ORGANIC
LETTERS
2011
Vol. 13, No. 11
2936–2939
Iron-Catalyzed Cycloaddition of
Alkynenitriles and Alkynes
Brendan R. D’Souza, Timothy K. Lane, and Janis Louie*
Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City,
Utah 84102, United States
Received April 14, 2011
ABSTRACT
The combination of Fe(OAc)2 and an electron-donating, sterically hindered pyridyl bisimine ligand catalyzes the cycloaddition of alkynenitriles
and alkynes. A variety of substituted pyridines were obtained in good yields.
The abundance and affordability of iron makes it an
attractive catalyst source. However, until recently, the
number of catalytic processes (other than oxidation1 and
polymerization2) iron complexes could facilitate has
been low. Over the past decade, the quantity of efficient
iron-based catalyst systems has significantly risen.3 For
example, effective Fe-catalyzed cross-coupling chemistry4
and cycloaddition chemistry5 have emerged. To date,
Fe-catalyzed cycloadditions have been mostly limited to
the formation of carbocycles. In 1872, Sir Ramsay demon-
strated that passing acetylene and hydrocyanic acid through
a red-hot iron pipe led to the formation of pyridine.6 Despite
this very early observation, an effective and general Fe-based
catalyst that mediates cycloadditions to form pyridines is still
absent.7 Herein, we describe a general iron catalyst that
couples alkynenitriles and alkynes to form pyridines.8
Given the efficacy of Fe-catalyzed cycloadditions to gene-
rate carbocyclic structures, we surmised that the inability
to prepare pyridines was due to limited reactivity of the
nitrile (i.e., for either oxidative coupling or insertion). Thus,
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10.1021/ol2009939
Published on Web 05/10/2011
2011 American Chemical Society