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Synthesis 2011(16): 2567-2578  
DOI: 10.1055/s-0030-1260098
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© Georg Thieme Verlag Stuttgart ˙ New York

Palladium-Catalyzed Construction of Polycyclic Heterocycles by an Alkyne Insertion and Direct Arylation Cascade

Hiroaki Ohno*a,b, Mio Yamamotoa, Mutsumi Iuchia, Nobutaka Fujiib, Tetsuaki Tanaka*a
a Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
Fax: +81(6)68798214; e-Mail: hohno@pharm.kyoto-u.ac.jp; e-Mail: t-tanaka@phs.osaka-u.ac.jp;
b Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
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Publication History

Received 15 May 2011
Publication Date:
08 July 2011 (online)

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Abstract

Cascade cyclization of bromoenynes bearing an aryl group with catalytic amounts of palladium(II) acetate and cesium carbonate led to the direct construction of tri- or tetracyclic heterocycles. Direct arylation of a pyrrole, furan or thiophene ring in the cascade reaction affords the corresponding fused heteroarenes in moderate to good yields.

Key words

tandem reaction - palladium - polycycles - fused-ring systems - ring closure

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11

For example, the reaction of 11b with Pd(OAc)2 (2 mol%) using K2CO3 (2 equiv) as the base stereoselectively gave the monocyclic product 13b in 94% yield (Scheme  [4] ).

Scheme 4

12

A similar result was obtained with malonate congener 19c, which produced diyne 21 in 69% yield (Scheme  [5] ).

Scheme 5