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Synlett 2005(18): 2847-2850  
DOI: 10.1055/s-2005-918944
LETTER
© Georg Thieme Verlag Stuttgart · New York

NH-1,2,3-Triazoles from Azidomethyl Pivalate and Carbamates: Base-Labile N-Protecting Groups

Jon C. Loren, Antoni Krasiński, Valery V. Fokin, K. Barry Sharpless*
The Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, BCC-315, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Fax: +1(858)7845672; e-Mail: sharples@scripps.edu;
Further Information

Publication History

Received 17 August 2005
Publication Date:
12 October 2005 (online)

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Abstract

NH-1,2,3-triazoles have been prepared via the copper(I)-catalyzed 1,3-dipolar cycloaddition between terminal alkynes and three N-protected organic azides, azidomethyl pivalate, azido­methyl morpholine-4-carboxylate, and azidomethyl N,N-diethylcarbamate. These organic azides were easily prepared on 0.1-mol scale in one or two steps from inexpensive commercially available materials. The cleaving properties of N-substituents in the resulting 1,2,3-triazole products with aqueous sodium hydroxide vary from <10 minutes at room temperature in the case of N-methyl pivalate, to 24 hours at room temperature in the case of N-methyl morpholine-4-carboxylate, to 24 hours at 85 °C in the case of N-methyl ­diethylcarbamate.

Key words

triazoles - click chemistry - azides - protecting groups - alkynes - cycloaddition - heterocycles

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Suporting information (experimental procedures, yields and characterizations for compounds 4a-k, 5a-k, 6a-l) is available from the authors upon request . Aryl and alkyl alkyne groups (R′) are found in Table [1] .

13

Azidomethyl N-tert-butyl carbamate was also studied. It is quantitatively removed from the 1,2,3-triazole nitrogen under conditions similar to the morpholine 4-carboxymethyl group. However N,N′-di-tert-butyl urea byproduct complicated product purification.