Nitronyl nitroxide as a coupling partner: Pd-mediated cross-coupling of (nitronyl nitroxide-2-ido)(triphenylphosphine)gold(i) with aryl halides

Article abstract of DOI:10.1246/cl.131162

A cross-coupling reaction using nitronyl nitroxide (NN) as a coupling partner was developed: Refluxing a mixture of [AuI(NN-2-ido)(PPh3)] and aryl iodide (ArI) in THF in the presence of 10 mol% [Pd(PPh3)4] produced a cross-coupling product NN-Ar in a high yield. This method allowed the direct introduction of the NN radical onto various poly- and heterocyclic aromatic rings.

Full text of DOI:10.1246/cl.131162

CL-131162
Received: December 11, 2013 | Accepted: January 17, 2014 | Web Released: January 24, 2014
Nitronyl Nitroxide as a Coupling Partner: Pd-Mediated Cross-coupling
of (Nitronyl nitroxide-2-ido)(triphenylphosphine)gold(I) with Aryl Halides
Ryu Tanimoto, Shuichi Suzuki, Masatoshi Kozaki, and Keiji Okada*
Department of Chemistry, Graduate School of Science, Osaka City University,
3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585
(E-mail: okadak@sci.osaka-cu.ac.jp)
A cross-coupling reaction using nitronyl nitroxide (NN) as
dure using 2,3-dimethylbutane-2,3-diamine followed by oxy-
genation and oxidation was developed.
a coupling partner was developed: Refluxing a mixture of
[AuI(NN-2-ido)(PPh3)] and aryl iodide (Ar-I) in THF in the
presence of 10 mol % [Pd(PPh3)4] produced a cross-coupling
product NN-Ar in a high yield. This method allowed the
direct introduction of the NN radical onto various poly- and
heterocyclic aromatic rings.
In addition to these condensation methods, the cross-
coupling of NN derivatives with aryl halides is an attractive
route to introduce the NN-skeleton directly onto aromatic rings.
To date, the cross-coupling of NN-C6H4-X (X = Br or I), at a
remote position of NN, with terminal acetylenes (Sonogashira
coupling)17 or arylboronates/acids (Suzuki coupling)18 have
been reported; however, there have been no reports on the cross-
coupling reaction at the C2-position of NN utilizing NN-X
(X = Br or I). The preliminary experiments to achieve Pd(0)-
mediated cross-coupling of NN-X (X = Br or I) with phenyl-
boronate pinacol ester or tributyl(phenyl)stannane in the
presence of tetrakis(triphenylphosphine)palladium ([Pd(PPh3)4])
have failed to efficiently produce the cross-coupling products,
NN-Ph (Supporting Information, Table S1).19
Recently gold(I)-catalyzed reactions have attracted a great
deal of attention because of their wide applicability to various
chemical transformations.20 Especially, the Pd(0)-mediated
cross-coupling reactions of organogold(I) phosphanes with aryl
halides developed by Sarandeses, Sestelo, and co-workers
proceed under mild conditions in high yields.21 We expected
that the metalloid radical 1 and the radical products could
survive under these neutral and mild conditions. Herein, we
report the first successful cross-coupling of NN at the 2-position
with aryl halides by utilizing 1 (Scheme 1b).
Stable open-shell molecules have attracted considerable
attention in the field of materials science.1-3 In the past few
decades, various interesting properties based on open-shell
molecules have been developed.1-8 Especially, substituted
nitronyl nitroxide (NN-Rs) radicals have been widely used as
stable spin sources.1,9,10 Metal-radical systems involving NN-Rs
as a ligative spin have also been extensively invesigated.1
However, only a few studies of metal complexes coordinated
by NN-2-ide radical anion (metalloid radical, NN-MLn;
M = metal ion, Ln = ligands) have been reported. The NN-2-
ide radical anion is an unstable species (¸ < 30 min at room
temperature in solution)11 but is a useful synthetic intermediate
for C-C bond formation.12 We recently reported the synthesis
and the unique redox properties of NN-Pt(NCN) pincer
complexes.13 The advantages of these metalloid radicals are
due to their high stability in contrast to the NN-2-ide radical
anion. Therefore, the metalloid radical species are expected to
have potential applicability to various fields in science. In this
study, we demonstrate that metalloid radical [AuI(NN-2-
ido)(PPh3)] (1) can be utilized as an effective cross-coupling
agent in Pd-mediated cross-coupling reactions with various aryl
halides.
[AuI(NN-2-ido)(PPh3)] (1) was readily synthesized by
mixing NN-H and [AuI(PPh3)Cl] with NaOH in CH2Cl2-
MeOH.13,19,22 Figure 1 shows the molecular structure of 1 at
50% ellipsoid level.23 The Au-C2 bond length (2.032 ¡) is close
to that of Ph-Au(PPh3) (2.044 ¡).24 The N-O bond lengths
(1.286 and 1.287 ¡) are typical values in NNs.25 Metalloid
radical 1 was stable under aerated conditions (decomposition
temperature: ca. 185 °C) and was purified by chromatography
using deactivated Al2O3.
The NN radicals were generally prepared by the condensa-
tion reaction of N,N¤-dihydroxy-2,3-dimethylbutane-2,3-diamine
with various aldehydes followed by oxidation (Scheme 1a);9
however, the procedure was unsuccessful sometimes, par-
ticularly when highly electron-donating4b,9,14 or electron-
deficient9,15 aromatic aldehydes were used. In a study reported
by Rey and co-workers,16 the merits and disadvantages of this
method were described and an alternative condensation proce-
Refluxing the mixture of haloacetophenone (o-, m-, or p-
isomer, ca. 1.1 equiv, halo: I and Br) and 1 (1.0 equiv) in THF
in the presence of 10 mol % [Pd(PPh3)4] produced the desired
Figure 1. Molecular structure of [AuI(NN-2-ido)(PPh3)] (1) at a
50% ellipsoid level. Hydrogen atoms are omitted for clarity.
Scheme 1. General (a) and new (b) routes to NN-R (Ar).
678 | Chem. Lett. 2014, 43, 678–680 | doi:10.1246/cl.131162
© 2014 The Chemical Society of Japan

