Palladium-Catalyzed Synthesis of α-Diimines from Triarylbismuthines and Isocyanides

Article abstract of DOI:10.1021/acs.orglett.5b01566

In this study, we report a highly selective coupling reaction between triarylbismuthines and isocyanides using palladium diacetate as the catalyst, affording α-diimines, with the formation of three C-C bonds. Among several aryl sources (Ar-YL_n: Y = B, Sn, Pb, Sb, Bi, I), only triarylbismuthines successfully undergo coupling with isocyanides to selectively afford α-diimines. The coupling reaction exhibits the advantages of high atom economy and convenient operation, with no need for any additive.

Full text of DOI:10.1021/acs.orglett.5b01566

Letter
pubs.acs.org/OrgLett
Palladium-Catalyzed Synthesis of α‑Diimines from
Triarylbismuthines and Isocyanides
Yohsuke Kobiki, Shin-ichi Kawaguchi, and Akiya Ogawa*
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai,
Osaka 599-8531, Japan
S
* Supporting Information
ABSTRACT: In this study, we report a highly selective coupling reaction
between triarylbismuthines and isocyanides using palladium diacetate as the
catalyst, affording α-diimines, with the formation of three C−C bonds. Among
several aryl sources (Ar−YLn: Y = B, Sn, Pb, Sb, Bi, I), only triarylbismuthines
successfully undergo coupling with isocyanides to selectively afford α-diimines.
The coupling reaction exhibits the advantages of high atom economy and
convenient operation, with no need for any additive.
a
rganic isocyanides have been reported to be attractive
sources of carbon and nitrogen for use in organic
Table 1. Reaction of Phenyl Sources with Isocyanide 2a
O
synthesis,1 and a number of imine derivatives and N-containing
heterocycles have been synthesized using isocyanides as starting
materials. For these transformations in particular, transition-
metal-catalyzed reactions of isocyanides are useful tools.2
However, only a few examples of the double insertion of
isocyanides in the presence of catalysts have been reported,3,4
because generally isocyanides are easily oligomerized in the
presence of transition-metal compounds.5
On the other hand, triarylbismuthines (BiAr3) have been
used as an effective, environmentally friendly aryl source for
some arylation reactions6 because of their low toxicity7 and low
bond-dissociation energy of the Bi−C bond.8 In particular, the
latter property allows for transmetalation between BiAr3 and
transition-metal complexes, affording the M−Ar bond in situ.9
As isocyanides can smoothly insert into the Pd−C bond, imine
derivatives can be obtained by the reaction of BiAr3 with
isocyanides in the presence of a palladium catalyst. Interest-
ingly, the reaction between triphenylbismuthine (1a) and tert-
butyl isocyanide (2a) in the presence of palladium(II) acetate
selectively afforded α-diimine 3aa, which consists of two imine
moieties and two phenyl groups (eq 1). In this synthesis of α-
b
b
entry
phenyl source
yield of 3aa
yield of 4aa
1
2
3
4
BiPh3 (1a, 0.2 mmol)
PhB(OH)2 (5a, 0.6 mmol)
PhBpin (5b, 0.6 mmol)
PhI (6, 0.2 mmol)
90%
3%
9%
trace
trace
ND
0%
4%
ND
18%
15%
28%
19%
c
5
c
SbPh3 (7, 0.2 mmol)
SnPh4 (8, 0.2 mmol)
PbPh4 (9, 0.2 mmol)
PbPh4 (9, 0.1 mmol)
6
ND
72%
65%
7
8
a
b
1
Bpin = boronic acid pinacol ester. Determined by H NMR. ND =
not detected. A complex mixture was also formed.
c
yield (entries 2 and 3, respectively), while phenyl iodide (6) did
not afford 3aa (entry 4). Under the reaction conditions,
triphenylstibine (7) and tetraphenylstannane (8) afforded
complex mixtures (entries 5 and 6, respectively). On the
other hand, tetraphenylplumbane (9), an organometallic
compound containing lead, which is located in the same
period as bismuth, afforded α-diimine 3aa and imine 4aa in
good yields (entries 7 and 8, respectively). However, the
selectivity of products between 3aa and 4aa was insufficient.
