 (dd,
H, 3JHH = 12.8 Hz, 2JHH = 4.0 Hz, NCH), 4.34 (dd, 1H, 3JHH = 12.8 Hz,
1
5b White solid. The ee was determined on a Daicel Chiralpak ID
2
3 3
HH = 4.0 Hz, NCH), 2.24 (s, 3H, CH CN, 100 MHz):
); 13C NMR (CD
J
column with n-hexane/2-propanol 99/1, flow 0.8 mL/min,
wavelength = 254 nm. Retention times: 8.7 min (minor), 9.6 min (major).
=
=
δ 134.6-129.3 (18C, Ar), 80.0 (1C, AsC), 43.5 (s, 1C, NC), 21.1 (s, 1C,
CH ). HRMS (+ESI) m/z: (M + H)+ calcd for C21 As, 394.0788;
found, 394.0786.
3
H21NO
2
1H NMR (CD
3
CN, 500 MHz): δ 7.75-7.15 (m, 15H, Ar), 4.98 (dd, 1H,
3JHH = 13.1 Hz, 3
3
J
HH = 13.1 Hz, AsCH), 4.62 (dd, 1H, JHH = 13.6 Hz,
2JHH = 3.8 Hz, NCH), 4.38 (dd, 1H, JHH = 12.6 Hz, 2JHH = 3.8 Hz, NCH).
HRMS (+ESI) m/z: (M + H) calcd for C20
3
+
2h White solid. The ee was determined on a Daicel Chiralpak ID
2
H18ClNO As, 414.0242; found,
column with n-hexane/2-propanol 99/1, flow 0.8 mL/min,
=
=
414.0242.
wavelength = 254 nm. Retention times: 9.3 min (minor), 10.1 min
1
(
major). H NMR (CD
3
CN, 400 MHz): δ 7.65-7.64 (m, 2H, Ar), 7.36-7.34
5c White solid. The ee was determined on a Daicel Chiralpak ID column
(
m, 3H, Ar), 7.24-7.12 (m, 7H, Ar), 6.84-6.79 (m, 2H, Ar), 5.08 (dd, 1H,
with n-hexane/2-propanol = 99/1, flow = 0.8 mL/min, wavelength = 254
3
HH = 12.4 Hz, 3JHH = 12.4 Hz, AsCH), 4.68 (dd, 1H, JHH = 11.96 Hz,
3
J
nm. Retention times: 7.4 min (minor), 8.1 min (major). [α]D = -1.48 (c
2JHH = 3.9 Hz, NCH), 4.60 (dd, 1H, JHH = 12.6 Hz, 2JHH = 3.9 Hz, NCH).
HRMS (+ESI) m/z: (M + H) calcd for C21
4
3
.54, MeOH)(measured for Table 6 Entry 13). Mp: 101.6-104.3ºC. 1
0
H
+
3
H21NO As, 410.0737; found,
NMR (CD
Ar), 7.33-7.24 (m, 5H, Ar), 7.12-7.10 (m, 2H, Ar), 7.05-7.03 (m, 2H, Ar),
.94 (dd, 1H, 3JHH = 12.8 Hz, 3JHH = 12.8 Hz, AsCH), 4.56 (dd, 1H, 3JHH
3
CN, 400 MHz): δ 7.66-7.64 (m, 2H, Ar), 7.47-7.45 (m, 3H,
10.0738.
4
2
i White solid. The ee was determined on a Daicel Chiralpak ID column
= 12.8 Hz, 2JHH = 4.0 Hz, NCH), 4.34 (dd, 1H, 3JHH = 12.8 Hz, 2
4.0 Hz, NCH), 2.24 (s, 1C, CH
); 13C NMR (CD
129.3 (18C, Ar), 80.0 (1C, AsC), 43.5 (s, 1C, NC), 21.1 (s, 1C, CH
J
HH
=
with n-hexane/2-propanol = 99/1, flow = 0.8 mL/min, wavelength = 254
3
3
CN, 100 MHz): δ 134.6-
nm. Retention times: 12.6 min (minor), 14.2 min (major). [α]D = +4.18
3
).
(
c 0.12, MeOH)(measured for Table 6 Entry 8). Mp: 98.4-99.6ºC. 1
H
2
HRMS (+ESI) m/z: (M + H)+ calcd for C21H21AsNO , 394.0788; found,
3
NMR (CD CN, 400 MHz): δ 7.66-7.64 (m, 2H, Ar), 7.47-7.46 (m, 3H,
394.0789.
