Rhodium-catalyzed ortho-alkylation of aromatic aldimines and ketimines via C-H bond activation

Article abstract of DOI:10.1016/S0040-4039(01)00865-6

The aldimines reacted with alkenes under a rhodium catalytic system, Rh[(coe)₂Cl]₂ and Cy₃P, to give mainly the double alkylated products with moderate to high yields. On the other hand, the ketimine 9 gave the mono alkylated product predominantly.

Full text of DOI:10.1016/S0040-4039(01)00865-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4853–4856
Rhodium-catalyzed ortho-alkylation of aromatic aldimines and
ketimines via CꢀH bond activation
a,
b
b
b
Yeong-Gweon Lim, * Jong-Soo Han, Seung-Sun Yang and Jong Han Chun
a
1
-2-6, Agency for Defense Development, Yuseong PO Box 35-1, Daejeon 305-600, South Korea
b
Department of Industrial Chemistry, Hanbat National University, Daejeon, South Korea
Received 16 April 2001; revised 14 May 2001; accepted 18 May 2001
Abstract—The aldimines reacted with alkenes under a rhodium catalytic system, Rh[(coe) Cl]2 and Cy P, to give mainly the
2
3
double alkylated products with moderate to high yields. On the other hand, the ketimine 9 gave the mono alkylated product
predominantly. © 2001 Elsevier Science Ltd. All rights reserved.
Recently, the CꢀC bond formation as a result of CꢀH
Cy P on rhodium metal led to high conversion yields
3
bond activation by transition-metal complexes has
and short reaction times. Thus, we decided to apply this
rhodium catalytic system to the alkylation of aromatic
aldimines and ketimines with alkenes. To investigate
the effects of substituent substrates, we also carried out
the alkylation of substrates having electron-donating
and electron-withdrawing groups on the benzene ring.
Herein, we report the alkylation of aromatic aldimines
and ketimines with alkenes by a rhodium catalytic
system, [RhCl(coe) ] and Cy P, proceeded without a
1
become a useful synthetic method for chemists. The
activation of inactive CꢀH bonds has been achieved by
2
many research groups. By using the CꢀH bond activa-
tion, alkylation of the aromatic ring through the cou-
pling reaction with alkenes and alkynes has been
3
4–10
reported by us and other groups.
In spite of many
reports of CꢀC bond formation, the alkylation of
aldimines and ketimines is still rare. The alkylation of
aromatic aldimines by a ruthenium complex has been
2
2
3
need for additives (see Scheme 1).
4f
reported by the Murai group. Moreover, the alkyla-
tion of aldimines and ketimines using Wilkinson’s cata-
Aldimine 1a reacted with 2a (5 equiv.) under
1
0
lyst has been reported very recently by Jun. However,
while the Ru-catalyzed alkylation of aldimines shows a
high reactivity for vinyl siloxanes, it has some prob-
lems; for example, low reactivity for other alkenes such
as 2a and producing undesired dehydrogenated prod-
[RhCl(coe) ] (5 mol%) and Cy P (30 mol%) in THF at
2
2
3
140°C for 24 h with stirring to give the anti-
Markovnikov ortho-alkylated benzaldehydes in 93%
isolated yields (4a:5a=11:89) after hydrolysis and chro-
matographic isolation (Table 1, run 1). This rhodium
4
f
4f
ucts. In the case of using RhCl(PPh ) , the ketimines
catalytic system showed higher reactivity than that of
3
3
show a high reactivity with alkenes, but the aldimines
Ru (CO) for 2a. The ligand-exchange step for forma-
3
12
10
do not react with alkenes without a co-catalyst. We
have already reported that in the alkylation of 2-
phenylpyridines, exchange of ligands from PPh3 to
tion of RhCl(Cy P) from [RhCl(coe) ] and Cy P is
3 3 2 2 3
essential for this alkylation before the addition of sub-
strate and alkene. When the alkylation was carried out
Scheme 1.
Keywords: alkylation; CꢀC bond formation; rhodium catalyst; aldimines; ketimines.
*
Corresponding author.
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00865-6

4
854
Y.-G. Lim et al. / Tetrahedron Letters 42 (2001) 4853–4856
without a ligand-exchange step, the yield of the alkyl-
ated product was low (20–30%). However, 2-
phenylpyridines do not require this ligand-exchange
step. In an attempt to obtain the mono alkylated
product 4a as a major product, 1 equiv. of 2a was used.
However, 5a was still the major product (run 2). Even
though 0.7 equiv. of 2a was used, this alkylation pre-
ferred double alkylation (run 3). This result indicates
that after mono alkylation, the next catalytic cycle
takes place without dissociation of the nitrogen of the
imine on the rhodium metal center. The Wilkinson’s
3
c
complex
RhCl(Ph P) ,
(Ph P) Rh(CO)Cl
and
3
3
3
2
a
Table 1. Results of the alkylation of aromatic aldimines and ketimines

Y.-G. Lim et al. / Tetrahedron Letters 42 (2001) 4853–4856
4855
Scheme 2.
Ph P) Ir(CO)Cl were inactive under similar reaction
(
Another substrate, naphthalene derivative 13, reacted
with 2a (5 equiv.) to give the alkylated 1-naphthalde-
hyde 14 in 99% yield after hydrolysis and chromato-
graphic isolation (see Scheme 2).
3
2
conditions. The results of the alkylation are listed in
Table 1. To investigate the effect of substituted groups
on the benzene ring, aldimines bearing electron-donat-
ing and electron-withdrawing groups were examined
under the same reaction conditions. The p-methoxy
group, an electron-donating group, accelerated the
alkylation and gave quantitative yields of the alkylated
products (run 4). Another electron-donating group, the
p-methyl group, also showed high reactivity (run 5). On
the other hand, the aldimine-bearing electron-with-
In conclusion, we have found that aldimines and
ketimines reacted with alkenes under a rhodium cata-
lyst without additives to give mainly the double alkyl-
ated products with moderate to high yields. The
aldimines bearing H, p-CH O, p-CH , p-Cl and p-CF
3
3
3
2
groups have high reactivities, but m-CH O and p-NO
3
drawing group, p-NO , reacted slowly with alkene (6%;
exhibit low reactivities. The ketimine 9 gave the mono
alkylated products predominantly.
2
mono:double=88:12). However, another aldimine-
bearing electron-withdrawing group, p-CF , shows an
3
unexpectedly high reactivity (run 8). The reason for this
exceptional reactivity is not clear at the present time.
Acknowledgements
However, the exceptional reactivity of the p-CF group
3
can be found in Murai’s results of the alkylation of
aromatic esters. Another electron-withdrawing group,
4
e
This work was supported by the KOSEF through the
Advanced Material Research Center for a Better Envi-
ronment at Hanbat National University.
m-CH O, reacted slowly (run 7). m-Methoxy substi-
3
tuted aldimine has two different sites (positions 2 and
6) for alkylation. This alkylation only gave the 6-posi-
tion alkylated product 4e together with small amount
of double alkylated product 5e. The product alkylated
at the 2-position was not detected in the reaction
mixture. This may be due to steric effects. The meta-
substituent interferes with the approach of rhodium
metal for CꢀH bond activation. Thus, the double alkyl-
ated product 5e must come from 4e. Unlike the case of
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