Synthesis 2012; 44(12): 1809-1817
DOI: 10.1055/s-0031-1290814
special topic
© Georg Thieme Verlag Stuttgart · New York

Tandem Transformations of Nitriles into N-Heterocyclic Compounds by Electrophilic Trapping of Blaise Reaction Intermediates

Ju Hyun Kim
a  Department of Chemistry and Nano Science (BK21), Ewha Womans University, 120-750 Seoul, Korea
,
Yu Sung Chun
a  Department of Chemistry and Nano Science (BK21), Ewha Womans University, 120-750 Seoul, Korea
,
Hyunik Shin*
b  Chemical Development Division, LG Life Science, Ltd/R&D, Daejeon 350-380, Korea, Fax: +82(2)32774505   Email: sanggi@ewha.ac.kr
,
Sang-gi Lee*
a  Department of Chemistry and Nano Science (BK21), Ewha Womans University, 120-750 Seoul, Korea
› Author Affiliations
Further Information

Publication History

Received: 24 February 2012

Accepted after revision: 07 March 2012

Publication Date:
17 April 2012 (online)

Abstract

Tandem transformations of nitriles into various N-heterocycles have been accomplished through the reaction of electrophiles with Blaise reaction intermediates formed in situ. The reaction of the Blaise reaction intermediates with propiolates gives 2-pyridones through consecutive C- and N-nucleophilic reactions. The tandem reactions of the Blaise reaction intermediate with 1,3-enynes proceed through C-nucleophilic addition followed by an electrocyclization–aromatization cascade to give pyridines. Exocyclic enamino esters can be prepared by transformations of ω-chloroalkyl nitriles through chemoselective intramolecular alkylation of the Blaise reaction intermediate. Palladium-catalyzed intramolecular arylations or copper-catalyzed intermolecular cross-coupling reactions of the Blaise reaction intermediate give a range of indole derivatives. Combinations of tandem alkylations and palladium-catalyzed couplings of the Blaise reaction intermediates of ω-chloroalkyl nitriles give N-fused indoles.

 
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