Ar), 7.30-7.24 (m, 5H, Ar), 7.14-7.12 (m, 2H, Ar), 6.79-6.76 (m, 2H, Ar),
4
=
4
1
.93 (dd, 1H, 3JHH = 12.8 Hz, 3JHH = 12.8 Hz, AsCH), 4.56 (dd, 1H, 3JHH
Computational methods. All calculations were performed with
12.8 Hz, 2
J
HH = 4.0 Hz, NCH), 4.32 (dd, 1H, 3JHH = 12.8 Hz, 2
J
=
HH
Gaussian 09 (Rev. E.01) programs.[29] Geometry optimization was
.0 Hz, NCH), 3.71 (s, 3H, OCH); 3C NMR (CD
1
CN, 100 MHz): δ
3
conducted by the WB97D functional.[30] The Def2-SVP set was
34.6-129.6 (16C, Ar), 115.0 (s, 2C, Ar), 80.0 (1C, AsC), 56.0 (s, 1C,
), 43.2 (s, 1C, NC). HRMS (+ESI) m/z: (M + H)+ calcd for
As, 410.0737; found, 410.0735.
atoms.[31]
employed for all
The vibrational analysis and
OCH
C H21NO
21 3
3
thermodynamics energetic information at 298.15 K were calculated
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201902138
FULL PAPER
with the keyword Freq in Gaussian. The PCM solvent model has been
used to calculate free energy change in the solution for proton transfer
[9]
For selected examples, see a) A. A. Watson, A. C. Willis, S. B. Wild,
J. Organomet. Chem. 1993, 445, 71-78; b) W.-M. Dai, A. Wu, H. Wu,
Tetrahedron: Asymmetry 2002, 13, 2187-2191; c) P. A. Gugger, A. C.
Willis, S. B. Wild, G. A. Heath, R. D. Webster, J. H. Nelson, J.
Organomet. Chem. 2002, 634-644, 136-153; d) M. L. Weir, I. A. Cade,
N. L. Kilah, X. Zhou, S. B. Wild, Inorg. Chem. 2009, 48, 7482-7490;
e) P. M. Uberman, M. R. Caira, S. E. Martín, Organometallics 2013,
- + [32]
process: HAsPh
2
+ MeOH → AsPh + MeOH .
2 2
Acknowledgements
32, 3220-3226; f) M. Bonaterra, S. E. Martín, R. A. Rossi, Org. Lett.
W. S. T. acknowledges NTU for the award of a research
scholarship. The MOE Tier 1 grant (M4011794 RG16/17),
M4080454 and (RG116/15) are acknowledged for funding this
work. We are also grateful to Prof. R. D. Webster and Dr M. E.
Tessensohn of NTU for their assistance in the conductivity
measurements conducted.
2003, 5, 2731-2734; g) P. M. Uberman, M. N. Lanteri, S. C. Parajón
Puenzo, S. E. Martín, Dalton Trans. 2011, 40, 9229-9237.
10] P. T. Anastas, J. C. Warner, in Green Chemistry: Theory and Practice,
Oxford University Press, New York, 1998, pp. 30.
[
[
11] a) A. D. Sadow, I. Haller, L. Fadini, A. Togni, J. Am. Chem. Soc. 2004,
1
26, 14704-14705; b) A. D. Sadow, A. Togni, J. Am. Chem. Soc. 2005,
27, 17012-17024; c) L. Rosenberg, ACS Catal. 2013, 3, 2845-2855;
1
d) H. Pellissier in Enantioselective Nickel-Catalysed Transformations,
Royal Society of Chemistry, 2016; e) J. J. Eller, K. J. Downey, J.
Comput. Chem. 2015, 36, 1947-1953.
Keywords: arsenic • asymmetric • catalysis • nickel • pincer
complex
[
[
12] W. R. Cullen, W. R. Leeder, Can. J. Chem. 1970, 48, 3757-3760.
13] a) J. Wyman, J. Am. Chem. Soc. 1931, 53, 3292-3301; b) P. S.
Albright, L. J. Gosting, J Am. Chem. Soc. 1946, 68, 1061-1063.
14] a) K. Issleib, R. Kꢀmmel, J. Organomet. Chem. 1965, 3, 84-91; b) J.-
N. Li, L. Liu, Y. F, Q.-X. Guo, Tetrahedron 2006, 62, 4453-4462.
15] Refer to ESI pages s70-75 for details of the supporting study
conducted.
