Palladium-catalyzed addition of arylboronic acids to isocyanates

Article abstract of DOI:10.1016/j.tetlet.2009.01.054

The addition of arylboronic acids to isocyanates catalyzed by palladium acetate in the presence of triphenylphosphine as the ligand is described.

Full text of DOI:10.1016/j.tetlet.2009.01.054

Tetrahedron Letters 50 (2009) 1687–1688
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Tetrahedron Letters
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Palladium-catalyzed addition of arylboronic acids to isocyanates
*
Ebrahim Kianmehr , Azam Rajabi, Mohammad Ghanbari
School of Chemistry, University College of Science, University of Tehran, Tehran 14155-6455, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
The addition of arylboronic acids to isocyanates catalyzed by palladium acetate in the presence of tri-
phenylphosphine as the ligand is described.
Received 23 October 2008
Revised 2 January 2009
Accepted 13 January 2009
Available online 19 January 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Arylboronic acids are extremely useful organometallic reagents
because they are non-toxic and stable compounds.1 There are sev-
eral methods available for the synthesis of complex arylboronic
acids and large numbers are commercially available. Organobo-
ronic acids and boronates are widely used in reactions catalyzed
by transition metals such as palladium,2 rhodium3 and copper.4
They are useful practically for carbon–carbon and carbon–hetero-
atom bond formation. Copper-catalyzed arylboronic acid coupling
reactions with amines, sulfoximines, phenols and alkyl thiols en-
able carbon–heteroatom bond formation.
are no reports concerning the addition of arylboronic acids to iso-
cyanates catalyzed by palladium. Herein, we report the palladium-
catalyzed addition of arylboronic acids to isocyanates under very
mild reaction conditions.
We examined the reaction of phenylboronic acid and phenyliso-
cyanate in different solvents such as CH2Cl2, DMF, toluene, dioxane
and acetonitrile, in the presence of 5 mol % of Pd(OAc)2. However,
only a trace of the desired benzamide was obtained. To our delight,
using THF as the solvent under an inert atmosphere increased the
yield greatly. Other palladium catalysts, such as PdCl2 and
Pd(dba)2, led to lower yields. It has been reported that the use of
2,20-bipyridine (bpy) as a ligand is crucial in the addition of arylbo-
ronic acids to nitriles,13c however, no reaction was observed be-
tween arylboronic acids and isocyanates in the presence of bpy
as ligand. The results are summarized in Table 1. Also, in the pres-
ence of the oxidant benzoquinone (BQ),14 only a trace of the de-
In 1997, Miyaura reported the conjugate addition of aryl- and
alkenylboronic acids to a,b-unsaturated ketones, which was shown
to proceed under catalysis by a rhodium complex.5 Miyaura also
reported rhodium-catalyzed additions of arylboronic acids to alde-
hydes and imines.6 Recently, rhodium-catalyzed addition of aryl-
and alkenylboronic acids to isocyanates7 and enantioselective
additions of arylboronic acids to aliphatic imines,8 N-Boc imines9
and N-tert-butanesulfinyl imino esters10 have been reported. Palla-
dium-catalyzed addition reactions of arylborons were reported by
Uemura, who demonstrated that palladium catalyzes the conju-
Table 1
Optimization of the reaction conditions for the addition of PhB(OH)2 to phenyliso-
cyanate (1:1)
gate addition to a
,b-unsaturated carbonyl compounds.11 Now, pal-
Pd(OAc)2/PPh3
ladium-catalyzed addition of arylboronic acids to carbon–carbon
double and triple bonds and insertion of carbon–carbon multiple
bonds into carbon–palladium bonds, as a facile method for car-
bon–carbon bond formation, are very important reactions in orga-
nopalladium chemistry.2,12 However, in contrast to the numerous
reports on the insertion of carbon–carbon multiple bonds into car-
bon–palladium bonds, direct insertion of carbon–heteroatom mul-
tiple bonds without using stoichiometric organopalladium
reagents has received scant attention. Palladium complex catalysts
show rare activity for the 1,2-addition of arylborons to carbon–het-
eroatom double bonds and only a few reports of the use of arylpal-
ladium species as nucleophiles for reaction with polar electrophilic
multiple bonds are available.13 To the best of our knowledge, there
ArB(OH)2
+
+
RNCO
RNHCOAr
Ar
Ar
THF, rt, Ar, 40 h
1
2
Entry
Catalyst (mol %)
Ligand
Solvent
1 (%)
1
2
3
4
5
6
7
8
9
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (10)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
PdCl2 (10)
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
bpy
dppe
dpbp
PPh3
PPh3
bpy
THFa
64
DMFa
CH2Cl2
Trace
Trace
Trace
Trace
Trace
<5
<5
<5
21
18
a
Toluenea
Dioxanea
MeCNa
THFa
THFb
THFb
10
11
12
THFa
Pd(dba)2 (10)
Pd(dba)2 (10)
THFa
THFa
<5
a
Ratio of Ligand:Pd = 4:1.
Ratio of Ligand:Pd = 2:1.
* Corresponding author. Tel.: +98 21 61112480; fax: +98 21 66495291.
E-mail address: kianmehr@khayam.ut.ac.ir (E. Kianmehr).
b
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.01.054

