ORGANIC
LETTERS
2012
Vol. 14, No. 7
1876–1879
Highly Efficient Synthesis of
N-Substituted Isoindolinones and
Phthalazinones Using Pt Nanowires as
Catalysts
Linyan Shi,† Lei Hu,† Jiaqing Wang,† Xueqin Cao,*,†,‡ and Hongwei Gu*,†
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering and Materials Science, and National Engineering Laboratory for
Modern Silk, Soochow University, Suzhou 215123, China
xqcao@suda.edu.cn; hongwei@suda.edu.cn
Received February 24, 2012
ABSTRACT
A series of N-substituted isoindolinones have been successfully synthesized through the reductive CÀN coupling and intramolecular amidation
of 2-carboxybenzaldehyde and amines. This one-pot synthesis gives excellent yields using ultrathin Pt nanowires as catalysts under 1 bar of
hydrogen. These unsupported catalysts can also be used for the synthesis of phthalazinones in high yield when hydrazine or phenyl hydrazine is
used instead of amines.
The importance and widespread use of the isoindolinone
skeleton in many drugs, of natural and synthetic origin,
has led to interest in its synthesis.1 Much effort has been
focused toward preparing 3-substituted isoindolinones.2
N-Substituted isoindolinones are common compounds
with important biological activities (Scheme 1).3 Norman
et al.4 described a number of synthetic strategies to obtain
this skeleton, such as the condensation of aminoalkanols
with phthalide, reacting 2-(bromomethyl)benzoate with
primary amines, and the monoreduction of phthalimide
followed by alkylation of the isoindolinone. Beller5 devel-
opedanovel monoreduction ofphthalimide usinglow-cost
polymethylhydrosiloxane and fluoride ions as a catalyst,
giving up to 78% yield. Transition metal catalysis like
† Key Laboratory of Organic Synthesis of Jiangsu Province.
‡ National Engineering Laboratory for Modern Silk.
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ꢀ
6
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€
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€
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r
10.1021/ol300471a
Published on Web 03/15/2012
2012 American Chemical Society