Construction of a bidentate arsenic ligand library starting from a cyclooligoarsine

Article abstract of DOI:10.1246/cl.190540

Bidentate ligands are, needless to say, pivotal in organo-metallic chemistry. In contrast to phosphorus ligands, practical synthetic protocols for the arsenic analogues remain to be developed, resulting in a lack of bidentate arsenic ligands. Herein the methods that we have recently developed were applied for bidentate arsenic ligands whose frameworks are well known in phosphorus ligand systems such as dppe, dppp, dppf, xantphos, etc. The palladium dichloride complexes of the obtained ligands were synthesized and used for the Suzuki-Miyaura coupling reaction.

Full text of DOI:10.1246/cl.190540

Advance Publication Cover Page
Construction of BidentateArsenic Ligand Library Starting from a Cyclooligoarsine
Hiroaki Imoto, Masafumi Konishi, Shintaro Nishiyama, Hiroshi Sasaki, Susumu Tanaka,
Takashi Yumura, and Kensuke Naka*
Advance Publication on the web August 21, 2019
doi:10.1246/cl.190540
© 2019 The Chemical Society of Japan
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Publication manuscripts.

1
Construction of BidentateArsenic Ligand Library Starting from a Cyclooligoarsine
Hiroaki Imoto,1,3 Masafumi Konishi,1 Shintaro Nishiyama,1 Hiroshi Sasaki,1 Susumu Tanaka,1 Takashi Yumura2,3 and Kensuke Naka1,3*
1Faculty of Molecular Chemistry and Engineering, Graduate School of Science and Technology, Kyoto Institute of Technology,
Goshokaido-cho, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
2 Faculty of Material Science and Technology, Graduate School of Science and Technology, Kyoto Institute of Technology, Goshokaido-
cho, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
3 Materials Innovation Lab, Kyoto Institute of Technology, Goshokaido-cho, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
E-mail: kenaka@kit.ac.jp
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Bidentate ligand is, needless to say, pivotal in
organometallic chemistry. In contrast to phosphorus ligands,
practical synthetic protocols for the arsenic analogues
remain to be developed, resulting in lack of bidentate
arsenic ligands. Herein the methods that we have recently
developed were applied for the bidentate arsenic ligands
whose frameworks are well known in phosphorus ligand
systems such as dppe, dppp, dppf, xantphos, etc. The
palladium dichloride complexes of the obtained ligands
48 systems due to lack of the practical synthetic methods; only
49 monodentate-type ligands have been examined.7,8
50
Meanwhile, our research group has broken through the
51 synthetic barrier via development of practical routes towards
52 arsenic ligands (Scheme 1).9 Cyclooligoarsines, in which
53 five (1: R = Me) or six (2: R = Ph) arsenic atoms are linked
54 through As−As bonds, are key intermediates because they
55 are readily prepared by reduction of non-volatile inorganic
56 arsenic precursors.10 As−As bond cleavage reactions by
57 iodine (I2) generates diiodoarsines in situ, and subsequent
10 were synthesized and used for the Suzuki-Miyaura coupling
11 reaction.
58 reactions with nucleophiles give As−C bonds (Scheme 1a).
12 Keywords: Arsenic, Bidentate ligand, Cyclooligoarsine,
13 Palladium complex, Coupling reaction
11
59
This strategy has contributed to studies on functional
60 organoarsenic molecules and polymers.12,13 Reactions of
61 cyclooligoarsines with organometallic reagents such as
62 organolithium or Grignard reagents generate arsenic
63 nucleophiles, which can be utilized for syntheses of
64 asymmetric and bidentate organoarsenic ligands (Scheme
65 1b).14 Furthermore, As−C bonds can be cleaved by halogen
66 reagents such as iodine and iodine monochloride. In this
67 reaction, a methyl group substituted to an arsenic atom is
68 converted to a halogen group, and substituent conversion is
69 attained by the subsequent substitution reaction (Scheme
70 1c).15
14
In the early 20th century, coordination chemistry of
15 arsenic ligands was an active field; organoarsenic chemistry
16 was studied for medical and military purposes during and
17 just after the World War I.1 However, arsenic ligands were
18 then overtaken by the phosphorus analogues because of
19 superior coordination ability of phosphorus ligands to hard
20 metals, and of development of 31P-NMR technique.
21 Numerous kinds of phosphorus ligands have been developed
22 and are commercially available. Needless to say, they
23 currently play primary roles in coordination chemistry,
24 particularly in the field of transition metal catalysts. In
25 contrast, a lineup of available arsenic ligands is very poor.
26 This is because typical synthetic precursors for
27 organoarsenic compounds, e.g., arsenic hydrides and
28 chlorides, are volatile and toxic. Miserably, such kinds of
29 compounds were misused as chemical weapons: Adamsite,
30 Luisite, sneezing gas, etc.2 Serious concern to the danger of
31 their hazardous natures has made people avoid experimental
32 studies on organoarsenic chemistry in this century.
33
It is known that arsenic atom has bulkiness and poor -
34 donation to transition metals compared with phosphorus
35 atom.1 Accordingly, arsenic ligands enhance reactivity
36 and/or selectivity from those of the phosphorus analogues in
37 some catalytic reactions.3-6 For example, a significant rate
38 acceleration was observed in Pd-catalyzed Stille coupling
39 reaction by changing the ligand from triphenylphosphine to
40 triphenylarsine.3 Nishibayashi developed an arsenic-
41 nitrogen-arsenic pincer ligand for a ruthenium catalyst
42 giving high selectivity.4 It was reported that triphenylarsine
43 is beneficial for copper-free Sonogashira coupling for
44 porphyrin substrates.5 It is evidential that arsenic ligands
45 have great potential in coordination chemistry, especially in
46 catalytic chemistry. Nevertheless, there are few studies on
47 structure-catalytic activity relationship in arsenic ligand
71
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73
Scheme 1. Synthetic routes towards organoarsenic compounds that
we have recently developed.
74
These accumulated synthetic tools motivated us to
75 construct organoarsenic library. We previously reported
76 monodentate ligands for Mizoroki-Heck reaction by
77 employing the route shown in Scheme 1a.8 Herein, bidentate
78 ligands, which have particularly contributed advancement of
79 transition metal catalysts, are focused. In phosphorus
80 coordination chemistry, various ligands have been utilized:
81 dppe, dppp, dppf, xantphos, etc. (Chart 1). In this work,

