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Synthesis 2011(20): 3332-3342  
DOI: 10.1055/s-0030-1260186
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of 4,4-Disubstituted Piperidine-2-carbonitriles and Piperidine-2,6-dicarbonitriles as Precursors for New α-Amino Acids

Cornelia E. Schmaunz, Klaus T. Wanner*
Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-University Munich, Butenandtstr. 5-13, 81377 Munich, Germany
Fax: +49(89)218077247; e-Mail: klaus.wanner@cup.uni-muenchen.de;
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Publication History

Received 22 June 2011
Publication Date:
24 August 2011 (online)

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Abstract

An easy and straightforward method for the synthesis of 4,4-disubstituted pipecolic acid and piperidine-2,6-dicarboxylic acid derivatives has been developed, based on the addition of cyanide ions to 4,4-disubstituted 1,4-dihydropyridines, which are easily accessible by trapping activated N-silylpyridinium ions with diorganomagnesium reagents. Acidic hydrolysis of the resulting 4,4-disubstituted piperidine-2-carbonitriles and the individual dia­stereomers of the piperidine-2,6-dicarbonitriles led to the corresponding α-amino acids in high yields.

Key words

piperidines - pyridines - carboxylic acids - nitriles - nucleophilic addition - reduction

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