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Synthesis 2010(6): 1000-1008  
DOI: 10.1055/s-0029-1218632
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Direct, Copper-Catalyzed Functionalization of Pyridines with Alkynes

Ramsay E. Beveridgea,b, Bruce A. Arndtsen*a
a Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, QC, H3A 2K6, Canada
Fax: +1(514)3982382; e-Mail: bruce.arndtsen@mcgill.ca;
b Pfizer Global Research and Development, Groton, CT 06340, USA
e-Mail: ramsay.beveridge@pfizer.com;
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Publication History

Received 6 November 2009
Publication Date:
04 January 2010 (online)

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Abstract

A one-pot, copper-catalyzed method to construct 2-alk­ynylpyridines is presented. This provides a route to access these products directly from terminal alkynes and the parent pyridine, and without prefunctionalization of the pyridine core. In addition, (Z)-alk-2-enylpyridines can be prepared via a related procedure. These reactions are used to synthesize a number of new alkynyl- and alkenyl­-substituted pyridines in one pot.

Key words

pyridine - copper - catalytic - alkyne - alkene

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22

Minor amounts of the 2,5-substituted pyridine isomer are observed with the product in Table  [³] , entry 2.

27

The coupling constant J for trans-isomers is always larger (>10 Hz) than cis-isomers and is typically ∼15 Hz for E-alkenylpyridines (see ref. 25).