N-heterocyclic carbene-rhodium(I) complexes derived from proline for the 1,4-conjugate addition of arylboronic acids to enones in neat water

Article abstract of DOI:10.1007/s10562-011-0563-9

N-Heterocyclic carbene-rhodium(I) complexes derived from N-benzyl substituted proline have been successfully synthesized and were found to be efficient catalysts for the 1,4-conjugate addition of arylboronic acids to enones in neat water at 40 °C. Under the optimal reaction conditions, all reactions gave the addition products in good to high yields.

Full text of DOI:10.1007/s10562-011-0563-9

Catal Lett (2011) 141:705–708
DOI 10.1007/s10562-011-0563-9
N-Heterocyclic Carbene–Rhodium(I) Complexes Derived
from Proline for the 1,4-Conjugate Addition of Arylboronic Acids
to Enones in Neat Water
Yi-Qiang Tang
•
•
Huan Lv
Jian-Mei Lu Li-Xiong Shao
•
Xiao-Na He
•
Received: 26 December 2010 / Accepted: 13 January 2011 / Published online: 26 February 2011
Ó Springer Science+Business Media, LLC 2011
Abstract N-Heterocyclic carbene–rhodium(I) complexes
derived from N-benzyl substituted proline have been suc-
cessfully synthesized and were found to be efficient cata-
lysts for the 1,4-conjugate addition of arylboronic acids to
enones in neat water at 40 °C. Under the optimal reaction
conditions, all reactions gave the addition products in good
to high yields.
complexes are air- and moisture-stable and have been proved
to be efficient catalysts for the formation of carbon–carbon
and carbon–heteroatom bonds. But, by contrast, only very
few examples among NHC-Rh(I) complexes catalyzed 1,4-
conjugate addition of arylboronic acids to a,b-unsaturated
carbonyl compounds, have been reported in the literature
[57–59]. In recent years we addressed our attention to the
development of proline-based NHC–metal complexes and
some NHC–Pd(II) complexes derived from proline have
been successfully synthesized [60]. These results prompted
us to further develop other NHC–metal complexes derived
from proline. Herein, we wish to report the synthesis of
NHC–Rh(I) complexes derived from N-benzyl substituted
proline and their catalytic activity towards the 1,4-conjugate
addition of arylboronic acids to enones in neat water under
mild reaction conditions.
Keywords N-heterocyclic carbene ꢀ Rhodium complex ꢀ
1
,4-Conjugate addition ꢀ Arylboronic acids ꢀ Water ꢀ
Synthetic methods
1
Introduction
The Rh(I) catalyzed 1,4-conjugate addition of arylboronic
acids to a,b-unsaturated carbonyl compounds has attracted
much attention since its first report by Miyaura in 1997 [1–3].
Various ligands, such as phosphine-based ligands [4–26],
diene-based ligands [27–38], phosphine-alkene based
ligands [39–46], aimed at obtaining higher efficiency of the
addition reaction, have been developed during the past years.
Since the isolation of the first free carbene by Arduengo et al.
in 1991 [47], the chemistry of N-heterocyclic carbene (NHC)
and their metal complexes has made great progress and some
reviews have been reported [48–56]. Many NHC–metal
2 Results and Discussion
First, the imidazolium salts 1a and 1b were prepared as
previously reported [60]. Then, NHC–Rh(I) complexes 2a
and 2b were synthesized by treatment of 1a and 1b with
t
[Rh(cod)Cl] in the presence of KO Bu in refluxing THF,
2
respectively [61, 62]. These two NHC–Rh(I) complexes
were isolated as yellow semi-solids in 69 and 62% yields,
respectively, both of which are stable towards air and
moisture, and even in solution (Scheme 1). The structures
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-011-0563-9) contains supplementary
material, which is available to authorized users.
1
13
of these two complexes were determined by H NMR,
C
NMR, MS, Elemental analysis (see Supporting Information
for the details).
Y.-Q. Tang ꢀ H. Lv ꢀ X.-N. He ꢀ J.-M. Lu ꢀ L.-X. Shao (&)
College of Chemistry and Materials Engineering, Wenzhou
University, Chashan University Town, Wenzhou 325035,
Zhejiang, People’s Republic of China
With the NHC–Rh(I) complexes in hand, we then turned
our interest to their applications in the 1,4-conjugate addi-
tion of arylboronic acids to enones. Initial examinations
were carried out at room temperature using phenylboronic
e-mail: Shaolix@wzu.edu.cn
123