1688
E. Kianmehr et al. / Tetrahedron Letters 50 (2009) 1687–1688
Table 2
The catalytic cycle is presumably initiated by oxidative addition of
the arylboronic acid to a Pd(0) complex which generates an arylpal-
ladium(II) species 3. Subsequent insertion of the isocyanate double
Addition of various arylboronic acids to different isocyanates (1:1)
Ar
R
1 (%)
2 (%)
bond into the
r-aryl-Pd–C bond produces intermediate 4. It is rea-
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
64
49
52
60
32
32
33
56
40
43
37
56
27
3
15
12
7
sonable to assume that boron departs in the form of a boric acid
derivative such as metaboric acid15 and affords intermediate 5.
Reductive elimination then regenerates the palladium(0) catalyst
and the addition product.
In summary, we have developed a Pd-catalyzed addition of aryl-
boronic acids to the C@N double bond of isocyanates in the pres-
ence of PPh3 as a ligand to yield benzamides in moderate to good
yields.
3,4-(MeO)2C6H3
4-t-BuC6H4
3-MeC6H4
4-BrC6H4
4-ClC6H4
1-Naphthyl
Ph
3-MeC6H4
1-Naphthyl
4-BrC6H4
4-t-BuC6H4
6
17
11
10
16
19
30
3-Cl,4-MeC6H4
3-Cl,4-MeC6H4
3-Cl,4-MeC6H4
3-Cl,4-MeC6H4
3-Cl,4-MeC6H4
Acknowledgement
Financial support by the research council of the University of
Tehran is gratefully acknowledged.
Table 3
Influence of the amount of phenylboronic acid on the reaction (rt, 40 h)
References and notes
PhB(OH)2 (equiv)
Catalyst (mol %)
1 (%)
2 (%)
3.0
2.5
2.0
1.5
1.0
5
5
5
5
5
24
34
40
53
64
65
60
51
32
27
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sired benzamide was obtained. Finally, for comparison, the reac-
tion was carried out in the absence of Pd(OAc)2 and no benzamide
product could be detected. With the optimized conditions in hand,
the addition of various arylboronic acids to different isocyanates
was studied, and the results are shown in Table 2. The influence
of the amount of the phenylboronic acid is shown in Table 3. A high
yield of biphenyl 2 was obtained using 2.0 equiv of phenylboronic
acid. Electronic effects in the arylboronic acids showed a remark-
able influence on the reaction; electron-rich arylboronic acids re-
acted easily. On the other hand, arylboronic acids with electron-
withdrawing groups gave benzamides in lower yields.
A possible mechanism for this palladium-catalyzed addition
reaction of arylboronic acids to isocyanates is shown in Scheme 1.
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