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Synlett 2008(20): 3115-3120  
DOI: 10.1055/s-0028-1087417
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Novel Synthesis of Pyrido[2,1-a]isoindoles via a Three-Component Assembly Involving Benzynes

Chunsong Xiea,b, Yuhong Zhang*a, Peixin Xua
a Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China
Fax: +86(571)87953244; e-Mail: yhzhang@zju.edu.cn;
b Center for Biomedicine and Health, Hangzhou Normal University, Hangzhou 310012, P. R. of China
Further Information

Publication History

Received 12 July 2008
Publication Date:
27 November 2008 (online)

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Abstract

A novel three-component assembly involving benzynes has been developed for the synthesis of pyrido[2,1-a]isoindoles in moderate yields. Reaction conditions have been optimized and the scope of the reaction has been studied. A plausible mechanism has been proposed to account for the three-component reaction.

Key words

three component - benzyne - aryne - pyrido[2,1-a]iso­indole

    References and Notes

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    Other materials were purchased from common commercial sources and used without additional purification. ¹H NMR spectra were recorded at 400 MHz using TMS as internal standard. ¹³C NMR spectra were recorded at 100 MHz using TMS as internal standard. Mass spectroscopy data of the reaction product were collected on an HRMS (EI) instrument.

13

The CCDC number of the X-ray structure is 701719.

15

General Procedure of the Three-Component Reaction: An oven-dried flask was charged with 2-bromo-1-phenyl-ethanone (0.6 mmol), pyridine (1.0 mmol), CsF (1.5 mmol) and MeCN (3 mL). Benzyne precursor (0.5 mmol) in MeCN (2 mL) was added dropwise under the protection of N2. The reaction mixture was then allowed to react at 80 ˚C for 2 h. After the completion of the reaction, the mixture was cooled to r.t. and filtered through a pad of celite. The solvent was then removed in vacuum, and the final product was obtained by flash chromatography on a silica gel column as a yellow powder.