7
06
Y.-Q. Tang et al.
We were delighted to find out that all reactions gave the
corresponding 1,4-conjugate addition products 5 in good to
high yields (Table 2). The electron-donating or -with-
drawing groups on the arylboronic acids 3 did not have
significant effect on the reactions (Table 2, entries 1, 3–5,
N
R
N
N
N
t
R
KO Bu
+
[Rh(cod)Cl]2
N
Rh Br
N
THF, reflux
Br
Ph
Ph
1
1
a: R = Me
9–10). It seems that ortho- or meta-substituents on the
i
2a: R = Me, 69%
b: R = Pr
i
arylboronic acids have somewhat effect on the reactions
and the corresponding reactions gave a little lower yields
(Table 2, entries 2, 6–8).
2
b: R = Pr, 62%
Scheme 1 Synthesis of NHC–Rh(I) complexes
We further investigated the NHC–Rh(I) complex 2a-
catalyzed 1,4-conjugate addition reactions of various
arylboronic acids 3 to other enones as cyclopent-2-enone
4b, chalcone 4c and 4-phenyl-but-3-en-2-one 4d. The
results are elucidated in Table 3. For the cyclic- or acyclic
enones studied, all gave the addition products 5 in good
to high yields (Table 3). Substituents on the arylboronic
acids 3 did not have obvious effect on the reactions,
except for the reaction of 4-fluorophenylboronic acid 3e
with cyclopent-2-enone 4b, only 79% yield of product 5n
was obtained (Table 3, entry 3). The structures of all
acid 3a (1.2 mmol) and cyclohex-2-enone 4a (1.0 mmol) as
the substrates, KOH (75 mol%) as the base, NHC–
Rh(I) complex 2a (1.0 mol%) as the catalyst and toluene
(
3.0 mL) as the solvent. The reaction was completed within
3 h to give the corresponding addition product 5a in 97%
yield (Table 1, entry 1). When the reaction temperature was
6
elevated to 40 °C, the same reaction can complete within
24 h to give 5a in 98% yield (Table 2, entry 2). When the
used amount of KOH was reduced to 25 mol%, the reaction
only gave 5a in 76% yield within 24 h (Table 1, entry 3).
When H O (3.0 mL) was used as the solvent, 87% yield of
1
13
2
the products were established by H and C NMR
spectroscopic data and were fully determined according to
the reported ones (see Supporting Information for the
details).
5a was achieved within 24 h (Table 1, entry 4) and the yield
can be further increased to 98% when the used amount of
H O was decreased to 1.0 mL (Table 1, entry 5). NHC–
2
Rh(I) complex 2b showed inferior result under the identical
reaction conditions (Table 1, entry 6). So the optimal
reaction conditions were established as using NHC–
Rh(I) complex 2a (1.0 mol%) as the catalyst, KOH
Table 2 NHC–Rh(I) complex 2a-catalyzed 1,4-conjugate addition of
arylboronic acids 3 to cyclohex-2-en one 4a
B(OH)2
O
O
(
75 mol%) as the base, H O (1.0 mL) as the solvent at the
2
temperature of 40 °C.
NHC-Rh(I) 2a (1.0 mol%)
+
To survey the generality of the optimal reaction condi-
tions, we next investigated the reactions of a variety of
arylboronic acids 3 with cyclohex-2-enone 4a (Table 2).
KOH (75 mol%)
o
R'
H2O, 40 C, 24 h
3
4a
5
R'
a
0
b
Yields (% )
Entry
3 (R )
Table 1 Optimization for the NHC–Rh(I) complexes 2 catalyzed
reaction of phenylboronic acid 3a with cyclohex-2-enone 4a
1
2
3
4
5
6
7
8
9
3b (4-Me)
3c (3, 5-Me
3d (4-Cl)
3e (4-F)
5b, 95
5c, 79
5d, 92
5e, 87
5f, 86
5g, 77
5h, 81
5i, 81
5j, 97
5k, 96
B(OH)2
O
O
2
)
NHC-Rh(I) 2a (1.0 mol%)
+
KOH, solvent, temp.
Ph
3f (4-MeO)
3g (2-Me)
3a
4a
5a
a
Entry Sol. (mL)
b
3h (2-MeO)
3i (3-MeO)
3j (4-Br)
KOH (mol%) Time (h) Temp Yield (%)
1
2
3
4
5
6
a
Toluene (3.0) 75
63
24
24
24
24
24
RT
97
Toluene (3.0) 75
Toluene (3.0) 25
40 °C 98
40 °C 76
40 °C 87
40 °C 98
40 °C 90
1
0
B(OH)2
2
H O (3.0)
2
H O (1.0)
2
H O (1.0)
75
75
75
3k
c
a
Otherwise specified, all reactions were carried out using 3a
1.2 mmol), 4a (1.0 mmol) in the presence of NHC–Rh(I) 2a
All reactions were carried out using 3 (1.2 mmol), 4a (1.0 mmol) in
the pressence of NHC–Rh(I) complex 2a (1.0 mol%) and KOH
(75 mol%) in H
O (1.0 mL) at 40 °C for 24 h
(
(
b
1.0 mol%) in the listed amount of KOH and solvent. Isolated
2
c
yields. NHC–Rh(I) 2b as the catalyst
b
Isolated yields
1
23