Table 1. Cross-coupling reaction of 1 with acetophenones 2-4
Table 2. Cross-coupling of 1 with various ArXs
Entry
Ar-X
Catalyst
Product
Yielda/%
1
2
3
4
5
6
2a
2a
2a
2b
3a
4a
[Pd(PPh3)2]Cl2
[Pd2(dba)3]¢CHCl3
[Pd(PPh3)4]
[Pd(PPh3)4]
[Pd(PPh3)4]
2P
2P
2P
2P
3P
4P
0
traceb
80
83
86
[Pd(PPh3)4]
85
b
aIsolated yield. Detected by TLC.
Entry
Ar-X
Product
Yielda/%
1
2
5a
6a
5P
6P
92
89
3
7a
7P
83
4
5
6
8a
8b
9a
8P
8P
9P
71
traceb
83
7
8
9
10
11
12
13
14
15
16
10a
11a
11b
12b
13a
14a
15a
16a
17a
18a
10P
11P
11P
12P
13P
14P
15P
16P
17P
18P
73
69
traceb
74
64
65
84
50
83
88
b
aIsolated yield. Detected by TLC.
Figure 2. ESR-spectral change during the cross-coupling reaction of
1 with 2a in the presence of [Pd(PPh3)4] in dry degassed THF at 60 °C.
than aryl bromides for electron-rich aryl halides (Entries 4, 5 and
Entries 8, 9); detailed comparisons between various aryl iodides
and bromides are listed in Table S2.19 The reaction proceeded in
the presence of various functional groups and heterocyclic rings
(Entries 2, 3, 13, 16, etc.). o-Pyridyl iodide (16a) produced 16P
with a somewhat poor yield (Entry 14), probably owing to the
complexation reaction of 16P with the Pd-catalyst.
The reaction was effectively extended to introduce multiple
NN-groups. The reaction of 1 (2 equiv) with m- and p-
diiodobenzene (1 equiv) in refluxing THF in the presence of
[Pd(PPh3)4] produced (m-phenylene)bisNNs 19P and (p-phenyl-
ene)bisNNs 20P in 69% and 79% yields, respectively. However,
a similar reaction with o-diiodobenzene (1 equiv) only produced
the mono cross-coupling product 21P in 55% yield (Scheme 2).
No bisadduct was detected probably because of the large steric
interference.
We also examined the synthesis of trisNNs 22P. The
condensation-oxidation procedure could not be applied for this
compound because of the unavailability of trialdehyde 23:
Several attempts (Vilsmeier-Haack reaction of trioxytriphenyl-
amine4b,8,26 with a large excess (100 equiv) of DMF-POCl3
reagent4b or trilithiation of 22b,8 followed by addition of a
formylation reagent) to synthesize 23 were unsuccessful. The
coupling products 2P-4P in good yields (Table 1). The obtained
radical products were characterized and identified using spectro-
scopic techniques.19 The Pd catalysts, bis(triphenylphosphine)-
palladium(II) dichloride ([Pd(PPh3)2]Cl2) and tris(dibenzylidene-
acetone)dipalladium(0)-chloroform adduct ([Pd2(dba)3]¢CHCl3)
were not effective, although they were reported to be active for
the usual aryl-aryl cross-coupling reactions using ArAuPPh3
(Ar = aryl) with aryl halides.21
Interestingly, the progress of the reaction could be visible by
a color change from blue-purple to blue, corresponding to the
colors of radicals 1 (blue-purple) and 2 (blue). This conversion
in the reaction of 2a was directly monitored by electron spin
resonance (ESR) spectroscopy (Figure 2). The initial ten-line
spectrum of 1 that could be attributed to the hyperfine couplings
of 14N («aN« = 0.769 mT) and 31P («aP« = 0.235 mT)19 nuclei
were converted to a typical five-line spectrum of a NN derivative
(«aN« = 0.736 mT) (2P),19 thereby demonstrating a clean con-
version of this coupling reaction.
The reactions were conducted using various aromatic
halides as shown in Table 2. Aryl iodides were more reactive
Chem. Lett. 2014, 43, 678–680 | doi:10.1246/cl.131162
© 2014 The Chemical Society of Japan | 679

