ORGANIC
LETTERS
1999
Vol. 1, No. 12
1977-1979
New Access to 2,3-Disubstituted
Quinolines through Cyclization of
o-Alkynylisocyanobenzenes
Michinori Suginome, Takeshi Fukuda, and Yoshihiko Ito*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of
Engineering, Kyoto UniVersity, Kyoto 606-8501, Japan
Received October 8, 1999
ABSTRACT
o-Alkynylisocyanobenzenes underwent nucleophile-induced intramolecular cyclization to give 2,3-disubstituted quinoline derivatives in high
yields. In addition to the oxygen and nitrogen nucleophiles such as methanol and diethylamine, the nucleophilic carbon of the enolate of
malonate induced the cyclization effectively. Reaction of 1,4-di(trimethylsilylethynyl)-2,3-diisocyanobenzene with methanol afforded 2,9-dimethoxy-
1,10-phenanthroline in good yield.
Cyclization of ortho-functionalized aryl isocyanides has been
an attractive strategy for the synthesis of nitrogen-containing
heterocyclic aromatic compounds. This protocol has provided
an effective synthetic method for five-membered heterocyclic
aromatics including indole derivatives.1-3 On the other hand,
six-membered ring formation with ortho-functionalized aryl
isocyanides has only been reported quite recently.4,5
In a very recent paper, Rainier and co-workers reported
the synthesis of indole derivatives by radical cyclization of
o-alkynylisocyanobenzenes.6 They briefly described the
formation of quinolines as undesired byproducts of the radical
cyclization. The appearance of this paper prompted us to
publish our quinoline synthesis by the cyclization of o-
alkynylisocyanobenzenes.7 Herein, we report a new and
versatile synthesis of substituted quinolines through nucleo-
phile-triggered 6-endo cyclization of o-alkynylisocyano-
benzenes, which are readily available from o-iodoaniline and
alkynes.
o-(Trimethylsilylethynyl)isocyanobenzene (3a) was pre-
pared in high yield from o-iodoaniline (1) and trimethyl-
silylacetylene via Sonogashira-Hagihara coupling and N-
formylation, followed by dehydration (Scheme 1).8 The
compound 3a could be isolated by silica gel column
chromatography.
Scheme 1. Synthesis of
o-(Trimethylsilylethynyl)isocyanobenzene 3a
(1) For anionic cyclizations, see: Ito, Y.; Kobayashi, K.; Saegusa, T. J.
Am. Chem. Soc. 1977, 99, 3532. Ito, Y.; Kobayashi, K.; Saegusa, T.
Tetrahedron Lett. 1979, 20, 1039. Haefliger, W.; Knecht, H. Tetrahedron
Lett. 1984, 25, 289. Orita, A.; Fukudome, M.; Ohe, K.; Murai, S. J. Org.
Chem. 1994, 59, 477.
(2) For Lewis acid mediated cyclization, see: Ito, Y.; Kobayashi, K.;
Saegusa, T. Chem. Lett. 1980, 1563.
(3) For radical cyclizations, see: Fukuyama, T.; Chen, X.; Peng, G. J.
Am. Chem. Soc. 1994, 116, 3127. Shinada, T.; Miyachi, M.; Itagaki, Y.;
Naoki, H.; Yoshihara, K.; Nakajima, T. Tetrahedron Lett. 1996, 37, 7099.
(4) Kobayashi, K.; Matoba, T.; Irisawa, S.; Matsumoto, T.; Morikawa,
O.; Konishi, H. Chem. Lett. 1998, 551.
(5) Synthesis of quinolines by radical reaction of aryl isocyanide with
o-alkynyliodobenzenes was reported. See: Josien, H.; Ko, S.-B.; Bom, D.;
Curran, D. P. Chem. Eur. J. 1998, 4, 67 and references therein.
10.1021/ol991133w CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/12/1999