[
[
[
[
[
1]
2]
3]
4]
5]
For an overview of catalytic asymmetric hydrofunctionalization
reactions, see a) V. P. Ananikov, M. Tanaka, Top. Organomet. Chem.,
[
[
[
2013, 43, 1; b) J. L. Vicario, D. Badía, L. Carrillo, Synthesis 2007, 14,
2065-2092.
a) C. M. Crudden, D. Edwards, Eur. J. Org. Chem. 2003, 24, 4695-
712; b) C. C. Chong, R. Kinjo, ACS Catal. 2015, 5, 3238-3259; c) A.-
M. Carroll, T. P. O’Sullivan, P. J. Guiry, Adv. Synth. Catal. 2005, 347,
09-631.
a) R. Malacea, R. Poli, E. Manoury, Coord. Chem. Rev. 2010, 254,
29-752; b) D. Addis, S. Das, K. Junge, M. Beller, Angew. Chem. Int.
Ed. 2011, 50, 6004-6011; c) D. Troegel, J. Stohrer, Coord. Chem. Rev.
011, 255, 1440-1459.
a) P. W. Roesky, T. E. Müller, Angew. Chem. Int. Ed. 2003, 42, 2708-
4
16] The newly-generated chiral center at the tertiary carbon bears a
highly-acidified proton due to the adjacent nitro moiety. Potentially,
facile deprotonation may occur thus resulting in 1) racemization of the
arsine product or 2) elimination of the adjacent As moiety. The C–As
bond on a primary carbon is also poorly shielded from potential bond
hydrolysis.
6
7
2
[
[
[
17] Refer to ESI pages s46-69 for details of the DFT calculation
conducted.
2
1
710; b) K. D. Hesp, M. Stradiotto, ChemCatChem 2010, 2, 1192-
207; c) A. L. Reznichenko, K. C. Hultzsch, Top. Organomet. Chem.
18] X.-Y. Yang, W. S. Tay, Y. Li, S. A. Pullarkat, P.-H. Leung,
Organometallics, 2015, 34, 1582-1588.
2
013, 43, 51-114.
a) V. Koshti, S. Gaikwad, S. H. Chikkali, Coord. Chem. Rev. 2014,
65, 52-73; b) D. S. Glueck, Synlett 2007, 17, 2627-2634; c) S. A.
19] a) D. Duncan, E. G. Hope, K. Singh, A. M. Stuart, Dalton Trans. 2011,
40, 1998-2005; b) E. A. Standley, S. J. Smith, P. Muller, T. F. Jamison,
2
Organometallics, 2014, 33, 2012-2018; c) J.-Y. Li, H.-J. Sun, Jiegou
Huaxue 2015, 34, 1735; d) J. Cornella, E. Gómez-Bengoa, R. Martin,
J. Am. Chem. Soc. 2013, 135, 1997-2009; e) V. Thangavadivale, P.
M. Aguiar, N. A. Jasim, S. J. Pike, D. A. Smith, A. C. Whitwood, L.
Brammer, R. N. Perutz, Chem. Sci. 2018, 9, 3767-3781; f) Y.-H. Liu,
C. Chen, L.-M. Yang, Acta Cryst. E 2008, 64, m1225; g) Z. Yang, D.
Liu, Y. Liu, M. Sugiya, T. Imamoto, W. Zhang, Organometallics 2015,
Pullarkat, P.-H. Leung, Top. Organomet. Chem. 2013, 43, 145-166.
a) D. Enders, K. Lüttgen, A. A. Narine, Synthesis 2007, 7, 959-980,
b) A. Ishii, N. Nakata, Top. Organomet. Chem. 2013, 43, 21-50.
a) B. M. Trost, R. J. Kulawiec, A. Hammes, Tetrahedron Lett. 1993,
[
[
6]
7]
34, 587-590; b) B. M. Trost, J. A. Flygare, J. Org. Chem. 1994, 59,
1078-1082; c) M. G. Tabor, R. A. Shenvi, Org. Lett. 2015, 17, 5776-
5779; d) C. G. Hartung, C. Breindl, A. Tillack, M. Beller, Tetrahedron
34, 1228-1237; h) J. M. Weber, A. R. Longstreet, T. F. Jamison,
2000, 56, 5157-5162; e) Stereoselective Synthesis of Drugs and
Organometallics 2018, 37, 2716-2722; i) X. Zheng, Q. Yang, Z. Li, Z.