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arsenic analogues of traditional bidentate phosphorus
ligands were synthesized by employing our practical
methods. We, for the first time, systematically studied the
structures and catalytic activities of the palladium(II)
dichloride complexes having the bidentate arsenic ligands.
32
33
34
Scheme 4. Synthesis of palladium(II) dichloride complexes with the
bidentate ligands.
35
Palladium(II) dichloride complexes of the bidentate
were synthesized using cis-
36 ligands
37 bis(benzonitrile)palladium(II) chloride (cis-[PdCl2(PhCN)2])
38 as shown in Scheme 4. The chemical structures of the
39 complexes were determined by NMR spectroscopy.
40 Unfortunately, the complex of dpam was not isolated due to
41 the unidentified impurities. Single crystals of six complexes
42 suitable for X-ray crystallography were prepared:
6
7
Chart 1. Representative bidentate phosphorus ligands.
8
9
Six bidentate arsenic ligands were synthesized by
using an arsenic nucleophile and bifunctional electrophiles
10 (Scheme 2). Synthesis of alkylene-linked arsenic ligands
11 (Ph2As−(CH2)n−AsPh2) was carried out: n = 1 (dpam), 2
12 (dpae), 3 (dpap), 4 (dpab). Hexaphenylcyclohexaarsine 2
13 was reacted with phenyllithium to generate diphenylarsino
14 lithium (Ph2AsLi) in situ, and then addition of alkyl
15 dihalides gave the corresponding bidentate ligands dpam,
16 dpae,14 dpap, and dpab. The same protocol was applied to
17 the reaction with cis-1,2-dichloroethylene and 2,3-
18 dichloroquinoxaline offered dpav14 and dpaq, respectively.
43 [PdCl2(dpae)],
[PdCl2(dpap)],
[PdCl2(dpab)],
44 [PdCl2(dpaq)], [PdCl2(dpaf)], and [PdCl2(xantas)].16,17
45 Electron-donation ability is crucial for catalytic activity, and
46 was evaluated based on the trans-influence of the Pd−Cl
47 bond lengths. Besides, a bite angle of a bidentate ligand is
48 an important structural parameter in reaction yield and/or
49 selectivity of catalytic reactions. Judging from the shorter
50 Pd−As and longer Pd−Cl bond lengths, triaryl type ligands
51 dpaf and xantas are less electron-donating than diaryl type
52 ligands dpae, dpap, and dpab. In the case of dpaq, the
53 Pd−As bond lengths were shortest because of the strong -
54 acceptance due to the quinoxaline moiety.
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56
57
Table 1. Selected bond lengths and angles of palladium dichloride
complexes with bidentate arsenic ligands
Bond length [Å]
Angle [°]
Complex
As−Pd−As
Pd−As
Pd−Cl
19
2.344(2)
2.339(2)
2.352(2)
2.339(2)
2.358(5)
2.341(4)
2.328(1)
2.327(1)
2.3840(7)
2.3691(6)
2.3769(5)
2.3927(5)
2.345(2)
2.334(3)
2.334(2)
2.346(2)
2.331(5)
2.335(6)
2.341(2)
2.338(1)
2.333(1)
2.334(1)
2.315(1)
2.333(1)
20 Scheme 2. Syntheses of bidentate ligands using diphenylarseno lithium.
[PdCl2(dpae)]
[PdCl2(dpap)]
[PdCl2(dpab)]
[PdCl2(dpaq)]
[PdCl2(dpaf)]
[PdCl2(xantas)]
85.70(2)
89.62(1)
92.73(4)
87.87(2)
97.64(2)
99.47(2)
21
In
a
previous
paper, we
reported
that
22 iododiphenylarsine (Ph2AsI) can be generated by addition of
23 iodine (I2) to a solution of methyldiphenylarsine (MePh2As),
24 which is prepared from Ph2AsLi and iodomethane.14 The
25 halogenation proceeds via removal of iodomethane under
26 heating condition. The obtained solution of Ph2AsI was used
27 for the reaction with dilithiated ferrocene and 9,9-
28 dimethylxanthene to produce dpaf and xantas, respectively
29 (Scheme 3).
58
59
Among alkylene-linked ligands dpae, dpap, and dpab,
60 the bite angle got bigger as the chain was longer.
61 Interestingly, the bite angle of xantas 99.47(2)° was slightly
62 smaller than that of the phosphorus analogue xantphos
63 (natural bite angle:108°18a and estimated P−Pd−P angle of
64 the palladium(II) dichloride complex: 101.64°18b).
65 Coordination direction of an arsenic atom is flexibly
66 changed due to the s-character of the lone pair, and hence
67 the coordination angles around the square planar palladium
30
31
Scheme 3. Syntheses of bidentate ligands using iododiphenylarsine.