BiAr3 were found to be the most suitable organometallic
compounds for the synthesis of α-diimines in terms of the
selectivity of 3aa, as well as toxicity.
diimines, three carbon−carbon bonds are successfully formed
simultaneously. α-Diimines are known to be typical π-acceptor
ligands;10 their metal complexes have been used in several
catalytic reactions.11 Thus, we believed that the above reaction
is an effective synthetic route to α-diimines and investigated the
proposed method in detail.
Next, we optimized the reaction conditions of the synthesis
of α-diimines using BiAr3 (Table 2). The reactions between 2a
(0.4 mmol) and 1a (1/3 equiv) were conducted in the presence
of Pd(OAc)2 (5 mol %) under N2 (entry 1). α-Diimine 3aa was
First, we investigated the synthesis of α-diimines by using
different aryl sources (Table 1). The use of phenylboronic acid
(5a) and its pinacol ester 5b afforded α-diimine 3aa in low
Received: May 28, 2015
© XXXX American Chemical Society
A
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Table 2. Optimization of Reaction Conditions
Scheme 1. Pd-Catalyzed Synthesis of α-Diimines
a
entry
reaction condition
18 h, 70 °C, under N2
18 h, 70 °C, under air
18 h, 70 °C, under O2
18 h, RT, under air
yield
24%
1
2
3
4
5
6
7
8
85%
41%
62%
93%
85%
88%
87%
80%
4 h, 70 °C, under air
2 h, 70 °C, under air
4 h, 70 °C, under dry air
b
4 h, 70 °C, under air, H2O (2 equiv)
4 h, 90 °C, under air
4 h, 70 °C, under air
c
9
d
10
>99% (80%)
a
Determined by 1H NMR (isolated yield is indicated within
b
c
parentheses). Air was dried by passing through P2O5. Instead of
benzene, toluene was used as the solvent. Instead of benzene, MeCN
d
was used as the solvent.
obtained as the major product with high selectivity, albeit in
low yield (24%), along with minor amounts of 4aa (4%). After
the reaction, the residual bismuth precipitated as metallic
bismuth. Surprisingly, the yield of 3aa dramatically improved
under air (entry 2). In entry 2, 10aa (Figure 1, right), not 4aa,
Figure 1. Byproducts in the synthetic reaction of 3aa.
was obtained in 8% yield as the byproduct. Moreover, when the
reaction was conducted under O2, the yields of both 4aa and
10aa increased (ca. 10% yield, entry 3). When the reaction was
conducted at room temperature, 3aa was obtained in moderate
yield (entry 4). On the other hand, when the reaction was
conducted at 70 °C, it was completed in a shorter time (4 and 2
h) (entries 5 and 6, respectively). As the reactions were
conducted under air, the effect of moisture (water) on the
reaction was investigated (entries 7 and 8): regardless of the
presence or absence of water, the reaction afforded 3aa in a
similar yield. The effect of temperature on the reaction was also
investigated, and the yield of 3aa slightly decreased at higher
temperature (entry 9). By employing the conditions listed in
entry 5, the optimization of the palladium catalyst and solvent
was carried out (see the Supporting Information). From the
optimization results, palladium acetate and MeCN were found
to be the most suitable catalyst and solvent, respectively, and
3aa was obtained with excellent yield and selectivity (entry 10).
Using the optimized conditions, we next investigated the
scope of isocyanides and bismuthines (Scheme 1). Primary,
secondary, and tertiary aliphatic isocyanides were applied to the
palladium-catalyzed synthesis of α-diimines, and the corre-
sponding N-alkylated α-diimines (3aa−3ae) were obtained in
good yields. Electron-rich aromatic isocyanides such as 2f and
2g smoothly afforded the corresponding α-diimines. On the
other hand, electron-deficient aromatic isocyanides such as 2i
and 2j did not form imines. Moreover, BiAr3 containing
halogen substituents at the para position could also be used in
a
b
Isolated yield. Reaction conditions: 2 (0.4 mmol) and Pd(OAc)2 (5
mol %) were used. Yield was calculated on the basis of the amount of
c
d
2. Obtained as mixtures of geometric isomers. The reaction was
conducted in toluene (2 mL) at 100 °C. The reaction was conducted
in benzene (2 mL).
e
this reaction under the optimized conditions, and the
corresponding halogenated diimines 3ba and 3ca were
obtained in high yield. The electron density of the aryl rings
on bismuth strongly affected the accessibility of α-diimine 3.