Zhu, X. Cui, H. Fu, H. Chen, R. Li, Catal. Commun. 2014, 57, 143-
Natural Products, 2V Set, First Edition, John Wiley & Sons, Inc.,
Hoboken, New Jersey, 2013.
147; j) B. J. Boro, D. A. Dickie, K. I. Goldberg, R. A. Kemp, Acta Cryst.
[
8]
a) A. J. Roering, J. J. Davidson, S. N. MacMillan, J. M. Tanski, R.
Waterman, Dalton Trans. 2008, 4488-4498; b) H.-O. Berger, H. Nöth,
J. Organomet. Chem. 1983, 250, 33-48; c) K. Maitra, V. J. Catalano,
J. Clark III, J. H Nelson, Inorg. Chem. 1998, 37, 1105-1111; d) M. L.
Bungabong, K. W. Tan, Y. Li, S. V. Selvaratnam, K. G. Dongol, P.-H.
Leung, Inorg. Chem. 2007, 46, 4733-4736; e) F. Liu, S. A. Pullarkat,
Y. Li, S. Chen, P.-H. Leung, Eur. J. Inorg. Chem. 2009, 4134-4140; f)
Y. L. Cheow, S. A. Pullarkat, Y. Li, P.-H. Leung, J. Organomet. Chem.
E 2008, 64, m1304; k) A. Zeller, E. Herdtweck, T. Strassner, Eur. J.
Inorg. Chem. 2003, 2003, 1802-1806.
[
20] a) S. Tanaka, H. Imoto, T. Yumura, K. Naka, Organometallics 2017,
36, 1684-1687; b) W. T. Pennington, A. W. Cordes, J. C. Graham, Y.
W. Jung, Acta Cryst. C 1983, 39, 1010; c) J. E. Stuckey, A. W. Cordes,
L. B. Handy, R. W. Perry, C. K. Fair, Inorg. Chem. 1972, 11, 1846-
1
848; d) A. Camerman, J. Trotter, J. Chem. Soc. 1965, 730-738; e)
M. Fukuyo, K. Nakatsu, A. Shimada, Bull. Chem. Soc. Jpn 1966, 39,
614-1615; f) J. Trotter, Can. J. Chem. 1962, 40, 1590-1593; g) N.
2012, 696, 4215-4220; g) W. S. Tay, X.-Y. Yang, Y. Li, S. A. Pullarkat,
1
P.-H. Leung, Chem. Commun. 2017, 53, 6307-6310; h) W. S. Tay, X.-
Y. Yang, Y. Li, S. A. Pullarkat, P.-H. Leung, Dalton Transactions,
Burford, C. L. B. MacDonald, D. J. LeBlanc, T. S. Cameron,
Organometallics 2000, 19, 152-155; h) N. L. Kilah, S. B. Wild,
Organometallics 2012, 31, 2658-2666; i) A. S. Batsanov, S. M. Cornet,
K. B. Dillon, A. E. Goeta, P. Hazendonk, A. L. Thompson, J. Chem.
Soc., Dalton Trans. 2002, 4622-4628; j) L. Dostal, R. Jambor, A.
Ruzicka, R. Jirasko, J. Holecek, F. de Proft, Dalton Trans. 2011, 40,
2019, 48, 4602-4610; i) C. Marquardt, G. Balázs, J. Baumann, A. V.
Virovets, M. Scheer, Chem. Eur. J. 2017, 23, 11423-11429; j) R. S.
P. Turbervill, J. M. Goicoechea, Eur. J. Inorg. Chem. 2014, 1660-
1668; k) M. Stubenhofer, G. Lassandro, G. Balázs, A. Y. Timoshkin,
M. Scheer, Chem. Commun. 2012, 48, 7262-7264; l) C. A. Bange, R.
Waterman, Polyhedron 2018, 156, 31-34.
8922-8934.
[
21] S. Murugesan, K. Kirchner, Dalton Trans. 2016, 45, 416-439.
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201902138
FULL PAPER
[
22] For an excellent review of halide effects in transition metal catalysis,
see K. Fagnou, M. Lautens, Angew. Chem. Int. Ed. 2002, 41, 26-47.
[29] Gaussian 09, Revision E.01, M. J. Frisch, G. W. Trucks, H. B.
Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani,
V. Barone, G. A. Petersson, H. Nakatsuji, X. Li, M. Caricato, A.
Marenich, J. Bloino, B. G. Janesko, R. Gomperts, B. Mennucci, H. P.
Hratchian, J. V. Ortiz, A. F. Izmaylov, J. L. Sonnenberg, D. Williams-
Young, F. Ding, F. Lipparini, F. Egidi, J. Goings, B. Peng, A. Petrone,
T. Henderson, D. Ranasinghe, V. G. Zakrzewski, J. Gao, N. Rega, G.
Zheng, W. Liang, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J.
Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T.
Vreven, K. Throssell, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro,
M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov,
T. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J.
C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, J. M. Millam, M. Klene,
C. Adamo, R. Cammi, J. W. Ochterski, R. L. Martin, K. Morokuma, O.
Farkas, J. B. Foresman, D. J. Fox, Gaussian, Inc., Wallingford CT,
2016.
[
23] a) D. A. Evans, J. A. Murry, P. vonMatt, R. D. Norcross, S. J. Miller,
Angew. Chem. 1995, 107, 864-867; Angew. Chem. Int. Ed. Engl.
1995, 34, 798-800; b) D. J. R. OxMahoney, D. B. Belanger, T.
Livinghouse, Synlett 1998, 443-445.
[
24] For an overview of transition metal halide complexes and their role in
catalysis, see a) B. L. Pagenkopf, E. M. Carreira, Chem. Eur. J. 1999,
5, 3437-3442; b) N. M. Doherty, N. W. Hoffman, Chem. Rev. 1991,
91, 553-573; c) R. O. Duthaler, A. Hafner, Angew. Chem. 1997, 109,
43-45.
[
[
25] a) V. P. Ananikov, ACS Catal. 2015, 5, 1964-1971; b) J. Montgomery,
Angew. Chem. Int. Ed. 2004, 43, 3890-3908; c) S. Z. Tasker, E. A.
Standley, T. F Jamison, Nature 2014, 509, 299-309.
26] J. J. Brunet, D. Neibecker in Catalytic Heterofunctionalization: From
Hydroamination to Hydrozirconization, Wiley-VCH Verlag GmbH,
Weinheim, Germany, 2001, pp. 91-141.
[30] J.-D. Chai, M. Head-Gordon, Phys. Chem. Chem. Phys. 2008, 10,
6615-6620.
[
[
27] G. M. Bodner, M. P. May, L. E. McKinney, Inorg. Chem. 1980, 19,
1951-1958.
[31] F. Weigend, R. Ahlrichs, Phys. Chem. Chem. Phys. 2005, 7, 3297-
3305.
28] a) X.-Y. Yang, Y.-X. Jia, W. S. Tay, Y. Li, S. A. Pullarkat, P.-H. Leung,
Dalton Trans. 2016, 45, 13449-13455; b) X.-Y. Yang, W. S. Tay, Y. Li,
S. A. Pullarkat, P.-H. Leung, Chem. Commun. 2016, 52, 4211-4214;
c) X.-Y. Yang, W. S. Tay, Y. Li, S. A. Pullarkat, P.-H. Leung,
Organometallics 2015, 34, 5196-5201.
[32] M. Cossi, V. Barone, R. Cammi,, J. Tomasi, Chem. Phys. Lett. 1996,
255, 327-335.
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201902138
FULL PAPER
Entry for the Table of Contents
Layout 1:
FULL PAPER
Asymmetric C–As bond formation:
Key catalytic steps were examined for
the PCP Ni(II) pincer complex-catalyzed
asymmetric hydroarsination reaction.
This was investigated with catalytic
Ni–Cl–As
interaction
W. S. Tay, Y. Lu, X.-Y. Yang, Y. Li, S.
A. Pullarkat, P.-H. Leung*
R
R
Up to 99%
yield, 80% ee
Ph2P Ni PPh2
Page No. – Page No.
Cl
Catalytic
Asymmetric
Hydroarsination
Catalytic and mechanistic
developments of the Nickel(II)
pincer complex-catalyzed
hydroarsination reaction
screening,
DFT
calculations,
conductivity measurements and NMR
studies. A unique Ni–Cl–As interaction
was identified in the key catalytic
intermediate which was not previously
identified in other closely-related
hydrofunctionalization reations.
AsPh2
CATALYSIS DFT
NMR
This article is protected by copyright. All rights reserved.