ORGANIC
LETTERS
2012
Vol. 14, No. 16
4262–4265
Ru(II)-Catalyzed Amidation of
2‑Arylpyridines with Isocyanates
via CÀH Activation
Krishnamoorthy Muralirajan, Kanniyappan Parthasarathy, and Chien-Hong Cheng*
Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan
Received July 18, 2012
ABSTRACT
An efficient Ru(II)-catalyzed amidation of 2-arylpyridines with isocyanates via CÀH bond activation is described.
In recent decades, chelation-assisted CÀH bond activa-
tion and subsequent addition to alkynes, alkenes, and
allenes has attracted increasing attention in metal-
catalyzed organic synthesis.1aÀe These methods have been
broadly applied in the syntheses of natural products,
drugs, and materials.1fÀh Previously, a number of direct
CÀH additions to various polar bonds have been demon-
strated.2 Recently, ortho aromatic CÀH bond activation
and additions across polar unsaturated bonds has been
studied considerably for the construction of substituted
amides and amines at the ortho-position. In this context,
Kuninobu and Takai initially observed a rhenium-
catalyzed addition of aromatic and heteroaromatic aldimine
CÀH to isocyanates leading to the formation of
phthalimidine3a and amidated3b,c derivatives. In 2011, Shi,
Bergman, and Ellman et al. independently developed a
Rh(III)-catalyzed selective CÀH activation and subsequent
addition to N-sulfonyl arylaldimines4 and boc-imines5a
respectively. Very recently, Bergman and Ellman reported
a synthesis of N-acyl anthranilamides and β-enamine amides
via Rh(III)-catalyzed amidation of aryl and vinyl CÀH
bonds with isocyanates.5b However, these methods re-
quired an expensive catalyst or harsh reaction conditions.
Recently, the use of Ru(II) complexes as inexpensive,
readily available, and environmentally friendly catalysts
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r
10.1021/ol302000a
Published on Web 08/08/2012
2012 American Chemical Society