5
6
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O
N
O
N
Au complex 1
10 mol% Pd-catalyst
I
N
O
I
N
O
THF, reflux
19P (69%), 20P (79%)
19 (meta), 20 (para)
7
8
9
I
I
O
N
Au complex 1
10 mol% Pd-catalyst
I
N
O
THF, reflux
21
21P
Scheme 2. Cross-coupling reactions of 1 with diiodobenzenes.
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N
N
O
O
O
O
X
Au complex 1
10 mol% Pd-catalyst
O
O
THF, reflux
N
O
N
O
O
N
O
N
X
X
N
N
O
22a (X = I), 22b (X = Br)
23 (X = CHO)
O
22P
(70% from 22a)
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Scheme 3. Cross-coupling reaction of 1 with 22a.
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present cross-coupling scheme was applied to triiodide 22a; the
reaction proceeded smoothly to afford the desired product (22P)
in 70% yield (Scheme 3). Triradical 22P is a precursor of 22P
radical cation which is expected to be a quintet tetraradical
monocationic species with a possible large intramolecular
exchange interaction.4b
In summary, we have developed a new cross-coupling
reaction of [AuI(NN-2-ido)(PPh3)] (1) with aryl halides. The NN
radical was directly introduced onto various aryl rings. This
method provides a potential scheme for the synthesis of NN
derivatives; moreover, this can be used in a complementary
fashion to expand the application of open-shell materials for
spintronics.
16 C. Hirel, K. E. Vostrikova, J. Pécaut, V. I. Ovcharenko, P. Rey,
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This work was partially supported by Grant-in-Aid for
Scientific Research from JSPS (No. 22350066 to K.O.) and
Grant-in-Aid for Scientific Research on Innovative Areas
“Stimuli-responsive Chemical Species for the Creation of
Functional Molecules” from MEXT (No. 25109537 to S.S.).
S.S. is also grateful for financial support from the Asahi Glass
Foundation and the Tokuyama Science Foundation.
22 We thank Prof. Akira Izuoka (Ibaraki University) for the synthetic
information of this compound in private communication: A. Yoshida,
A. Itoi, A. Izuoka, Proceedings of the 89th Annual Meeting of the
Chemical Society of Japan, 2PA-074.
23 Crystallographic data of Au complex 1: monoclinic, space group: P21/c
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¹3
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680 | Chem. Lett. 2014, 43, 678–680 | doi:10.1246/cl.131162
© 2014 The Chemical Society of Japan