amount of bromobenzene (2a, 1.5 mmol) under similar
reaction conditions, except for the increased amount of
K CO (2.0 mmol), the ratio of diphenylated product 4aa
2 3
was increased to 61:39 with a good yield of 92%; however,
the formation of monophenylated product 3aa was still
predominant (entry 2). Steric interaction between the first
introduced phenyl group and the methyl group on the imino
moiety would prevent the second phenylation. Although
introduction of an ethyl group on the imino moiety (1d) was
expected to increase the ratio of monophenylated product
substituents on the arylbromides. As shown in entries 11-
14, all of the reactions proceeded smoothly, affording only
the monoarylated products selectively in good yield. Alk-
enylation was also observed when 1g was treated with
1-bromo-2-methylbutene (2f) to afford monoalkenylated
product 3gf in 73% yield (entry 15).
As was proposed in our previous paper for arylation of
7
pyridylbenzenes, tetravalent aryl- or alkenylruthenium spe-
cies is considered to be a key intermediate, which is
generated by the oxidative addition of bromide 2 to ruthe-
nium(II) complex. A presumed reaction mechanism is shown
in Scheme 2. The tetravalent arylruthenium complex 5 reacts
3da, the ratio was similar to that from 1a (entry 3). On the
other hand, the imine from benzaldehyde (1e) bearing a
hydrogen on the imino group underwent diphenylation
predominantly (3ea:4ea ) 10:90) even when 1.2 equiv of
bromobenzene was used (entry 4). Thus the use of an excess
amount of bromobenzene (3 equiv) gave only diphenylated
product 4ea in a good yield of 92% (entry 5).
Scheme 2
The reaction of imine 1f bearing a methyl group at the
ortho position of the benzene ring with bromobenzene gave
only 17% yield of product 3fa (entry 6). The low yield can
be also explained by steric interaction between the o-methyl
group and the methyl group on the imino moiety. m-Methyl
substituted imine 1g underwent the arylation only at the less
hindered ortho position where monophenylated product 3ga
was formed exclusively in 83% yield (entry 7). Similarly,
imines having substituents at the meta position of the benzene
rings (1h and 1i) gave only monophenylated products, 3ha
and 3ia, selectively in very good yield (entries 8 and 9).
These results also indicate that the reaction is compatible to
either an electron-withdrawing or -donating substituent on
the reacting aromatic ring. The reaction of imine 1j bearing
a methyl group at the para position gave both mono- and
diphenylated products (3ja and 4ja) in 81% total yield with
a 3ja:4ja ratio of 67:33 (entry 10).
electrophilically with reactant 1 by the aid of the chelation
of the imino group to yield the arylated ruthenacycle 6, and
the reductive elimination of ruthenium affords the product
3.
In conclusion, the reaction reported herein provides a new
method of direct arylation and alkenylation of the ortho
position of imino group substituted aromatic compounds with
the corresponding organic halides. The imino group acts as
a directing group of the ortho metalation. Further investiga-
tions to extend the scope of these reactions are currently in
progress.
The arylation of m-methyl-substituted imine 1g with
substituted bromobenzenes were then examined. The present
arylation reaction also showed good compatibility with the
(
8) (a) Kakiuchi, F.; Yamauchi, M.; Chatani, N.; Murai, S. Chem. Lett.
1
996, 111. (b) Kakiuchi, F.; Sato, T.; Tsujimoto, T.; Yamauchi, M.; Chatani,
N.; Murai, S. Chem. Lett. 1998, 1053. (c) Kakiuchi, F.; Tsujimoto, T.;
Sonoda, M.; Chatani, N.; Murai, S. Synlett 2001, 948. (d) Lim, Y.-G.; Han,
J.-S.; Yang, S.-S.; Chun, J. H. Tetrahedron Lett. 2001, 42, 4853.
(9) Deprotection of benzylamines: (a) Bravo, P.; Capelli, S.; Crucianelli,
M.; Guidetti, M.; Markovsky, A. L.; Meille, S. V.; Soloshonok, V. A.;
Sorochinsky, A. E.; Viani, F.; Zanda, M. Tetrahedron 1999, 55, 3025. (b)
Amii, H.; Kishikawa, Y.; Kageyama, K.; Uneyama, K. J. Org. Chem. 2000,
Acknowledgment. This work was partly supported by
Grant-in-Aid for Scientific Research (no. 13555250) from
JSPS (Japan Society for the Promotion of Science) and
Konica Award in Synthetic Organic Chemistry, Japan.
6
5, 3404.
10) Representative Procedure. (Table 1, entry 3) A mixture of 1d
119.7 mg, 0.5 mmol), 2a (94.2 mg, 0.6 mmol), K2CO3 (138 mg, 1.0 mmol),
(
(
6
PPh3 (13.1 mg, 0.05 mmol), and [RuCl2(η -C6H6)]2 (6.3 mg, 0.0125 mmol,
available from Aldrich) in 1 mL of dried NMP was stirred at 120 °C for 20
h under a N2 atmosphere in a Schlenk tube. The reaction mixture was diluted
with 20 mL of Et2O, washed with water (20 mL × 3), and dried over
MgSO4. After the solvent was evaporated in vacuo, the residue was purified
by silica gel column chromatography (hexanes-EtOAc, 5:1) to give the
phenylated products 3da (112.0 mg, 71%) and 4da (39.2 mg, 20%).
Spherical, neutral silica gel (Silica Gel 60 N, 100-210 µm, Kanto Chemical)
was used for column chromatography.
Supporting Information Available: Characterization
data for 3 and 4. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL025851L
Org. Lett., Vol. 4, No. 10, 2002
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