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center can be adjusted to be close to 90°. This means that
arsenic atoms can reduce the distortion derived from the
ligand skeletons.
To demonstrate the effect of the arsenic ligands on
catalytic activity, Suzuki-Miyaura coupling reaction was
carried out. p-Bromotoluene and phenylboronic acid were
reacted in the presence of the palladium catalysts having the
arsenic ligands (Scheme 5). Comparing the alkylene-linked
ligands, bite angle drastically affected the catalytic activity.
10 The larger the bite angle, the higher the reaction yield,19 and
11 dpab gave the best yield (60%) among the alkylene-linked
12 ligands. This is because large bite angle in general
13 accelerates a reductive elimination step.20 In addition, the
14 relatively electron-donating ligands dpam, dpae, dpap, and
15 dpab gave lower catalytic activity than dpaq, dpaf, and
16 xantas. These results mean that the reductive elimination is
17 the rate-determining step of this reaction system as shown
18 by the computational calculation below (Figure 1); the
19 activation energies for the oxidative addition were 6.1
20 (dpae) and 6.3 (dppe) kcal/mol, while those for the
21 reductive elimination were 12.7 (dpae) and 13.5 (dppe)
22 kcal/mol.
23
43
44
24
25
Scheme 5. Suzuki-Miyaura coupling reaction using palladium
Figure 1. Optimized geometries for local minima, corresponding to
45 reactants, intermediates, and products in (I) oxidative addition and (II)
dichloride complexes with bidentate arsenic ligands.
46
reductive elimination processes.
26
Finally, we conducted density functional theory (DFT)
27 calculations to answer the question of the difference
28 between arsenic and phosphorus bidentate ligands in the
29 oxidative addition and reductive elimination processes of
30 the Suzuki-Miyaura coupling (Figure 1). For the evaluation,
31 dpae and dppe were selected for the reaction of p-
32 bromotoluene and phenylboronic acid.21 As a result,
33 negligible differences between the dpae and dppe systems
34 were observed in the activation energies and heat of
35 formation for the oxidative addition and reductive
36 elimination processes. This computational evaluation well
37 accords to the experimental results of our previous work on
38 monodentate arsenic ligands; bulky and electron-rich
39 ligands were beneficial for a coupling reaction as known in
40 catalytic systems of phosphorus ligands.8 It is implied that
41 the accumulated knowledge on design of phosphorus
42 ligands can be applied for that of arsenic ligands.
47
In conclusion, we demonstrated that various kinds of
48 bidentate arsenic ligands can be synthesized from
49 cyclooligoarsine. Notably, volatile arsenic precursors, which
50 should be used in the conventional synthetic routes, were
51 circumvented
in
the
present
protocols.
X-ray
52 crystallography revealed the conformational and electronic
53 differences between the palladium dichloride complexes of
54 the obtained ligands, and their catalytic activity for Suzuki-
55 Miyaura coupling reaction was shown. This is the first
56 systematic study on bidentate arsenic ligands for
57 transition-metal catalyst. The bidentate arsenic ligand
58 library that is constructed by the practical synthetic routes
59 will lead to remarkable expansion of abundance of metal
60 complexes. Further development of arsenic ligands and
61 investigation on advanced functions of the complexes are
a
62 now under way.
63
64
65 Acknowledgement
66 This study was supported by JSPS KAKENHI Grant
67 Number JP19H04577 (Coordination Asymmetry).
68

4
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64 16 CCDC 1916737 ([PdCl2(dpae)]), 1916734 ([PdCl2(dpap)]),
61
63
65
66
67
68
69
1916733 ([PdCl2(dpab)]), 1916735 ([PdCl2(dpaq)]), 1916736
([PdCl2(dpaf)]), and 1916738 ([PdCl2(xantas)]) contain the
supplementary crystallographic data for this paper. These data
are provided free of charge by The Cambridge Crystallographic
Data Centre.