ORGANIC
LETTERS
2003
Vol. 5, No. 12
2161-2164
Palladium-Catalyzed Rearrangement/
Arylation of 2-Allyloxypyridine Leading
to the Synthesis of N-Substituted
2-Pyridones
Kenichiro Itami,* Daisuke Yamazaki, and Jun-ichi Yoshida*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of
Engineering, Kyoto UniVersity, Yoshida-Honmachi, Kyoto 606-8501, Japan
itami@sbchem.kyoto-u.ac.jp; yoshida@sbchem.kyoto-u.ac.jp
Received April 11, 2003
ABSTRACT
The Pd-catalyzed one-pot rearrangement/arylation of 2-allyloxypyridine is described. The catalyst/base combination of Pd[P(t-Bu)3]2/Ag2CO
3
was found to be optimal for this one-pot rearrangement/arylation. The initial rearrangement of 2-allyloxypyridine was found to be catalyzed by
both Pd(0) and Pd(II) complexes with different mechanisms.
N-Substituted 2-pyridones, as exemplified by camptothecin1
and cerpegin,2 have emerged as a new class of compounds
with interesting biological and pharmacological functions3
and, hence, an efficient entry into the N-substituted 2-pyri-
done structure has become an important task in organic
synthesis.4 During the course of our investigation using
2-allyloxypyridine (1) as a substrate for the chelation-
controlled Mizoroki-Heck reaction,5 we have discovered the
Pd-catalyzed one-pot rearrangement/arylation of 2-allyloxy-
pyridine (1) with aryl iodides as a novel synthetic method
for N-substituted 2-pyridones.
In the course of the screening of catalyst and reaction
conditions for Mizoroki-Heck reaction of 1, we have
encountered somewhat surprising results. Under the influence
of Herrmann’s palladacycle catalyst,6 1 underwent the
expected Mizoroki-Heck arylation with iodobenzene (Scheme
1). However, when we switched the arylating agent from
iodobenzene to bromobenzene and base from NaOAc to Cy2-
NMe, quantitative conversion of 1 to N-allyl-2-pyridone (2)
was observed (Scheme 1). Although somewhat apart from
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Ferrari, A.; Biasotti, B.; Merlini, L.; Penco, S.; Gallo, G.; Marzi, M.; Tinti,
M. O.; Martinelli, R.; Pisano, C.; Carminati, P.; Carenini, N.; Beretta, G.;
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(4) (a) Sato, T.; Yoshimatsu, K.; Otera, J. Synlett 1995, 845. (b) Liu,
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(5) (a) Itami, K.; Mitsudo, K.; Kamei, T.; Koike, T.; Nokami, T.; Yoshida,
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10.1021/ol0346234 CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/08/2003