NHC-Rh(I) Complexes Catalyzed 1,4-Conjugate Addition of Arylboronic Acids to Enones
707
Table 3 NHC–Rh(I) complex 2a-catalyzed 1,4-conjugate addition
of arylboronic acids 3 to enones 4
3.2.2 General Procedure for the NHC–Rh(I) Complex 2a-
Catalyzed 1,4-Conjugate Addition of Arylboronic
Acids to Enones
O
B(OH)2
+
O
NHC-Rh(I) 2a (1.0 mol%)
Under N2 atmosphere, arylboronic acid 4 (1.2 mmol),
complex 2a (1.0 mol%), KOH (75 mol%), and H O
KOH (75 mol%)
2
o
R'
H O, 40 C, 24 h
2
3
4
5
(1.0 mL) were added into a Schlenk reaction tube, then 3
(1.0 mmol) was added. The mixture was stirred at 40 °C
for 24 h. Then the solvent was removed under reduced
pressure and the residue was purified by a flash column
chromatography (SiO2).
R'
O
O
O
Me
4
c
4d
4b
a
0
b
Entry
3 (R )
4
Yields (%)
1
2
3
4
5
6
7
8
9
3a (H)
4b
4b
4b
4b
4c
4c
4c
4d
4d
4d
5l, 84
5m, 97
5n, 79
5o, 86
5p, 99
5q, 97
5r, 95
5s, 97
5t, 93
5u, 91
4 Conclusions
3d (4-Cl)
3e (4-F)
In conclusion, we herein present the synthesis of NHC–
Rh(I) complexes derived from N-benzyl substituted proline
and their catalytic activity towards 1,4-conjugate addition
of arylboronic acids to enones. It was found that the
complexes were effective enough to give the corresponding
addition products in good to high yields in neat water under
mild conditions. Efforts are underway to modify the
structure of the complexes to match them in asymmetric
synthesis.
3f (4-MeO)
3a
3e
3f
3a
3d
3f
1
0
a
All reactions were carried out using 3 (1.2 mmol), 4 (1.0 mmol) in
the presence of NHC–Rh(I) complex 2a (1.0 mol%) and KOH
75 mol%) in H
Acknowledgments Financial support from the National Natural
Science Foundation of China (Nos. 21002072 and 20702013), the
Department of Education of Zhejiang Province (No. Y200907072)
and the start-up fund of Wenzhou University is greatly acknowledged.
Yi-Qiang Tang thanks Science and Technology Department of
Zhejiang Province for financial support (No. 2010R424050).
(
2
O (1.0 mL) at 40 °C for 24 h
b
Isolated yields
3
Experimental
3
.1 Materials
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