For instance, when electron-deficient bismuthine such as 1d
was used, high temperature was required for the completion of
the reaction, affording 3da in moderate yield. On the other
hand, electron-rich bismuthines such as 1e and 1f smoothly
afforded the corresponding α-diimines 3ea and 3fa, respec-
tively.
Before gaining insight into the possible mechanistic pathway
to α-diimines from BiAr3 and isocyanides, related studies are
mentioned below. Organobismuth compounds have been
reported to smoothly undergo transmetalation with transition
metals.9 Boschi has reported the formation of a phenylimidoyl
(Ph−C(=NPh)−) ligand on palladium by the reaction between
phenyl derivatives of heavy metals, such as triphenylbismuthine,
and a palladium(II)-phenylisocyanide complex.12 The ligand
was probably formed by the transmetalation of triphenylbismu-
thine with the palladium complex, followed by the insertion of
B
DOI: 10.1021/acs.orglett.5b01566
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Letter
isocyanide into the Pd−C bond. Moreover, Amii has reported
that α-diimines were obtained from the palladium complex
bearing one arylimidoyl ligand by heating13 and indicated that
the reaction was accomplished by the intermolecular ligand
exchange of the palladium complexes.
With these precedent studies, a plausible reaction pathway is
proposed (Figure 2). First, a reaction between palladium(II)
potassium acetate to this reaction, the reaction smoothly
proceeded, affording 3aa in high yield. These results indicated
that complex 11 acts as a precatalyst for the reactions between
1a and 2a, acetate is essential for the smooth progress of this
reaction, and complex C plays a significant role in the synthesis
of α-diimines. In addition, acetate anions can back onto Pd
atom from Bi(OAc)3.
In conclusion, we developed a novel synthetic route to α-
diimines starting from triarylbismuthines and isocyanides using
palladium diacetate as the catalyst. This reaction affords
symmetrical α-diimines under air without the use of additives
via the formation of three carbon−carbon bonds. Of note, α-
diimines are formed only when triarylbismuthines were used as
organometallic reagents. The details of the reaction mechanism
are currently under way.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures, spectroscopic data of all new
1
compounds, and copies of H and 13C NMR spectra. The
Supporting Information is available free of charge on the ACS
Publications website at DOI: 10.1021/acs.orglett.5b01566.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: ogawa@chem.osakafu-u.ac.jp.
Notes
The authors declare no competing financial interest.
Figure 2. A plausible reaction pathway.
ACKNOWLEDGMENTS
■
diacetate and isocyanide afforded a palladium(II)-isocyanide
complex A in situ. Second, complex A reacts with BiAr3,
affording complex B bearing a Pd−Ar bond. Third, complex B
is smoothly converted to arylimidoyl complex C by insertion of
isocyanides into the Pd−Ar bond. Next, ligand exchange occur
between two arylimidoyl complexes (C), followed by
disproportionation to afford complex A and complex D bearing
two arylimidoyl ligands.14 Finally, the desired product 3 is
obtained by the reductive elimination of complex D. The
palladium(0) complex E is reoxidized by molecular oxygen and
bismuth acetate.15 In this reaction, residual bismuth is
precipitated as metallic bismuth and a small amount of an
insoluble white solid.
To confirm the formation of intermediate C, the reactions
between 1a and 2a were conducted in the presence of
palladium complex 11 (Figure 3). The palladium complex 11,
which was synthesized by Amii’s method,13 has a structure
similar to that of complex C in Figure 2. Diimine 3aa was
obtained in only 13% yield. However, by the addition of
This work is supported by Grant-in-Aid for JSPS Fellow (No.
15J11739). We greatly appreciate the editor and reviewers
fruitful suggestion of reaction pathway.
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DOI: 10.1021/acs.orglett.5b01566
Org. Lett. XXXX, XXX, XXX−XXX